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Essential
Pediatrics
Seventh Edition
Editors
OP Ghai
Vinod K Paul
Arvind Bagga
Essential
Pediatrics
Seventh Edition
Prof. OP Ghai
Essential
Pediatrics
Seventh Edition
Editors
CBS
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rof. Om Prakash Ghai had a distinguished academic tenure at the Ail India Institute of
P Medical Sciences, New Delhi. He started the Department of Pediatrics in 1959 with six beds
for children. Under his leadership, the department evolved into a multispecialty centre of
international repute.
After his retirement as Dean of the Institute and Professor and Head of the Department of
Pediatrics, he chaired the Department of Pediatrics at the University College of Medical Sciences,
Delhi, where he served until 1991.
Prof. Ghai was President of the Indian Academy of Pediatrics in 1978 and President of the
International College of Pediatrics from 1987 to 1990. The International Pediatric Association
presented him the prestigious 'Insignia of Merit Medallion' (1977) for his outstanding contributions
to child welfare. The Indian Council of Medical Research awarded him the Dr. Kamla Menon
Prize (1983) and Amrut Mody Prize (1985). The Medical Council of India bestowed on him the
Dr. BC Roy Memorial Award for 'Eminent Medical Teacher' (1987). He was also awarded the
Dr. KC Choudhry Oration by Calcutta University (1984) and Prof. JB Chatterjee Oration (1990)
by the Calcutta School of Tropical Medicine. He was awarded the honorary fellowships of the
American Academy of Pediatrics, the National Academy of Medical Sciences and the Indian
Academy of Pediatrics.
Prof. Ghai served as a short-term consultant to the World Health Organization and Asian
Development Bank. He was a member of the Technical Advisory Group of the Control of
Diarrheal Diseases Program of the World Health Organization, Geneva (1987-89). He has been
a member of the Scientific Advisory Boards of the National Institutes of Nutrition, Cholera and
Enteric Diseases, Public Cooperation and Child Development. He was member of the National
Children's Board and several expert groups of the Government of India, UNICEF and Indian
Council of Child Welfare. He was the editor of Indian Pediatrics and World Pediatrics and Child
Care and memPer of the editorial advisory boards of the Annals of National Academy of
Medical Sciences and Indian Journal of Pediatrics.
Professor Ghai was a teacher par excellence, an inspiring leader and a true visionary. His
name shall always remain etched in the annals of pediatrics of our country.
Preface to the Seventh Edition
his edition of the Essential Pediatrics marks the for physicians practising in developing countries.
T completion of more than 25 years of its
existence as a beacon of art and science of
The chapters on hematological,
nervous system and renal disorders have been
endocrine,
pediatrics in the country and beyond. Essential thoroughly updated and reorganized. New
Pediatrics began in 1982 with Dr. OP Ghai as its sections on hypertension, interventional
lead author and founder editor. He directed ana cardiology, newer vaccines, poisonings and
steered this book until his sudden passing away in accidents, national and WHO guidelines on
May 2008. Dr. Ghai was actively involved in the management of common conditions and IMNCI
preparation of this edition, which continues to bear are incorporated. The inclusion of multiple
an indelible imprint of his creative instinct and diagnostic and therapeutic algorithms shall serve
scholarship. as a useful educational resource. Fresh chapters
The present edition comes at a time of on skin and ocular disorders, practical procedures
unprecedented focus and investments on child and rights of children provide a comprehensive
survival and health in the country. There is a review on issues pertaining to the care of children.
heightened interest in child health education and Some of the best-known academics have
training and a global endeavour for improving child contributed to Essential Pediatrics and we are
health. It also comes at a juncture when indebted to them for their scholarly writings. They
subspecialties of pediatrics are taking root in the all have a remarkable understanding of the
country. The coming years will mark a transition of learning needs of the students, and their chapters
pediatrics from the existing priorities such as nutrition reflect the essence of their knowledge and
and infectious diseases to emerging areas such as experience. We are grateful to Dr Aditi Sinha for
genetics, adolescence, intensive care ana care of meticulous work at every stage of the preparation
children with chronic systemic diseases. of this edition. Through tireless effort, she ensured
This edition upholds and advances the accuracy of contents and quality of presentation
traditional core values, focus and scope of the of this edition. Mrs Veena Arora accomplished the
book even as it encompasses significant changes. composing with great patience. We thank the
There are major revisions in most chapters, aimed technical team at our publishers, CBS Publishers &
at meeting the contemporary needs of Distributors, for their tremendous effort in improving
undergraduate and postgraduate medical and the presentation of this book.
nursing students, and pediatricians. The chapters Humbled by the faith reposed by the successive
on growth and development have been rewritten waves of our readers, we are ever conscious of
with inclusion of fresh illustrations and WHO growth our responsibility in ensuring this book's relevance
norms. Chapters on nutrition and neonatology in the changing health scenario, and in the
have been completely revised with emphasis on backdrop of the advances in knowledge. We
practical and evidence-based management of hope this edition would succeed in continuing to
common conditions. The chapter on infections has make a genuine ana lasting contribution towards
also been rewritten keeping in view their relevance the health and well-being of children.
Vinod K Paul
Arvind Bagga
Preface to the First Edition
e health problems of the children in the third chapter on "Nutrition" written by Dr. Tara Gopaldas
? world are the most pressing. Physicians in these
countries often have to work under constraints of
and me from the book Progress in Clinical
Medicine, Series IV, published by Arnold
poor resources and a lack of access to the Heinemann, New Delhi.
modern diagnostic aids. They, therefore, of neces I acknowledge my gratitude to all my
sity require a more exhaustive training in clinical colleagues in the department who gave me
skills and a sharper clinical acumen than their unstinted support and stood solidly beside me in
counterparts more fortunately placed. The present our joint endeavour for upgrading the status of
textbook is primarily aimed to fulfil this need. pediatric services in India. The erudition and
This book covers a broad spectrum of the scholarship of Professors KL Wig and V Ramalinga-
subject, laying a special emphasis on the swami have been a great source of inspiration to
nutritional and infectious disorders. Rare diseases me. I am grateful to Professors PN Taneja and
are referred to only briefly. This has helped to restrict Harish Chandra, who encouraged me to write this
the size of the book to a manageable level so that book.
the undergraduate medical students may find it I take this opportunity to thank Dr. PSN Menon,
handy ana useful. my erstwhile student, now a dear colleague, who
The sections on the applied aspects of anatomy helped me at every stage of preparation of this
and physiology of the various body systems and edition. The book bears an indelible imprint of his
pathophysiology of the disease processes meticulous efforts. I am grateful to my colleague
affecting them will appeal to the postgraduate Dr. HS Wasir for his valuable suggestions on the
medical students. These may help them in section on hypertension. Drs RK Menon,
understanding the biological basis of diagnosis Vedanarayanan and Anil Gupta read through
and management. The sections on the use of several sections and made helpful suggestions.
drugs, clinical approach to the diagnosis and Many medical students, especially Mr. Gurkirpal
details of diagnostic and therapeutic procedures Singh, helped at several stages in preparation of the
will be useful especially for the general book. I am grateful to Messrs Ganguly, Mitra, Ghosh
practitioners and clinical residents. and Awasthi for their help in artwork. Shri Suraj Bhan
Most references used in the preparation of the did the typing work with great patience. Shri JN
manuscript have been cited but if some have Mathur of Mehta Offset Works, toiled painstakingly
been left out through oversight, I offer my sincere to give the finishing touches to the book. Shri SN
apologies. I thank Prof. MMS Ahuja for the Mehta, our publisher, was very co-operative and took
permission to include some excerpts from the a special pride in publishing this volume.
OP Ghai
List of Contributors
Contents
Contents
Contents
Contents
1
2 Essential Pediatrics
weight of the placenta increases to cater to the increased Nutrition: Growth of children suffering from protein-
needs of the baby. There are important functional and energy malnutrition, anemia and vitamin deficiency states
structural changes in the placenta that makes this is retarded. Among the nutrients, calcium, iron, zinc,
adaptation more efficient. The total villous surface area iodine, vitamins A and D, have been closely related to
increases, the diffusion distance decreases, the fetal disorders of growth and development and increase in
capillaries dilate and the resistance in fetoplacental adverse health events in children. On the other hand
vasculature falls. This positive remodeling facilitates the overeating and obesity accelerate somatic growth.
enhanced nutrient transport across the placenta.
Infections: In India one of the commonest contributors to
Maternal factors: The mother's own fetal and childhood poor childhood growth are infections. Persistent or
growth and her diet, nutrient intake and body composition recurrent diarrhea and respiratory tract infections are
at the time of conception as well as during pregnancy, common causes of growth impairment. Systemic
plays an important role in determining the lifelong well infections and parasitic infestations may also retard the
being of her children. Teenage or advanced age, recent velocity of growth.
pregnancy, high parity and anemia negatively influence
fetal size and health. Maternal tobacco (smoked or Chemical agents: Administration of androgenic hormones
chewed), drug or alcohol abuse also retards fetal growth. initially accelerates the skeletal growth. Ultimately,
Obstetric complications such as pregnancy induced epiphyses of bones close prematurely and therefore, the
hypertension, pre-eclampsia and multiple pregnancies bone growth ceases relatively early in these cases.
produce fetal growth restriction. Both pre-existing chronic
Trauma: Fracture of the end of bone may damage the
systemic disorders (chronic renal failure, congestive heart
growing epiphysis and thus hamper the skeletal growth.
failure) and acquired infections (rubella, syphilis, hepatitis
B, HIV, CMV, toxoplasmosis) influence fetal growth.
Social Factors
Postnatal Period Socioeconomic level: Children from families with high
socioeconomic level usually have a superior nutritional
The growth of the child during postnatal life is determined
by genetic potential other than internal and external state. They suffer from fewer infections because of more
influences. hygienic living conditions.
Sex: The pubertal growth spurt occurs earlier in girls. Poverty. Hunger, undernutrition and infections are closely
However, their mean height and weight are usually less associated with poverty.
than those in boys of corresponding ages at the time of
Natural resources: Plentiful natural resources encourage
full maturity.
industrial and agricultural enterprise in the country.
Intrauterine growth retardation: About 20% of growth Improved nutrition of children in the community is
retarded newborns develop postnatal growth failure and secured when there is a climb in gross national product
short stature. Newborns that have asymmetrical growth and per capita income is high.
retardation, with preserved length are more likely to have
catch up growth in the first 2-3 years and subsequently Climate: The velocity of growth may alter in different
normal stature. seasons and is usually higher in spring and low in summer
Genetic factors: Both chromosomal disorders and other months. Infections and infestations are common in hot
disorders related to gene mutation can affect growth. and humid climate. Weather also has a pivotal effect on
Chromosomal defects like Turner syndrome and Down agricultural productivity, ready availability of food and
syndrome manifest growth retardation. Mutation of a capacity for strenuous labor by the population.
single or multiple genes may result in inherited retar
Emotional factors: Children from broken homes and
dation of growth, e.g. Prader Willi syndrome, Noonan
orphanages do not grow and develop at an optimal rate.
syndrome. While most of these disorders lead to short
Anxiety, insecurity, lack of emotional support and love
stature, some of the genetic defects can also lead to tall
from the family prejudice the neurochemical regulation
stature, e.g. Klinefelter syndrome, Soto syndrome, etc.
of the growth hormone. Parents who had happy
Hormonal influence: Normal development cannot proceed childhood and carry a cheerful personality are more likely
without the right milieu of hormones in the body to have children with similar countenance.
throughout childhood and adolescence. Absence of growth
hormone, thyroxine or cortisol results is dwarfism, Cultural factors: Methods of child rearing and infant
underscoring the importance of these factors in promoting feeding in the community are determined by cultural
growth. These factors influence both somatic and skeletal habits and conventions. There may be religious taboos
growth. During adolescence, androgens and estrogens against consumption of particular types of foodstuffs.
have an important influence on the growth spurt and final These affect the nutritional state and growth performance
adult height. of children.
Normal Growth and its Disorders 3
Parental education: Mothers with more education are more especially in the first few months. Thereafter there is
likely to adopt appropriate health-promoting behaviors, slower but steady rate of growth during mid-childhood.
having a direct and indirect influence on growth and A second phase of accelerated growth occurs at
development. puberty. Growth decelerates thereafter for some time
after that and then ceases altogether.
Consequences of Impaired The Infancy-childhood-puberty (ICP) model
Growth and Undernutrition proposed by Karlberg describes postnatal growth has
3 different biological/endocrinal periods of growth. It
Maternal and child undernutrition is the underlying cause
begins with infancy when growth is principally
of 3-5 million deaths annually, and 35% of the disease
influenced by nutrition. This period is followed by the
burden in children younger than 5 years. It is estimated
childhood period influenced by growth hormone and
that India, has more than 61 million stunted children, 34%
thyroid hormone. And finally the pubertal growth
of the global total. Recent research suggests that several
spurt influenced by sex steroids and growth hormone.
of the major disorders of later life including coronary heart Though simplistic, this model provides an instrument
disease, hypertension and type 2 diabetes, originate in to detect and understand growth failure at various ages.
impaired intrauterine growth and development. These b. Growth pattern of every individual is unique. Order
diseases may be consequences of "programming," of growth in human beings is cephalocaudal and distal
whereby a stimulus or insult at a critical, sensitive period to proximal. During fetal life, growth of head occurs
of early life has permanent effects on structure, physiology before that of neck and arms grow before legs. Distal
and metabolism. The "fetal origins" hypothesis (Barker parts of the body such as hands increase in size before
hypothesis) proposes that alterations in fetal nutrition and upper arms. In the postnatal life, growth of head slows
endocrine status result in developmental adaptations that down but limbs continue to grow rapidly. Head control
permanently change structure, physiology and which involves the use of neck muscles develops early.
metabolism, thereby predisposing individuals to It is followed by coordination of spinal muscles and
cardiovascular, metabolic and endocrine disease in adult effective use of hands. Creeping and crawling which
life. As a result, infants born low birth weight have entails the use of legs is learnt later.
increased risk of diabetes, hypertension, coronary artery c. Different tissues of the body grow at different rates (Fig.
disease and hyperlipidemia in adult life. 1.1)
General body growth: The general body growth is rapid
LAWS OF GROWTH
during the fetal life, first one or two years of postnatal life
a. Growth and development of children is a continuous and also during puberty. In the intervening years of mid
and orderly process. There are specific periods in a childhood, the somatic growth velocity is relatively
child's life when the rate of growth is steady, accelerates slowed down.
and decelerates (Table 1.1). The fetus grows fast in the
first half of gestation. Thereafter, the rate of growth is
slowed down until the baby is born. In the early
postnatal period the velocity of growth is high,
The brain growth: The brain enlarges rapidly during the To determine the skeletal age, in infants between 3 and
latter months of fetal life and early months of postnatal 9 months, radiograph of shoulder is most helpful. A single
life. At birth, the head size is about 65 to 70% of the film of hands and wrists is adequate in children between
expected head size in adults. It reaches 90% of the adult the ages of 1 and 13 years. For children between 12 and 14
head size by the age of 2 years. Thus, the fetal phase and years, radiographs of elbow and hip give helpful clues.
the first two years are crucial periods for brain
development and thereafter for acquiring neuromotor Eruption of Teeth
functions and cognitive ability. Primary teeth: The teeth in the upper jaw erupt earlier than
those in the lower jaw, except for lower central incisors.
The growth of gonad: Gonadal growth is dormant during
childhood and becomes conspicuous during pubescence. Permanent teeth: These erupt in the following order; 1st
molar 6-7 years; central and lateral incisors 6 to 8 years;
Lymphoid growth: The growth of lymphoid tissue is most
canines and premolars 9 to 12 years; second molars 12
notable during mid-childhood. During this period, the
years; third molars 18 years or later.
lymphoid tissue is overgrown and its mass may appear
to be larger than that of the fully mature adult. A sign of Growth of body fat and muscle mass: Body tissues can be
this accelerated lymphoid growth is the frequent finding divided into fat and fat free components. The lean body
of large tonsils and palpable lymph nodes in normal mass includes muscle tissue, the internal organs and
children between ages of 4 to 8 years. skeleton. It contains only a small amount of fat. The
growth in lean body mass is primarily due to increase in
SOMATIC GROWTH muscle mass. Lean body mass further corelates closely
with stature. Taller children have greater lean body mass
Skeletal Growth than shorter children of the same age. After the pubertal
growth spurt boys have greater lean body mass compared
Skeletal growth is a continuous process occurring during
to girls.
the whole of childhood and adolescence. It is steady until
the pubertal growth spurt when it accelerates and Body fat is the storehouse of energy: It is primarily deposited
subsequently slows considerably. The skeleton is mature in the subcutaneous adipose tissue. Girls have more
once the epiphysis or growth plates at the end of long subcutaneous adipose tissue than boys. Moreover the sites
bones fuse to the shaft or diaphysis. This occurs by 18 years and quantity of adipose tissue differs in girls and boys.
or so in girls and by 20-22 years in boys. The degree of Girls tend to add adipose tissue to breasts, buttocks, thighs
skeletal maturation closely correlates with the degree of and back of arms during the adolescence.
sexual maturation. A child who has advanced sexual
maturity will also have earlier skeletal maturation. Skeletal ASSESSMENT OF PHYSICAL GROWTH
maturation is assessed by noting the appearance and
Weight: The weight of the child in the nude or minimal
fusion of epiphysis at the ends of long bones. Apart from light clothing is recorded accurately on a lever or electronic
this the bone mineral density can now be ascertained by
type of weighing scale (Fig. 1.2). Spring balances are less
duel energy X-Ray absorptiometry [DXA]. This method accurate. The weighing scale should have a minimum unit
allows assessment of bone mineral content and density at of 100 gm. It is important that child be placed in middle
different ages. Possibly in the near future it may provide of weighing pan. The weighing scale should be corrected
an accurate tool to assess the skeletal mass, density and for any zero error before measurement.
determine the need for remedial measures in children
found deficient. Length: Length is recorded for children under 2 years of
age. The child is placed supine on a rigid measuring table
Bone Age Estimation
Assessment of bone age postnatally is based on (i) number,
shape and size of epiphyseal centers and (ii) size, shape
and density of the ends of bones.
Tanner and Whitehouse described 8 to 9 stages of
development of ossification centers and gave them
"maturity scoring". Fifty percent of the score was given
for carpal bones, 20% for radius and ulna and 30% for
phalanges. Twenty ossification centers are generally used
for determining the bone age. These include (i) carpal
bones, (ii) metacarpal and patella in both sexes, (iii) distal
and middle 'phalanges in boys and distal and proximal Fig. 1.2 : Beam scale for accurate measurement of weight. The child
phalanges in girls, and (iv) distal and proximal toes. should be nude or in minimal light clothing
Normal Growth and its Disorders 5
Weight: The average birth weight of neonates is about 3 A useful guide for normal range is target height + 7 cm
kg. During the first few days after birth, the newborn loses for girls and target height + 8.5 cm for boys.
extracellular fluid equivalent to about 10% of the body
Head circumference: Head growth is rapid especially in the
weight. Most infants regain their birth weight by the age
first half of infancy. It reflects the brain growth during
of 10 days. Subsequently, they gain weight at a rate of
this period. The head growth slows considerably
approximately 25 to 30 g per day for the first 3 months of
thereafter. Beginning at 33-35 cm at birth the head
life. Thereafter they gain about 400 g weight every month,
circumference gains 2 cm per month for first 3 month, 1
for the remaining part of the first year. An infant usually
cm per month between 3-6 month and half cm per month
doubles his birth weight (taken as 3 kg) by the age of 5
for the rest of the first year of life. The mean head
months. The birth weight triples at 1 year and is four times
circumference is 40 cm at 3 month, 43 cm at 6 month, 46-
at 2 years of age. Thus the weight at 5 months, one year
47 cm at 1 year, 48 cm at 2 years. By 12 years it is 52 cm.
and 2 years is approximately 6, 9 and 12 kg, respectively.
The weight of a child at the age of three years is usually Chest circumference: The circumference of chest is about 3
five times that of the birth weight. At 5 years, the expected cm less than the head circumference at birth. The
weight is calculated by multiplying the birth weight by 6, circumference of head and chest are almost equal by the
at 7 years by 7 and at 10 years by 10. It follows that the age of 1 year. Thereafter the chest circumference exceeds
expected weight at 3, 5, 7 and 10 years is approximately the head circumference.
15, 18, 21 and 30 kg, respectively. On an average, a child Body mass index (BMI): The formula to calculate BMI is
gains about 2 kg every year between the ages of 3 and 7 weight (kg)/height (meter)2. BMI is primarily used to
years and 3 kg per year after that till the pubertal growth assess obesity. BMI at or above the 95th centile for age or
spurt begins (Table 1.2). more than 30 is obesity. Obesity is emerging as an
important health concern all over the world particularly
Table 1.2: Approximate anthropometric values in in affluent populations.
relation to age
Weight Length or Head GROWTH CHARTS
Age
(kg) height (cm) circumfe If the growth measurements are recorded in a child over
Birth 3 50 34 a period of time and are plotted on a graph, the deviation
6 months 6 (doubles in the growth profile of the child from the normal pattern
in 5 months) 65 42 of growth for that age can be easily interpreted. This is a
1 year 9 (triples) 75 45 good tool to diagnose deviation of growth from normal.
2 years 12 (quadruples) 85 47 If the height or weight measurements in a large
3 years 14 95 49 population of normal children are arranged in a regular
4 years 16 100 50 order starting from the lowest, going to the highest, a bell
shaped curve is formed. Most of the measurements fall
around the middle of the curve, which tapers off on either
side because only a few individuals have extreme
Length or height: The infant measures 50 cm at birth, 60 cm
measurements. If the selection and distribution of the
at 3 months, 70 cm at 9 months, 75 cm at 1 year and 90 cm
sampled group is properly stratified and represents the
at 2 years. A normal Indian child is 100 cm tall at the age
group as a whole, the curve should be symmetrical with
of 4 Vi years. Thereafter, the child gains about 6 cm in
nearly half of the observations lying above and half below
height every year, until the age of 12 years. After this,
the median or the 50th percentile. This is called Gaussian
increments in height vary according to the age at the onset
distribution (bell-shaped curve).
of puberty. There is a marked acceleration of the growth
Allowable normal range of variation in observations is
during puberty. The estimated target height is important
conventionally taken between 3rd and 97th percentile
to assess the child's growth potential. The correct
curves or mean ± 2 standard deviation (SD).
acceptable range of height for a child is within two
The term standard deviation (SD) is used to denote the
standard deviations of the target height percentile. Target
degree of dispersion or the scatter of observations away
height is calculated as follows:
from the mean. It is estimated that 68.3% (approximately
Boys (cm) two-thirds) of the observations lie within one standard
deviation (SD) above or below the mean value of the
Father's height (cm) + mother's height (cm)
= ------------------------------------------------------------------------ + 6.5 observations. A range of 2 SD around the mean is expected
2 to include 95.4% of all observations.
Girls (cm) In a typical Gaussian distribution, the median is
expected to be equivalent to the arithmetic mean. The
Father's height (cm) + mother's height (cm)
----------------------------------------------------------------------------- 6.5 mean is obtained by dividing the sum of all observations
2 by the number of observations. The median, on the other
Normal Growth and its Disorders 7
hand, indicates that 50% of observations are above and across the world's major regions when their needs for
50% are below this point. health and care are met. These standards also include new
Percentile curves represent frequency distribution growth indicators beyond height and weight that are
curves. For example, 25th percentile for height in a particularly useful for monitoring the increasing epidemic
population would mean that height of 75% of individuals of childhood obesity, such as the skinfold thickness. The
is above and 24% are below this value. One standard study's longitudinal nature will further allow the
deviation above the mean coincides with 84th percentile development of growth velocity standards, enabling the
curve. Likewise 16th percentile curve represents one early identification of children in the process of becoming
standard deviation below the mean. under or over-nourished.
Z scores: In a population with observations in a typical Figures 1.8 to 1.17 provides percentile curves for weight,
Gaussian distribution, any individual value can be length/height, weight for height and head circumference
expressed as how many standard deviations it lies above for girls and boys upto 5 years of age based on WHO
standards. Tables 1.3A and B and 1.4A and B summarize
or below the mean. This is the Z score for that observation.
the data on length, weight and head circumference for
Thus if a child's weight is at 2 SD below the mean, it is
these children. Tables 1.5A and B show data on height,
equivalent of -2Z. If the value lies above the mean, Z score
weight and body mass index in girls and boys,
is positive, otherwise it is negative. The formula for
respectively, between 5 to 10 years of age. Detailed growth
calculating the Z score is:
charts are available at http://www.who.int/
Observed value-mean value childgrowth/standards/en.
Z scorG = --------------- ----------------------------------------
Standard deviation
VELOCITY OF GROWTH
Z score allows comparison of different observations in
an individual. For example, one can compare the height Plotting a child's height and weight on a growth chart
and weight of an individual by obtaining the respective helps to determine if he or she is within the expected
Z score. normal range for his or her age. One time measurement,
however, does not indicate if the rate of growth of the
Growth Standards child has been normal in the recent past. Likewise, a clearly
Growth standards represent norms of growth and can be abnormal percentile position on the growth chart becomes
presented in tabular or graphical manner. These are evident only when the factors retarding growth are
obtained by either cross-sectional or longitudinal studies profound or if they have persisted for a considerable time.
in large populations. Based on data obtained from US On the other hand serial measurements provide rate of
children, the National Center for Health Statistics (NCHS) growth per unit time. Plotting growth velocity is a useful
developed growth charts in 1977, which were also adopted supplement to monitor rate of growth in children. Growth
by the WHO for international use. In the year 2000 revised velocity is a better tool for early identification of factors
growth charts provided by CDC offered an improved tool affecting growth and also for assessment of usefulness of
to assess child health. But these charts were again based social and remedial measures. Velocity of growth more
on data obtained from US children who were formula fed. accurately helps in predicting the ultimate adult height.
Sensing the need for more internationally applicable
growth standards, the WHO conducted the "Multicentre GROWTH MONITORING
Growth Reference Study" (MGRS) and published the new
The Indian Academy of Pediatrics has given guidelines
growth charts in 2006. The MGRS was a community-based,
to monitor growth during childhood (Table 1.6). During
multi-country project conducted in Brazil, Ghana, India,
infancy the monitoring is conveniently done during visits
Norway, Oman, and the United States. The children
for vaccination. Later it can be integrated into visits for
included in the study were raised in environments that
vaccination, minor illnesses or into school health
minimized constraints to growth such as poor diets and
programme. During adolescence sexual maturity rating
infection. In addition, their mothers followed healthy
(SMR) staging is an additional measure to be monitored.
practices such as breastfeeding their children and not
smoking during and after pregnancy.
The new WHO Child Growth Standards are unique on
Suggested reading
several accounts. They provide data on "how children 1. World Health Organsiation. http://www.who.int/nutgrowthdb/en.
should grow," and go beyond the traditional descriptive 2. Guidelines on growth monitoring from birth to 18 years. IAP
references. The new standards make breastfeeding the National Guidelines 2006.
3. Graham CB. Assessment of bone maturation—methods and
biological "norm" and establishes the breastfed infant as
pitfalls. Radiol Clin North Am 1972,10:185-202.
the normative growth model. The pooled sample from
4. Agarwal DK, Agarwal KN et al. Physical and sexual growth pattern
the six participating countries makes it a truly international of affluent Indian children from 5-18 years of age. Indian Pediatrics
standard (in contrast to the previous international 1992; 29: 1203-1282.
reference based on children from a single country) and 5. Agarwal DK, Agarwal KN et al. Physical growth assessment in
reiterates the fact that child populations grow similarly adolescence. Indian Pediatrics 2001; 38: 1217-1235.
8 Essential Pediatrics
1 •3A: Summary table of length/height, weight and head circumference (HC) percentiles for girls aged 0-30 months
Length/height (cm) Weight (kg) HC (cm)
Me 3rd 50th 97th 3rd 50th 97th 3rd 50th 97th
percentile c entile centile percentile centile centile percentile centile centile
0 45.6 49.1 52.7 2.4 3.2 4.2 31.7 33.9 36.1
Height
25 80.4 86.6 92.8 9.3 11.7 14.9 44.7 47.3 49.9
:: 1.3B: Summary table of height, weight and head circumference (HC) percentiles for girls aged 31 -£0 months
Height (cm) Weight (kg) HC (cm)
3rd 50th 97th 3rd 50th 97th 3rd 50th 97th
percentile centile centile percentile centile centile percentile centile centile
0
1
2
3
4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Normal Growth and its Disorders 11
1.4B: Summary table of height, weight and head circumference (HC) percentiles for boys aged 31-60 months
Height (cm) Weight (kg) HC (cm)
3rd 50th 97th 3rd 50th 97th 3rd 50th 97th
percentile centile centile percentile centile centile percentile centile centile
Table 1.5A: Summary table of height, weight and body mass index (BMI) percentiles for girls aged 5-10 years
Normal Growth and its Disorders
14 Essential Pediatrics
Fig. 1.15: Weight for height (boys) from 2 to 75 80 85 90 95 100 105 110 115 120
Birth V V ✓
m, 3 Vi, 6, 9,15 mo ✓ ✓ ✓
Table 1.9: Clues to etiology of short stature from Table 1.10: Stepwise investigative work-up for short stature
examination
Level 1 (essential) investigations for short stature
Examination finding Etiology 1. Complete hemogram with ESR
Disproportion Skeletal dysplasia, rickets, 2. Bone age
hypothyroidism 3. Urinalysis including microscopy, osmolality and pH
4. Stool examination for parasites, steatorrhea and occult
Dysmorphism Congenital syndromes
blood
Pallor Chronic anemia, chronic renal
5. Blood - urea, creatinine, venous gas, calcium, phosphate,
failure
alkaline phosphatase, fasting glucose, albumin and
Hypertension Chronic renal failure transaminases
Frontal bossing, Growth hormone deficiency Level 2 investigations for short stature
depressed nasal
1. Serum thyroxin and thyroid stimulating hormone to rule
bridge, crowded
out hypothyroidism
teeth, small penis
2. Karyotype to rule out Turner syndrome in girls
Goiter, coarse skin Hypothyroidism
Level 3 investigations for short stature
Central obesity, striae Cushing syndrome
1. Celiac serology (anti-endomysial or anti-tissue transgluta
minase antibodies) and duodenal biopsy
2. Growth hormone stimulation test with clonidine or insulin
Investigations
and serum insulin-like growth factor-1 (IGF-1) levels.
The investigative work up to be done is guided by clues
from history and physical examination.
Bone age (BA) assessment should be done in all children Salient Clinical Features of
with short stature. The appearance of various epiphyseal Some Causes of Short Stature
centers and fusion of epiphyses with metaphyses tells Endocrine causes: These are discussed in the chapter on
about the skeletal maturity of the child. BA is endocrinological disorders.
conventionally read from radiograph of the hand and
wrist using either Gruelich-Pyle atlas or Tanner- Familial Short Stature
Whitehouse method. BA gives an idea as to what
Familial short stature is the condition in which child is
proportion of the adult height has been achieved by the
short as per the definition of short stature (i.e. height is
child and what is the remaining potential for height gain.
below the 3rd centile) but is normal according to his own
BA is delayed compared to chronological age in almost
genetic potential as determined by the parents' height.
all causes of short stature. Few exceptions to this are
The child is short because the parents are short. These
familial short stature, in which BA equals chronological
children have a normal height and weight at birth and
age and precocious puberty, in which BA exceeds
then show a catch down growth, so that the height and
chronological age. In case of constitutional delay,
weight come to lie on their target (mid-parental) centiles
undernutrition and systemic illness, BA is less than
by the age of 2 years. Subsequently, the growth velocity
chronological age and equals height age. In cases of
remains normal throughout childhood and adolescence.
growth hormone deficiency (GHD) and hypothyroidism,
The body proportion is appropriate and bone age equals
BA may be even less than height age if the endocrine
the chronological age. Puberty is achieved at appropriate
condition is diagnosed late.
age and final height is within the target range.
In all children with disproportionate short stature,
skeletal survey should be done to rule out skeletal
dysplasia and rickets.
Constitutional Growth Delay
The essential screening investigations (also called level These children are born with a normal length and weight
1 investigations) that should be done in all children with and grow normally for the 1st 6-12 months of life. Their
short stature are listed in Table 1.10. If these investigations growth then shows a deceleration so that the height and
are normal and bone age is delayed, level 2 investigations weight fall below the 3rd centile for age. By 2-3 years of age,
should be done. If these investigations are also normal, height velocity again accelerates and they continue to grow
then the diseases that still remain to be excluded are GHD just below and parallel to the 3rd centile with a normal
and malabsorption. If the child's height is borderline short, height velocity. The onset of puberty and adolescent
i.e. between -2 and -3 SD, then it is prudent to wait for 6- growth spurt is also delayed in these children but final
12 months and observe for height velocity. On the other height is within normal limits. Bone age is lower than chro
hand, if the child is significantly short (< -3SD) at nological age and corresponds to the height age. History
presentation or if height velocity over 6-12 months is also of delayed puberty and delayed height spurt is usually
low for age, one should proceed to level 3 investigations. present in one or both parents with eventual normal height.
20 Essential Pediatrics
Some of the differentiating features between Children Born Small for Gestational Age (SGA)
constitutional delay and familial short stature are listed in
Birth weight below the 10th centile for gestational age can
Table 1.11
be caused by maternal, placental or fetal factors. Most of
these babies show catch-up growth by 2 years of age.
Undernutrition
However, an estimated 20-30% of babies born SGA fail
This is one of the commonest cause for short stature in our to show catch up growth and remain short. Subtle defects
country. Chronic undernutrition leads to stunting. A in the Growth hormone- Insulin-like growth factor (GH-
good dietary history and presence of other features of IGF) axis are considered responsible for the short stature.
malnutrition such as low mid-arm circumference and low
weight for height on examination suggest the diagnosis. Management
Skeletal Dysplasias The general principles of management for any child who
presents with short stature include counseling of parents
Inborn errors in the formation of various components of and dietary advice. Parents should be counseled to highlight
the skeletal system can cause disturbances of cartilage and the positive aspects in child personality and not put undue
bone, grouped under the general term chondrodysplasias emphasis on stature. Intake of a balanced diet containing
or skeletal dysplasias. These conditions may be inherited the recommended amounts of macro and micronutrients
or sporadic, and are usually associated with abnormal should also be recommended.
skeletal proportions and severe short stature (except The specific management depends on the underlying
hypochondroplasia, where growth retardation is mild). cause. For physiological causes, reassurance and annual
A careful elicitation of family history, measurement of monitoring of height and weight is sufficient. Dietary
body proportions, examination of the limbs and skull and rehabilitation for undernutrition and treatment of
skeletal survey are required for diagnosis. underlying condition such as renal tubular acidosis or
celiac disease are generally associated with good catch
Genetic Syndromes
up growth.
Turner syndrome with an incidence of 1:2000 live births For skeletal dysplasias, limb lengthening procedures
is a common cause of short stature in girls and should be are offered at few orthopedic centers. For hypothyroidism,
ruled out in all short girls, even if the typical phenotypic levothyroxine replacement is advised.
features are absent. Some other syndromes associated with For GHD, treatment with daily subcutaneous injections
short stature are Down's, Prader-Willi, Russell-Silver and of GH is recommended. GH therapy is also approved for
Seckel syndrome. several other conditions though the doses required are
generally higher and improvement in final height smaller
Psychosocial Dwarfism and more variable as compared to GHD. Some of these
This condition is also known as emotional deprivation conditions are Turner syndrome; children born SGA who
dwarfism, maternal deprivation dwarfism or hyperphagic fail to show catch up growth by 2 years of age and children
short stature. It is seen in children in unhappy homes with chronic renal failure prior to transplant.
where the emotional needs of the child are totally With any form of therapy, monitoring with regular and
neglected. accurate recording of height is mandatory for a good
It is characterized by functional hypopituitarism outcome.
indicated by low IGF-1 levels and inadequate response of
GH to stimulation. Therapy with GH is however, not Suggested reading
beneficial. Good catch-up growth is usually seen when 1. Hintz RL. Management of disorders of size. In Brook CGD,
the child is placed in a less stressful environment and Hindmarsh PC, eds. Clinical Pediatric Endocrinology. London:
nurtured with love and affection. Blackwell Science, 2001:124-39.
Normal Growth and its Disorders 21
Diagnosis Prognosis
Flistory, physical examination and observation of parent-
If managed early and adequately, the prognosis for
child interaction are important. Detailed laboratory
physical growth recovery is good. However, the outlook
investigations are needed only if history and physical for cognitive, emotional and behavioral development is
examination suggest that an organic cause is responsible variable and less certain. The growth and development
for FTT and to localize the systems involved. For initial of these children should be monitored regularly.
evaluation the following investigations are adequate:
Suggested reading
Management
1. Frank D, Silva M, Needlman R. Failure to thrive: Mystery, myth
The goals of management are nutritional rehabilitation, and method. Contemporary Pediatrics 1993;10:114-9.
treatment of organic causes if present and remedial 2. Hank DA, Jiesel SH. Failure to thrive. Pediatr Clin North Am
measures for psychosocial factors involved. 1998;35:1187-205.
Normal and
2 Abnormal Development
Development, the maturation of function with age, is from these, parental attitudes, involvement, education and
reflected by the sequential attainment of various desire for the child also have an impact on the develop
milestones. Matching the formation of new synapses in ment of the child.
the brain, increasingly complex skills are learnt starting
from the more basic capabilities. Appropriate sensory Genetic Factors
input, e.g. through hearing and vision, and secure and There are many genetic causes for developmental delay
responsive relationships help build a healthy brain and subsequent mental retardation (MR). Prominent
architecture that provides a strong foundation for lifelong genetic factors include chromosomal abnormalities (e.g.
learning, behavior, and health. Down syndrome), X-linked MR (fragile X and other
mutations), subtelomeric deletions, single gene disorders
RULES OF DEVELOPMENT ____________
causing disorders of brain formation (lissencephaly) and
To understand this complex process, it would be pertinent other metabolic disorders (phenylketonuria).
to understand a few basic facts about human development.
Maternal Factors
Development is a continuous process, starting in utero and
progressing in an orderly manner until maturity. The A host of factors which impair growth in utero also can
sequence of attainment of milestones is essentially same in potentially affect brain growth, particularly if they are
all children, e.g. all babies learn to babble before speaking severe and/or sustained. Prominent among these are
words or sit before they stand. Variations exist only in the maternal drug or alcohol abuse, pregnanacy induced
time and manner of attainment. As for growth, the process hypertension, hypothyroidism, malnutrition and feto
of development also progresses in a cephalocaudal direc placental insufficiency due to any cause. Acquired
tion. For example, head control precedes trunk control, infections (e.g. STARCH— syphilis, toxoplasmosis, AIDS,
which precedes lower limb control. The control of limbs rubella, CMV, herpes) can have a severe impact on fetal
proceeds in a proximodistal fashion, whereby hand use is physical and brain growth. Exposure to free radicals and
learnt before finger control. Certain primitive reflexes have oxidants in utero (e.g. chorioamnionitis) has been
to be lost before relevant milestones are attained, e.g. incriminated in the causation of cerebral palsy and
palmar grasp is lost before voluntary grasp is attained. developmental impairment. It has been shown that the
The initial disorganized mass activity is gradually overall quality of maternal care can produce lasting changes
replaced by more specific and wilful activity, e.g. when in stress reactivity, anxiety, and memory in the child.
shown a bright toy, a 3-4 month old will excitedly move
all limbs, and squeal loudly whereas a 3-4 year old may Neonatal Risk Factors
just smile and ask for it. Low Birth Weight
Babies with low birth weight include premature babies
FACTORS AFFECTING DEVELOPMENT
and those growth retarded in utero. The latter are more
Development depends on a variety of mutually interactive likely to have developmental impairment. Premature
factors such as hereditary endowment, biological integrity, babies are at risk due to other complications, including
physical and psychosocial milieu and emotional intracranial bleed, white matter injury, hypoxia, hyper
stimulation. bilirubinemia, hypoglycemia, etc.
22
Normal and Abnormal Development 23
Ventral Suspension
The child is held in prone position and then lifted from
the couch, with the examiner supporting the chest and
abdomen of the child with the palm of his hand. In the
newborn the head flops down (Fig. 2.4). At 6 weeks the
child momentarily holds head in the horizontal plane and
by 8 weeks he can maintain this position well (Fig. 2.5).
By 12 weeks he can lift his head above the horizontal plane
(Fig. 2.6).
Prone Position
At birth or within a few days, the newborn turns the head
to one side. At 4 weeks the child lifts the chin up
momentarily in the midline. By 8 weeks, face is lifted up at
Fig. 2.1 : Pull to sit; complete head lag in a newborn 45° and by 12 weeks the child can bear weight on forearms
with chin and shoulder off the couch and face up to 90° (Figs
2.7 and 2.8). At 6 months, he can lift his head and greater
part of the chest while supporting weight on the extended
arms (Fig. 2.9). Between 4 to 6 months, he learns to roll over,
at first from back to side and then from back to stomach. By
the age of 8 months, he crawls (with abdomen on the
ground) and by 10 months, creeps (abdomen off the
ground, with weight on knees and hands).
Fig. 2.4 : Ventral suspension; unable to hold neck in the line with
trunk at 4 weeks
Fig. 2.5 : Ventral suspension; head in line with the trunk at 8-10
Fig. 2.3 : Pull to sit; flexes the head on to chest at 5 months weeks
Normal and Abnormal Development 25
Sitting
By the age of 5 months, the child can sit steadily with
support of pillows or the examiner's hands (Figs 2.10 and
2.11). At first the back is rounded, but gradually it
straightens (Figs 2.10 and 2.11). Fie independently sits with
his arms forward for support (tripod or truly "sitting with
support") by the age of 6-7 months (Fig. 2.12). Steady
sitting without any support generally develops at around
8 months (Fig. 2.13). By 9-10 months he can pivot in sitting
position to play around with toys (Fig. 2.14).
Fig. 2.10: Sitting; back rounded but able to hold head at 8 weeks
Fig. 2.8 : In prone: face, head and chest off the couch at
4 months
Fig. 2.13: Sitting without support at 8 months Fjg. 2.15: Bears almost entire weightat 6 months
Fig. 2.14: Pivoting,- turns around to pick up an object at 11 months Fig. 2.1 6: Stands well at 15 months
Normal and Abnormal Development 27
Fig. 2.21: Mature grasp at 1 year of age, note the use of thumb and
Fig. 2.1 7: Hand resard (between 12-20 weeks) index finger
28 Essential Pediatrics
By offering pellets (smaller object), finer hand skills are Table 2.2: Key fine motor developmental milestones
assessed. By 9-10 months, the child approaches the pellet
by an index finger and lifts it using finger thumb
apposition (Fig. 2.22).
Fig. 2.22: Pincer grasp approach to small objects (index finger and
thumb)
starts smiling back (social smile) when anyone talks to smile (smile without any social interaction), which is
him or smiles at him by 6-8 weeks of age (Fig. 2.27). It is present even in neonates. By 3 months he enjoys looking
important to differentiate social smile from spontaneous around and recognizes his mother. By 6 months, he
30 Essential Pediatrics
vocalizes and smiles at his mirror image, and imitates acts around 100 words by 2 years, at which time 2-3 words are
such as cough or tongue protrusion. He becomes anxious joined to form simple sentences. By 3 years the toddler
on meeting strangers (stranger anxiety) by 6-7 months of continually asks questions and knows his full name. He can
age. At this age he inhibits to "no". At 9 months, he waves give a coherent account of recent experiences and events
"bye-bye" and also repeats any performance that evokes by the age of 4 years (Table 2.4).
an appreciative response from the observers. By 1 year, he
Hearing and Vision
can understand simple questions, such as "where is papa",
"where is your ball", etc. By 15 months he points to objects Adequate sensory inputs are essential for development.
Both normal vision and hearing are of paramount
in which he is interested. By 18 months he follows simple
importance for child development. The ability to see and
orders, and indulges in domestic mimicry (imitates mother
hear are apparent even in the newborn. Thereafter
sweeping or cleaning). At 2 years when asked he can point
maturation of visual and hearing pathways are reflected
to 5-6 familiar objects, name at least 2-3 objects and point
by specific visual and auditory behaviors.
to 3-4 body parts. He begins to count, identify 1-2 colors
and sing simple rhymes by age of 3 years. Much of these Vision
milestones depend on the caretaker's interaction and
The best stimulus to check visual behavior is the primary
opportunities provided to the child. The left and right
caretaker's face. At birth a baby can fixate on and follow a
discrimination develops by 4 years. By this age, the play
moving person or dangling ring held 8-10 inches away
activities are also very imaginative. By 5 years of age, upto a range of 45°. This increases to 90° by 4 weeks and
children can follow 3-step commands, identify four colors 180° by 12 weeks. At around 1 month the baby can fixate
and repeat four digits (Table 2.3). on his mother as she talks to him. At about 3-4 months
the child fixates intently on an object shown to him
Language
("grasping with the eye") it appears that the child wants
Throughout the development of language it is the receptive to reach for the object (Fig. 2.28). Binocular vision begins
ability and understanding which precedes expressive at around 6 weeks and is well established by 4 months.
abilities. Soon after appearance of social smile at around 8- By 6 months the child adjusts his position to follow objects
10 weeks the child begins to vocalize with vowel sounds of interest, but can follow rapidly moving objects only by
ah, uh. At 3-4 months he squeals with delight and laughs 1 year. Later the child displays more maturity in vision
loud. He begins to say ah, goo, gaga by 5 months age. By 6 by not only identifying smaller objects but also being able
months, he uses mono syllables (ba, da, pa). Later, he joins to recognize them.
consonants to form bisyllables (mama, baba, dada). Before
developing true meaningful speech, at around 9-10 months Hearing
the child learns to imitate sounds derived from his native Newborns respond to sounds by startle, blink, cry,
language. At his first birthday he can usually say 2-3 words quieting or change in ongoing activity. By 3 to 4 months
with meaning. At 18 months he has a vocabulary of 10-15 the child turns his head towards the source of sound. If
words. Thereafter, the vocabulary increases rapidly to we check hearing by producing sound IV2 feet away from
the ear (out of field of vision), we can observe a pattern of
evolving maturity of hearing. At 5 to 6 months the child
Table 2.3: Key social and adaptive milestones
Age Milestone
Normal and Abnormal Development 31
Prerequisites
The development assessment should be assessed in a place
which is free from distractions. It is important that the
child should not be hungry, tired, ill or irritated at time of
development assessment. It would be most desirable to
assess him when he is in a playful mood with his mother
around. Adequate time should be spent in making the
child and family comfortable. Observation for alertness,
concentration and skills of the child is an integral part of
assessment.
Equipment
A kit for development assessment typically contains
commonly available articles, including (i) a red ring
(diameter 6-7 cm) tied to a string, (ii) nine red cubes,
(iii) paper pellets, (iv) spoon, (v) cup with handle, (vi) a
Fig. 2.28: Grasping with the eye at 3 months book with thick pages, (vii) picture book, (viii) red pencil,
paper and (ix) doll and mirror. It is a good idea to always
carry a list of key milestones with normal age of their
turns the head to one side and then downwards if a sound achievement (as provided in this chapter) for a ready
is made below the level of ears. In a similar fashion, one reference, else one is likely to forget particularly the
month later he is able to localize sounds made above the personal-social and linguistic domains.
level of ears. By the age of 10 months the child directly
looks at the source of sound diagonally (Fig. 2.29). Steps
History
EVALUATION OF DEVELOPMENT
A detailed history is the starting point for any
Developmental delay is estimated to be present in about development assessment. Observations by parents are
10% of children. It is possible to recognize severe fairly accurate. Hence a well taken history will help in (a)
developmental disorders early in infancy. Speech determining the details of probable risk factors affecting
impairment, hyperactivity and emotional disturbances are development, (b) evaluation of rate of acquisition of skills
often not detected till the child is 3 to 4 years old. Learning and differentiating between delay and regression, and
disabilities are not picked up till the child starts schooling. (c) forming a gross impression about the development age
of the child. This helps to choose the appropriate tools for
further evaluation and confirmation.
Examination
This should be done to (a) assess physical growth and head
circumference, (b) do a physical assessment, particularly
for dysmorphism, stigmata of intrauterine infections and
signs of hypothyroidism, (c) screen for vision and hearing
and (d) neurological examination and primitive reflexes
(if required).
Developmental Assessment
The maximum time should be spent observing when the
baby is with the mother, especially social responsiveness,
alertness, concentration, interest and distractibility. It
would be most appropriate to assess vision and hearing at
the outset so that further observations are not confounded
by lack of sensory stimuli. The vocal responses, particularly
the nature, frequency and quality of the vocalizations is
noted. Subsequently, fine motor skills should be assessed,
including the interest, alertness and rapidity of responses.
The most annoying maneuvers, including assessment of
Fig. 2.29: Diagonal localization of the source of sound at 10 months reflexes, head circumference, ventral suspension and pull
32 Essential Pediatrics
to sit should be done at the end. It is preferable to perform respectively. The same is true for many other milestones
the developmental assessment before the systemic as is shown in Fig. 2.30. The bars illustrate the age range
examination so that the child's cooperation is solicited. By for normal children to attain that particular milestone. This
the end of the evaluation one should be able to arrive at a range of normalcy should always be kept in mind while
conclusion whether the neurological status and cognitive assessing development.
status are within normal range or not. Significant delays on Retardation should not be diagnosed or suggested on a
screening are an indication for a detailed formal assessment single feature. Repeat examination is desirable in any child
of development status. By assessment one can assign who does not have a gross delay. Factors such as recent
developmental quotient (DQ) for any developmental illness, significant malnutrition, emotional deprivation,
sphere. It is calculated as slow maturation, sensory deficits and neuromuscular
disorders should always be taken into account. One should
Average age of attainment
--------- 2—&--------------------- xl00 keep in mind the opportunities provided to the child to
Observed age at attainment achieve that milestone. For example, a child who has not
A DQ below 70% is taken as delay and warrants been allowed to move around on the ground sufficiently
detailed evaluation. by the apprehensive parents may have delay in gross motor
skills. At times there can be significant variations in
Interpretation
attainment of milestones in individual fields, this is called
In babies born preterm corrected age, rather than postnatal "dissociation". For example, a 1 year old child who speaks
age, is used for determining developmental status till two 2-3 words with meaning, has finger thumb opposition (10-
years of age. For example, a child born at 32 weeks 12 months), but cannot stand with support (less than 10
gestation (gestational age) seen at 12 week of age months). In such a situation, look for physical disorder
(postnatal age) should be considered as a 4 week old child affecting a particular domain of development. A child
for development assessment (corrected age). having normal development in all domains except
While drawing any conclusions about development, language may have hearing deficit. Table 2.5 gives the
one should remember the wide variations in normality. upper limits by which a milestone must be attained. A child
For example, let us consider the milestone of "standing who does not attain the milestone by the recommended
alone". The average age for attainment of this milestone limit should be evaluated for cause of developmental delay.
in a WHO survey was 10.8 months. However, the 3rd and The predictive value of different domains of
97th centiles for normal children were 7.7 and 15.2 months development for subsequent intelligence is not the same.
Normal and Abnormal Development 33
The fine motor, personal-social and linguistic milestones skilled caregiver over time to see the rate and pattern of
predict intelligence far better than gross motor skills. In development. Periodic screening helps to detect emerging
fact an advanced language predicts high intelligence in a disabilities as a child grows. However, using clinical
child. Therefore, one should spend sufficient time in judgment alone has the potential for bias, and it has been
assessing these domains. suggested that it would be appropriate to use periodic
screening tools during the course of ongoing develop
Table 2.5: Red flags signs in child development mental surveillance. The caregiver should choose a
standardized developmental screening tool that is
Milestone Age
practical and easy to use in office setting. Once skilled
No visual fixation or following by 2 months with the tool, it can be used as screening method to identify
No vocalization by 6 months at risk children. Some of the common screening tools
Not sitting without support by 9-10 months include the following.
Not standing alone by 16 months
Phatak's Baroda Screening Test
Not walking alone by 18 months
No single words by 18 months This is India's best known development testing system that
Lack of imaginative play at 3 years was developed by Dr. Promila Phatak. It is meant to be
Loss of comprehension, single words or phrases at any age used by child psychologists rather than physicians. It is the
Indian adaptation of Bayley's development scale. It
requires several testing tools and objects. The test items are
Development Screening arranged according to age. The kit is available commer
cially.
Screening is a "brief assessment procedure designed to
identify children who should receive more intensive Denver Development Screening Test
diagnosis or assessment". Such an assessment aids early
The revised Denver Development Screening Test (DDST)
intervention services, making a positive impact on
was restandardized and presented as the Denver II Test
development, behavior and subsequent school
in 1992. The Denver II assesses child development in four
performance. It also provides an opportunity for early
domains, viz., gross motor, fine motor adaptive, language
identification of co-morbid developmental disabilities.
and personal social behavior, which are presented as age
Ideally, all children should be periodically screened but
norms, just like physical growth curves.
in in short of this at least those with perinatal risk factors
should be screened. Trivandrum Development Screening Chart
Advantages of Screening This is a simplified adaptation of the Border development
• They are standardized and the norms are explicitly screening system. It consists of 17 items selected from BSID
stated Baroda norms. It is a simple test and can be administered
• They are more accurate to estimate developmental in 5 minutes by a health worker. It is recommended to be
status than informal clinical impressions used as a mass screening test.
• They reinforce the importance of development to
CAT/CLAMS (Clinical adaptive test/Clinical
caregiver
linguistic and auditory milestone scale)
• They are an efficient way to record observations
• They help identify more children with delay This is an easy to learn scale which can be used to assess the
child's cognitive and language skills. It uses parental report
Limitations of Screening and direct testing of the child's skills. It is used in ages of
Most limitations are due to inappropriate use of the tests 0-36 months and takes 10-20 minutes to apply. It is useful
• The assessor may not be fully trained, may not follow in discriminating children with mental retardation (i.e.
the instructions or the scoring appropriately both language and visual motor delay) and those with
• Relying on the screening test alone to make an communication disorders (low language scores).
assessment
• Using a screening test as a diagnostic tool (as distinct Goodenough Harris Drawing Test
from a preliminary assessment) It is simple nonverbal intelligence test which only requires
• Not following the screening tests with further a pencil/pen and white unlined paper. It is useful as a
evaluations and interventions can be damaging group screening tool. Here the child is asked to draw a
man in the best possible manner. Points are given for each
Developmental Surveillance detail that the child draws in the figure. One can then
Child development is a dynamic process and difficult to determine the mental age by comparing scores obtained
quantitate by a one time assessment. During surveillance and comparing with normative sample. This test allows a
repeated observations on development are made by a quick but rough estimate of a child's intelligence.
34 Essential Pediatrics
2
times ensues. Toilet training should be started after
years of age when the child has spontaneously started
indicating bladder and bowel fullness and is able to follow
mental age of 5 years. The prevalence of enuresis is 7% in
boys and 3% in girls at the age of 5 years and decreases to
3% for boys and 2% for girls by 10 years.
simple instructions. The general ambience should be Classification: Enuresis is classified as primary in which
conducive to learning and free from pressure. the child has never been dry at night and secondary in
Refusal to defecate in the toilet with development of which the child begins bedwetting after remaining
constipation is a common problem in children. This leads continent for 6 months or more. Enuresis may be further
to parental frustration and increased pressure on the child. classified into nocturnal, in which involuntary voiding
Parents should be advised for temporary cessation of toilet occurs only during sleep at night and diurnal in which it
training and making a fresh beginning after some time. occurs during daytime also while child is awake. Primary
36 Essential Pediatrics
nocturnal enuresis (PNE) is the commonest type com Motivational therapy: The components of this therapy are:
prising 90% of all cases of enuresis. • Child should assume active responsible role.
- Keep diary of wet and dry nights.
Etiology: No specific organic pathology is found in the
- Void urine before going to bed.
majority of children with enuresis. An underlying cause
- Change wet clothes and bedding.
for enuresis can be demonstrated in approximately 5% of
• Restrict fluids, especially caffeinated drinks like tea,
children with secondary enuresis and less than 1% of those
coffee and soda in evening.
with primary enuresis. Children with persistent diurnal
• Punishments and angry parental responses to be
incontinence along with features of voiding difficulty are the
avoided.
most likely to have an underlying organic pathology.
• Positive reinforcements to be given for each dry night
A complex interaction of genetic, physiological and
(praise, star chart).
psychological factors is the cause of enuresis in most cases.
The etiological factors can be divided into the following Alarm therapy: This involves using alarm systems to elicit
subgroups: a conditioned response of awakening to the sensation of
a full bladder. This device consists of an alarm, which is
• Genetic: The risk of PNE in a child is 40% if one parent
attached to the child's collar, and a sensor, which is
had it and 70 % if both parents had PNE in childhood.
attached to the child's undergarments. As soon as the child
• Physiological factors: There is some evidence to
starts micturating, the sensor activates the alarm thus
suggest that children with enuresis secrete less
awakening the child. Alternatively ordinary alarm clocks
antidiuretic hormone (ADH) at night, sleep more
can be used to waken up the child prior to the usual time
soundly compared to other children and have
of bedwetting. Gradually after a period of 4-6 months the
delayed maturation of urethral sphincter control.
child starts wakening up to the sensation of full bladder.
• Psychological factors: Secondary enuresis may be
precipitated by acute stressful condition or traumatic The combination of motivational and alarm therapy is
successful in up to 60-70% of children.
experience.
• Increased bladder irritability: Urinary tract infection Pharmacotherapy should be resorted to only if the above
(UTI) and severe constipation with the full rectum measures fail and bedwetting is causing significant
impinging on the bladder can cause enuresis by distress.
increasing the bladder irritability. Imipramine works by altering the arousal-sleep mecha
• Polyuria: Diabetes mellitus or insipidus can present nism. It gives a satisfactory initial response at a dose of
as secondary enuresis. 1-2.5 mg/kg/day, but relapse rate after discontinuation
• Organic causes: Spina bifida (neurological bladder of therapy is high. Cardiac conduction disturbance is a
dysfunction), ectopic ureter. serious adverse event effect. This medication is rarely
• Giggle and stress incontinence cause diurnal enuresis used.
in young girls. Oxybutinin is an anticholinergic drug that reduces
• Micturition deferral (waiting till the last minute to uninhibited bladder contractions. It is useful in children
void) is a common cause of diurnal incontinence in who have significant daytime urge incontinence besides
younger children. nocturnal enuresis. The dose is 10-20 mg/day.
Assessment: A careful history should be taken to determine Desmopressin (DDAVP) (10 pg orally or intranasally) works
whether the enuresis is primary or secondary, whether by reducing the volume of urine produced at night. The
any daytime symptoms are present and whether any relapse rate is high after stopping of the drug. Its fast onset
voiding difficulty is present. In cases of secondary of action makes it a good choice for special occasions like
enuresis, history should be taken to rule out acute stressful staying out for the night. Water intoxication and
conditions, polyuria and features of bladder irritability hyponatremia are rare adverse effects.
such as frequency and urgency. Physical examination
should focus on spinal anomalies. Laboratory test should Indiscipline and Temper Tantrums
include complete urinalysis for all children and urine A parent's ability to discipline and teach is central to
culture for all with secondary enuresis. Additional studies raising emotionally healthy children who can learn societal
like radiograph of dorso-lumbar spine, ultrasonography rules, live, play and eventually work with others.
or urodynamic study may be done if indicated by history Modelling desirable behavior by their own language and
or examination. actions is the most effective tool for disciplining children.
The reaction to unwanted behavior should be consistent,
Treatmen t: No treatment is recommended in children below
logical and reasonably immediate.
6 years of age because of high spontaneous cure rate. The
Punishment is best given in the form of loss of privileges
first line of treatment should be non-pharmacological.
such as not allowing to watch a favourite television show
Non-pharmacological therapy comprises motivational or playing with friends for a day. Physical punishment is
therapy and use of alarm devices. commonly used by parents to make the child stop the
Normal and Abnormal Development 37
unwanted behavior quickly. However, this gives the Diagnosis is quite simple due to typical history and
subconscious message to the child that aggression toward settings in most cases. The differential diagnoses include
another person can get the desired results. Children may seizures, cardiac arrhythmias or brainstem tumor or
feel that the punishment has cancelled the crime, allowing malformation. History of provoking event, stereotyped
the unwanted behavior to be repeated on some other pattern of events and presence of color change before loss
occasion. Hence this form of punishment should be of consciousness help in distinguishing breath holding
avoided. spells from seizures. In case of pallid spells, electro
cardiogram can be done to rule out conditions associated
Temper Tantrums with cardiac arrhythmias such as long QT syndrome.
From the age of 18 months to 3 years, the child begins to
Management
develop autonomy and starts separating from primary
caregivers. At this age they also develop negativism, that Parents' worries are allayed by doing a thorough
is, they do things opposite to what has been requested. examination of the child and explaining the mechanism of
When they cannot express their autonomy they become breath holding spells. Both parents as also the grandparents
frustrated and angry. Some of these children show their if staying with the child should be counseled together. They
frustration, opposition and defiance with physical should be asked to be consistent in their behavior with the
aggression or resistance, such as biting, crying, kicking, child. During the episode, they should pinch the child at the
pushing, throwing objects, hitting and head banging. This onset of the spell and should not exhibit undue concern or
kind of behavior is known as temper tantrum. This excessively cuddle the child as this reinforces the 'gain' in
behavior reaches its peak during second and third year of attention. Iron supplementation (3 mg/kg/day) is
life and gradually subsides by the age of 3 to 6 years as definitely effective in children with iron deficiency. Its role
the child learns to control his negativism. in children without iron deficiency is not yet clear.
Parents should be advised to talk to the child about Molecular genetic studies have identified abnormalities
his/ her fears or anxieties. Indulging in some enjoyable in dopamine transporter gene and thyroid receptor beta
activity like reading a story to the child at bedtime helps gene in some patients.
him/her to relax.
Clinical Manifestations
Thumb sucking is normal behavior in infants and toddlers.
It peaks between the ages of 18-21 months and most These children display some or all of the following
children spontaneously drop the habit by 4 years of age. symptoms (Table 2.6).
Its persistence in older children is socially unacceptable • Inattention and early distractibility
and can lead to dental malalignment. Before 4 years of • Impulsivity
age, parents should be reassured and asked to ignore the • Motor restlessness and hyperactivity
habit. If it persists beyond the age of 4-5 years, the parents • Difficulty with planning and organizing tasks
should gently motivate the child to stop thumb sucking • Emotional lability
and praise and encourage him when he tries to actively Examples of inattentive, hyperactive and impulsive
restrain himself from sucking the thumb. Application of behavior included within the criteria for diagnosis of
noxious agents over the thumb is useful as an adjunctive ADHD are listed in Table 2.6. For making the diagnosis,
second-line treatment in motivated children. the behavior must begin before 7 years of age, be present
for at least 6 months, be pervasive (present in at least 2
Tics are involuntary and purposeless movements or
different settings) and impair the child's ability to function
utterances that are sudden, spasmodic and repetitive.
normally. The symptoms should not be secondary to
These mostly involve the muscles of eyes, mouth, face and
another disorder.
neck. Tics can range from simple blinking of eyes or facial
twitching to extreme ones like obscene gestures and Diagnosis
vocalizations (coprolalia). The estimated prevalence of tic
Diagnosis is made primarily on clinical grounds after a
disorders is 1-2%, with a 2:1 male preponderance. It is most
thorough clinical interview of parents and use of behavior
common in the school-aged children. According to DSM-
rating scales. Physical examination includes direct
IV, tic disorders are classified into transient, chronic,
observation of the child and ruling out any chronic
Tourette syndrome or 'tic disorder not otherwise specified'.
systemic illness that may affect child's attention span.
Transient tic disorders are characterized by mild tics
Neuropsychological evaluation using standard tests of
which occur several times daily for a period ranging from
general intelligence and educational achievement should
4 weeks to 12 months.
also be done to exclude learning disorders or mental
Chronic tic disorder is much more rarer. It is char
retardation, which may present as ADHD.
acterized by either motor or vocal tics which occur daily
or intermittently for more than a year. The condition may Management
persist in adulthood when tics appear during conditions
of stress or fatigue. The management of ADHD should begin with educating
Tourette syndrome is the severest of the tic disorders. It the parents about the effect of ADHD on child's learning,
begins in early childhood with simple tics like blinking and behavior and social skills and helping them in setting
facial tics. Over a period of time, the child also starts having
complex motor tics like sudden squatting while walking.
These are followed after 1-2 years by vocal tics like grunt Table 2.6: Examples of inattentive and hyperactive/ impulsive
ing, barking and coprolalia. Attention deficit hyperactivity behavior included within the criteria for diagnosis of ADHD
disorder and obsessive compulsive disorders are common Inattentive behavior
comorbid conditions. Dopaminergic antagonists like
1. Early distraction by extraneous stimuli
haloperidol and aypical antipsychotics like quiteapine are
2. Often makes careless mistakes in schoolwork or other
useful in relieving the symptoms.
activities
Psychotherapy also has an adjunctive role.
3. Often has difficulty sustaining attention in tasks or play
activities
Attention Deficit Hyperactivity Disorder
4. Often forgetful in daily activities
Definition and Epidemiology 5. Does not seem to listen to what is being said to him
6. Often fails to finish schoolwork or other chores
It is the commonest neurobehavioral disorder of childhood
affecting 3-5% of school-aged children. It is 3 times Hyperactive/impulsive behavior
commoner in boys.
1. Runs about or climbs excessively in situations where it is
inappropriate
Etiology
2. Fidgets with hands and feet and squirms in seat
For most children, no etiology is identified. Twin and 3. Has difficulty awaiting turn in games or group situations
family studies suggest that genetic factors may play a role. 4. Blurts out answers to questions
Normal and Abnormal Development 39
realistic goals of treatment. The treatment involves a western estimates, 5-15% of school-aged children suffer
combination of behavioral therapy and medications. from dyslexia.
Behavioral therapy: Behavioral modification methods that Etiology: Genetic factors play a strong role. Up to 50% of
have been used with variable success are children of a dyslexic parent and 50% of siblings of a
dyslexic child have dyslexia. Functioning brain imaging in
1. Clear and explicit instructions to the child about
children with dyslexia shows that the temporoparieto-
desirable and non-desirable behavior.
occipital regions of the left cerebral hemisphere do not
2. Positive reinforcement of desirable behavior by
function properly during reading compared to normal
praise or small tangible rewards.
children.
3. Punishment strategies like verbal reprimand, non
verbal gestures or 'time out' for undesirable Clinical manifestations: Dyslexic children have an inaccurate
behavior. and labored approach to reading. They also have difficulty
4. Extinction technique, i.e. systematic ignoring of in spelling because of underlying problem with word
undesirable behavior. decoding. Listening comprehension is typically normal.
Providing a well-structured and organized routine for Dyslexia may co-occur with ADHD in 15-40% of children.
the child at home as well as school is helpful. At school, Diagnosis: Diagnosis of dyslexia is clinical based on
giving brief and consistent instructions to the child, clear presence of "unexpected" difficulties in reading at the level
and consistent response to the child's behavior, seating in of phonologic processing of words.
an area with few distractions and allowing the child to
Management: In younger children, the focus is on
change activities and move about periodically are helpful.
remediation. The affected children are best taught in small
Medications groups, by teachers trained in the principle of phonics.
The children are taught how letters are linked to sounds.
• Stimulants: The 2 main classes of stimulants are
The stress is on improving phonemic awareness, i.e. the
methylphenidate and its derivatives and amphetamine
ability to focus on and manipulate phonemes (speech
and its derivatives. These are the first line treatment for
sounds) in spoken syllables and words. One or two
ADHD and are effective in amelioration of the chief
phonemes are taught at a time with sufficient time spent
complaints of inattention, hyperactivity and impulsivity
on reading and writing words using those phonemes.
in 70-80% of all children. However, no improvement is
Usually these programs improve the reading accuracy
noted in academic achievement or social skills. Adverse
significantly and fluency to a lesser extent.
effects are usually mild and include abdominal
For older children, the management stresses more on
discomfort, loss of appetite and initial weight loss.
accommodation rather than remediation, e.g. use of laptop
• Antidepressants like imipramine and bupropinone are
computers with spell-check, recorded books and giving
considered second-line drugs that are effective in
extra time for writing tests or multiple choice questions
treatment of ADHD, especially in the presence of co-
(MCQ) type of tests.
morbid depression.
Language Delay and Disorders of Communication
Learning Disabilities Stuttering
Learning disabilities are considered to arise from specific Stuttering is a defect in speech characterized by hesitation
neurodevelopmental dysfunctions that prevent expectable or spasmodic repetition of some syllables with pauses.
learning in one or more academic areas. The important There is difficulty in pronouncing the initial consonants
defining principle is that such disabilities are unexpected caused by spasm of lingual and palatal muscles. It is a
given the overall intellectual functioning of the child. common problem affecting up to 5% of children between
These disorders are not the result of global developmental 2-5 years of age, a period in which there is non-fluency of
delay, major vision or hearing handicaps or consequences speech. Environmental and emotional stress or excitement
of major social or emotional stressors. may exacerbate stuttering.
Management: Parents of a young child with primary
Dyslexia stuttering should be reassured that stuttering during the
Dyslexia or specific reading difficulty is the commonest phase of non-fluent speech between the age of 2-5 years
learning disability. It is characterized by difficulty with usually resolves on its own. Making the child conscious of
accurate and/or fluent word recognition and by poor his stutter or pressurizing him to repeat the word without
spelling and word decoding abilities. Word decoding is stuttering will further increase the stress and the stutter.
the ability to apply principles of phonetics to sound the In about 1% of children who continue to have significant
words, i.e. understanding that each letter or letter stuttering, referral to a speech therapist should be advised.
combination in the word has a sound and by combining In older children with late onset of stuttering, the help of
these, the word can be read and spelled. According to a child psychologist should also be sought.
40 Essential Pediatrics
Clinical manifestation: Most commonly, the victims are records of the child. Monitoring by hidden television
infants and young preverbal children. The child's cameras in the ward may be useful. Once the diagnosis is
symptoms, their pattern or response to treatment may not made, the offending caregiver should be confronted,
conform to any recognizable disease and always occurs separated from the child and provided psychotherapy.
when mother is with the child. Apnea, seizures (which
Suggested reading
may be induced by suffocating the child or injecting
1. Mitchell I, Brummet J, De Forest J. Apnea and factitious illness
insulin), fever, diarrhea and skin conditions are the
(Munchausen syndrome) by proxy. Pediatrics 1993;92:810-5.
common symptoms. Confirmation of diagnosis needs 2. American Academy of Neurology: Practice parameter: Screening
careful history, reviewing of all past and current hospital and diagnosis of autism. Neurology 2000;55:468-79.
Adolescent Health
3 and Development
Table 3.2: Emotional and social changes social and economic factors that are beyond the individu
al's control and that can put young people at higher or
• Preoccupied with body image
• Want to establish own identity lower risk of infection. Significant social changes that have
• Fantasy/daydreaming affected the whole society have affected the situation of
• Rapid mood changes, emotional instability the adolescents. Some of these social changes relate to
• Attention seeking behavior broadened opportunities for women who are going to
• Curious, inquisitive school for longer period and entering the workforce in
• Full of energy, restless large numbers. Fostered by other changes like urbaniza
• Self exploration and evaluation tion, liberalization and communication explosion, sexual
• Conflicts with family over control activity during the premarital phase seems to be on the
• Peer group defines behavioral code rise. This again has an impact on the health of the adoles
• Formation of new relationships
cents.
Often, diseases and injuries are a result of an unsafe
environment beyond the control of the adolescents.
VULNERABILITIES DURING ADOLESCENCE
Interpersonal environment (e.g. family and peers),
As seen earlier the very process of growth and develop physical environmental or community settings (e.g.
ment adds to their vulnerability and can have adverse schools), and societal (e.g. mass media, social and cultural
impact on their health. Adjusting to the concurrently oc norms) environment are important factors that contribute
curring physical, mental, emotional, social and behavioral to the vulnerability of adolescents.
changes may pose special challenges and opportunities. Some adolescents are especially vulnerable and hard
Some adolescents become anxious and stressed because to reach and therefore need extra support, they include
of these changes. Owing to tendency to explore and ex those who are denied the opportunities to complete their
periment and express new identity some of them can pick education, live on street, commercial sex workers, with
up a variety of health risk behaviors. mental and physical disability, orphans, adolescents in
Most young people lack access to age and sex conflict and war, and working adolescents.
appropriate health information, skills and services and
have many misconceptions and myths that lead to high ADOLESCENT ‘BODY IMAGE’ AND ITS IMPACT
risk sexual behaviour, mental ill health and social
Body image is an important factor that adds to the vul
problems. This ignorance and myths surrounding adole
nerability of the adolescents. Many of the attitudes, ac
scence also make adolescents vulnerable to consequences tions and behaviours that adolescents develop have body
of inappropriate sexual behaviors, sexual exploitation and image concerns as one of the major underlying factors.
abuse. Most adolescents lack experience and skills in self Body image is defined as "the way a person pictures his
protection that can help them remain safe and healthy— or her own body". It is an important ingredient of our
such as access to health and counseling services and self-concept, helping to determine whether we accept or
contraceptives like condoms. They may thus initiate sexual reject ourselves, whether we feel confident in social rela
behavior and substance abuse during this age and are tionships, and whether we have an idealized or realistic
more likely to have sex with high risk partners or multiple idea of our attractiveness, strength, skills, and sex appeal.
partners but are least likely to use condoms. Body image is comprised of two dimensions: the percep
Owing to rapid urbanization many adolescents tual (evaluation of the size of one's body) and the affec
accompany the immigrating rural population to cities. tive/cognitive (evaluation of abilities).
Adolescents that live on streets come in contact with Normal variations in physical growth, development and
various adults in largely unsupervised conditions and are sexual maturation can be a cause of undue anxiety in some.
exposed to new value systems, modern communications, Comparing themselves negatively to peers for one reason
and unfamiliar or hostile cultures. Adolescents between or the other may lead to loss of self-esteem and a feeling of
10-14 years who are working are exposed to work related inferiority. These may interfere with adolescents' day-to-
and work place hazards. Sexual violence and coercion are day functioning and studies, and may lead to problems in
serious problems, often hidden and unspoken of. These relationships with peers and family, jealousy, arguments
can be severely detrimental to physical and mental health and other negative expressions. Some behaviors that may
during their adult lives. A large number of adolescents, have adverse health outcomes, like early sexual initiation
especially, girls are the victims of trafficking and organized (including sex with commercial sex workers), are liable to
prostitution. The need to recognize adolescents as a vul be determined or influenced by body image concerns. Body
nerable target group and to develop strategies for image disturbances may also lead to anorexia nervosa,
promotion of adolescent health should be emphasized. bulimia, and body dysmorphic disorders.
Adolescents' ability to avoid HIV, STIs, unintended Body image is a powerful factor in coming to terms with
pregnancy or substance abuse depends only partly on how adolescents feel about themselves. Higher levels of
their own individual knowledge and skills. There are other body satisfaction are associated with higher levels of self
44 Essential Pediatrics
esteem. It is important to understand the troubling relation Table 3.3: Important health problems
ship between psychological health and body image while
1. Illness
managing adolescents with body image concerns.
• Problems related to growth and development like
ADOLESCENT SEXUALITY AND SEXUAL BEHAVIOR precocious or delayed puberty and short stature
• Endemic infectious diseases like tuberculosis, malaria
Adolescence brings about sexual changes and maturation 2. Consequences of risk taking behavior
which adds to the vulnerability of the adolescents. The • Unintended injuries: Automobile and sports related
sexual attitude, behaviour and practices of the adolescents accidents
make them vulnerable to many adverse health conse • Intended injuries: Violence, homicide, suicide
quences. Sex drive begins to be expressed in clear terms • STIs, HIV/AIDS
during adolescence, which is a period of heightened • Substance abuse related: tobacco, alcohol, drugs
3. Nutritional problems
feelings, arousal, urges and sexual feelings directed
• Undernutrition
towards self and the others. During adolescence, sexual
• Micronutrient deficiencies like iron deficiency anemia,
exploration and expression is common and normal. The
iodine deficiency
awakened sexual drive and thoughts produce a certain • Obesity
restlessness of character in the youth and they are often • Eating disorders
considered by their elders as different or difficult. 4. Reproductive health problems
Spontaneous erections, nocturnal emissions and • High maternal mortality
masturbation manifest in the mid or early adolescence in • High perinatal mortality, high low birth weight rate
majority of boys. Increased vaginal discharge, tingling and • Abortion related problems
pain in the breasts, masturbation and menstrual concerns • Menstrual problems
may be troublesome for young girls. The mood may • Reproductive tract infections
5. Mental health and related problems
become variable and impulsive. Both boys and girls may
• Behaviour disorders
be troubled, confused and feel guilty because of these
• Stress, anxiety
changes and may find redressal through behaviors that
• Depression and suicide
may be high risk, like smoking, alcohol use and sexual • Substance use
engagement that is more likely to be unsafe increasing • Violence
their vulnerability to STI, HIV, pregnancy and sexual • Other psychiatric disorders
exploitation. Similarly, they may find it difficult to
concentrate and remain distracted. Often, their school
performance or work suffers. This can lead to various within marriage -by 18 years of age. Sexual activity among
kinds of social and family maladjustment. adolescents is much higher and begins at an earlier age
than what is commonly believed. Adolescents thus are
IMPORTANT HEALTH PROBLEMS OF ADOLESCENTS
vulnerable and at risk of unwanted pregnancies due to
Challenges to adolescent health and development are ignorance and lack of access to contraceptives during early
numerous, and often underestimated. In general, teens. Other reproductive health related problems are also
adolescent mortality rates are lower than older age groups on the rise amongst adolescents in the age group 15-19
or childhood, because of which adolescents are generally years. About 10% women and 11% men aged 15-19 had
believed to be healthy - they have survived the diseases self-reported prevalence of sexually transmitted infection
of early childhood, and the health problems associated (STI) or symptoms (NFHS-3). The HIV prevalence is 0.04%
with ageing are still many years away. Table 3.3 lists major among 15-19 years and 0.18% among 20-24 year olds
health problems faced by adolescents. (NFHS-3).
There are significant sex differences in adolescent
Adolescent Nutrition
morbidity and mortality rates. Boys worldwide have
higher rates of morbidity and mortality from injuries due Adolescence is a significant period for physical growth
to interpersonal violence, accidents and suicide, while and sexual maturation. The foundation of adequate
adolescent girls have higher rates of morbidity and growth and development is laid before birth and during
mortality related to sexual and reproductive behaviors. childhood, and is followed in adolescence. Adolescent
growth and development is closely linked to the diet
Adolescent Reproductive and Sexual Health received during childhood and adolescence. Adolescent
In India, 47% of women ages 20-24 years were married growth spurt determines final adult size.
before the legal minimum marriage age of 18 years Proper food and good nutrition are essential for
according to the National Family Health Survey III (NFHS physical growth, mental development, performance,
3; 2005-06). Overall, 12% of women age 15-19 years have productivity, health and well-being of adolescents. The
already become mothers. Forty three percent of women adolescent growth spurt places extra demand on
and 11% of men aged 20-24 had sexual debut - including nutritional requirements. Adolescent girls need additional
Adolescent Health and Development 45
iron to compensate for menstrual blood loss. Over 80% of adolescents because of the rapid physical, psychological,
adolescent growth (attained weight and height) is social and sexual changes during adole-scence. They also
completed in the early part of adolescence (10-15 years). face new challenges as they are expected to assume more
Inadequate nutrition in adolescence can potentially responsibility, form or change relationships, and achieve
retard growth and sexual maturation, over and above the greater independence.
adverse consequences of chronic malnutrition during
infancy and childhood. Improper nutrition (e.g., junk Behavioral Problems
foods) can also affect adolescents' current health as well These include aggressive or disruptive behavior towards
as put them at high risk of chronic diseases later in life, parents, teachers, siblings and friends. These types of
particularly if combined with other adverse behaviors like behaviors are expressed either individually or in a group.
sedentary lifestyle. Risky behavior (such as unsafe sex, hazardous/drunken
driving, smoking), self-harm, physical inactivity,
Undernutrition and Anemia
educational failure and school dropout are associated with
Anemia during adolescent age group is rampant; 56% girls mental health problems.
and 30% boys have hemoglobin less than 13 g/dL (NFHS
3, 2005-06). Undernutrition prevalence is also quite Scholastic Issues
significant; 47% girls and 58% boys of 15-19 years age have
BMI less than 18 (NFHS 3,2005-06). Anemia and undernu Strong emphasis placed on educational achievement has
trition have adverse impact on reproductive health put a lot of pressure on adolescents. This causes a lot of
outcomes, scholastic performance, physical performance stress among adolescents, which could cause psycho
and general productivity. There is an inter-generational somatic symptoms like headaches, eye strain, difficulties
effect in terms of greater prevalence of low birth weight concentrating and sleep problems. Some adolescents are
babies born to undernourished and anemic women. slow or retarded in their development and may not do
well in school.
Overweight and Obesity
Lifestyle changes related to high fat, high carbohydrate Identity Problems
diet and low levels of physical activity have resulted in Adolescence is also a time when adolescents establish their
the rising prevalence of overweight and obese adolescents, individual identities. In today's world where there is so
particularly in urban areas. Overweight and obesity dur much diversity, mobility and opportunities it is a challenge
ing childhood and adolescence continue into adulthood, for adolescents to decide their identities.
increasing the likelihood of a range of health disorders
such as cardiovascular diseases, diabetes, hypertension, Others
stroke, gallbladder disease and some cancers. Obese
Early childbearing and parenthood, unwanted pregnancy,
teenagers are vulnerable to social discrimination. Poor self
abortion, sexually transmitted infection, social stigma and
esteem and body image are consistently associated with
isolation and loss of education opportunity may all impose
obesity in adolescents.
considerable stress on adolescents and could lead to other
Eating Disorders mental health problems or disorders.
Most adolescents are conscious about the changes in their
Tobacco, Alcohol and Other Substance
bodies. They want to conform to the "ideal" body image.
Use Amongst Adolescents
As such, they try unhealthy diets and engage in unhealthy
eating habits that can lead to eating disorders. Eating It is estimated that the most drug users are in the age group
disorders such as bulimia are often caused by anxiety, of 16-35 years with a bulk in the 18-25 years age group.
tension or worry about one's weight. Anorexia nervosa is a Of the nearly 1.15 billion smokers in the world today, low
psychological disorder where people suffer from the and middle-income countries account for 82% of all
mistaken notion that they are fat even though they are smokers. While smoking prevalence is declining steadily
actually thin and weak. in most high income countries, the tobacco epidemic is
Anorexia and bulimia can have serious psychological expanding in developing counties. In most developing
and medical consequences such as metabolic disturbances, countries, a significant percentage of the population
convulsions, renal failure, irregular heart beat and dental belongs to the adolescent and younger age groups.
erosion. In adolescent girls, anorexia can delay the onset of Tobacco use presently causes around 11,000 deaths every
menstruation, minimize stature and result in osteoporosis. day and the number of deaths in the next three decades is
projected at 10 million annually; 70% of these will occur
Mental Health and Adolescents
in the developing countries.
Emotional Problems It is established that almost all tobacco users commence
These include sadness (or grief), anxieties (or worries), use before the age of 18 years. Therefore the young in
anger and stress. Stress is very common among developing countries are now increasingly being targeted
46 Essential Pediatrics
by the tobacco industry to increase sales in order to offset Access to health services for adolescents is an impor
their losses in the developed countries. tant issue. Adolescents are reluctant to go to health centers
In recent years, drug abuse and injectable drug use and seek help for a variety of reasons. Even if they go to a
among young male adolescents has increased. The use of health center for help, they are unsatisfied with the way
alcohol and other drugs is a major contributing factor to in which they are treated. Most health services do not cater
accidents, suicides, violence, unwanted pregnancies and to their needs, are not perceived to be friendly by
STDs including HIV/AIDS among young people. adolescents and are poorly attended by them.
Violence, Injuries and Sexual abuse Urgent action is required to improve the ability of
health workers to respond to needs of adolescent clients
Accidents, interpersonal violence and self-inflicted vio
more effectively and with greater sensitivity and to make
lence are a major cause of morbidity and mortality amongst
health services more accessible and acceptable to them.
adolescents. Maltreatment and abuse including sexual
The phrase 'adolescent friendly health services' (AFHS) has
abuse is a significant, though usually "invisible" cause of
been coined to communicate this idea.
injuries amongst adolescents. Apart from physical injuries
such as bruises and welts, burns and scalds, lacerations and There are a growing number and variety of initiatives
fractures, child and adolescent maltreatment is associated to develop adolescent-friendly services. These include (i)
with a number of other consequences, including: (i) alco to set up adolescent or youth friendly health centers, (ii)
hol and drug abuse; (ii) delinquent, violent and other risk- to make existing ones more 'youth friendly' than they
taking behaviors; (iii) eating and sleep disorders; (iv) repro currently are, and (iii) to deliver services and supplies (in
ductive health problems; (v) post-traumatic stress disorder; a 'friendly' manner) to young people outside the health
(vi) depression and anxiety; and (vii) suicidal behavior and setting, e.g., school linked clinics, market place clinics and
self-harm. workplace clinics, etc.
BODY FLUIDS The compositions of plasma and ISF are roughly similar
(Fig. 4.1) except for the presence of protein in plasma. ECF
Fluid Compartments has a high concentration of sodium, chloride and
Total body water (TBW) constitutes approximately 75% of bicarbonate whereas potassium, magnesium and phos
the body weight at birth and declines to about 60% from phate are predominant intracellular ions. It is important to
the age of 2 years onwards. TBW is compartmentalized note that despite the differences in composition, each
into intracellular (ICF) and extracellular fluid (ECF). The compartment is electroneutral and all have similar
extracellular fluid comprises (i) plasma, (ii) interstitial fluid osmolality (290 mOsm/kg). Water is freely permeable across
and (iii) transcellular fluid. The proportion of extracellular capillaries and cell membranes. In a steady state, there is
water to body weight is about 40% at birth, 25% at 2 years no movement of water across compartments, since water
of age and 20% after the age of 7 years. The proportion of only moves down osmotic gradients. As the major osmotic
plasma at all ages is about 6%, and that of transcellular agent in the ECF is sodium chloride, the regulation of body
water about 2 to 3%; whereas interstitial fluid (ISF) declines water is linked to the regulation of sodium. The ionic
from a maximum at birth to about 18 to 20% of body weight composition of some transcellular fluids is shown in
by 2 years. Plasma along with blood cells constitutes the Table 4.1.
blood volume, and it transports substances to various parts Plasma Interstitial fluid Intracellular fluid
of the body. ISF buffers changes in plasma volume, and is
the medium of exchange of all substances between plasma
and the cells. Transcellular fluid comprises cerebrospinal
fluid, synovial fluid, digestive juices, intraocular, pleural,
pericardial and peritoneal fluids; these have specialized
functions.
Fluid Composition
The distribution of body fluid is determined by the
composition of electrolytes and proteins in different
compartments (Fig. 4.1). Electrolytes exist as ions, namely
cations (positively charged) and anions (negatively
charged). The concentrations of electrolytes are generally
expressed as mEq per liter. The equivalent weight is
calculated by dividing the atomic weight by the valence,
which gives the weight of the substance (in g) that can
combine with or displace 1 g of hydrogen. A thousandth
part of this is a mEq, e.g. if calcium level in blood is 10 mg/
dL (0.1 g/L), then for the atomic weight and valence of 40
and 2 respectively, the calcium level is expressed as 0.1/
40/2 Eq/L or 5 mEq/T. The osmolality of solutions
determines the movement of water across an intervening
semipermeable membrane. Osmolality is expressed as
mOsm/kg, but osmolarity (expressed as mMol/T) is close Fig. 4.1 : Ionic compositions of major fluid compartments, figures
enough for clinical purposes. represent concentration (mEq/L); sizes are not to scale
47
48 Essential Pediatrics
Table 4.1: Cations and anions in biological fluids tract (diarrhea, vomiting), polyuria or decreased intake.
(mEq/L) Patients who have a decrease in the effective circulating
volume may actually have a concomitant increase in total
body water, e.g. nephrotic syndrome, cirrhosis with portal
hypertension and congestive cardiac failure. Regulation of
sodium and water balance is mediated through ADH,
aldosterone and the thirst mechanism. ADH is synthesized
in the anterior hypothalamus and secreted from the
* Upper end of the range for cholera stools, lower end for posterior pituitary. It acts upon the renal collecting ducts
non-cholera to retain free water. Aldosterone is secreted by the adrenal
cortex in response to the production of renin and
angiotensin by the kidney. It increases the reabsorption of
REGULATION OF BODY WATER AND ELECTROLYTES
sodium from the distal convoluted tubules in exchange for
The regulation of water and electrolytes is complex, potassium; water passively follows the reabsorbed sodium.
involving close regulation of water, sodium, potassium and The intake of water is controlled by thirst. Thirst is regulated
divalent ions. by the hypothalamus in response to ECF volume and
osmolality. Atrial natriuretic peptide, released from right
Regulation of Water and Sodium Balance atrial myocytes, is important in disease states, e.g.
For every 100 Calories metabolized, the body loses about congestive cardiac failure. The distension of the right atrium
65 ml water in the urine, 40 ml by sweating, 15 ml from the results in sodium and water loss, reducing cardiac preload.
lungs and about 5 ml in the feces; whereas it gains 15 ml
Regulation of Potassium Balance
from production in metabolic processes. Thus, the net need
of water is 110 ml per 100 Calories metabolized. Loss of Potassium homeostasis is maintained by renal and extra-
water through sweating depends on body surface area, renal mechanisms (Fig. 4.3). Increased serum potassium
temperature and environmental humidity, from the lungs stimulates the production of aldosterone. Aldosterone acts
varies with respiratory rate and humidity of inspired gases upon the distal convoluted tubules to reabsorb Na+. To
and that in the feces depends on the frequency and maintain electroneutrality, K+ are excreted. Aldosterone also
consistency of the stools. The major site of regulation of plays a role in extrarenal potassium homeostasis by
water and sodium is the kidney (Fig. 4.2). causing potassium loss in the colon, in sweat and in saliva.
Fluid loss may be either due to an absolute deficit of ECF Hyperkalemia also stimulates a non-mineralocorticoid
or due to a decrease in the effective circulating volume. Examp dependent exchange of Na+ and K+ at the level of the distal
les of ECF deficit include losses from the gastrointestinal convoluted tubule by a direct stimulation of the Na+-K+-
ATPase pump. Conversely, an increased sodium load in
the tubular lumen results in an attempt by the distal tubule
to conserve Na+; K+ is lost in exchange. There are three
important factors that enhance movement of K+ into the
cells. Alkalosis causes an efflux of H+ from the cells, in
exchange K+ moves intracellularly. Insulin increases corrected for heart rate by dividing by the square root of the
potassium uptake by cells by directly stimulating Na+-K+- RR interval; values greater than 0.22 suggest hypocalcemia.
ATPase activity. P2-agonists act by stimulating cyclic AMP
via adenylate cyclase, which in turn activates the Na+-K+-
ACID-BASE EQUILIBRIUM
ATPase pump.
A neutral solution has equal numbers of H+ and OH' ions.
Regulation of Calcium, Phosphate If the concentration of H+, i.e. [H+], is higher than [OH-] in a
and Magnesium Balance
given solution, that solution is acidic and if [H+] is less
The key factors in the regulation of calcium, phosphate than [OH“] the solution is alkaline. Neutral solutions (e.g.
and magnesium balance are parathormone, 1,25-dihydro- plain water or sodium chloride dissolved in water) have
xyvitamin D3 (calcitriol) and calcitonin. The three key end- 10-7 moles of H+ per liter, and by definition an equal amount
organs are bone, kidney and intestine (Fig. 4.4). Hypo of OHA convenient way to handle information regarding
calcemia is the most potent stimulator of parathormone [H+] is to express it as pH, the negative logarithm of [H+], As
production, whereas hypomagnesemia inhibits hypocal the log of 10-7 is minus 7, the pH of a neutral solution is 7.
cemia-induced stimulation. Para- thormone, in the presence Thus, a change in pH by one unit means a tenfold change
of calcitriol, acts on bone cells to release Ca2+, and to a in [H+],
lesser extent phosphate into the serum. The increased
Buffer systems are mixtures of a weak acid and its
ionized Ca2+ acts through calcitonin, a hormone produced
conjugate base. They resist marked changes in [H+],
by the parafollicular cells of the thyroid, to inhibit Ca2+
provided moderate amounts of acid or base are added to
release from bones. Approximately half the Ca2+ in blood is
them. If a strong acid is added to a buffer system, the H+ is
bound to albumin. Hence, in hypoproteinemia, there is a
taken up by the conjugate base to produce a weak acid. If a
decline in total serum Ca2+ levels, but there is no change in
strong base is added, it combines with the weak acid to
the unbound ionized Ca2+. Since manifestations of Ca2+
produce water and conjugate base. These systems are
disturbance are due to its ionized fraction, it is important
regulated by the Henderson-Hasselbach equation, which
to estimate the latter. This can either be directly assayed, or
shows that the closer the pK of a buffer system is to the
indirectly by either calculating the Q0TC interval on the ECG
desired pH the more powerful is its buffering.
or by adjusting for the serum albumin level (for each 1 g/
dL decline in albumin below 3.5 g/dl, there is a 0.8 mg/dL
base
decline in Ca2+). QC1TC is determined by estimating the Q0T pH = pK + log
acid
interval (beginning of Q wave to beginning of T wave) and
50 Essential Pediatrics
Kidneys
Lungs Tissues Tubular cells Lumen
there had the pH been 7.4 and had the pC02 been 40 torr. hypotonic maintenance fluids were used instead of isotonic
The standard base excess is used in calculating the dose of saline.
bicarbonate and estimate the renal contribution to
bicarbonate retention. DYSELECTROLYTEMIAS
Management Management
In patients with low ECF volume, volume is expanded using If the patient is conscious, the hypernatremia is best
isonatremic solutions intravenously, or, if the patient can managed with standard WHO ORS, with the correction
drink, by administering standard WHO ORS. Patients who being spread over a longer duration than the conventional
are comatose or are seizuring should have their sodium 4-6 hr. Free water or breastfeeds should also be offered to
deficit corrected quickly. Acute hyponatremia may be fatal, the child. Neonates with hypernatremia need increase in
whilst the treatment for this is relatively safe. Such patients milk intake. Supplementary feeds may be required.
should be administered 3-5 ml/kg of 3% hypertonic saline Intravenous fluids are administered only if the patient's
(500 mEq/L) to acutely raise the serum sodium level by 5 sensorium is altered. Acute hypernatremia, which has an
mEq/L. However, in chronic hyponatremia the neurons adjust onset within a few hours, may be treated with sodium free
to the lowered serum osmolality by lowering their own fluids. All other cases of hypernatremia must be corrected
osmolality. Cerebral edema is less severe, but it is the rapid very slowly. The fluid deficit plus the maintenance
treatment that can cause mortality or central pontine requirement of 2 days should be given over a 48 hr period
myelinolysis. In such instances, the sodium requirement is with an infusate which has a sodium concentration
determined as follows: approximately equal to 40 mEq/L. Failure to correct the
hypernatremia slowly may cause cerebral edema. Salt
Sodium deficit (mEq) = [desired Na+-present Na+]
poisoning (serum Na+ >180 mEq/L) requires urgent
x weight x 0.6
dialysis.
The sodium deficit is repaired over 48 hr, at a rate less
than 25 mEq/L over 48 hr.
Hypokalemia (Serum Potassium <3.5 mEq/L)
SIADH is managed by restricting free water but not by
giving more sodium, unless there are seizures. CSW is Causes
treated by administering both increased fluids and sodium. 1. Increased losses
There are reports of the use of fludrocortisone in CSW. i. Diarrhea
ii. Renal: Renal tubular acidosis, cystic kidneys
Hypernatremia (Serum Sodium >150 mEq/L) iii. Endocrine: Cushing syndrome, hyper-aldosteronism
1. Decreased free water intake 3. Shift into intracellular compartment: alkalosis, high
insulin state.
2. High Na+ intake: accidental salt administration in ORS
or infant feeds
3. Increased free water loss Clinical Features
i. Extra-renal: burns, sweating, tachypnea Hypokalemia causes muscle weakness, hypotonia and
ii. Renal: central diabetes insipidus (craniopharyn paralytic ileus; EKG shows ST segment depression, T wave
gioma, granulomatous diseases involving hypo flattening or inversion, prominence of U waves and
thalamus, postoperative); nephrogenic diabetes arrhythmias. Long standing hypokalemia causes a
insipidus vacuolar nephropathy and polyuria. Malnourished
children with diarrhea and dehydration may have severe
Clinical Features hypokalemia.
Nutrition, also called nourishment, is the provision, to cells body are called non-essential amino acids, while others
and organisms, of the materials necessary in the form of known as essential amino acids must be supplied in the
food to support life. Our food is made up of essential, diet because the body cannot synthesize them.
natural complex chemical substances called nutrients. Essential amino acids include: leucine, isoleucine,
There are seven major classes of nutrients: carbohydrates, lysine, methionine, phenylalanine, threonine, tryptophan
fats, fiber, minerals, proteins, vitamins, and water. These and valine. Histidine and arginine are essential during
nutrient classes can be grouped into the categories of infancy because the rate of their synthesis is inadequate
macronutrients and micronutrients. The macronutrients are for sustaining growth.
needed in large quantities (e.g. carbohydrates, fats and
proteins), and are building blocks of the body. The Protein Quality
micronutrients (e.g. minerals and vitamins), on the other Food proteins differ in their nutritional quality depending
hand, are needed in tiny quantities, and are crucial for their on their amino acid profile and digestibility. Cereal grains
role in metabolic pathways and in enhancing immunity. are deficient in the essential amino acids like lysine,
Micronutrients are discussed in Chapter 6. threonine or tryptophan, whereas pulses are rich in lysine
but are limiting in sulphur containing amino acids, mainly
MACRONUTRIENTS methionine. When cereals are taken in combination with
the pulses, the deficiency in one is made good by an excess
Carbohydrates
in other.
Carbohydrates are the main source of energy in the In The following terms are used to describe protein quality:
dian diet contributing to 55-60% of total energy intake.
Nitrogen absorbed
Carbohydrates contribute taste, texture and bulk to the True digestibility (TD) = x 100
diet. Lack of carbohydrates (less than 30%) in the diet may Nitrogen intake
produce ketosis, loss of weight, and breakdown of pro
teins. Carbohydrates are divided into simple carbohydrates Nitrogen retained
(monosaccharide and disaccharides such as glucose and Biological value (BV) x 100
Nitrogen absorbed
fructose in fruits, vegetables and honey, sucrose in sugar
and lactose in milk) and complex carbohydrates (oligo TD
saccharides and polysaccharides such as starch in cereals, Net protein utilization (NPU) x BV
millets, pulses and root vegetables). The main source of 100
energy in the body is glucose derived from starch and Egg protein has the highest values for BV and NPU
sugars present in the diet. Glucose is used as a fuel by the and is therefore taken as the reference protein and the
cells and is converted to glycogen by liver and muscles. value of others is expressed as relative to egg (100).
Excess carbohydrates are converted to fat. Carbohydrates Generally, animal proteins have a higher BV than the plant
provide 4 kcal of energy per gram. proteins. The nutritive value of a mixture of two proteins
may be higher than the arithmetic mean of the two because
Proteins of the mutual supplementary effects.
Proteins are the second most abundant substance in the Requirements: The protein allowances shown in Table 5.1
body, after water. They are required for the growth and are given in terms of the mixed vegetable proteins
synthesis of tissues in the body; formation of digestive contained in Indian diets, the NPU of which is assumed
juices, hormones, plasma proteins, enzymes and hemo to be 65. Nearly 8-12 % of the total energy should be
globin; as buffers to maintain acid-base equilibrium in the provided from protein sources. An intake of 8% proteins
body ; and as alternate source of energy for the body. may be sufficient for those having a higher content of
Proteins are made of 20 different kinds of amino acids. animal proteins or high value proteins in the diet. Proteins
Amino acids that can be adequately synthesized in the provide 4 kcal energy per gram.
57
58 Essential Pediatrics
Nutrition 59
Fats caprylic acid and capric acid. Sources of MCT are coconut
Fats comprise a large and diverse group of compounds oil, palm kernel oil and butter (15% of MCT). MCT im
that are saponifiable esters of long-chain fatty acids (Fig. proves endurance performance, promotes fat burning,
5.1). The major functions of the fats are to act as major spares muscle glycogen, increases metabolic rate and low
structural element of the cell membranes; major source of ers blood cholesterol level. MCT is used in the dietary
energy, carriers of fat soluble vitamins (A, D, E and K); management of cystic fibrosis, pancreatic insufficiency,
precursors for biosynthesis of prostaglandins and hor AIDS, epilepsy, gallstones, high blood cholesterol levels,
mones. fat malabsorption, intestinal lymphangiectasias and as
The fats present in the diet or in human body are in the energy booster in athletes. LCT provides essential fatty
form of fatty acids (triglycerides), phospholipids and cho acids (EFAs) and requires carnitine to produce energy. It
lesterol. The fatty acids are of different carbon chain length is best to provide a combination of both MCT along with
and may be either saturated or unsaturated. There is a LCT because MCT provides immediate energy to critically
great variety in the structure and characteristic of indi ill patients whereas LCT gives EFAs. Prolonged use of
vidual fats, giving different nutritional properties to them. sole MCTs leads to EFA deficiency.
Fats are grouped as saturated or polyunsaturated fats
depending on the predominating fatty acids. Whether the
Essential Fatty Acids (EFA)
fats are solids or liquids at room temperature is largely EFA cannot be synthesized in the body and have to be
determined by the degree of their saturation. The more supplied through dietary fat. Linolenic acid, eicosapenta-
the level of saturation, more solid is the fat. noic acid (EPA) and docosahexanoic acid (DHA) are
About 25-30% of energy intake should be from fat. omega-3 type of fatty acids. EPA and DHA have
However in malnourished children, up to 45% of calories antithrombotic, anti-vasorestrictive, anti-hypertensive and
can be provided from fat safely. In India, almost 10-15% anti-arrhythmic influences. Omega-3 fatty acids also have
of fat is derived from invisible fat. Therefore visible fat anti-inflammatory properties. They are important
intake should be restricted to below 20%. Saturated fat components of gray matter of the brain and improve
should not exceed 7% of the total fat intake; poly intellectual performance. Infants fed omega-3 fatty acids
unsaturated fat should be restricted to 10% and rest 13% have demonstrated better cognitive development than
should be derived from monounsaturated fats. A mini those who are not. It is recommended that omega-3 fatty
mum of 3% energy should be derived from linoleic and acid content of the diet should be about 0.5 % of the total
0.3% from linolenic acid. Fats provide 9 kcal of energy calories or 1.0-1.5 g/day. Most omega-6 fatty acids are
per gram. consumed in the diet in the form of linoleic acid, which
gets converted to y-linolenic acid (GLA) in the body and
Triglycerides
then further broken down to arachidonic acid (AA). Excess
Triglycerides are divided on the basis of chain length into amount of AA/ linoleic acid are unhealthy because they
medium chain triglycerides (MCT; 6-12 carbon length) or promote inflammation. In contrast, GLA reduces inflam
long chain triglycerides (LCT; >12 carbon length). MCTs are mation. Deficiency of EFAs leads to cessation of growth,
an immediate source of energy as they are transported alopecia, diarrhea, impaired wound healing, decreased
directly from the small intestine to liver by portal vein calcium absorption, decreased calcium deposits in bones
and are burned immediately. They comprise primarily of and decreased bone strength.
60 Essential Pediatrics
Cereals, millets and pulses are the major source of most quent intervals to ensure adequate energy intakes by
nutrients in Indian diets. Milk provides good quality pro the child. Energy density of foods given to infants and
tein and calcium and hence, is an essential item of our young children can be increased without increasing the
diet. Eggs, flesh foods and fish enhance the quality of diet bulk by adding a teaspoon of oil or ghee in every feed. Fat
but Indians are predominantly a vegetarian society and is a concentrated source of energy and increases energy
most of our nutrients are derived from cereal/pulse and content of food without increasing the bulk. Sugar and
milk based diets. Oils and nuts are calorie rich foods and jaggery can also be added in infant foods. Amylase rich
are useful in increasing the calorie density. Vegetables and foods (ARF) such as malted foods reduce the viscosity
fruits provide protective substances such as vitamins, min of the foods and therefore, the child can eat more quan
erals, fiber and antioxidants. tities at a time (Malting is germinating whole grain
cereal or pulse, drying and then grinding). Thin gruels
Factors to be Considered while Planning do not provide enough energy; a young infant
a Feed or Food for the Child particularly during 6-9 months requires thick but
There are six cardinal factors to be considered while feed smooth mixtures.
ing the child: 2. Amount of feed: At 6 months of age, feed should be
1. Energy density: Most of our traditional foods are bulky started with small amount as much as 1-2 teaspoons
and a child cannot eat large quantities at a time. Hence, and the quantity is increased gradually as the child gets
it is important to give small energy dense feeds at fre older and starts to accept food better. Child should be
62 Essential Pediatrics
given time to adapt gradually to larger quantities from refers to both undernutrition as well as overnutrition.
teaspoon to table spoon and then to a katori. However, sometimes the terms malnutrition and protein
3. Consistency of feed: Infants can eat pureed, mashed and energy malnutrition (PEM) are used interchangeably with
semi-solid foods beginning at six months. By 8 months, undernutrition. In this chapter the term malnutrition is
most infants can also eat "finger foods" (snacks that used while referring to undernutrition.
can be eaten by children alone). By 12 months, most Malnourished children may also suffer from numerous
children can eat the same types of foods as consumed associated complications. They are more susceptible to
by the rest of the family. Foods that can cause choking infections, especially sepsis, pneumonia, and gastro
such as nuts, grapes, raw carrots should be avoided. enteritis. Vitamin deficiencies and deficiencies of minerals
For small children, the food should not contain and trace elements can also be seen. Malnutrition in young
particulate matter that may trigger gag reflex or children is conventionally determined through measure
vomiting. ment of height, weight, skin-fold thickness (or
4. Frequency of feeding: An average healthy breastfed infant subcutaneous fat) and age. The commonly used indices
needs complementary foods 2-3 times per day at 6-8 derived from these measurements are given in Table 5.3.
months of age and 3^ times per day at 9-24 months.
For children 12-24 months of age, additional nutritious Table 5.3: Indicators of malnutrition
snacks such as a piece of fruit should also be offered 1-
Indicator Interpretation
2 times per day. Snacks are defined as foods eaten
between meals, usually convenient and easy to prepare. Stunting Low height Indicator of chronic mal
If energy density or amount of food per meal is low, or for age nutrition, the result of
the child is no longer breastfed, more frequent meals prolonged food depriva
tion and/or disease or
should be provided.
illness.
5. Hygiene: Good hygiene and proper food handling
Wasting Low weight Suggests acute malnutri
should be practiced to prevent children from infections for height tion, the result of more
and malnutrition. Simple hygiene practices like: (a) recent food deficit or
Washing hands before food preparation and eating, (b) illness.
Serving freshly cooked foods (cooked food should not Under Low weight Combined indicator
be kept for more than 2-3 hours) (c) Using clean utensils weight for age to reflect both acute and
and covered properly, (d) Using clean cups and bowls chronic malnutrition
when feeding children, and (e) Avoiding use of feeding
bottles. As the child grows older, he should be shifted
to more appropriate foods suitable for his age. Epidemiology
6. Helping the child: Feeding the infants and children should Childhood malnutrition is an underlying cause in an
be an active, engaging and interactive affair. Often the estimated 35% of all deaths among children under five
food is left in front of the child to eat. This approach is and 11% of total global Disability Adjusted Life Years
not appropriate. Mother/father should actively engage (DALYs) lost. According to the recently released National
with the child in feeding. Make the child sit in the lap and Family Health Survey, NFHS-3, carried out in 2005-06,
feed him affectionately in small portions with spoon or 40% of India's children under the age of three are
with small morsels. Child is coaxed and encouraged to underweight, 45% are stunted and 23 % are wasted.
finish the desired amount of food. Comparable figures for NFHS-2 (1998-99) are 43%, 51%
and 20 %, respectively (Fig. 5.2).
Suggested reading The proportion of children who are stunted or
1. Ghafoorunissa, Krishnaswamy K. Diet and heart disease. underweight increases rapidly with the child's age (Fig.
Hyderabad, India: National Institute of Nutrition; 2004. 5.3). During the first six months of life, when most babies
2. Dietary guidelines for Indians: a manual. Hyderabad, India:
are breastfed, 20-30% of children are already malnouri
National Institute of Nutrition; 2005.
3. Gopalan C, Rama Sastri BV, Balasubramanian SC, Narasinga Rao shed. By 18-23 months, when many children are being
BS, Deosthale YG, Pant KC. Nutritive value of Indian foods. weaned from breast milk, 30% of children are severely
Hyderabad: National Institute of Nutrition; 1991. stunted and one-fifth are severely underweight. This
4. Venkatachalam PS, Rebello LM. Nutrition for mother and child. clearly shows that the onset of malnutrition in Indian
4th ed. Hyderabad: National institute of Nutrition (ICMR); 1994.
children occurs early, possibly even in utero and is the
consequence of maternal malnutrition and low birth
UNDERNUTRITION
weight.
Undernutrition is a condition in which there is inadequate Levels of malnutrition vary widely across Indian states.
consumption, poor absorption or excessive loss of nutri Punjab, Kerala, Jammu and Kashmir, and Tamil Nadu
ents. Overnutrition is caused by overindulgence or exces account for the lowest proportions of underweight
sive intake of specific nutrients. The term malnutrition children (27 to 33%); while Chhattisgarh, Bihar, Jharkhand,
Nutrition 63
- Stunted
■ Wasted
• Under wt
The current classification includes kwashiorkor and Mid upper arm circumference (MUAC): It is a widely used
marasmic kwashiorkor from older classifications. How measurement and requires minimum equipment. It
ever, to avoid confusion with the clinical syndrome of increases rapidly in the first year (11-16 cm) and then been
kwashiorkor, which includes other features, the term found to be relatively stable between the ages 1 to 5 years
"edematous malnutrition" is preferred. at a value of between 16 and 17 cm. Any value below 13.5
cm is abnormal and suggestive of malnutrition. A value
IAP Classification below 11.5 cms is suggestive of severe malnutrition.
This is based on weight for age values (Table 5.5). The Recently, it has been shown that MUAC may not be age
standard used in this classification for reference popula independent and therefore, the WHO recommends
tion was the 50th centile of Harvard standards. This clas MUAC-for-age reference data to be used in girls and boys
sification scheme is used in the ICDS program. 6-59 months old where possible. Certain tools have been
developed to simplify the measurement for field workers
Table 5.5: IAP classification of malnutrition and give a visible indicator of the degree of malnutrition.
Grade of malnutrition Weight-for-age of the standard Shakir tape method: This special tape has coloured zones-
(median) (%) red, yellow and green corresponding to <12.5 cm (wasted),
Normal >80 12.5 to 13.5 cm (borderline) and over 13.5 cm (normal)
Grade I 71-80 (mild malnutrition) mid upper arm circumference respectively.
Grade II 61-70 (moderate malnutrition)
Bangle test: A bangle with internal diameter of 4 cm is
Grade III 51-60 (severe malnutrition)
passed above the elbow. In severe malnutrition it is
Grade IV <50 (very severe malnutrition)
passable above the elbow in normal children it is not.
Older Classifications Skinfold thickness: It is an indication of the subcutaneous
Older classification like the Waterlow and Gomez classi fat. Triceps skin fold is the most representative of the total
fications do not take edema into account therefore cannot subcutaneous fat upto sixteen years of age. It is usually
differentiate between marasmus and kwashiorkor. The above 10 mm in normal children whereas in severely
Gomez classification also does not discriminate between malnourished it may fall below 6 mm.
wasting and stunting as height is not a part of it. These
Ratios: In addition to the above indices, comparison of
classifications are now rarely used.
environmentally sensitive and environmentally insensi
Age Independent Indices tive measures may yield indicators of environmental
influence which are independent of age. Examples of this
In many situations the child's age is not known, e.g. chil
approach are given in Table 5.6.
dren from orphanages, street children, during natural
disasters, etc., and this has prompted many attempts to
devise methods of interpreting anthropometric data, Etiology
which do not require knowledge of precise age. Some The causes of malnutrition could be viewed as immediate,
measures are relatively labile and susceptible to external underlying and basic as depicted in Fig. 5.4.
influence while others are relatively insensitive. This fact
has been applied in three ways to tackle the problem of Immediate Determinants
interpreting anthropometric data in children whose The immediate determinants of a child's nutritional status
chronological age is unknown. Various variables sensitive work at the individual level. They include inadequate
to external influences change only slowly over certain dietary intake and illness. These two often work
broad age ranges and thus they may be regarded as synergistically and have an immediate effect on the
independent of age over these ranges. nutritional status of the individual.
duration. The best measure of the efficacy of treatment of malnutrition as described above should be looked for. De
mild and moderate malnutrition is weight gain. tailed general and systematic examination should be
undertaken to detect complications.
Severe Malnutrition Clinical features shown to be of prognostic significance
The World Health Organization has developed guidelines include
for the management of severe malnutrition based on • Signs of dehydration
sound pathophysiological principles and extensive • Shock (cold hands, slow capillary refill, weak and rapid
research and these have been adapted for Indian scenarios pulse)
by the Indian Academy of Pediatrics. At the community
• Severe palmar pallor
level, the presence of severe wasting and/or edema or a
• Eye signs of vitamin A deficiency
Mid Upper Arm Circumference (MUAC) of <11.5 cm are
suitable criteria to identify severely wasted children aged • Localizing signs of infection including ear and throat
6-59 months. For children < 6 months, in place of using infections
anthropometric criteria visible severe wasting and/or • Skin infection or pneumonia, signs of HIV infection,
bilateral edema should be used for determining severe fever (temperature > 37.5°C or > 99.5°F)
malnutrition. WHO recommends exclusive inpatient • Hypothermia (rectal temperature <35.5°C or <95.9° F),
management of a severely malnourished child. mouth ulcers, skin changes of kwashiorkor.
1. Hypoglycemia ------------ ►
2. Hypothermia ------------ ►
3. Dehydration ------------ ►
4. Electrolytes
5. Infection --- ►
No iron With iron
6. Micronutrients
Contd.___________________________________________________________________ _________________________________________________
Treatment
• Treat with parenteral ampicillin 50 mg/kg/dose 6 hourly for at least 2 days followed by oral
amoxycilin 15 mg/kg 8 hourly for five days and gentamicin 7.5 mg/kg or amikacin 15-20
mg/kg I.M. or I.V. once daily for seven days
• If no improvement within 48 hour change to IV cefotaxime (100-150 mg/kg/day 6-8 hourly)
or ceftriaxone (50-75 mg/kg/day 12 hourly)
• If other specific infections are identified, give appropriate antibiotics
Prevention
• Follow standard precautions like hand hygiene
• Give measles vaccine if the child is >6 months and not immunized, or if the child is >9 months
and had been vaccinated before the age of 9 months
6. Micronutrients • Use up to twice the recommended daily allowance of various vitamins and minerals
• On day 1 give Vitamin A orally (if age >1 year give 2 lakh IU; age 6-12 m give 1 lakh IU; age
0-5 m give 50,000 IU)
• Folic acid 1 mg/d (give 5 mg on day 1)
• Zinc 2 mg/kg/d
• Copper 0.2-0.3 mg/kg/d
• Iron 3 mg/kg/d, once child starts gaining weight; after the stabilization phase
7. Initiate feeding • Start feeding as soon as possible as frequent small feeds
• If unable to take orally, initiate nasogastric feeds
• Total fluid recommended is 130 ml/kg/day; reduce to 100 ml/kg/day if there is severe,
generalized edema
• Continue breast feeding ad-libitum
• Start with F-75 starter feeds every 2 hourly
• F-75 contains 75 kcal/lOOml with 1.0 g protein/100 ml
• If persistent diarrhea, give a serial based low lactose F-75 diet as starter diet
• If diarrhea continues on low lactose diets give F-75 lactose free diets (rarely needed)
8. Catch-up growth • Once appetite returns in 2-3 days, encourage higher intakes
• Increase volume offered at each feed and decrease the frequency of feeds to 6 feeds per day
• Continue breast feeding ad-libitum
• Make a gradual transition from F-75 to F-100 diet
• F-100 contains 100 kcal/lOOml with 2.5-3.0 g protein/100 ml
• Increase calories to 150-200 kcal/kg/day, and the proteins to 4-6g/kg/day
• Add complementary foods as soon as possible to prepare the child for home foods at
discharge
9. Sensory stimulation • A cheerful, stimulating environment
• Age appropriate structured play therapy for at least 15-30 min/day
• Age appropriate physical activity as soon as the child is well enough
• Tender loving care
10. Prepare for follow-up • Primary failure to respond is indicated by:
—> Failure to regain appetite by day 4
—» Failure to start losing edema by day 4
—» Presence of edema on day 10
—> Failure to gain at least 5 g/kg/day by day 10
• Secondary failure to respond is indicated by:
—> Failure to gain at least 5 g/kg/day for consecutive days during the rehabilitation phase
glycemia (blood glucose level <54 mg/dl or 3 mmol/1), sugar in 3Vi tablespoons of water) should be given orally
hence blood glucose should be measured immediately at or by nasogastric tube followed by the first feed. For
admission. If blood glucose cannot be measured, one must correction of symptomatic hypoglycemia, 5 ml/kg of 10%
assume hypoglycemia and treat. dextrose should be given intravenously. This should be
Hypoglycemia may be asymptomatic or symptomatic. followed with 50 ml of 10% dextrose or sucrose solution
Symptomatic hypoglycemia manifesting as lethargy, by nasogastric tube. Blood glucose levels must be
unconsciousness, seizures, peripheral circulatory failure estimated every 30 min till the glucose level becomes
or hypothermia is more common in marasmus, where normal and stabilizes. Once stable, the 2 hourly feeding
energy stores are depleted or when feeding is infrequent. regimens should be started.
Nutrition 71
Feeding should be started with starter F-75 (Formula Step 3: Treat/Prevent Dehydration
75 which is a WHO recommended starter diet for severe Dehydration tends to be overdiagnosed and its severity
acute malnutrition containing 75 kcal/100 ml of feed- overestimated in severely malnourished children. Loss of
described later) diet as quickly as possible and then elasticity of skin may either be due to loss of the subcuta
continued 2-3 hourly day and night (initially l/4th of the neous fat in marasmus or loss of extracellular fluid in
2 hourly feed should be given every 30 minutes till the dehydration. In dehydration, the oral mucosa feels dry to
blood glucose stabilizes). Most episodes of symptomatic the palpating finger gently rolled on the inner side of the
hypoglycemia can be prevented by frequent, regular feeds cheek. Presence of thirst, hypothermia, weak pulses and
and one must ensure that the child is fed regularly oliguria are other signs of dehydration in severely mal
throughout the night. Hypoglycemia, hypothermia and nourished children. It is important to recognize the fact
infection generally occur as a triad. that low blood volume (hypovolemia) can co-exist with
Step 2: Treat/Prevent Hypothermia edema. Since estimation of dehydration may be tricky in
All severely malnourished children are at risk of hypo severely malnourished children, it is safe to assume that
thermia due to impairment of thermoregulatory control, all such children with watery diarrhea have some dehy
dration.
lowered metabolic rate and decreased thermal insulation
from body fat. Children with marasmus, concurrent The Indian Academy of Pediatrics has recommended
infections, denuded skin and infants are at a greater risk. the use of one single solution for all types of diarrhea in
all clinical settings and there is evidence to suggest that
Hypothermia is diagnosed if the rectal temperature is less
new reduced osmolarity ORS (RO-ORS) with potassium
than 35.5°C or 95.9°F or axillary temperature is less than
supplements given additionally works in severe malnu
35°C or 95°F. A low reading thermometer (range 29°C-
trition.
42°C) should be used to measure the temperature of
Dehydration should be corrected slowly over a period
malnourished children. If the temperature does not
of 12 hours. Some dehydration can be corrected with RO-
register on a normal thermometer, hypothermia should
ORS. Intravenous therapy should be given only for severe
be assumed and treated. It can occur in summers as well.
dehydration and shock or if the enteral route cannot be
The child should be rewarmed providing heat using
used. The RO-ORS should be given orally or by nasogastric
radiation (overhead warmer) or conduction (skin contact)
tube at 5 ml /kg every 30 minutes for first 2 hours and
or convection (heat convector). Rapid rewarming may lead
then at 5-10 ml/kg every hour for the next 4-10 hours.
to disequilibrium and should be avoided.
The exact amount actually depends on how much the child
In case of severe hypothermia (rectal temperature
wants, volume of stool loss, and whether child is vomiting.
<32°C) warm humidified oxygen should be given
Ongoing stool losses should be replaced with approxi
followed immediately by 5 ml/kg of 10% dextrose IV or mately 5-10 ml/kg of the ORS after each watery stool.
50 ml of 10% dextrose by nasogastric route (if IV access is
The frequent passage of small unformed stools should not
difficult). If clinical condition allows the child to take
be confused with profuse watery diarrhea as it does not
orally, warm feeds should be given immediately or else require fluid replacement.
the feeds should be administered through a nasogastric Breastfeeding should be continued during the rehydra
tube. If there is feed intolerance/contraindication for
tion phase. Refeeding must be initiated with starter F-75
nasogastric feeding, maintenance IV fluids (pre warmed) formula within 2-3 hours of starting rehydration. The
should be started. feeds must be given on alternate hours (e.g. hours 2, 4, 6)
In a hypothermic child, hypoglycemia must be looked with reduced osmolarity ORS (hours 1, 3, 5). Once rehy
for and managed. The child's temperature should be moni dration is complete, feeding must be continued and
tored every 2 hours till it rises to more than 36.5°C. ongoing losses replaced with ORS.
Temperature monitoring must be ensured especially at The progress of rehydration should be monitored every
night when the ambient temperature falls. half hourly for first 2 hours and then hourly for the next
In most cases, hypothermia may be prevented by fre 4-10 hours. Pulse rate, respiratory rate, oral mucosa, urine
quent feeding. Therefore, the child should be fed imme frequency or volume and frequency of stools and vomiting
diately and subsequently, every 2 hourly. All children should be monitored. One must be alert for signs of
should be nursed in a warm environment, clothed with overhydration (increase in respiratory rate by 5/min and
warm clothes and covered using a warm blanket. The head pulse rate by 15/min, increasing edema and periorbital
should also be covered well with a scarf or a cap. The child puffiness), which can be dangerous and may lead to heart
could also be put in contact with the mother's bare chest or failure. In case of signs of overhydration, ORS should be
abdomen (skin to skin) as in kangaroo mother care to stopped immediately and child reassessed after one hour.
provide warmth. Besides these measures, hypothermia can Diuretics must never be used in this setting. On the other
also be prevented by placing the child's bed in a draught hand a decrease in the heart rate and respiratory rate (if
free area away from doors and windows, minimizing increased initially) and increase in the urine output
exposure after bathing or during clinical examination, and indicate that rehydration is proceeding. The return of tears,
keeping the child dry always. a moist oral mucosa, less sunken eyes and fontanelle and
72 Essential Pediatrics
improved skin turgor are also indicators of rehydration. orally at 3-4 mEq/kg/day for at least 2 weeks. Potassium
Once any four signs of hydration (child less thirsty, can be given as syrup potassium chloride; the most
passing urine, tears, moist oral mucosa, eyes less sunken, common preparation available has 20 mEq of potassium /
faster skin pinch) are present, ORS for rehydration must 15 ml.
be stopped and continued only to replace the ongoing In addition, magnesium also needs to be supplemented.
losses. On day 1,50% magnesium sulphate (equivalent to 4 mEq/
ml) should be given at 0.3 ml/kg up to a maximum of 2
Severe Dehydration with Shock ml intramuscularly. Thereafter, 0.8-1.2 mEq /kg magne
sium should be given orally as a magnesium supplement
It is important to recognize severe dehydration in severely
mixed with feeds.
malnourished children. All such children with severe
dehydration with shock should be treated with intra Step 5: Treat/Prevent Infection
venous fluids. Ideally, Ringer's lactate with 5% dextrose Infection may not produce the classical signs of fever and
should be used as rehydrating fluid. If not available, half tachycardia in severely malnourished children. Instead,
normal saline (N/2) with 5% dextrose or Ringer's lactate severe infection may be associated with hypothermia.
alone can be used. One should never use 5% dextrose Localizing signs of infection are often absent. The most
alone. After providing supplemental oxygen, the common sites for infection to occur are the skin, the ali
rehydrating fluid should be given at a slow infusion rate mentary tract, the respiratory tract (including the ears, nose
of 15 ml/kg over the first hour with continuous moni and throat) and the urinary tract. Majority of the infections
toring of pulse rate, volume, respiratory rate, capillary and septicemia are caused by gram negative organisms.
refill time and urine output. Therefore, all severely malnourished children should be
If there is improvement (pulse slows, faster capillary assumed to have a serious infection on their arrival in
refill) at the end of the first hour of IV fluid infusion, a hospital. In addition, hypoglycemia and hypothermia are
diagnosis of severe dehydration with shock should be considered markers of severe infection in children.
considered and the rehydrating fluid repeated at the same Whenever and wherever feasible, the following
rate of 15 ml/kg over the next hour. This should be investigations may be done for identifying the infections
followed by reduced osmolarity ORS at 5-10 ml/kg/hour, in severely malnourished children.
either orally or by nasogastric tube. One must also (i) Hb, TLC, DLC, peripheral smear, (ii) Urine analysis
frequently monitor to look for features of overhydration and urine culture, (iii) Blood culture, (iv) Chest X-ray,
and cardiac decompensation. (v) Mantoux test, (vi) Gastric aspirate for AFB, (vii)
Peripheral smear for malaria (in endemic areas), (viii) CSF
Septic Shock examination (if meningitis suspected).
If at the end of the first hour of IV rehydration, there is no All children should be treated with broad spectrum
improvement or worsening, septic shock must be parenteral antibiotics-ampicillin and gentamicin or amika
considered and appropriate treatment started. cin (Table 5.11). Antimalarial and anti- tuberculosis
treatment should only be given when the particular
Step 4: Correct Electrolyte Imbalance conditions are diagnosed.
In severely malnourished children excess body sodium
Response to treatment will be indicated by resolution
exists even though the plasma sodium may be low.
of initial symptoms and signs of infection, if any. The
Sodium intake should be restricted to prevent sodium
child's activity, interaction with parents and appetite
overload and water retention during the initial phase of
should improve. If there is no improvement or deterio
treatment. Excess sodium in the diet may precipitate
ration of the symptoms/signs of infection, the child should
congestive cardiac failure.
be screened for infection with resistant bacterial
In addition, all severely malnourished children have
pathogens, tuberculosis, HIV and unusual pathogens.
deficiencies of potassium and magnesium which may take
two weeks or more to correct. Severely malnourished Prevention of Hospital Acquired Infection
children may develop severe hypokalemia and clinically
The healthcare personnel should follow standard
manifest with weakness of abdominal, skeletal and even
precautions. The effectiveness of hand hygiene should be
respiratory muscles. This may mimic flaccid paralysis.
emphasized to all health care providers, attendants and
Electrocardiography may show ST depression, T waves
patients. It is essential that adequate safety measures are
inversion and presence of U waves. If serum potassium is
taken to prevent the spread of hospital acquired infections,
<2 mEq/1 or <3.5 mEq/1 with ECG changes, correction
since these children are at higher risk of acquiring
should be started at 0.3-0.5 mEq/kg/hour infusion of
infections due to their compromised immune status.
potassium chloride in intravenous fluids, preferably with
continuous monitoring of the ECG. Step 6: Correct Micronutrient Deficiencies
Once severe hypokalemia is corrected, all severely All severely malnourished children have vitamin and
malnourished children need supplemental potassium mineral deficiencies. Micronutrients should be used as an
Nutrition 73
Tabic 5.11: Recommended antibiotics for infections in 1 mg/day (5 mg on day 1), zinc 2 mg/kg/day and copper
severely malnourished children 0.2-0.3 mg/kg/day (a multivitamin/ mineral commercial
Type of infection Recommended antibiotics preparation should be used) should be given daily. Iron 3
No obvious Oral cotrimoxazole (5 mg/kg 12 mg/kg/day should be added once child starts gaining
infections or hourly of trimethoprim) or oral weight, after the stabilization phase.
complications amoxicillin 10 mg/kg 8 hourly for
5 days Emergency Treatment of Severe Anemia
Infected child or IV ampicillin 50 mg/kg/dose 6 If a severely malnourished child has severe anemia with
complications hourly and IV gentamicin 2.5 mg/ a hemoglobin of less than 4 g/dl or hemoglobin (Fib) be
present kg/dose 8 hourly tween 4 and 6 g/dl but with respiratory distress, a blood
Add IV cloxacillin 100 mg/kg/day
transfusion should be given with whole blood 10 ml/kg
6 hourly if staphylococcal infection
bodyweight slowly over 3 hours. Furosemide should be
is suspected.
Revise therapy based on the given at the start of the transfusion. If the severely anemic
culture sensitivity report child has signs of cardiac failure, packed cells rather than
For septic shock or Add third generation whole blood should be transfused.
no improvement or cephalosporin i.e. IV cefotaxime The hemoglobin concentration may fall during the first
worsening in initial 100 mg/kg/day 8 hourly week of treatment. This is normal and no transfusion
48 hours should be given. In mild to moderate anemia, iron should
Meningitis IV cefotaxime 200 mg/kg/day IV be given for two months to replete iron stores but this
6 hourly with IV amikacin 15 mg/ should not be started until after the initial stabilization
kg/day 8 hourly phase has been completed.
Dysentery Ciprofloxacin 30 mg/kg/day in 2
divided doses. IV ceftriaxone 50 Step 7: Initiate Re-feeding
mg/kg/day in 24 or 12 hourly if Feeding should be started as soon as possible with a diet
child is sick or has already received which has osmolarity less than 350 mOsm/1; lactose not
nalidixic acid
more than 2-3 g/kg/ day; appropriate renal solute load
(urinary osmolarity <600 mOsm/1); initial percentage of
adjunct to treatment in safe and effective doses. Up-to calories from protein of 5%; adequate bioavailability of
twice the recommended daily allowance of various micronutrients; low viscosity, easy to prepare and socially
vitamins and minerals should be used. Although anemia acceptable; adequate storage, cooking and refrigeration.
is common, iron should not be given initially due to danger
Start Cautious Feeding
of promoting free radical generation and bacterial pro
liferation. It should be added only after a week of therapy Feeding should be started as soon as possible as frequent
when the child has a good appetite and starts gaining small feeds. If child is unable to take orally with a cup
weight. and spoon or takes <80% of the target intake, nasogastric
Vitamin A deficiency is not an infrequent association feeds should be initiated. Breastfeeding should be
and is an important cause of blindness caused by continued ad-libitum. The suggested starter formula and
keratomalacia. Vitamin A should therefore be given to all feeding schedules are designed to meet these targets. Milk-
severely malnourished children on day 1 at 50,000 IU, based formulas such as starter F-75 (with 75 kcal/100 ml
100,000 IU and 200,000 IU for infants 0-5 month, 6-12 and 0.9 gm of protein /100 ml) will suffice for most
months and children > 1 year of age unless there is definite children. Older children could be started on cereal-based
diets (Table 5.12).
evidence that a dose has been given in the last month. In
presence of xerophthalmia, the same dose should be re One should begin with 80 kcal/kg/day and gradually
peated on the next day and 2 weeks later. Children > 1 increase to 100 kcal/kg/day. To fulfill this, start with 2
year but weighing < 8 kg should receive half the age hourly feeds of 11 ml/kg/feed (Table 5.13). Night feeds
related dose. In presence of clinical evidence of xerophthal are essential. The volume of feeds should be increased
mia the administration of Vitamin A should be considered gradually while decreasing the frequency of adminis
an emergency as the changes may progress to kerato tration. The calories should be increased only after the
malacia within hours. child is able to accept the increased volume of feeds.
* Powdered puffed rice may be replaced by commercial pre-cooked rice preparations (in same amounts)
Note:
1. Wherever feasible, actual weighing of the constituents shoidd be carried out. Household measure should be used only as an alternative, as
they may not be standardized.
2. The above charts give the composition for 100 ml diet. Wherever there is a facility for refrigeration, 1 liter diet could be prepared by
multiplying the requirement of each constituent by 10.
Table 5.13: Feeding patterns in the initial days of is left uneaten. The frequency of feeds should be gradu
rehabilitation ally decreased to 6 feeds/day and the volume offered at
each feed should be increased till the child is being of
fered 200 ml/kg/day and 4-6 g/kg/day of protein.
Breastfeeding should be continued ad-libitum.
Complementary foods should be added as soon as pos
Source: WHO guidelines sible to prepare the child for home foods at discharge. They
should have comparable energy and protein concentra
tions once the catch-up diets are well tolerated. Khichri,
dalia, banana, curd-rice and other culturally acceptable
Table 5.14: Catch-up diets
and locally available diets can also be offered liberally (see
IMNCI Food Box, Table 5.2).
suggested classification and treatment system for acute Encephalitis Like Syndromes
malnutrition is given in Table 5.15 . Up to 1 / 5th of the children with kwashiorkor may become
drowsy within 3-4 days after initiation of dietary therapy.
Phenomena that may be encountered
Most often the condition is self limiting. Occasionally, it
during Nutritional Rehabilitation
may be accompanied by progressive unconsciousness
The following conditions are rarely seen now. with fatal outcome. Even more rarely a transient
Pseudotumor Cerebri phenomena marked by coarse tremors, parkinsonian
rigidity, bradykinesia and myoclonus may appear several
Over-energetic nutritional correction in malnourished in
days after starting the dietary rehabilitation. These
fants may be accompanied by transient rise of intracra
encephalitis states are considered to be the result of too
nial tension. The phenomenon is benign and self limiting.
much of proteins in the diet.
Nutritional Recovery Syndrome Suggested reading
It refers to a sequence of events seen in children who are Bhatnagar S, Lodha R, Choudhury P, Sachdev HP, Shah N, Narayan S,
being treated with very high quantity of proteins during et al. IAP guidelines 2006 on hospital based management of severely
the course of rehabilitation. It presents as (1) abdominal malnourished children (adapted from the WHO Guidelines). Indian
distention, (2) increasing hepatomegaly, (3) ascites, Pediatr. 2007; 44:443-61.
(4) prominent thoraco-abdominal venous network,
(5) hypertrichosis, (6) parotid swelling, (7) gynaecomastia, PREVENTION OF MALNUTRITION
(8)eosinophilia, (9) splenomegaly. Improvement of nutrition status of children is an essential
Its development may be related to endocrinal distur component of health care.
bances, possibly by an increase in the estrogen level and
by a variety of trophic hormones produced by the recov Prevention at National Level
ering pituitary gland. Nutrition supplementation: This can be done by improve
ment of food and feeding; by fortification of staple food;
iodination of common salt and food supplementation.
Table 5.15: Suggested classification and treatment
Nutritional surveillance: Surveillance defines the character
system for Malnutrition
and magnitude of nutritional problems and selects
Suggested classification Suggested treatment
appropriate strategies to counter these problems.
1. Severe acute malnutrition Stabilization center (SC): Nutritional planning: Nutritional planning involves a
with complications like in-patient care, also
political commitment by the government, formulation of
anorexia, lower respiratory known as "phase 1
a nutrition policy and planning to improve production
tract infection, high fever, treatment", for acutely
and supplies of food and ensure its distribution.
severe dehydration, severe malnourished children
anemia or lethargy. with medical complications
and no appetite using Prevention at Community Level
standard WHO guidelines. a. Health and nutritional education: Lack of awareness of
2. Severe acute malnutrition Outpatient therapeutic the nutritional quality of common foods, irrational
without complications programme (OPT): home beliefs about certain foods, and cultural taboos about
where the child is clinically based treatment and
feeding contribute to the development of malnutrition.
well, alert and has a good rehabilitation with a
People should be informed of the nutritional quality of
appetite. specially formulated RUTF
various locally available and culturally accepted low
(ready to use therapeutic
feed) provided on a weekly cost foods.
or two weekly basis, b. Promotion of education and literacy in the community,
medical treatment using especially non formal education and functional literacy
simplified medical among village women.
protocols and regular
c. Growth monitoring: The growth should be monitored
follow up for children with
periodically on growth cards. Velocity of growth is
severe acute malnutrition
more meaningful than the actual weight of a child.
without complications
3. Moderate acute Supplementary feeding d. Integrated health package: Primary health care package
malnutrition without programme (SFP): take should be made available to all sectors of population
complications where home ration for children including preventive immunization, oral hydration,
weight-for-height is with moderate acute periodic deworming, and early diagnosis and treatment
between 70-80% with no malnutrition without of common illnesses.
edema or MUAC is complications,
e. Vigorous promotion of family planning programs to limit
between 11-12.5 cm.
family size.
i
Nutrition 77
Prevention at Family Level e. Referral services: During health check-ups and growth
a. Exclusive breastfeeding of infants for first 6 months of monitoring, sick or malnourished children, in need of
life should be vigorously promoted and encouraged. prompt medical attention, are referred to the Primary
b. Complementary foods should be introduced in the diet Health Centre or its sub-centre.
of infants at the age of 6 months. f. Nutrition and health education.
c. Vaccination. However, the utilization of these services is still poor.
d. Iatrogenic restriction of feeding in fevers and diarrhea According to the NFHS-3 survey, 72% areas surveyed
should be discouraged. were covered by an angamvadi centre; only 33% of children
e. Adequate time should be allowed between two preg under 6 years of age received any kind of service from it.
nancies so as to ensure proper infant feeding and
attention to the child before the next conception.
National Programme of Mid-day Meals in Schools
With a view to enhancing enrolment, retention and
National Nutrition Policy attendance and simultaneously improving nutritional
The adoption of National Nutrition Policy (NNP) by the levels among children, the National Programme of
Government has been a significant achievement. Various Nutritional Support to Primary Education (rechristened
programs have been launched or strengthened in National Programme of Mid-Day Meals in Schools in 2007)
pursuance of these policies. Few of them are mentioned was launched as a centrally sponsored scheme on 15th
here. August 1995, initially in 2408 blocks in the country. The
National Programme of Mid-Day Meals in Schools covers
Integrated Child Development approximately 9.70 crore children studying at the primary
Services Programme (ICDS) stage of education in 9.50 lakh Government (including
The ICDS programme is an inter-sectoral programme local bodies), Government aided schools and the centres
which seeks to directly reach out to children, below six run under Education Guarantee Scheme (EGS) and
years, especially from vulnerable groups and remote areas. Alternative and Innovative Education (AIE) scheme.
The Scheme provides an integrated approach for converg The programme provides a mid-day meal of 450 kcal
ing basic services through community-based workers and and 12 g of protein to children at the primary stage. For
helpers. The services are provided at a centre called the children at the upper primary stage, the nutritional value
'Anganwadi'. A package of six services is provided under is fixed at 700 kcal and 20 g of protein. Adequate quantities
the ICDS Scheme: of micronutrients like iron, folic acid and vitamin A are
a. Supplementary nutrition: The norms are given in Table also recommended. The programme has helped in
5.16. protecting children from classroom hunger, increasing
b. Immunization: Immunization of pregnant women and school enrolment and attendance, improved socialization
infants is done against the six vaccine preventable dis among children belonging to all castes, addressing
eases malnutrition, and social empowerment through provision
c. Non-formal pre-school education of employment to women.
d. Health Check-up: This includes health care of children
less than six years of age, antenatal care of expectant National Nutrition Anemia Prophylaxis Programme
mothers and postnatal care of nursing mothers. These This programme was launched in 1970 to prevent nutri
services are provided by the ANM, Medical Officers tional anemia in mothers and children. Under this
under the RCH programme. The various health services programme, the expected and nursing mothers as well as
include regular health check-ups, immunization, acceptors of family planning are given one tablet contain
management of malnutrition, treatment of diarrhea, ing 100 mg elementary iron and 0.5 mg of folic acid.
deworming and distribution of simple medicines, etc. Children in the age group of 1-5 years are given one tablet
containing 20 mg elementary iron (60 mg of ferrous
Table 5.16: Norms for supplementary nutrition in ICDS sulphate) and 0.1 mg of folic acid daily for a period of 100
Beneficiaries Calories (kcal) Protein (g) days.
Children 3 yr 300 8-10
Children 3-6 yr 300 8-10 Suggested reading
Severely malnourished Double of above 1. Kapil U, Pradhan R. Integrated child development services scheme
children (ICDS) in India: its activities, present status and future strategy to
reduce malnutrition. J Indian Med Assoc. 2000;98:559-60.
Pregnant and lactating 500 20-25
2. Ghosh S. Integrated Child Development Services programme. Natl
mothers
Med J India. 2003;16 Suppl 2:20-3.
Micronutrients in
Health and Disease
INTRODUCTION MINERALS
Originally, global nutrition concerns were dominated Sixteen minerals are required to support human
by vitamin deficiencies; however, the focus changed biochemical processes by playing roles in cell structure
with time, and currently the concern is on both the and function as well as electrolytes. These are calcium,
macro- and micronutrient deficiencies. There is growing chloride, cobalt, copper, iodine, iron, magnesium,
interest globally, on micronutrient deficiencies; mainly manganese, molybdenum, nickel, phosphorus, potassium,
iodine, zinc, and vitamin A. Micronutrients play a selenium, sodium, sulfur and zinc.
central part in metabolism and in the maintenance of Many elements, e.g. chromium have been suggested
tissue function. An adequate intake, therefore- is as essential, but such claims have not been confirmed.
necessary, but provision of excess supplements may be Definitive evidence for efficacy comes from the char
harmful. Single micronutrient deficiency states are acterization of a biomolecule containing the element with
comparatively easily recognized and treated. Subclinical an identifiable and testable function.
deficiency, often of multiple micronutrients, is more Essential trace elements are required by humans in
difficult to recognize, and laboratory assessment is often amounts ranging from 50 micrograms to 18 milligrams
complicated by the acute phase response. Clinical benefit per day. Acting as catalytic or structural components of
is most likely in those children who are severely larger molecules, they have specific functions and are
depleted and at risk of complications.
indispensable for life. In addition to the long-known
deficiencies of iron and iodine, signs of deficiency for
VITAMINS
chromium, copper, zinc and selenium have been
A vitamin is an organic compound required as a nutrient identified. Marginal or severe trace element imbalances
in tiny amounts by an organism. A compound is called a can be considered risk factors for several diseases of public
vitamin when it cannot be synthesized in sufficient health importance. Proof of cause and effect relationships
quantities by an organism, and must be obtained from will depend on a more complete understanding of the
the diet. mechanisms of action and on better analytical procedures
Vitamins have diverse biochemical functions, including and functional tests.
function as hormones (e.g. vitamin D), antioxidants (e.g.
vitamin E), and mediators of cell signaling and regulators
of cell and tissue growth and differentiation (e.g. vitamin FAT-SOLUBLE VITAMINS
A). The largest number of vitamins (e.g. B complex
vitamins) function as precursors for enzyme cofactor
The fat-soluble vitamins A, D, E and K control protein
biomolecules (coenzymes), that help act as catalysts and
synthesis at either the transcriptional or post-trans-
substrates in metabolism. When acting as part of a catalyst,
criptional level. All of them are converted to active forms
vitamins are bound to enzymes and are called prosthetic
in the body, by oxidation, hydroxylation, reduction or
groups.
Vitamins are classified as either water-soluble, meaning simple ionization. Breast milk is deficient in both vitamins
that they dissolve easily in water, or fat-soluble vitamins, D and K and must be supplemented with these vitamins
which are absorbed through the intestinal tract with the to protect breastfed infants.
help of lipids (fats). In general, water-soluble vitamins are
readily excreted from the body. Each vitamin is typically VITAMIN A
used in multiple reactions and, therefore, most have
multiple functions. Vitamin A refers generically to all compounds structurally
In humans there are 13 vitamins: 4 fat-soluble related to retinol that have biological activity. Six isomers
(A, D, E and K) and 9 water-soluble (8 B vitamins and of retinol are known. In addition to the common all-trans
vitamin C). retinol, there are 13-cis, 11-cis, 9-cis, 7-cis and 9, 13-cis
78
Micronutrients in Health and Disease 79
retinols. The oxidation products of retinol, such as all-trans converted to all-''trans" retinol form and then transported
retinal, and all-trans retinoic acid are active forms of with an inter-photoreceptor retinol-binding protein (IRBP)
vitamin A. Carotenoids are provitamin A substances to the pigment epithelial cells. Further esterification into
found in vegetables. Hundreds of carotenoids have been all-"trans" retinyl esters allows this final form to be stored
identified in nature, but only a handful can be converted within the pigment epithelial cells to be reused when
to vitamin A. All-trans (3-carotene is the most effective needed.
precursor of vitamin A and the most widely distributed. The final conversion of 11-c/s-retinal will rebind to opsin
to reform rhodopsin in the retina. Rhodopsin is needed to
Absorption and Metabolism see black and white as well as see at night. It is for this
Vitamin A is absorbed in esterified form as part of chylo reason that a deficiency in vitamin A will inhibit the
microns. Absorption is affected by impaired chylomicron reformation of rhodopsin and lead to night blindness.
formation, or when fat absorption is altered. Retinol is The other functions of vitamin A are to maintain
absorbed as the free alcohol by an active transport system epithelial tissue, and to stimulate differentiation of a
containing a cellular retinol binding protein CRBPII. The number of tissues by controlling gene expression.
yellow (3-carotene also requires bile salts for absorption
and is converted to vitamin A in the intestinal tract. Once Vitamin A Deficiency
absorbed, vitamin A is stored in the liver as retinyl In developing countries, it is estimated that 500,000 pre
palmitate. The liver releases vitamin A to the circulation, school children become blind every year owing to vitamin
bound to retinol-binding protein (RBP) and to a preal A deficiency, and that many of them, will die because of
bumin (transthyretin). increased vulnerability to infections especially measles.
Defective dark adaptation is the most characteristic
Sources early clinical feature, resulting in night blindness. The
The richest sources of preformed vitamin A include oils syndrome of vitamin A deficiency in infants consists of
extracted from shark and cod liver. Carrots, dark-green Bitot spots, xerophthalmia, keratomalacia, corneal
leafy vegetables, squash, oranges, and tomatoes are also opacities, hyperkeratosis, growth failure and death. The
good sources. Many processed foods and infant formulas deficiency disease in humans was called xerophthalmia
are fortified with preformed vitamin A. (dry eyes) because of the prominence of the eye signs
(Table 6.1).
Recommended Daily Allowance Other findings include infertility, metaplastic bones and
The recommended daily allowance of vitamin A is as general keratinization of epithelial tissue particularly in
follow: Infants 300-400 pg; Children 400-600 pg; the skin, genitourinary system and the lung. Urinary
Adolescents 750 pg. calculi are common and fetal abnormalities are seen in
pregnancy. Diets consisting of polished rice with little or
1 pg retinol= 1 retinol equivalent (RE) no vegetables or fruits increase the risk of xerophthalmia.
1 pg (3-carotene = 0.167 pg RE Laboratory tests show a mild leukopenia occurring in
1 pg other pro-vitamin A carotenoids = 0.084 pg RE vitamin A deficiency, with a serum retinol level of 15 pg/
dl or less (normal 20 to 80 pg/dl). Clouding of the cornea
in a child with vitamin A deficiency is a medical
Physiological Functions
emergency and requires parenteral administration of
There are two main functions of vitamin A: (a) 50,000 to 100,000 IU (15 to 30 mg retinol).
maintenance of vision, particularly night vision; and (b)
maintenance of epithelial tissues and differentiation of
many other tissues, particularly during reproduction and Table 6.1: WHO classification of xerophthalmia
gestation. Primary signs Secondary signs
The role of vitamin A in the vision cycle is specifically X1A Conjunctival xerosis XN Night blindness
related to the retinal form. Within the eye, 11-ds-retinal is X1B Bitot's spots XF Fundal changes
bound to rhodopsin (rods) and iodopsin (cones) at X2 Corneal xerosis XS Corneal scarring
conserved lysine residues. As light enters the eye the 11- X3A Corneal ulceration(<l/3 of cornea)
c/s-retinal is isomerized to the all-"trans" form. The all- X3B Corneal ulceration(>l/3 of cornea)
"trans" retinal dissociates from the opsin in a series of
steps called bleaching. This isomerization induces a
nervous signal along the optic nerve to the visual center Hypervitaminosis A and Teratogenicity
of the brain. Upon completion of this cycle, the all-"trans"- Toxicity has been observed in children and adults
retinal can be recycled and converted back to the ll-"cis"- ingesting more than 50,000 IU /day of vitamin A for
retinal form via a series of enzymatic reactions. several months. Pediatric toxicity is commonly related to
Additionally, some of the all-"trans" retinal may be excessive doses of fish liver oil or therapeutic vitamin
80 Essential Pediatrics
preparations. In adolescents, its occurrence is related to coverage in most of the states. Currently, vitamin A is given
excessive use of retinol or retinoic acid for various skin only to children less than three years old who are at
disorders, particularly globular acne. The presenting greatest risk, and the administration of the first two doses
symptoms are fatigue, malaise, anorexia, vomiting, is linked with routine immunization to improve the
headache, and diplopia related to elevated cerebral spinal coverage. A dose of 100,000 IU is given along with measles
fluid pressure. Other findings are bone pain, dermatitis, vaccine at nine months of age and 200,000 IU with DPT
hepatomegaly with liver abnormalities, hypercalcemia, booster at fifteen months. Dietary improvement is,
hypo- prothrombinosis, and fetal abnormalities. undoubtedly, the most logical and sustainable strategy to
When taken by women at early stages of gestation at prevent VAD. Availability alone, however, does not
daily levels of more than 7500 pg, fetal anomalies and poor ensure programmatic success. A change in dietary habits
reproductive outcomes have been reported. The WHO and increased access to vitamin A-rich foods are required.
expert group recommend that daily intakes in excess of
3000 pg or weekly intakes in excess of 7500 pg should not VITAMIN D
be taken at any period during gestation.
Vitamin D is the generic term for a family of secosteroids
Carotenemia with antirachitic activity. In the secosteroid rings, A, C
and D are intact whereas the opened ring B is converted
Carotene is a pigment normally present in keratin and
into a conjugated system of double bonds. All molecules
subcutaneous fat. When plasma carotene levels are above
with vitamin D activity have the same interrupted ring
250 pg, yellow pigmentation (carotenemia) shows in
system but vary in their side chains.
superficial areas of the skin, such as face, palms, and soles;
however, yellow pigmentation is uncommon in mucosal Vitamin D comprises a family of fat-soluble vitamins
areas such as the sclerae. This is the result of excessive and hormones that, when deficient in the diet, causes
dietary intake of carotene-containing foods, most com rickets from defective mineralization of growing bone, and
monly carrots and carrot-containing products. osteomalacia in non-growing bones.
P-Carotene is the most important precursor of vitamin It is now known that vitamin D is a precursor of a
A in vegetable-based diets. Six micrograms of (3-carotene hormone that is the active form of vitamin D (1,25-
have the biological potency of 1 pg of retinol. Excessive dihydroxycholecalciferol), synthesized in the kidney and
^ intake of carotene does not produce symptoms other than secreted by the kidney under the control of parathyroid
I yellow skin pigmentation, probably because it is not hormone and tissue phosphate concentration. Vitamin D
Q absorbed as well as vitamin A and is metabolized too is a facultative vitamin that is required in the diet when
I] slowly to cause hypervitaminosis. The peak time for the there is insufficient vitamin D3 made from 7-dehydro-
I appearance of carotenemia is 6 months to 5 years of age. cholesterol in the skin by irradiation with ultraviolet light.
U The skin color will return to normal within 2-6 weeks after In Northern and Western countries where sunlight is less
discontinuing intake of carrots. The only known hazard available due to cloudiness of the poor angle of radiation,
of carotenemia is that it could be mistaken for jaundice dietary vitamin D is essential. In the tropics, however,
and stimulates an unnecessary work-up for liver disease. dietary vitamin D is not necessary when there is sufficient
exposure to sunlight.
Treatment of Vitamin A Deficiency (VAD)
Specific treatment consists of oral vitamin A in a dose of Absorption and Metabolism
50,000,1 lakh, and 2 lakh IU in children aged <6 months, Vitamin D is absorbed in the small intestine, mainly in
6-12 months, and > 1 year respectively. The same dose is the duodenum by an active transport system that delivers
repeated next day and 4 weeks later. Alternatively, vitamin D to the enterocyte; there it is incorporated into
parenteral water-soluble preparation can be administered chylomicrons for delivery to the liver. In the liver, vitamin
in children with persistent vomiting or severe malabsor D is hydroxylated to 25(OH)D3 and secreted in association
ption (parenteral dose is half of the oral dose for children with an a-2 globulin. This carrier transports all three forms
above 6-12 months and 3/4th in <6 months old). In of vitamin D of which 25(OH)D3 is in the highest
addition, local treatment with antibiotic drops and concentration in plasma (20 to 40 ng/ml) whereas vitamin
ointment and padding of the eye enhances healing. D itself is present in a concentration of 2 to 4 ng/ml and
the hormone l,25(OH)2D3 is present in very small
Prevention amounts, normally 20 to 40 pg/ml.
The National Vitamin A Prophylaxis Program was started Vitamin D is hydroxylated twice, once in the liver and
with the primary aim of reducing blindness in children. then again in the kidney to produce the hormone 1,25-
Under this program, sponsored by the Ministry of Health dihydroxycholecalciferol (Fig. 6.1). This hormone which
and Family Welfare, children between 1-5 years were is secreted by the kidney travels to the gut where it
given oral doses of 200,000 IU vitamin A every six months. increases calcium absorption and to the bones where it
Evaluation studies since then revealed inadequate increases calcium turnover.
Micronutrients in Health and Disease 81
Sources
Most foods contain only small amounts of preformed
vitamin D. Fish, liver and oils are good sources. Human
milk contains only 30-40 IU/L. Exposure to sunlight and
vitamin D supplementation for the nursing mother can
increase the vitamin D content in breast milk.
In addition to dietary sources, photoconversion by the
action of sunlight in the ultraviolet band is an important
source of vitamin D for infants and children. It is estimated
that an infant needs to have about 20 cm2 of skin exposed
to sunlight for 15-20 minutes daily in order to synthesize
enough vitamin D to prevent rickets. The cultural practice
of keeping babies tightly covered may prevent adequate
exposure. Persons with dark skin appear to have less
25-hydroxycholecalciferol
capacity to photoconvert vitamin D than do fair-skinned
(25-hydroxyvitamin D)
individuals, but this limited capacity can be overcome by
increasing exposure to sunlight.
Vitamin D Requirements
Since vitamin D3 is produced endogenously in the skin
through the action of sunlight on 7-dehydrocholesterol,
there is no nutritional requirement for vitamin D when
sufficient sunlight is available. However, when shielded
from sunlight, breast-fed infants will develop rickets
unless supplemented with vitamin D.
1,25-dihydroxycholecalciferol
The recommended daily allowance in infants is 5 pg
(1,25-dihydroxyvitamin D)
(200 IU) per day and children 10 pg (400 IU) per day.
Human milk is deficient in vitamin D and contains only
30-40 IU per liter, mostly from 25(OH) D3. Breast-fed
infants must receive an additional source of vitamin D.
Hypervitaminosis D
An epidemic of "idiopathic hypercalcemia" in infants,
with anorexia, vomiting, hypertension, renal insufficiency,
and failure to thrive in England in the 1950s was traced to
Fig. 6.1 : Vitamin D metabolism an intake of vitamin D between 2,000 and 3,000 IU /day.
In adults, dosages of 10,000 IU/day of vitamin D for
Thus, vitamin D is a vitamin when sunlight is limiting, several months have resulted in marked disturbances in
and its hydroxylated derivative, l,25(OH)2D3, is a calcium metabolism with hypercalcemia, hyper
hormone. phosphatemia, hypertension, anorexia, nausea, vomiting,
The organs affected by vitamin D hormone in its control weakness, polyuria, polydipsia, azotemia, nephrolithiasis,
of calcium homeostasis are the intestine, kidney, and ectopic calcification, renal failure and, in some cases,
bones. In the intestine, the hormone induces a calcium death.
transport system involving transport proteins and an
Vitamin D Deficiency and Rickets
intracellular calcium-binding protein (CBP) called
calbindin, which aids in the transport of calcium across A lack of adequate mineralization of growing bones results
the enterocyte. In the kidney, vitamin D hormone in rickets, and that of trabecular bone in osteomalacia.
enhances calcium reabsorption in the tubule by a Osteoporosis is due to proportionate loss of bone volume
mechanism similar to that in the gut. It also inhibits the and mineral, which in children is often caused by excessive
synthesis of 1-a hydroxylase activity (to diminish hormone administration of corticosteroids.
synthesis) and stimulates 25(OH)D3 24-hydroxylase In most developed countries nutritional rickets
activity which inactivates both the substrate and the (vitamin D deficiency rickets) was virtually eradicated by
82 Essential Pediatrics
Vitamin D is administered orally either in a single dose low, which implies a deranged response of renal 1-a
of 600,000 IU or over 10 days (60,000 IU daily for 10 days) hydroxylase to a low phosphate signal. Limb deformities
followed by a maintenance dose of 400 IU/day and oral such as coxa vara, genu valgum, genu varum and short
calcium supplements (50-75 mg/kg/day). stature may occur. Abnormalities of maxillofacial region
Patients with vitamin D deficiency rickets show evidene and premature fusion of cranial sutures may lead to
of radiological healing (Fig. 6.4) within 4 weeks of therapy. deformities of skull. Dental abnormalities are commonly
seen including pulp deformities with intraglobular
Reduction in blood levels of alkaline phosphatase and
dentine, and frequent dental abscesses. Symptoms of
resolution of clinical signs occur slowly.
hypocalcemia (tetany and muscle weakness) are absent.
If no healing can be demonstrated with 2 mega doses
Changes of active rickets in spine and pelvis are rarely
of vitamin D, patients should be evaluated for refractory
seen even in advanced stages.
rickets (Fig. 6.5).
The level of serum calcium is normal or slightly low
Familial Hypophosphatemic Rickets (9-9.5 mg/dl), that of phosphate decreased (1.5-3
mg/dl). Serum alkaline phosphatase level is raised. PTH
This is the most commonly inherited form of refractory
levels are normal. Blood levels of l,25(OH)9D3 are
rickets, being inherited as X-linked dominant with variable inappropriately low for the level of serum phosphate.
penetrance. The mother of affected children may have
Urinary phosphate excretion is increased with decreased
bowing of legs and short stature or fasting hypo
tubular reabsorption of phosphate.
phosphatemia. Sporadic instances are frequent and an
Oral phosphate and vitamin D supplements are
autosomal recessive inheritance has also been reported.
administered. Phosphates are provided in a dosage of 30
The gene for X-linked hypophosphatemic rickets has
to 50 mg/kg (total 1-3 g elemental phosphorus) divided
been cloned and termed the PHEX gene (phosphate
into 5 to 6 equal parts and can be given in the form of
regulating gene with homology to endopeptidases on the
Joulie's solution or as neutral phosphate effervescent
X-chromosome). The underlying defect involves impaired
tablets. Joulie's solution contains 30.4 mg of phosphate/
proximal tubular reabsorption of phosphate. Despite
ml. Diarrhea is a frequent problem with higher doses.
hypophosphatemia the blood levels of l,25(OH)2D3 are
Vitamin D supplementation is necessary for healing of
rickets. Treatment is started with alfacalcidiol at a dose of
25-50 ng/kg/day (maximum 2 pg/day) until there is
biochemical and radiological evidence of healing of rickets.
Periodic monitoring of serum and urine levels of calcium
and phosphate is essential. A level of serum phosphate
greater than 3.0 to 3.2 mg/dl is desirable.
VDDR Type I
This condition is characterized by a deficiency of the
enzyme, 25-hydroxyvitamin D-l-a-hydroxylase. Reduced
blood levels of calcium, normal to low phosphate and
elevated alkaline phosphatase are characteristic. Blood
levels of 25(OH)D3 are normal but those of l,25(OH)-,D3
are markedly decreased despite hypocalcemia.
The clinical features are similar to vitamin D deficiency
rickets and include hypotonia, growth failure, motor
retardation (poor head control, delayed standing and
walking), convulsions due to hypocalcemia, anemia and
occasionally respiratory difficulty. Physical examination
shows thickening of wrists and ankles, frontal bossing,
widely open anterior fontanelle, rickety rosary, bony
deformities, and positive Trousseau and Chvostek signs.
Dentition is delayed and development of tooth enamel
Fig. 6.5 : Biochemical evaluation of a child with refractory rickets impaired.
84 Essential Pediatrics
The treatment of VDDR type I is with physiological prominent in some. There are no biochemical
doses of alfacalcidiol or calcitriol (1-2 pg daily). Most abnormalities except for the occasional presence of
subjects require concomitant treatment with calcium with hypercalcemia in Jansen metaphyseal chondrodysplasia.
or without phosphate supplements. With appropriate Radiological changes resemble rickets. There is no
therapy the serum calcium levels rise and radiological treatment for these disorders.
healing occurs within 6 to 8 weeks.
Fluorosis
VDDR Type II
Endemic fluorosis occasionally presents with bony
The features are similar to VDDR type I. There is end organ deformities and radiological features suggestive of rickets
resistance to l,25(OH)2D3. This leads to virtual abolition in school going children. Presence of pain in the limbs
of actions of l,25(OH)2D3, despite its markedly raised and spine, mottling of teeth and family history of a similar
levels in circulation (secondary to hypocalcemia and low illness are important features. Osteosclerosis and
24-hydroxylase activity). calcification of ligaments may be found in older children
Early onset of rickets, a high prevalence of alopecia and and adults. Blood levels of alkaline phosphatase and
ectodermal defects (oligodontia, milia and epidermal parathormone are raised. Levels of fluoride are increased
cysts) are characteristic. Hypocalcemia, secondary hyper in the water consumed, urine and blood.
parathyroidism, elevated circulating levels of l,25(OH)2D3
and an absence or decreased response to vitamin D VITAMIN E
analogs are seen.
The response to treatment in patients with VDDR type Vitamin E or tocopherol is a fat-soluble vitamin whose
II is not satisfactory. An occasional patient may get clinical major function is as an antioxidant. In humans, the main
and biochemical improvement and radiological healing manifestations of vitamin E deficiency are (a) a mild
following long-term administration of large amounts of hemolytic anemia associated with increased erythrocyte
intravenous or oral calcium. hemolysis, and (b) spinocerebellar disease, mostly
observed in children who have fat malabsorption due to
Other Causes of Rickets abetalipoproteinemia, chronic biliary disease with
cholestasis, or other types of malabsorption.
Renal Tubular Acidosis
^ Proximal as well as distal renal tubular acidosis (RTA) are Absorption and Metabolism
I important causes of refractory rickets in children. The
Only 20% to 40% of orally ingested tocopherol and/or its
>3 conditions are characterized by hyperchloremic metabolic
esters are absorbed. Tocopherol esters are almost
lJ| acidosis with normal blood levels of urea and creatinine.
completely hydrolyzed by a duodenal mucosal esterase
I Appropriate correction of acidosis with bicarbonate
prior to absorption. The efficiency of absorption is
W supplements and phosphate supplementation (in
enhanced by the simultaneous digestion and absorption
proximal RTA) results in healing of rickets.
of dietary lipids. Medium-chain triglycerides enhance
Chronic Kidney Disease absorption, whereas polyunsaturated fatty acids are some
what inhibitory. Both bile and pancreatic juice are
Refractory rickets may occasionally be the presenting
necessary for maximal absorption of vitamin E.
manifestation of chronic kidney disease (GFR below 30-
Unlike cholesterol or vitamin A, a-tocopherol is not
35 ml/min/1.73 m2), particularly in patients with
reesterified prior to its incorporation into the chylomicron
tubulointerstitial disease. The clinical features of osteo
and its delivery to the liver in the chylomicron remnant.
dystrophy depend on the patient's age and duration of
From the liver it is secreted with VLDL and delivered to
disease. Elevated blood levels of creatinine and phosphate
LDL [and high-density lipoproteins (HDL) via lipid
are characteristic. Therapy consists of restricting
exchange] and is delivered to peripheral tissues via the
phosphate intake and providing supplements of calcium
LDL receptor. Red blood cells, which contain about 20%
and active vitamin D analogs.
of the vitamin E in plasma, also participate in the transport
Oncogenous Rickets of the vitamins.
Vitamin E is metabolized to oxidized and chain-
Rarely benign mesenchymal tumors may secrete a
shortened products. Less than 1% of orally ingested
circulating substance that results in phosphaturia, hypo
vitamin E is excreted in the urine as metabolites; most is
phosphatemia, rickets and muscle weakness. The tumor
found in the gut where excretion occurs by the hepato
may be small and difficult to detect but its removal reverses
biliary system.
the biochemical abnormalities and heals the rickets.
Several types of these disorders are described. Short The principal function of vitamin E is to serve as a
stature with bowing of legs and waddling gait are physiological membrane-bound antioxidant. Since radical-
Micronutrients in Health and Disease 85
catalyzed lipid peroxidation seems to be a continual Other manifestations include the neurologic syndrome
biologic process that damages cellular and intracellular of spinocerebellar ataxia with loss of deep tendon reflexes,
structures, vitamin E appears to promote health by truncal and limb ataxia, loss of vibration and position
inhibiting this process and terminating radical chain sense, ophthalmoplegia, muscle weakness, ptosis and
reactions. dysarthria. A pigmented retinopathy may also occur.
A rare, isolated form of vitamin E deficiency without
Nutritional Requirements general fat malabsorption has been reported. Most of these
The vitamin E requirement of normal infants, estimated malabsorption syndromes respond to massive doses of
from the amount needed to prevent peroxidative oral vitamin E (100 to 200 mg/kg/day) with amelioration
hemolysis, is approximately 0.4 pg/kg body weight/day. of the deficiency and prevention of the neurological
For premature infants, 15 to 20 mg/day may be required sequelae.
to maintain normal plasma values. The RDA for infants
Hypervitaminosis E
increases from 3 to 6 mg of a-tocopherol from birth to 2
years of age. One mg of a-tocopherol provides 1.5 IU Relatively large amounts of vitamin E, in the range of 400
activity of vitamin E. to 800 mg of 1-a-tocopherol, have been taken daily by
adults for months to years without causing any apparent
Sources harm. Occasionally, muscle weakness, fatigue, nausea and
diarrhea have been reported in persons taking 800 to 3,200
The most common sources of vitamin E are vegetable oils
mg/day. The most significant toxic effect of vitamin E at
(corn, cottonseed, safflower) and their products
dosages exceeding 1,000 mg/day is the antagonism to
(margarine). Other good sources include green leafy
vitamin K action and the enhancement of the effect of oral
vegetables and nuts. Animal fat, fish and fruits are poor
coumarin anticoagulant drugs, with overt hemorrhage.
sources. Breast milk is rich in vitamin E, and colostrum
contains even higher concentrations. Most infant formulas
VITAMIN K
currently in use are fortified with tocopherol.
Vitamin K is a generic term for derivatives of 2-methyl-l,
Vitamin E Deficiency 4-naphthoquinone with procoagulation activity. The
natural forms are substituted in position 3 with an alkyl
Infants are born in a state of relative tocopherol deficiency; side chain. Vitamin K1, called phylloquinone, has a phytol
smaller the infant, the greater the degree of deficiency. side chain in position 3 and is the only homologue of
Term infants who are breast-fed quickly attain adult blood
vitamin K in plants. Vitamin K2 is a family of homologues
tocopherol values. The vitamin E-deficient state of
of 2-methyl-l, 4-naphthoquinone substituted in position
premature infants during the first few weeks of life can
3 with isopropyl side chains. These are called menaqui-
be attributed to limited placental transfer of vitamin E,
nones. The menaquinones synthesized by bacteria in the
low tissue levels at birth, relative dietary deficiency in
intestinal tract of humans can contribute to vitamin K
infancy, intestinal malabsorption and rapid growth. As
requirements. Vitamin K is essential for humans because
the digestive system matures, tocopherol absorption
the 1,4-naphthoquinone moiety cannot be synthesized in
improves and blood vitamin E levels rise. animal cells.
Hemolytic anemia in premature infants may be a
manifestation of vitamin E deficiency. The anemia presents Absorption and Metabolism
with hemoglobin levels in the range of 7 to 9 g/dl and is
accompanied by low plasma vitamin E levels, The absorption of phylloquinone and the menaquinones
reticulocytosis and hyperbilirubinemia. In these children requires bile and pancreatic juice for maximum effective
administration of iron may exacerbate red blood cell ness. Dietary vitamin K is absorbed in the small bowel,
destruction unless vitamin E is also administered. This incorporated into chylomicrons, and delivered to the
anemia has been associated with ingestion of formulas circulation via the lymph. The liver appears to be the
high in PUFA and low in a-tocopherol. Parenteral vitamin primary target of administered vitamin K in animals and
E improves the anemia and corrects the hemolysis. humans. The total body pool of vitamin K in animals and
In children and adults, fat malabsorption generally humans is surprisingly small, 80% of which is in the liver.
underlies vitamin E deficiency. Abetalipoproteinemia, The principal sites of uptake, after liver, are skin and
caused by the genetic absence of apolipoprotein B, causes muscle. The terminal oxidation of vitamin K and its
serious fat malabsorption and steatorrhea, with epoxides involves chain shortening and excretion in urine
progressive neuropathy and retinopathy in the first two and stool mainly as glucuronides of vitamin K lactones.
decades of life. Plasma vitamin E levels are sometimes
undetectable. High-dose vitamin E has improved Physiological Function
symptoms in young patients and arrested the neurological The main role of vitamin K is as a cofactor in the
disorder in older patients. posttranslational carboxylation of glutamic acid to form
86 Essential Pediatrics
glutamate (Gla), which takes place in the liver. The diagnosis depends on a rapid therapeutic response to
physiological function of vitamin K is to carboxylate administration of vitamin K intramuscularly.
selected glutamic acids to the translation products of The current guidelines recommend the prophylactic
vitamin K-dependent proteins to produce y- administration of vitamin K to all newborns, 0.5-1.0 mg
carboxyglutamates. Factors II (prothrombin), VII, IX, and i.m. and a weekly i.m. supplementation with 1 mg of
X are procoagulant proenzymes whereas proteins C and vitamin K for parenterally fed infants and children.
S are anticoagulant proenzymes. The function of these
proteins is to facilitate the chelation of calcium ions to Gla Hypervitaminosis K
and platelet phosphatide, which is essential for the Menadione unsubstituted in the 3 position causes toxicity
coagulation cascade to operate. in children, expressed as jaundice, hemolysis and
kernicterus. Phylloquinone is essentially nontoxic.
Nutritional Requirements
The vitamin K requirement is met by a combination of
WATER-SOLUBLE VITAMINS
dietary intake and microbiological biosynthesis in the gut.
The vitamin K-dependent coagulation factors are
depressed to 30% of normal at birth in full-term infants VITAMIN B GROUP
and even lower in premature newborns. The vitamin K
requirement for the normalization of prothrombin and Thiamine (Vitamin Bl)
other factor levels in newborns is 3 to 5 pg/day. Since Thiamine is water-soluble, composed of an imidazole and
breast milk contains only 2 pg phylloquinone per liter, a pyrimidine ring, connected by a methylene link.
breast-fed infants must be fortified with vitamin K in order Thiamine deficiency or beriberi has been known to affect
to prevent the hemorrhagic disease of the newborn. The people who consumed diets based on polished rice.
allowance for infants increases from 5 pg/day at birth to Nowadays, refined cereals are fortified with thiamine.
10 pg/day at 2 years. The requirement for older children
is in the range of 10 to 30 pg/day or 0.2 to 0.5 pg/kg/day. Sources
Sources Dietary sources include unrefined or fortified cereal
grains, enriched bakery products, organ meats (liver,
Green leafy vegetables are rich in phylloquinone, while
kidney), and legumes. The vitamin is sensitive to heat,
animal foods are intermediate, and cereals low, in this
sulfites, and pasteurization and sterilization. The thiamine
vitamin. The bacterial flora of the human intestine are
content of human milk is relatively low (16 pg/ml)
capable of synthesizing substantial amounts of vitamin
compared to cow's milk which contains 40-50 pg/ml.
K, which presumably is sufficient to fulfill the daily
Freezing foods results in little loss.
requirements in adults with normal intestinal flora.
Absorption and Metabolism
Vitamin K Deficiency
Thiamine is absorbed both actively and passively from
Most natural foods consumed by humans have a high the gastrointestinal tract, mainly the jejunum. It is
vitamin K content relative to its low requirement. Thus, dependent on the sodium ion for active absorption. Active
primary deficiency is very rare. Conversely, elimination absorption can be inhibited by ethanol, and unless higher
of the bacterial flora of the intestine, or exclusive parenteral doses are administered, the usually physiologic dose is
alimentation with no added vitamins K are reported insufficient to maintain normal levels in the chronic
mechanisms of secondary vitamin K deficiency. Among alcoholic.
other conditions favoring deficiency are fat malabsorption, Although thiamine deficiency during pregnancy has
biliary obstruction, cystic fibrosis and short bowel been described, the fetus appears to be protected by an
syndrome. active placental transport, and thiamine levels in cord
The hemorrhagic disease of the newborn is a syndrome blood are usually higher than in maternal blood.
of gastrointestinal bleeding and ecchymoses appearing in
the first week of life, predominating in breast-fed infants Biologic Action
because of the low vitamin K content of human milk. The active form of thiamine, thiamine pyrophosphate, is
Because of the routine administration of prophylactic involved in several key enzymatic steps of carbohydrate
vitamin K at birth, most cases of hemorrhagic disease of metabolism. It acts as a cofactor for the oxidative
the newborn are of late onset (after 2 weeks of life) and decarboxylation of pyruvate to form acetyl-CoA, a step
are also associated with a variety of conditions such as catalyzed by the pyruvate dehydrogenase complex.
antibiotic therapy, cholestasis, maternal use of antagonist Thiamine pyrophosphate is also a cofactor for
drugs (primidone, warfarin, diphenylhydantoin), low transketolase, an enzyme of the pentose pathway. This
dietary intake and fat malabsorption. Confirmation of the pathway is not directly involved in carbohydrate
Micronutrients in Health and Disease 87
metabolism, but is the major source of five carbon Riboflavin (Vitamin B2)
compounds for nucleic acid synthesis and of the NADPH Riboflavin is a flavoprotein which is widely distributed
used in fatty acid synthesis. The transketolase reaction is in plants.
affected rapidly in thiamine deficiency, and its rate in
erythrocytes is used as an index of thiamine status. Sources
Deficiency Meat, poultry fish, and dairy products are good sources
of riboflavin. Many cereals are also fortified or enriched
Thiamine deficiency or beriberi occurs in adults when the
with the vitamin. Among the vegetables, broccoli, spinach
level of intake drops below 1 mg/day. The classic signs
and asparagus are good sources. Riboflavin is quite
of beriberi appear after prolonged periods of low thiamine
resistant to oxidation and to heat, and is not destroyed by
intake. Three forma of beriberi have been described: dry,
pasteurization or evaporation.
wet, and acute. The dry and wet (edematous) forms are
Human milk contains 40-70 pg/100 kcal of riboflavin,
different manifestations of a polyneuritis. The "dry" form
and cow's milk has around 250 pg/100 kcal. Maternal
has no edema, and typically includes severe muscle
riboflavin supplementation may be used to increase
wasting and cardiomegaly.
Wet beriberi is characterized by peripheral edema, concentration in breast milk in deficiency states.
ocular paralysis, ataxia and mental impairment. The
pathogenesis of edema in wet beriberi is unclear. Infantile Absorption and Metabolism
beriberi may be more subtle than that found in adults. It Riboflavin is absorbed efficiently from the small intestine
occurs in breast-fed infants of thiamine-deficient mothers by a site-specific, saturable, specialized transport process.
(who may not have signs of beriberi), or in other conditions Biliary obstruction, high dietary fiber, and antacids
of very low thiamine intake. The clinical picture is decrease the bioavailability of the vitamin.
dominated by cardiac involvement, with cardiomegaly,
cyanosis, dyspnea and aphonia. The disease when Biologic Action
untreated may result in death after a few weeks, in the
It is a constituent of two coenzymes involved in oxidation-
infantile form.
reduction reactions: flavin adenine dinucleotide (FAD)
Diagnosis of Thiamine Deficiency and flavin mononucleotide (FMN). A number of important
redox enzymes, including glutathione reductase and
Thiamine deficiency may be suspected in all cases of mal
xanthine oxidase, require flavin coenzymes. The enzymes
nutrition. The diagnosis may be confirmed by measure
catalyzing the synthesis of niacin from tryptophan and
ment of 24-hr urinary thiamine excretion which in children
the conversion of pyridoxal phosphate to an active
is normally about 40 to 100 pg /day. Values less than 15
pg /day are in the deficient range. Diagnosis of deficiency coenzyme are also flavin-dependent, and thus, link
can also be based on the response of red cell transketolase riboflavin with these two vitamins. Riboflavin deficiency
to the addition of thiamine in vitro. Erythrocytes from affects fatty acid synthesis, and causes a decrease in plasma
deficient persons have a greater response to thiamine levels of linoleic and linolenic acids. By impairing the
pyrophosphate addition than do those of normal controls. conversion of phosphorylated vitamin B6 to its coenzyme,
An increase in transketolase activity of less than 15% it affects reactions involved in amino acid metabolism
constitutes a normal status, 15-25% is considered mild requiring this vitamin.
deficiency, and responses of over 25% are defined as
Deficiency
severely deficient.
Riboflavin deficiency may occur from inadequate intake
Thiamine Requirements or malabsorption. It takes 1-2 months to develop and is
Requirements are generally based on carbohydrate intake usually associated with other vitamin deficiencies. The
since thiamine functions primarily in the metabolism of classic presentation of ariboflavinosis includes photo
carbohydrates. The recommended daily allowance is 0.4 phobia, glossitis, angular stomatitis, seborrheic dermatitis,
mg/1000 kcal consumed. corneal vascularization and cataracts. Nonspecific
symptoms of anorexia, weight loss, weakness, dizziness
Treatment of Beriberi and confusion may precede. Late complications of
Treatment of beriberi with thiamine usually leads to ariboflavinosis are unusual with prompt therapy.
resolution of neurologic and cardiac symptoms within 24
to 48 hr. Treatment of children with mild beriberi with an Diagnosis of Riboflavin Deficiency
oral dose of 5 mg thiamine per day is usually satisfactory. Diagnosis should be considered with a history of dietary
Severely ill children should receive 10 mg intravenously deficiency and clinical manifestations. A reliable, although
twice daily. In the management of fulminant heart disease, not always practical indicator of riboflavin status is the
higher doses with vigorous treatment of congestive heart 24-hour urinary excretion of the vitamin. Excretion of less
failure are necessary. than 10% of intake over 24 hours is indicative of deficiency.
88 Essential Pediatrics
Activity of glutathione reductase in the erythrocytes Clinical features of niacin deficiency are chronic,
provides a functional index of flavin coenzyme relapsing, and popularly characterized by three D's:
activity. The enzyme activity in red cells is measured in dermatitis, diarrhea, and dementia. The cutaneous lesions
vitro before and after the addition of FAD. A cofactor- consist of a pigmented rash aggravated by sunlight. More
induced increase of 20% above the basal level is indicative acute cases may progress to vesiculation, ulceration and
of deficiency. secondary infection. Classically, the erythema progresses
to roughening and keratosis with scaling. A characteristic
Riboflavin Requirements red coloration of the tongue may also be seen. Although
Requirements are often based on caloric intake. The neurologic manifestations may appear without skin
recommended daily intake is 0.4 mg /1000 kcal for infants manifestations, they usually follow development of skin
and 0.8-1.2 mg /1000 kcal for children. lesions. Neurologic symptoms include apathy, headaches
and loss of memory. In most chronic forms, posterolateral
Treatment of Riboflavin Deficiency cord degeneration and peripheral nerve lesions are seen.
Children may be successfully treated with 1 mg riboflavin Only in the most severe and chronic cases do the
three times daily for several weeks, and infants respond neurologic lesions persist after adequate treatment with
to 0.5 mg twice daily. Often therapeutic doses of vitamin niacin.
A will improve the corneal lesions more rapidly.
Diagnosis of Niacin Deficiency
Niacin (Vitamin B3)
Diagnosis may be suspected by a history of inadequate
Nicotinic acid and nicotinamide, which are biologically diet, INH treatment, or chronic alcohol ingestion when
equivalent vitamins, are both referred to as niacin. the typical manifestations are present. Determination of
Biosynthesis of this vitamin occurs in almost all urinary excretion of N'-methylnicotinamide is the most
organisms; and in humans the conversion ratio of helpful. Normal twenty-four hour excretion of N1 -
tryptophan to nicotinic acid is only about 60 to 1, making methylnicotinamide is between 4 and 6 mg and values
it possible for large amounts of tryptophan to meet niacin below 3 mg are indicative of deficiency state. In pellagra
requirements. these values are usually 0.5 to 0.8 mg/day.
collectively known as the folates. Folic acid participates carboxylase forms methyl-malonyl-CoA, permitting the
in several important metabolic processes in the body. It is entry to the Krebs cycle of carbons derived from branched
essential for the normal growth and maintenance of all chain amino acids, fatty acids with odd-numbered carbon
cells because it acts as a coenzyme for normal DNA and chains, and cholesterol; (d) methylcrotonyl-CoA
RNA synthesis. Folate is vital for the reproduction of the carboxylase participates in the catabolism of leucine.
cells within the fetus. A deficiency affects normal cell divi Dietary sources include liver, egg yolk, milk, yeast
sion and protein synthesis, especially impairing growth. extracts and meat.
Folic acid, with the collaboration of vitamin B12 converts Biotin deficiency has been observed in individuals who
homocysteine in methionine therefore reducing blood consume large number of raw eggs (rich in avidin) for
levels of homocysteine and lowering risks of heart disease. several months. The avidin is not hydrolyzed by gastro
It also maintains nervous system's integrity and intestinal intestinal enzymes; it binds biotin, and prevents its
tract functions. It is involved in the production of neuro absorption. Cooking of eggs destroys avidin.
transmitters such as serotonin, which regulate mood, sleep
Clinical features of biotin deficiency include anorexia,
and appetite. Leafy vegetables such as spinach, turnip
vomiting, dry scaly dermatitis, glossitis, and hyper
greens, lettuces, dried beans and peas, fortified cereal
cholesterolemia. Long-term parenteral alimentation
products, sunflower seeds and certain other fruits and
without biotin can also lead to deficiency in pediatric and
vegetables are rich sources of folate. adult patient. Multiple carboxylase deficiency is a genetic
Deficiency of folic acid limits cell function (cell division metabolite disorder affecting the activity of carboxylase
and protein synthesis) and affects the normal growth and synthetase, which catalyzes the transfer of biotin to the
repair of all cells and tissues in the body. The tissues that apocarboxylase moiety. This condition responds to large
have the fastest rate of cell replacement are affected first. doses of biotin. Another genetic defect affects the activity
Since folate deficiency limits cell division, erythropoiesis, of biotinidase, an enzyme involved in the recycling of
is hindered and leads to megaloblastic anemia. Other biotin.
symptoms are impaired brain and nerve functions espe
Requirements are difficult to determine since biotin is
cially memory problems. Deficiency of folate in pregnant
produced by bacteria in the gastrointestinal tract.
women has been implicated in neural tube defects.
Recommendations are 0.15 mg biotin in the multivitamin
Therefore peri-conceptional folic acid supplementation a supplements for infants and children.
month before conception and at least 3 months afterward
For treatment of biotin deficiency oral administration
is recommended to potentially reduce the risk of having
of 2 to 5 mg daily for 2 to 3 weeks is recommended for
a fetus with a neural tube defect.
mild cases. A parenteral biotin dose of 200 pg daily for 2
Recommended Daily Allowance to 5 days can be used in more severe cases.
Sources
CALCIUM
Dietary sources include vegetables (cauliflower, broccoli,
cabbage) and fruits (strawberries, citrus). Much of the Calcium is the most abundant mineral in the body, and is
vitamin C in foods may be lost in cooking as a result of located primarily in bone tissue (98%). It is involved in
heat and oxidation. Ascorbate is relatively stable in canned coagulation cascade, nerve conduction and muscle
and frozen foods. stimulation. Intestinal absorption of calcium varies in
Vitamin C in human milk ranges from 5-15 mg/ 100 inversely with intake and is regulated by l,25(OH)D3,
kcal, compared with 0.2-2.0 mg/100 kcal in cow's milk. which controls the synthesis of calcium-binding protein
at the brush border. In the presence of Vitamin D, calcium
Absorption and Metabolism absorption can adapt to a wide range of dietary calcium
Ascorbic acid is absorbed by an active, sodium-dependent intake, varying from less than 10-80% of available calcium.
process in the upper small intestine. Ascorbic acid Calcium absorption also depends on the interaction of
circulates in plasma in its free, anionic form and is widely calcium with other dietary constituents, including fiber,
distributed in the body, reaching the highest concentration phytate, oxalate, fat, and lactose.
in the adrenal and pituitary glands and in leukocytes. The main sources of calcium for infants are milk and
Vitamin C appears unchanged in the urine or as the sulfate dairy products, with smaller amounts derived from grains
when the renal threshold is exceeded. and fruits once solid foods are introduced. Children
consuming strict vegetarian diets may develop calcium
Biologic Action deficiency, either alone or in combination with vitamin D
Vitamin C appears to function primarily as a strong deficiency. Strict vegetarian diets may provide as little as
reducing agent or in reactions involved in electron 250 mg of calcium per day, and include generous amounts
transport within biological systems. Ascorbic acid is also of substances that inhibit calcium absorption, such as fiber
essential for the normal function of leukocytes, fibroblasts, and phytates. Secondary calcium deficiency may develop
osteoblasts, and microsomes, and it participates in the in association with steatorrhea, chronic malabsorption
metabolism of carnitine, serotonin, and folate. In these syndromes, or intestinal or renal abnormalities of calcium
systems, ascorbic acid affects the immune response, metabolism.
detoxification, collagen synthesis, and wound healing. Children aged 1 to 10 years require an intake of 500 to
Deficiency 800 mg per day. During the pubertal growth spurt calcium
requirements are as high as 1000 to 1200 mg per day.
Prolonged vitamin C deficiency results in scurvy. It Pregnant and lactating women require 400 mg per day.
usually occurs in those who are deprived of citrus fruits,
Calcium deficiency may cause tetany characterized by
fresh vegetables, or vitamins for some cultural or muscle cramps, numbness and tingling in limbs. Rickets
geographic reasons. and osteoporosis may occur with chronic deficiency.
In infancy, clinical features of scurvy (Barlow's disease)
are anorexia, diarrhea, pallor, irritability and increased
MAGNESIUM
susceptibility to infections. Sub-periosteal hemorrhages
and long bone tenderness (pseudoparalysis of the lower Magnesium is essential for bioenergetic reactions
extremities) can occur. Radiologic abnormalities are the controlling fuel oxidation, membrane transport, and signal
most frequent manifestations. In older children, hemor transmission, contributing to the action of more than 300
rhagic signs usually predominate, with bleeding of gums, enzymes. Over 80% of the total body magnesium is in bone
conjunctiva, and the intestinal tract. and skeletal muscle. Rich sources of magnesium include
legumes, nuts, bananas, and whole grains.
Diagnosis of Scurvy Magnesium is absorbed efficiently by the intestine
Diagnosis can be made by the presence of characteristic primarily by diffusion. Regulation of magnesium balance
physical findings and history of inadequate dietary intake depends mainly on renal tubular reabsorption. Deficiency
of vitamin C. X-rays of long bones are diagnostic in is usually secondary to intestinal malabsorption, excessive
infantile scurvy. gastrointestinal losses through fistulae or continuous
Vitamin C therapy often results in dramatic improve suction or renal disease affecting tubular cation
ment within 24^18 hrs. reabsorption. Clinical manifestations of magnesium
deficiency include irritability, tetany and hypo or hyper-
Requirements for Vitamin C reflexia. Magnesium requirements in the first 6 months
Daily requirements are 30 to 40 mg for infants and 40 to range between 40-50 mg/day; 60 mg/day for 6-12 months
70 mg for children. and approximately 200 mg/day for older children.
92 Essential Pediatrics
Deficiency
TRACE ELEMENT DEFICIENCIES
More commonly, zinc deficiency develops as part of
malnutrition or malabsorption syndromes, caused by low
BIOLOGICAL FUNCTION OF THE TRACE ELEMENTS
intake of zinc in the diet or by intestinal disease. Severe zinc
Eleven "major" elements constitute 99% of human body deficiency syndromes have occurred in patients main
weight. These essential-for-life elements are hydrogen tained on prolonged total intravenous feeding without
carbon, nitrogen, oxygen, sodium, potassium, chlorine, adequate trace element supplements. Poor physical growth
calcium, phosphorus, sulfur, and magnesium. In addition, is a documented feature of zinc depletion in preschool and
the body is composed of numerous "trace" elements. The school-age children. Zinc supplementation has been
term trace elements comprise an increasing number of reported to accelerate growth in adolescents suffering from
compounds with proven or putative essentiality for intestinal malabsorption and sickle-cell disease. Delayed
human nutrition. Each of these contributes less than 0.01% sexual maturation is also a prominent feature of zinc
of total body weight. deficiency in adolescents. The typical syndrome of zinc
deficiency in humans consists of growth retardation,
The major functions of the trace elements are related to
hypogonadism, and anemia. Other major symptoms
enzyme systems where they may act either as cofactor for
include diarrhea, hair loss, anorexia, dermatitis impaired
metal-ion-activated enzymes or as specific constituents of
immune function and skeletal abnormalities. Acro
metalloenzymes.
dermatitis enteropathica is an autosomal recessive
This section provides an overview of all trace elements syndrome of severe zinc deficiency, caused by defective
of established importance in human nutrition. intestinal absorption. Anorexia is a prominent feature of
untreated acrodermatitis enteropathica. Pica may also be
ZINC present in some cases. Impaired taste perception has been
demonstrated in zinc-depleted children.
Functions
Catchup growth has followed the introduction of zinc
Zinc is a component of over 100 zinc- metalloenzymes and therapy in patients with acrodermatitis enteropathica.
participates exclusively in many biological processes. Wound healing is delayed in zinc-deficient animals.
However, most attention has been directed to its catalytic Epithelialization of burns may also be improved with zinc
role. There is growing evidence to support a structural therapy. Eye lesions that occur with zinc deficiency
role for zinc in biological membranes. Its role as an include photophobia, blepharitis, and corneal opacities.
intracellular regulatory ion is analogous to the role of A definitive diagnosis of zinc deficiency is difficult and
calcium. is often derived from the combination of a dietary history
It has been hypothesized that zinc functions as an of chronic low zinc intake and /or excessive intestinal
intracellular hormone contributing to the regulation of losses, the presence of clinical signs compatible with zinc
cellular growth and also impacts on nucleic acid deficiency, such as growth delay or skin lesions, and low
metabolism and protein synthesis. Thymidine kinase, levels of zinc in plasma or hair.
DNA polymerase, and RNA polymerase have each been
Requirements
reported to be zinc dependent. Zinc has a crucial role in
the conformation of the "ZiD fingers" that allows them to The requirements for infants range between 3.5 and 5.0
bind with DNA to initiate the transcription process. mg per day.
Treatment of Deficiency
Absorption and Metabolism Acquired zinc deficiency states can be treated with 0.5 to 1.0
Zinc is absorbed throughout the small intestine probably mg elemental zinc/kg/day for several wks or months. Oral
by a process of facilitated diffusion. Most of the absorbed zinc can be administered as the sulfate or acetate. One mg
zinc is taken up temporarily by the liver, which plays a of elemental zinc is equivalent to 4.5 mg zinc sulfate or 3 mg
central role in zinc metabolism. Absorbed zinc is zinc acetate. Intravenous requirements for patients
transported in the portal system attached to albumin or maintained on prolonged intravenous feeding approxi
transferrin. In the systemic circulation, the major fraction mate 50 pg of elemental zinc/kg body weight/day. These
of plasma zinc is loosely bound to albumin. Zinc is requirements can be considerably higher in the presence of
distributed in most tissues, but almost 90% of total body excessive zinc losses. Zinc therapy should be monitored
zinc is localized in bone and skeletal muscle. with plasma zinc and copper concentrations as excessive
Zinc status is regulated both at the absorptive step and zinc therapy can lead to a copper deficiency syndrome.
by intestinal re-excretion. The major excretory route for
Toxicity
endogenous zinc is via the feces. The quantity excreted in
the feces depends on the quantity of dietary zinc absorbed Zinc is relatively nontoxic, but acute ingestion of large
and on zinc nutritional status. amounts may cause liver and kidney failure. Competitive
Micronutrients in Health and Disease 93
interaction of zinc with other minerals in the intestinal copper transporting membrane proteins. Central nervous
lumen, may lead to copper deficiency in persons receiving system manifestations include hypotonia, psychomotor
chronic zinc supplementation at high doses. retardation, and apneic episodes. In the Menkes's steely-
hair syndrome there is severe neurological degeneration
COPPER leading to a fatal outcome by early childhood. Laboratory
findings include hypocupremia, low plasma cerulo
Copper is a component of several metalloenzymes that
plasmin, neutropenia and anemia.
are required for oxidative metabolism, including cyto
chrome oxidase, ferroxidases, amine oxidases, superoxide
Toxicity
dismutase, ascorbic acid oxidase and tyrosinase. Cyto
chrome oxidase, the terminal enzyme in the electron Acute ingestion of large doses of copper cause diarrhea,
transport chain, is the key enzyme necessary for the abdominal pain, and may lead to liver and kidney failure.
production of most of the energy of metabolism in aerobic Chronic intoxication occurs from copper released from
cells. Ceruloplasmin, a glycoprotein that contains eight water piping, by extensive use of topical copper-
copper atoms per molecule, accounts for more than 95% containing medications, or by hemodialysis with solutions
of the copper present in the blood plasma. that have high copper content. Chronic copper intoxication
has been proposed as the mechanism causing Indian
Absorption and Metabolism childhood cirrhosis.
Approximately 40% of ingested copper is absorbed in the
stomach and small intestine. Absorbed copper is SELENIUM
transported to the liver attached to albumin. In the liver it Selenium is a constituent of glutathione peroxidase, an
is utilized by the hepatocytes in the synthesis of antioxidant system present in red blood cells and in other
ceruloplasmin, which is subsequently released into the tissues. Glutathione peroxidase scavenges free hydro
systemic circulation. Biliary excretion plays an important peroxides generated during fatty acid oxidation, thus
role in copper homeostasis. Approximately one-third of protecting the cell from damage caused by free radical
fecal copper is contributed by copper in bile acids, the rest formation. Severe selenium deficiency is the major
coming from unabsorbed copper and from epithelial etiological factor in Keshan disease, which presents
desquamation. Urinary excretion of copper contributes primarily as a cardiomyopathy in young children. Skeletal
minimally to copper balance. myopathies have also been reported. Mild selenium
deficiency is associated with macrocytosis and loss of hair
Sources pigment.
The richest sources are meats, liver, seafood, nuts and
seeds. Additional copper may enter the food chain through CHROMIUM
the use of copper-containing pesticides and by conta
mination of water by copper pipes and copper cooking Glucose intolerance, which complicates malnutrition in
young children, has been attributed in part to chromium
utensils.
deficiency. Chromium acts in glucose homeostasis by
Deficiency potentiating insulin action, possibly by interacting with
Primary dietary deficiency is infrequent. Secondary this hormone and its receptor, facilitating binding.
deficiency may develop in malabsorption syndromes, liver Symptoms of chromium deficiency are usually seen in the
setting of total parenteral alimentation with low chromium
disease, peritoneal dialysis, and other conditions causing
content for long periods of time and include glucose
excessive copper losses. Classical manifestations of copper
intolerance, peripheral neuropathy, and evidence of
deficiency include a microcytic, hypochromic anemia
disturbed nitrogen and lipid metabolism.
unresponsive to iron therapy, neutropenia, and
osteoporosis. Copper deficiency decreases the lifespan of
the erythrocyte and impairs mobilization of stored iron IODINE
from liver and bone marrow. Skeletal lesions include The term iodine deficiency disorders (IDD) refers to all
periosteal elevation, cupping and flaring of long-bone the ill-effects of iodine deficiency in a population that can
metaphyses with spur formation, and, in some cases, be prevented by ensuring an adequate intake of iodine.
submetaphyseal fractures, flaring of the anterior ribs, and Iodine deficiency disorders (IDD) jeopardize children's
spontaneous fractures of the ribs. Deficient infants show mental health and often their very survival. Serious iodine
pallor, depigmentation of skin and hair, prominent dilated deficiency during pregnancy can result in stillbirth,
superficial veins, skin lesions resembling seborrheic spontaneous abortion, and congenital abnormalities such
dermatitis, anorexia, diarrhea, and failure to thrive. as cretinism, a grave, irreversible form of mental
Copper transport is disrupted in two human diseases: retardation that affects people living in iodine-deficient
Wilson disease and Menkes disease. Both have defects in areas. However, of far greater significance is IDD's less
94 Essential Pediatrics
visible, yet pervasive, mental impairment that reduces observations indicate a much greater risk of mental defect
intellectual capacity at home, in school and at work. in severely iodine-deficient populations than is indicated
The effects of iodine deficiency on growth and by the presence of cretinism. They provide strong evidence
development are summarized in Table 6.3. for the need to correct the iodine deficiency.
Fetus Abortions
Stillbirths
Congenital anomalies
Increased perinatal mortality
Endemic cretinism
Neonate Neonatal goiter
Neonatal hypothyroidism
Endemic mental retardation
Child and adolescent Goiter
Subclinical hypothyroidism
Impaired mental function
Retarded physical development
Fis. 6.6 : A 14-year-old girl with goiter
Micronutrients in Health and Disease 95
The National Goiter Control Program (1962) was Evidence indicates that iron deficiency anemia is
begun by the Ministry of Health in India for control of associated with impaired performance on a range of
iodine deficiency disorders. It was started by establish mental and physical functions in children including
ment of salt iodination plants to ensure an adequate physical coordination and capacity, mental development
supply of iodized salt in the country. Based on an cognitive abilities, and social and emotional development.
assumption of a mean intake of salt of 5 g/day, the Other health consequences include reduced immunity,
recommended level of iodination is one part of iodine in increased morbidity, increased susceptibility to heavy
25,000 to 50,000 parts of salt. metal (including lead) poisoning. The precise effects vary
with the age groups studied. The health consequences of
iron deficiency during first two years of life are not only
IRON
serious but also irreversible. It is evident that concerted
Iron deficiency remains a major nutritional problem efforts need to be undertaken to improve the scenario.
among infants and young children in India. The National There is an urgent need to initiate specific public health
Family Health Survey (NFHS) II, conducted in 1998-99, action to prevent iron deficiency in young children.
documented that about 74% children between the ages of A detailed description of clinical features, diagnosis,
6-35 months were anemic. The NFHS III (2005-06) shows treatment and prevention of iron deficiency anemia is
similar data. given in chapter 11.
7 Newborn Infants
Newborn infants are unique in their physiology and the Term neonate: Any neonate born between 37 and <42 weeks
health problems that they experience. Neonatal period is (259-293 days) of gestation irrespective of the birth weight.
characterized by transition to extrauterine life and
Pre-term neonate: Any neonate born before 37 weeks (<259
exquisitely rapid growth and development. This is the
days) of gestation irrespective of the birth weight.
phase in life with the greatest risk of mortality as well as
the maximum potential for long-term physical and Postterm neonate: A neonate born at a gestation age of 42
neurocognitive development. Almost half of under five weeks or more (294 days or more) gestation irrespective
child deaths occur in the neonatal period. Bacterial infec of the birth weight.
tions, manifesting as sepsis and pneumonia, are the
Low birth weight (LBW) neonate: Any neonate weighing less
foremost cause of death. Other causes of neonatal
than 2500 g at birth irrespective of the gestational age.
mortality are prematurity, birth asphyxia and congenital
malformations. Almost three-fourths of all neonatal deaths Very low birth weight (VLBW) neonate: Any neonate
occur among the low birth weight newborns. Of all the weighing less than 1500 g at birth irrespective of the
neonatal deaths, about 40% occur within 72 hours of birth. gestational age.
Health of the mother and her care during pregnancy and
Extremely low birth weight (ELBW) neonate: Any neonate
at childbirth has profound influence on neonatal outcome.
weighing less than 1000 g at birth irrespective of the
Newborn health is indeed the key to child health and
gestational age.
survival.
Neonatal mortality rate (NMR): Deaths of infants under the
DEFINITIONS first 28 days of life per 1000 live births.
Neonatal period: From birth to under four weeks (<28 days) RESUSCITATION OF A NEWBORN
of age. An infant is called a neonate during this phase.
First week of life (<7 days or <168 hours) is known as early Of the 25 million infants born every year in India, 3-5%
neonatal period. Late neonatal period extends from 7th experience asphyxia at birth. Asphyxia is characterized
to <28th day. by progressive hypoxia, hypercapnia, hypoperfusion and
acidosis. It may lead to multiorgan dysfunction including
Post-neonatal period: Period of infancy from 28 days to <365 hypoxic ischemic encephalopathy (HIE) which might
days of life. result in long-term neuromotor sequelae.
Perinatal period: Perinatal period extends from 20th week There is a broad consensus on the evidence-based
of gestation (or weighing 500 g or more at birth) to less resuscitation of newborn babies at birth. The American
than 7 days of life. Heart Association (AHA) and the American Academy of
Pediatrics (AAP) have recently updated the resuscitation
Live birth: A product of conception, irrespective of weight
guidelines that are being propagated worldwide through
or gestational age, that, after separation from the mother,
the Neonatal Resuscitation Program (NRP). A summary
shows any evidence of life such as breathing, heartbeat,
of the recommendations of AHA-AAP (2005) is provided
pulsation of umbilical cord or definite movement of the
here.
voluntary muscle.
Fetal death: A fetal death is a product of conception that, Physiology of Asphyxia
after separation from the mother, does not show any
When an infant is deprived of oxygen, an initial brief
evidence of life.
period of rapid breathing occurs. If the asphyxia continues,
Still-birth: A fetal death at a gestational age of 20 weeks of the respiratory movements cease, the heart rate begins to
more or weighing more than 500 g is designated as still fall, neuromuscular tone gradually diminishes, and the
birth or still-born. infant enters a period of apnea known as primary apnea. In
96
Newborn Infants 97
most instances, tactile stimulation and exposure to oxygen arterioles remain constricted and ductus arteriosus remains
during this period will induce respiration. open. This results in persistence of fetal circulation. As long
If the asphyxia continues, the infant develops deep as decreased pulmonary blood flow exists, proper
gasping respiration, the heart rate continues to decrease, oxygenation of the tissues of the body is impossible, even
the blood pressure begins to fall, and the infant becomes when the infant is being properly ventilated.
nearly flaccid. The respirations become weaker and In mildly asphyxiated babies whose oxygen and pH
weaker until the infant takes a last gasp and enters a period are only slightly lowered, it may be possible to increase
of secondary apnea. The infant is now unresponsive to pulmonary blood flow by quickly restoring adequate
stimulation and will not spontaneously resume respiratory ventilation. Pulmonary perfusion in severely asphyxiated
efforts unless resuscitation in the form of positive pressure infants may not improve with ventilation alone. The
ventilation is initiated. combination of oxygenation and correction of metabolic
It is important to note that as a result of fetal hypoxia, acidosis would result in opening the pulmonary arterioles
the infant may go through the phases of primary and and thereby an improvement in pulmonary blood flow.
secondary apnea in-utero itself. Thus an apneic infant at
birth may be in either primary or secondary apnea. These Cardiac Function and Systemic Circulation
two are virtually indistinguishable from one another. In
In asphyxia, there is redistribution of blood flow to pre
both instances, the infant is not breathing and the heart serve blood supply to vital organs. There is vasocons
rate may be below 100 beats per minute. The clinical triction in the bowel, kidney, muscles, and skin, thus
significance of this is that when faced with an apneic infant preserving blood flow to the heart and brain.
at birth, one should assume that one is dealing with As asphyxia is prolonged, myocardial function and
secondary apnea and be ready to undertake full resus cardiac output deteriorate, and blood flow to all organs is
citation efficiently. reduced. This sets in the stage for progressive organ
damage. At this point it may be necessary to provide
Lungs and Respiration
cardiac stimulants (epinephrine) and volume expanders
During intrauterine life the lungs do not play a role in gas (normal saline) to support the heart and circulation.
exchange which is taken care of by the placenta. The lung
alveoli in the fetus are filled with fluid. The process of Being Prepared for Resuscitation
fluid removal starts with onset of labor or even before.
With careful consideration of antepartum and intrapartum
Contrary to what was previously thought, squeezing the
risk factors, asphyxia can be anticipated in up to half of
infant's chest during a vaginal delivery plays only a minor
the newborns who will eventually require some form of
role in clearing lung fluid. The majority of the fluid passes
resuscitation. In others, the need for resuscitation can come
from the air spaces into perivascular space and is absorbed
as a complete surprise. Therefore, each delivery should
into the blood and lymphatic channels within the lungs.
be viewed as an emergency, and basic readiness must be
The process of labor may facilitate removal of lung fluid,
ensured to manage asphyxia. Preparation for delivery
whereas removal is slowed when labor is absent (as in
should include: (i) a radiant heat source ready for use;
elective cesarean section).
(ii) all resuscitation equipments immediately available and
Removal of lung fluid from the air spaces is facilitated
in working order (Table 7.1); and (iii) at least one person
by respiration soon after birth. The first few breaths after
skilled in neonatal resuscitation.
birth are effective in expanding the alveoli and replacing
the lung fluid with air. Problems in clearing lung fluid
Signs to Evaluate
occur in infants whose lungs do not inflate well with the
first few breaths such as those who are apneic at birth or Evaluation is based primarily on the following three signs:
have a weak initial respiratory effort as with prematurity respiration, heart rate (HR) and color. Though all three
and sedation. signs are evaluated simultaneously, low heart rate is the
most important sign for proceeding to the next step.
Pulmonary Circulation
Oxygenation depends not only on air reaching the alveoli, Role of Apgar Score in Resuscitation
but also on pulmonary blood flow. During intrauterine The Apgar score is an objective method of evaluating the
life, there is a very little blood flow in the pulmonary newborn's condition. It is generally performed at 1 minute
circulation since capillaries are in a state of vasocons and again at 5 minutes of age. However, resuscitation must
triction. After birth, pulmonary vasodilatation takes place be initiated before the 1-minute score is assigned. If the
resulting in fall in pulmonary vascular resistance and infant requires interventions based on assessment of
increased blood flow in the pulmonary circuit. respiration, heart rate, or color, they should not be delayed
An asphyxiated infant has hypoxemia (low-oxygen for want of Apgar score at 1 minute. Therefore, the Apgar
content of the blood) and acidosis (a fall in pH). In the score is not used to determine the need or the steps
presence of hypoxemia and acidosis, the pulmonary necessary for resuscitation.
98 Essential Pediatrics
Positioning
While the Apgar score is not useful for decision making The baby should be placed on her back or side with the
at the beginning of resuscitation, the change of score at neck slightly extended. This will bring the posterior
sequential time points following birth can reflect how well pharynx, larynx, and trachea in line and facilitate air entry.
the baby is responding to resuscitative efforts. Hence, Care should be taken to prevent hyperextension or flexion
additional scores should be obtained every 5 minutes for of the neck, since either may decrease air entry. To help
up to 20 minutes, if the 5-minute Apgar score is less maintain the correct position, one may place a rolled
than 7. blanket or towel under the shoulders, elevating them 3A
or 1 inch off the mattress. This shoulder roll may be
TABC of Resuscitation particularly helpful if the infant has a large occiput result
The components of the neonatal resuscitation procedure ing from molding, edema, or prematurity (Fig. 7.2).
related to the TABC of resuscitation are shown here:
T-Temperature: Provide warmth, dry the baby and Clear Airway
remove the wet linen. The appropriate method for clearing the airway will
A-Airway: Position the infant, clear the airway (wipe depend on the presence or absence of meconium.
baby's mouth and nose or suction mouth, nose and in If no meconium is present, secretions may be removed
some instances, the trachea). If necessary, insert an from the airway by wiping the nose and mouth with a
endotracheal (ET) tube to ensure an open airway. towel or by suctioning with a bulb syringe or suction
B-Breathing: Tactile stimulation to initiate respirations, catheter. The mouth is suctioned first to ensure that there
positive-pressure breaths using either bag and mask or is nothing for the infant to aspirate, if he/she should gasp
bag and ET tube when necessary. when the nose is suctioned. If the infant has copious
C-Circulation: Stimulate and maintain the circulation of secretion from the mouth, the head should be turned to
blood with chest compressions and medications as the side. This will allow secretions to collect in the mouth,
indicated. from where they can be easily removed.
Newborn Infants 99
However, one should not waste too much of time in • If the baby is breathing well, HR >100 but has central
providing tactile stimulation. cyanosis, administration of supplemental oxygen is
indicated.
Management of Infant born through • If the baby is not breathing well or HR <100, then
Meconium-stained Liquor (MSL) positive pressure ventilation is needed.
It is extremely important to observe whether meconium
is present in the amniotic fluid or not. When baby passes Supplemental Oxygen
meconium in utero, there is a chance that the meconium Central cyanosis requires supplemental oxygen, which is
will be aspirated into infant's mouth and potentially into provided by using an oxygen mask or by oxygen tubing
the trachea and lungs. Appropriate steps must be taken held in cupped hand over baby's face. The flow of oxygen
immediately after delivery to reduce the risk of serious should be at least 5 L/minute.
consequences resulting from aspiration of the meconium.
(Note: Intrapartum suctioning of the mouth and nose (after Positive Pressure Ventilation (PPV)
delivery of the head and before delivering the shoulders) is no PPV is usually given by using a self-inflating bag and face
longer recommended). mask (bag and mask ventilation or BMV).
After delivery, the first step would be to identify
whether the infant is vigorous or non-vigorous. A newborn Indications: BMV is Indicated if
infant is classified as vigorous, if he has all the three signs i. The infant is apneic or gasping or
that include strong respiratory efforts, good muscle tone ii. HR is less than 100 beats per minute, even if breathing
and a heart rate greater than 100/min. Absence of even a iii. The infant has persistent central cyanosis despite
single sign would mean a non-vigorous baby. The vigorous administration of 100% free flow oxygen
baby does not require any tracheal suctioning and the usual The resuscitation bag should be self-inflating type with
initial steps are provided. For non-vigorous babies, the a capacity of 240 to 750 mL. The bag should be attached to
initial steps are modified as below: an oxygen source (at 5-6 liter/min) and a reservoir so as
• Place the baby under radiant warmer. Postpone drying to deliver 90-100% oxygen to the baby. In case oxygen is
and suctioning to prevent stimulation. not available, baby can be resuscitated using room air also.
• Residual meconium in the mouth and posterior In suspected or confirmed diaphragmatic hernia, bag and
pharynx should be removed by suctioning under direct mask ventilation is contraindicated. Similarly, in non-
vision using a laryngoscope. vigorous babies born through MSL, bag and mask
• The trachea should then be intubated and meconium ventilation is carried out only after tracheal suctioning.
suctioned from the lower airway.
Tracheal suctioning is best done by applying suction Procedure
directly to the endotracheal tube (ET). Continuous suction The infant's neck should be slightly extended to ensure
is applied to the tube as it is withdrawn with the negative an open airway. One should be positioned at head end or
pressure set to approximately 100 mm Hg. Tracheal at the side of baby to have an unobstructed view of infant's
suctioning can be repeated if the previous suctioning chest and abdomen. One should select an appropriate
revealed meconium and baby has not developed signi sized facemask that covers the mouth and nose but not
ficant bradycardia. eyes of the infant (Fig. 7.3). The facemask should be held
firmly on face to obtain a good seal.
Evaluation
After providing initial steps, the baby should be evaluated
for three vital signs—respiration, HR and color.
Respiration is evaluated by observing the infant's chest
movements. HR can be assessed by auscultating the heart
or by palpating the umbilical cord pulsation for 6 seconds.
The number of beats is multiplied by 10 to obtain the HR
per minute (e.g. a count of 12 in 6 seconds is a HR of 120
per minute). Color is evaluated by looking at tongue,
mucous membranes, and trunk. A blue hue to the lips,
tongue, and central trunk indicates central cyanosis.
Presence of cyanosis in extremities (acrocyanosis) does not
have any value.
• If the baby has good breathing, HR >100 and pink color,
then he does not require any additional intervention.
He should be monitored frequently in a transitional
area of the nursery (observational care). Fig. 7.3: Properly fitting mask
Newborn Infants 101
The bag should be compressed using fingers. One decreases. As a result there is diminished flow of blood
should observe for an appropriate rise of the chest. If and oxygen to the vital organs. Chest compressions help
chest does not rise, the steps outlined in Table 7.2 should in mechanically pumping the blood to vital organs of the
be followed. body. It must always be accompanied by BMV so that only
oxygenated blood is being circulated during chest
compressions.
Chest compressions consist of rhythmic compressions
of the sternum that compress the heart against the spine,
increase intrathoracic pressure and circulate blood to the
vital organs of the body.
Chest Compressions
The heart circulates blood throughout the body delivering
oxygen to vital organs. When an infant becomes hypoxic,
the heart rate slows and myocardial contractility Fig. 7.5 : Chest compression with two finser technique
102 Essential Pediatrics
When chest compressions are performed on a neonate, vocal cord guide and centimeter markings. ET tube size
pressure is applied to the lower third of the sternum. Care depends on the weight or gestation of the baby. Appro
must be used to avoid applying pressure to the xiphoid. priate sizes of the tube for newborns of different gestation
To locate the area, slide your finger on the lower edge of are shown in Table 7.4.
thoracic cage and locate xiphisternum. The lower third of
the sternum is just above it. Table 7.4: Appropriate endotracheal tube size
Rate
It is important to ventilate between chest compressions. A
ventilation breath should follow every third chest
compression. In one minute, 90 chest compressions and 30
breaths are administered, (a total of 120 events). To obtain
the proper ratio of 90 compressions and 30 ventilations in
1 minute (3:1), you must compress the chest three times in
1Vi seconds, leaving approximately Vi second for ventilation.
Most endotracheal tubes currently manufactured for
Your thumbs or the tips of your fingers (depending on
neonates have a black line near the tip of the tube which
the method you use) should remain in contact with the
is called a vocal cord guide. Such tubes are meant to be
chest during compression and release. Do not lift your
inserted so that the vocal cord guide is placed at the level
thumbs or fingers off the chest between compressions.
of the vocal cords. This usually positions the tip of the
It is important to know whether the blood is being
tube above the bifurcation of the trachea.
circulated effectively by chest compressions. To determine
For intubation, a neonatal laryngoscope, with straight
this, the carotid or femoral pulse should be checked
blades of sizes '0' (for preterm babies) and T (term babies)
periodically.
is required. Before intubating, the appropriate blade is
Chest compressions can cause trauma to the infant. The
attached to the handle of laryngoscope and the light is
dangers of chest compressions are: broken ribs, laceration
turned on.
of liver and pneumothorax.
Procedure
EVALUATION
The infant's head should be in midline and the neck kept
After a period of 30 seconds of chest compressions, the
slightly extended. The laryngoscope is held in the left hand
heart rate is checked.
between the thumb and the first three fingers, with the
• HR below 60: Chest compressions should continue
blade pointing away from oneself. Standing at the head
along with bag and mask ventilation. In addition,
end of the infant, the blade is introduced in the mouth
medications (epinephrine) have to be administered.
and advanced to just beyond the base of the tongue so that
• HR 60 or above: Chest compressions should be
its tip rests in the vallecula. The blade is lifted (as shown
discontinued. BMV should be continued until the heart
in Fig. 7.6) and landmarks looked for; the epiglottis and
rate is above 100 beats per minute and the infant is
breathing spontaneously. glottis should come into view. The glottic opening is
surrounded by vocal cords on the sides. Once the glottis
Endotracheal Intubation and vocal cords are visualized, the ET tube is introduced
into the right side of the mouth and its tip inserted into
Endotracheal (ET) intubation is required in only a small
the glottis till the vocal cord guide is at the level of the
proportion of asphyxiated neonates. Intubation is a
glottis, thus positioning it halfway between the vocal cords
relatively difficult skill to master and it requires frequent
and carina.
practice to maintain mastery over this skill.
Indications
The indications of ET intubation are: (i) when tracheal
suction is required (in non-vigorous babies born through
MSL), (ii) when prolonged bag and mask ventilation is
required, (iii) when BMV is ineffective, (iv) when
diaphragmatic hernia is suspected. The other conditions
where ET intubation is to be considered are: before starting
chest compressions and for administering medications.
Endotracheal Tube
The tube should be of uniform diameter throughout the
length of the tube (and not tapered near the tip) and have Fig. 7.6 : Direction of pull on the laryngoscope
Newborn Infants 103
Medications Indications
The majority of infants requiring resuscitation will have a Use of adrenaline is indicated if heart rate remains below
response to prompt and effective ventilation with 100% 60 despite adequate ventilation with 100% oxygen and
oxygen. Only a few will require medications. chest compressions for 30 seconds.
Medications used in resuscitation are epinephrine and Table 7.5 shows indications and effects of drugs used
volume expanders. Sodium bicarbonate and naloxone are for neonatal resuscitation.
indicated only for special circumstances (Table 7.5). There
is no role of atropine, dexamethasone, calcium, mannitol Suggested reading
and dextrose for resuscitation in the delivery room. Kattwinkel). Textbook of Neonatal Resuscitation. In: Kattwinkel) (ed).
5th ed. American Academy of Pediatrics and American Heart
Route of medication: Since veins in scalp or extremities
Association, 2005.
are difficult to access during resuscitation, umbilical vein
is the preferred route via a catheter. No intracardiac
CARE AT BIRTH AND DURING
injections are recommended in neonates.
FIRST FEW WEEKS OF LIFE
For umbilical vein catheterization, 3.5 Fr or 5 Fr
umbilical catheter (or a feeding tube in an emergency), is Prevention of Infection
inserted into the umbilical vein such that its tip is just In every step of newborn care and for every person who
inside the skin surface and there is free flow of blood. comes in contact with neonates (especially health care
There is no need to insert the catheter any further. Direct staff, who come in contact with multiple neonates, and
injection into the umbilical cord is undesirable and should older children, who are ideal vehicles for infection
not be attempted. transmission), the importance of maintaining cleanliness
Epinephrine may be injected directly into the bronchial and asepsis cannot be overemphasized. A few simple and
tree through endotracheal tube. Since absorption by this inexpensive ways to ensure this are:
route is erratic, this method is to be used only if venous • Clean environment: One should follow the "5 cleans" of
access cannot be obtained. The drug is injected by a needle birthing process, including clean hands, clean delivery
or a feeding tube (5 Fr) into the endotracheal tube, flushed surface, clean cord cut (using a sterile instrument or
with 0.5 mL of normal saline and disseminated into the new blade to cut the umbilical cord), clean cord tie and
lung by positive pressure ventilation. clean cord stump.
Note: Use of sodium bicarbonate is required only if asphyxia is very prolonged and there is a documented metabolic acidosis even after the use
of epinephrine and volume expanders. It should be remembered that the mainstay of therapy of metabolic acidosis is oxygenation and volume
expansion, and not sodium bicarbonate. Sodium bicarbonate therapy, if used, must be preceded, accompanied and followed by ventilation.
104 Essential Pediatrics
sufficient. A draught-free warm room, warm water and for concern. The parents should be reassured accor
quick completion of bath ensure that the baby doesn't dingly to allay their anxiety.
get cold during bathing. The head constitutes a large • Breast discharge: Under the effect of transplacentally
surface area of the baby; therefore, it should be washed transmitted hormones, the breasts of both boys and girls
last and dried first. Bathing time can be used to inspect may get hypertrophied and may even secrete a milk
baby's cord, eyes and skin for any discharge, rash or like fluid from the enlarged breast bud. Squeezing it
redness. causes pain and can harm the baby, hence it must be
Cosmetics: Babies have a sensitive skin and use of avoided. It resolves spontaneously in a few days and
cosmetics should be minimized. A low alkalinity, mild, should cause no worry.
non-perfumed/non-medicated soap should be used. • Rashes and skin peeling: Papular lesions on an
Any oil except mustard oil can be used; massaging erythematous base can be seen in many babies;
babies increases human touch and contact with baby dispersed over the trunk and face, these are commonly
and is beneficial. Sprinkling talc on babies can result in seen on day two or three of life. These lesions called
inhalation and so should be avoided; one should apply erythema toxicum, are eosinophil-filled sterile lesions that
it sparingly if at all and avoid products containing boric are normal, resolve spontaneously and require no
acid (present in most prickly heat preparations). Knjal treatment (Fig. 7.8). Pus filled lesions or pyoderma, on
can be harmful to the baby's eyes and, therefore, should the other hand, are neutrophil-filled lesions occurring
not be applied. in response to local infection of glands in the skin,
Redness around umbilicus: Umbilical cord normally falls commonly in skin creases where dirt accumulates, like
off in 7-10 days and the wound heals in about 15 days. thigh fold, back of neck, etc. If these are <10 in number
It should be kept dry, without any application or and there are no signs of sepsis, local cleaning with
bandaging. To avoid soiling, diaper should be folded antiseptic solution and application of 0.5% gentian
such that its upper margin lies below stump. If soiled, violet along with monitoring for resolution and new
the cord should be washed with clean water and soap lesions suffices. Further investigation, and treatment
and dried with a clean cloth. as for sepsis, is indicated if there are >10 lesions, signs
Any redness or induration around the umbilicus or pus of sepsis or non-resolution after topical treatment. Skin
drainage from it should alert the clinician to omphalitis. peeling is another normal skin finding noted especially
Omphalitis starts as a local infection of the umbilicus, in post-term and IUGR babies. Oil massaging can
usually from unclean handling or application of decrease the flaking but no other intervention is
unclean substances to the cord. It can spread to cause required.
life-threatening systemic sepsis. One should take a swab • Physiological jaundice: Almost 60% of normal newborn
for gram staining and culture if any discharge is present. babies develop clinically detectable jaundice (>5 mg/
If the area of redness extends to <1 cm of surrounding dL). Onset is usually on day 2-3 of life, reaching a peak
area and no other sign of sepsis is present, local cleaning on day 3-4 and subsiding spontaneously within 7-10
with antiseptic solution, followed by application of 0.5% days. However, in some babies this level can reach high
gentian violet four times a day till redness subsides, enough to cause brain damage. Signs suggesting
usually suffices. If redness in surrounding area is >1 pathological jaundice are discussed later on page 147.
cm or there are signs of sepsis, then, in addition to local
therapy, systemic antibiotic should be started as in
management of septicemia.
Regurgitation: Babies commonly regurgitate small
amount of curdled milk soon after feeding. This
behavior is normal and as long as the baby gains weight
and passes urine 6-8 times a day it does not require
any treatment other than reassurance.
Frequent stools: During the first few days of life, the stool
color in breastfed neonates changes from green
meconium to yellow seedy stools by the end of the
week. In between the stools appear loose ('transitional
stools') and may cause unnecessary anxiety to the
family. The stool frequency can increase to several times
per day, and is attributed to the enhanced gastrocolic
reflex in neonates which results in the passage of small
stools just after feeding. If the baby remains well
hydrated, has no signs of sepsis, feeds well, passes urine
6-8 times per day and gains weight, there is no cause Fig. 7.8: Erythema toxicum
106 Essential Pediatrics
* Oral thrush: White patchy lesions on the oral mucosa - Poor feeding
and tongue that are difficult to wipe off and leave - Fever or low body temperature
hemorrhagic points when removed suggest candidiasis. - Lethargy or less movements
Neonatal period is the only time when candidiasis - Yellowish discoloration of legs and hands
occurs in otherwise healthy babies. Nystatin application - Fit(s)
four times a day after feed, till 2 days after resolution, - Fast breathing
is recommended. Application of nystatin on mother's - Excessive crying
breast during this treatment ensures that mother is • A date for follow up has been assigned: A normal
treated for any local infection and recurrent infection newborn in whom breastfeeding is well established can
of baby is prevented. be seen at 6 weeks of age when the next vaccinations
• Diaper rash: Two types of diaper rash are seen, namely, are scheduled. In presence of any high risk factor (e.g.
ammoniacal and candidal. Their key features and low birth weight, prematurity, jaundice, or feeding not
treatment are shown in Table 7.6. established), the baby should be seen within 3 days of
discharge.
Table 7.6: Comparison of types of diaper rash
Feature Ammoniacal Candidal EVALUATION OF NEWBORN
Etiology Dermatitis from Skin infection with Most neonates are born healthy, normal and free from
prolonged skin Candida; source disease. Only a few (approx 3%) of them need observation
contact with being commensals in an intensive care in the nursery. The newborn
irritating from environment examination yields different information at different times
chemicals in causing infection in
and hence, the newborn should be examined in detail at
urine predisposed normal
least at four points of time, namely, (1) soon after birth (2)
newborns
Presentation Skin creases are at 24 hours of birth (3) before discharge from hospital and
Skin creases are
spared; red primarily affected; again (4) at follow up visit.
areas with or red lesions with Immediately after birth, the Apgar scores are assigned
without blisters; edges showing at 1 and 5 minutes (Table 7.8). If the score is less than 7, it
painful satellite lesions is assigned every 5 min until 20 minutes or till two succes
Treatment Leave open; Application of sive score are 7 or greater. These scores rapidly assess the
change diapers nystatin cream four cardiopulmonary status; tell about need for resuscitation
frequently; times a day till and its effectiveness. These scores may be falsely low in
application of lesions resolve. very preterms, maternal drug intake, congenital heart
zinc oxide for
disease and central nervous system malformations. Hence,
soothing effect
low Apgar scores should not be equated to asphyxia. The
1 min Apgar does not correlate with future outcome; a
• Eye discharge: Eye discharge is a common problem score of 0 to 3 at 5 minutes is associated with a risk of
among neonates. It may represent minor problems such cerebral palsy (0.3% to 1%). Scores of less than 3 at 10,15
as sticky eyes or transient nasolacrimal duct obstruc and 20 minutes have a higher correlation but are
tion, or may be due to serious infections (Table 7.7). nonspecific in the absence of other clinical correlates such
as evidence of neuroencephalopathy.
At Discharge
If systemic examination reveals an abnormal finding, a
In cases of institutional delivery, the following should be more thorough physical examination and laboratory
ensured at discharge: evaluation is warranted. Table 7.9 provides one of the
• Through counseling, parents have been enabled to be sequences that can be used for the comprehensive history
confident to look after the baby at home. and examination of the newborn.
• BCG, OPV and hepatitis B vaccine have been admini
stered, and information regarding when and where to General Observation
come for future immunization given. The least disturbing examination should be done first; this
• The baby has been examined, at discharge, with special gives an opportunity to assess the state, posture, sponta
attention to the following: neous activity, color, any obvious respiratory distress or
- Vital signs malformation. The five states of an infant are deep sleep,
- Signs of illness (no 'danger signs') light sleep, awake and quiet, awake and active, and awake
- Skin for jaundice and crying. The states 2 and 3 (light sleep and quiet awake)
- Cardiovascular system for new murmurs are best for newborn examination.
• Parents have been explained the following 'danger A newborn with undue hypotonia may have an
signs', in presence of any of which they should bring unflexed posture as seen in a baby with hypoxic
the baby to the hospital: encephalopathy. A clear note of the color of the baby,
Newborn Infants 107
Vital signs
In a sick baby vitals take a priority over all other
examination. Temperature is measured in the apex of the
baby's axilla by holding the thermometer for at least 3
minutes. Rectal temperature may be recorded to differen
tiate fever associated with infection and environmental
hyperthermia. The finding of hypothermia (temperature
108 Essential Pediatrics
Contd.
Table 7.9: Newborn history and examination:
a format for case presentation Anthropo Weight, length, head circumference, chest
HISTORY metry circumference.
Gestation Assessment by physical criteria; more
General Mother's name and age, parity, last detailed assessment by New Ballard,
menstrual period, expected date of delivery. examination.
Past obstetric Past pregnancies: when, gestation, neonatal Classification Appropriate/small/large for gestational age;
history problems, present status. by intrauterine symmetric or asymmetric small for
Antenatal Registration, contacts (when, number), growth gestational age; signs of IUGR (loose folds
care where/by whom, tests (Hb, urine albumin/ of skin, poor muscle mass, wrinkles over
sugar, cultures, ultrasound, blood group, thighs/buttocks.
VDRL, HIV, others), TT immunization, diet, Congenital Head to toe examination for malformations/
supplements (iron, folic acid, calcium, anomalies abnormalities.
iodine). Birth trauma Search for trauma; cephalohematoma.
Common signs Cyanosis, jaundice (extent), bleed, pustules,
Obstetric/ Obstetric complications (toxemia, UTI,
edema, pallor, bleeding, fontanel.
medical twins/triplets, placenta previa, accidental
Special signs Caput, eye discharge, umbilical examination
complications hemorrhage); fetal problems (IUGR,
(stump, discharge, redness), jitteriness, eye
hydrops, Rh isoimmunization); medical
discharge, oral thrush development pecu
problems (diabetes, hypertension);
liarities (toxic erythema, Epstein pearls,
investigations, medications, course.
breast engorgement, vaginal bleeding,
Labor Presentation, lie, onset of labor (spontane capillary hemangiomas, Mongolian spot).
ous /induced), rupture of membranes Feeding Observe feeding on breast (check signs of
(spontaneous/artificial), liquor (clear/ positioning and attachment).
meconium stained); duration of first and Reflexes Moro, grasp, rooting.
second stage of labor; fetal heart rate
(tachycardia, bradycardia, irregular). SYSTEMIC EXAMINATION
Delivery Place of delivery, conducted by whom, Chest Shape, distress, retractions, air entry,
vaginal (spontaneous/ forceps /vacuum), adventitious sounds.
cesarean (indication, elective/emergency); CVS Precordium, apical impulse, heart sounds/
local/general anesthesia; other drugs; murmur.
duration of third stage; postpartum Abdomen Distension, wall edema, tenderness,
hemorrhage. palpable liver/spleen/kidneys, any other
Immediate Resuscitation, time of first breath /cry, lump, ascites, hernial sites, gonads, genitalia.
care at birth Apgar scores if known; cord care; passage Musculo- Deformities, tests for developmental
of urine/stool. skeletal system dysplasia of hip, club foot.
Feeding What feeds; breastfeeding (when initiated,
Central State; cranial nerve examination (vision,
history frequency, adequacy); other feeds (what,
nervous pupils, eye movement examination, facial
how fed).
system sensation and motility, hearing, sucking and
Postnatal Any problems experienced (e.g. feeding
swallowing); motor examination (tone and
problems problems, jaundice, eye discharge, fever,
posture, power, tendon reflexes)
etc.), their course/investigations/treatment;
any problems at present. UTI urinary tract infection, IUGR intrauterine growth
Family history History of health problems in the family. retardation
Past medical History of past medical problems, if any.
problems of less than 36.5°C) in neonate has very important
Personal/ Socioeconomic status, family support. connotations. Cold stress is assessed by touching the
social history abdomen and the palms/soles. In cold stress, palms and
EXAMINATION soles are colder to touch than the abdomen. Neonates have
Weight, gestation, congenital anomalies, sex a normal respiratory rate of 40-60 breaths/minute. The
Immediately
after birth assigning, Apgar scores, umbilical vessel heart rate is faster in preterms compared to term. The
examination, examination of placenta. normal range is 110-160 beats per minute. Bradycardia
(rate <80/min) may be associated with heart disease while
GENERAL
tachycardia (rate >160/min) maybe due to sepsis, anemia,
Appearance Overall appearance: well/sick look; alert/ fever or congestive cardiac failure. Blood pressure may
unconscious.
be measured by the flush method, doppler monitoring or
Vital signs Temperature, cold stress; respiratory rate,
direct intravascular measurement. The measurement may
retractions, grunt/stridor; heart rate,
be inaccurate due to activity of the baby or wrong cuff
palpable femorals; blood pressure, capillary
refill time; cry; apneic spells. size (the cuff should ideally have a width 50-67% of arm
length and bladder should cover the full limb). Capillary
Newborn Infants 109
3600
of length in cm Len th (cm)3 ' Parameter is usually
3400
less than 2 in asymmetrically growth retarded baby and 2
3200
or more in a baby who has either normal growth or has
3000
symmetrical growth retardation.
2800
a?
S
2000 weeks). In preterm infants (i) deep sole creases are absent
■g 1800 or limited to anterior 1 /3rd; (2) breast nodule is less than
m
1600 5 mm; (iii) ear cartilage has poor elastic recoil; (iv) hair is
1400 fuzzy; (v) testes are at the external ring and scrotum has few
1200 rugosities; and labia majora in females are widely separated
1000 exposing labia minora and clitoris. Figs 7.11 (A) to (L) depict
800 the differences in physical characteristics that help
600 differentiate between preterm and term neonates at birth.
The detailed evaluation requires evaluation of physical
31 32 33 34 35 36 37 38 39 40 41 42 43 44
features and neurological maturity. The scoring system
Gestation (weeks)
commonly used is the Expanded New Ballard Scores
Fig. 7.9 : Intrauterine growth curves (ENBS) which has a range of accuracy to within 1 week.
Figs 7.11 A to F: Salient difference in physical characteristics of preterm and term neonates (A) Well-curved pinna, cartilage reaching up to
periphery (B) Flat and soft pinna, cartilage not reaching up to periphery (C) Well pigmented and pendulous scrotal sacs, with fully descended
testes (D) Light pigmentation and not yet descended testes (E) Deep transverse creases on the soles (F) Faint marks on the sole, no deep
creases
111
TERM BABIES PRETERM BABIES
Figs 7.11G to L: Salient difference in physical characteristics of preterm and term neonates (G) Well formed breast bud (>5 mm) (H) Poorly
developed breast bud (I) Silky hair-individual strands can be made out (J) Fuzzy hair (K) Labia majora covering clitoris and labia minora (L)
Prominent labia minora and clitoris
112 Essentia! Pediatrics
shed in two periods; one at 28 weeks and later at term. Table 7.10: Salient differences between caput succedaneum
The common finding on examination of nails is the and cephalohematoma
presence of hypoplastic nails that may be transient in the Characteristic Caput succedaneum Cephalohematoma
toe, but, if present in fingers, may indicate in utero Less common
Incidence Common
exposure to valproate. Location Subcutaneous plane Located over
Head and fontanelles: The size and shape of the head along parietal bones,
between skull and
with sutures and fontanelle should be examined carefully.
periosteum.
Upon palpation, molding gives the impression of a cliff
Time of Maximum size and Increasing size for
with rise on one side and a sharp fall on the other side, 12- 24 hrs and
presentation firmness at birth
whereas a synostosis (fusion of bones) feels like a mountain than stable.
range with rise on both sides of elevation. Some neonates Clinical time Softens Takes 3 to 6 weeks
have delayed ossification and resorption of bones making course progressively to resolve
the skull feel soft like a ping pong ball. This condition, from birth and
termed craniotabes, is a benign condition in neonates that resolves within
resolves spontaneously. The most common findings after 2 or 3 days
birth are caput succedaneum and cephalohematoma (Fig. 7.12). Characteristic Diffuse, crosses Does not cross
These should be differentiated as shown in Table 7.10. A findings suture line suture line, has
distinct margins.
full and tense fontanelle is abnormal in a quiet neonate.
Association None Linear fracture of
Large fontanelles and split sutures are most often normal
skull bone in 5 to
variants but they can be associated with increased
25%; hyperbiliru
intracranial pressure, certain chromosomal abnormalities, binemia (due to
hypothyroidism and impaired bone growth like breakdown of
osteogenesis imperfecta. hemoglobin in the
bleed)
Fis. 7.12; Cephalohematoma: note the overlying bruising Fig. 7.13 : Absent depressor anguli oris muscle depicting asymmetry
of face on crying. Note presence of nasolabial folds and closed eyes
Neck, face, eyes and ears: Newborns universally have short
differentiating it from facial palsy
necks. The neck is examined for masses like enlarged
thyroid gland, sternomastoid tumor and cystic hygroma.
Facial nerve paresis may occur due to birth injury; this is regardless of the cause. The newborn infants are obligatory
identified by the presence of asymmetric facies while the nose breathers because of the apposition of the relatively
baby is crying with open eyes, and the inability to move large tongue to the palate. Hence, bilateral choanal atresia,
the lips. This should be differentiated from the absence of if present, causes severe respiratory distress. The alveolar
depressor anguli oris in which asymmetric crying facies ridge may have natal teeth or retention cysts (also called
is observed; however, in this condition, the eyes remain Epstein pearls) that disappear in few weeks. It is very
tightly shut while crying (Fig. 7.13). Nose is looked for its important to examine the palate for cleft. The eyes of the
size, shape, secretions, patency and flaring. The patency infant may be opened spontaneously with to and fro
of the nose can be checked by holding a wisp of cotton at rocking during which the head is elevated; this permits
the orifice while occluding the other nares. The flaring of eyes to be inspected and observed for visual tracking
the nostrils indicates an increase in respiratory efforts assessment of the examiner's face. The globe in a neonate
113
is 70% the size in an adult and the cornea is 80% of the Extremities: One should make sure that the arms and limbs
adult size. The two eyes and the space in between the eyes are fully movable with no evidence of dislocation or
are in 1-1-1 relation. The nasolacrimal duct is not fully asymmetry of movements. The fingers are counted and
patent in most neonates, but epiphora is observed in only any abnormality noted like nail hypoplasia, syndactyly,
few newborns. Subconjunctival hemorrhages are common polydactyly, oligodactyly or unequal limbs. A calcaneo-
after vaginal delivery and resolve spontaneously. The valgus deformity is usually self-correcting within the next
cornea should be clear. Pupils should be equal in size, few months but equinovarus is much more sinister and
reactive to light, and symmetrical. The pupil should be should be brought to the notice of an orthopedic specialist
inspected for the red reflex. The wide beam of the (Fig. 7.15).
ophthalmoscope or a torch is used so that the circle of
light covers both the eyes, and the focus is adjusted to
give a distinct glow in the pupils. One should look for the
brightness and position of the red reflex. A positive red
reflex rules out lenticular and anterior or posterior
chamber opacity.
Gross hearing is often inaccurately assessed by looking
for blink on response to noise. More formal hearing
screening for all newborns is now recommended.
Accessory auricles and preauricular tags are a common
finding that may be associated with renal anomalies.
relation to mesenteric axis of any other abdominal mass vision is demonstrated as early as 2 months of age.
palpated should be described in detail. Tenderness of Binocular vision and perception of depth also appear by
abdomen is an important sign in necrotizing enterocolitis 3 to 4 month postnatal age. Reaction to light begins to
(NEC) and can be elicited during palpation. On appear at 30 weeks but consistent response is seen to
percussion, rarely a fluid thrill may be obtained in cases develop by 35 weeks. The tracking movements of the full
of neonatal ascites. All the quadrants of the abdomen term and post term infants at first are rather jerky and
should be auscultated for sufficient time period (3 become smooth by third month of life. By 28 weeks the
minutes) before making a comment on bowel sounds. The infant startles or blinks to loud noise. Sucking and
quantity, nature and location of bowel sounds should be swallowing are important aspects that should be examined
described whenever they are present. as they give insight into the proper functioning of the V,
VII, IX, X and XII cranial nerves. The act of sucking
Musculoskeletal system: The common alterations are
requires the concerted action of breathing, sucking and
deformations caused by adverse mechanical factors in
swallowing. Sucking and swallowing are coordinated
utero. Most positional deformities are mild and resolve
sufficiently for oral feeding as early as 28 weeks. At an
in time. The hips are to be examined because physical
early stage, however, the synchrony of breathing with
examination is the only method of detecting hip problems
sucking and swallowing is not well developed, and thus
before permanent damage occurs by one year of age.
oral feeding is difficult till 32 to 34 weeks of gestation.
Developmental dysplasia of hips girls, (DDH) occurs
Motor examination: By 28 weeks there is minimal resistance
in 1 of 800 live births, more commonly in those with a
to passive manipulation in all the limbs, and a distinct
family history and delivered by breech. There are two
flexor tone is appreciated in lower extremities by 32 weeks.
major tests to detect developmental dysplasia of hip
By 36 weeks flexor tone is palpable in both the lower and
(DDH). Ortolani's sign: The baby is placed on its back with
upper extremities. Differential hypotonia, in which there
the knees fully flexed and the hips flexed to a right angle.
is selective hypotonia in the upper and proximal muscle
The thighs of the baby are grasped in both hands with
group compared to the lower and distal group, is seen in
the middle finger of each placed over the greater
the early phase of hypoxic ischemic encephalopathy.
trochanter on the outside and with the thumb placed on
Ankle clonus of upto 5 to 10 beats is accepted as a normal
the inner side. The thighs are then abducted and the
finding in the newborn but clonus of more than a few beats
middle fingers of the examining hands used to press
beyond the 3 months of age is abnormal. The plantar
forward on the greater trochanters. In DDH, the femoral
response depends on the way it is elicited in the newborn.
head suddenly slips into the acetabulum with a distinctly
If elicited by thumbnail, a flexion response is obtained. If
palpable "clunk". If pressure is now applied with the
the same is elicited by pin drag, extension response is
thumbs outwards and backwards of the inner side of the
obtained 95% of the time. Primary neonatal reflexes: Moro
thigh, the femoral head again slips over the posterior lip
reflex is best elicited by the sudden dropping of the baby's
of the acetabulum. If the femoral head slips into the
head in relation to trunk; the response consists of opening
acetabulum again when the pressure is released, it is
of the hands and extension and abduction of the upper
merely unstable, rather than dislocated. This test is
extremities, followed by anterior flexion (embracing) of
important because the treatment in early neonatal life is
upper extremities with an audible cry (Figs 7.16A and B).
simple and efficient, and consists simply in maintaining
The hand opening is present by 28 weeks, extension and
the hips in full abduction and at least 90° flexion with
abduction by 32 weeks and anterior flexion by 37 weeks.
malleable metal splints. Barlow maneuver: This is done to
Audible cry appears at 32 weeks. Moro reflex disappears
dislocate the unstable hip joint. With the hip initially
by 3-6 months in normal infants. The most common cause
abducted, the right hand is positioned to apply a soft
of depressed or absent Moro reflex is a generalized
pressure in the directions necessary to dislocate the
disturbance of the central nervous system. The most useful
femoral head posteriorly. As the leg is adducted to at least
abnormality of the Moro reflex to elicit is distinct
20° post midline, a lateral pressure is applied with the
asymmetry, which is almost always a feature of root
thumb and a posterior pressure with the hand to dislocate
plexus or nerve disease. The palmar grasp is clearly
the hip. A positive test leads to knee height discrepancy.
present at 28 weeks of gestation and is strong by 32 weeks.
Neurological examination: This consists of the assessment of This allows the lifting of the baby at 37 weeks of gestation.
the level of alertness (already discussed), cranial nerve This becomes less consistent on development of voluntary
examination, motor examination, sensory examination grasping by 2 months. The tonic neck response is another
and the examination of the primitive neonatal reflexes. important response elicited by rotation of the head, that
Cranial nerves: Neonates respond to cotton soaked in causes extension of the upper extremity on the side to
peppermint by 32 wks of gestation. By 26 weeks the infant which the face is rotated and flexion of the upper extremity
consistently blinks in response to light, and by term, on the side of the occiput (Fig. 7.17). This disappears by 6
fixation and following are well established. The fluffy red to 7 months. Sensory examination: Even a neonate of 28
yarn ball is seen to be a useful target in assessing this. Color weeks has the ability to discriminate touch and pain,
115
Fig. 7.17: Asymmetrical tonic neck reflex Response to hypothermia: Babies attempt to conserve heat
by peripheral vasoconstriction. This leads to increased
anaerobic metabolism at the ill-perfused areas with
wherein pain would result in alerting and slight motor acidosis (Fig. 7.18). The latter predisposes to pulmonary
activity and then later withdrawal and cry. vasoconstriction, raised pulmonary arterial pressure and
further hypoxemia, with anaerobic metabolism and
THERMAL PROTECTION acidosis leading to a positively reinforcing vicious cycle.
Newborn babies have poor heat regulating mechanisms With continued hypothermia, usually when temperature
making them prone to hypothermia and its ill effects. drops to 32°C, oxygen cannot be released from hemo
Hypothermia is responsible for much morbidity and globin, resulting in the blood having a bright red color,
mortality among neonates. which should not be mistaken for good perfusion. With
116 Essential Pediatrics
severe hypothermia, hypoxemia, hypoglycemia and babies who are progressing well, two-three times daily
metabolic acidosis develop, leading to mortality. for healthy small babies (2.4-1.5 kg), four times daily for
Hyperthermia: An immature thermoregulating brain center very small babies (<1.5 kg) and every two hour for sick
and decreased ability to sweat also predispose newborns babies. Frequent assessment by mother using touch should
to hyperthermia. Overclothing, environmental exposure be encouraged.
in summer, poor feeding, dehydration and sun exposure
are common reasons that can lead to hyperthermia. Hypothermia
Prevention
Definitions
The most effective management strategy for hypothermia
Thermoneutral environment: This is a gestational and is its prevention, practised using the following:
postnatal age specific temperature range in which the basal • Warm chain: Warm chain is a sequence of ten steps (see
metabolic rate of the baby is at a minimum, oxygen Table 7.12) aimed at decreasing heat loss, initiating heat
utilization is least and baby thrives well. gain and ensuring that, from the time of birth
Hypothermia: Axillary temperature of baby <36.5°C throughout the neonatal period, no episode of exposure
• Cold stress 36.0-36.4°C to hypothermia generating environment is allowed.
• Moderate hypothermia 32-35.9°C • After delivery, baby should be put immediately either
• Severe hypothermia <32°C on mother's abdomen or in a preheated bassinet; one
should quickly dry body and head, discard the wet
Hyperthermia: Axillary temperature of baby >37.5°C
towel and use another dry warm sheet to wrap baby,
Measurement of Temperature using a head cap to cover head (Fig. 7.19).
Recommended type of thermometer for measuring • Skin-to-skin contact between baby and the mother,
neonatal temperature should have low reading values till called as Kangaroo mother care (KMC).
30°C, so that degree of severe hypothermia can be • Breastfeeding; frequent feeding.
accurately assessed. Methods of measurement are listed • Bathing and weighing postponed.
in Table 7.11. • During summer months term babies can be sponged
after first 24 hours. During winters and for sick or LBW
Frequency of Measurement babies this can be postponed by several days usually
Unless dictated by specific clinical needs, the frequency until umbilical cord falls off, often by the end of first
of temperature measurement can be once daily for healthy week. Dressing the baby in layers of warm light
Newborn Infants 117
Skin The probe of the thermal sensor called Continuous Purpose is for continuous monitoring of babies
thermister is attached to the skin over upper monitoring under servo control, radiant warmer,
abdomen from where it reads the tempera incubators, etc.
ture and displays it on the panel.
Human Temperature is felt at the abdomen, feet Intermittent Method cruder than others but helps mother
touch and hands of the baby by back of hand measurement and health worker get a quick idea about
of the examiner: temperature without a formal measurement;
• Abdomen, feet and hands are accuracy improves with experience of the
warm —> normal examiner
• Abdomen is warm but feet
and hands are cold —» cold stress
• Abdomen, feet and hands are
cold —> hypothermia
Table 7.12: Steps of warm chain garments gives better insulation and heat than single
1. Warm delivery room layer of heavy woolen clothing. Covering of the head
2. Warm resuscitation is an important part of heat conservation.
3. Immediate drying • Mother and baby co-bedding: 'rooming in'.
4. Skin to skin contact • Warm transportation: This is the weakest link in the
5. Breastfeeding warm chain with greatest possibility of severe and
6. Bathing postponed undetected hypothermia.
7. Appropriate clothing • Training/awareness of healthcare providers: unless
8. Mother and baby together persons involved in the care of newborns realize the
9. Professional alertness
implications of hypothermia it cannot be detected or
10. Warm transportation
managed effectively.
Management
Methods for temperature maintenance include skin to skin
contact, warm room, radiant warmers, incubators and
exposure to sources of heat such as hot air blowers, 200
watt bulb, etc.
Transition from fetal to extrauterine life is accompanied Babies with birth weight <1500grains: The urine output in a
by remarkable changes in body fluid composition. Before preterm LBW baby is similar to a term baby. However,
assessing fluid and electrolyte balance and planning fluid the fluid requirement is higher due to increased IWL and
therapy, it is important to understand normal postnatal increased weight loss (extracellular fluid loss). Baby
changes in body fluid composition. In a neonate born at should be well dressed including use of caps and socks to
term gestation total body water (TBW) constitutes about reduce the IWL under the radiant warmer. Using this
80% of body weight as compared to an adult in whom method, 80 mL/kg/day of 10% dextrose is adequate on
TBW constitutes 60% of body weight. Neonates are born day 1 of life (Table 7.14). As the skin matures in a preterm
with an excess of total body water, primarily in the extra baby, the IWL progressively decreases and becomes
cellular fluid (ECF) compartment. This excess of TBW is similar to a term baby by the end of the first week. Hence,
normally lost by diuresis during first week of life. In
neonates born at term gestation, this physiological diuresis
Table 7.14: Daily fluid requirements during first week of life
results in a weight loss of 5-10% during first 3 to 5 days of
(mL/kg/day)
life. Preterm neonates have proportionately higher TBW
Birth Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7
and, therefore, may lose up to 10-15% of birth weight
weight and
during first week of life.
onwards
The heart, kidneys, the skin and the neuroendocrine
system play the most important role in regulation of fluid <1500 g 80 95 110 120 130 140 150
>1500 g 60 75 90 105 120 135 150
and electrolyte balance in neonates. Neonates lose body
120 Essential Pediatrics
the fluid requirement in a preterm baby, initially higher Body weight: Serial weight measurements can be used as a
due to increased IWL, would become similar to a term guide to estimate the fluid deficit in newborns. Term
baby by the end of the first week. Fluids need to be neonates lose 1-3% of their birth weight daily with a
increased at 10-15 mL/kg/day till a maximum of 150 mL/ cumulative loss of 5-10% in the first week of life. Preterm
kg/day. neonates lose 2-3% of their birth weight daily with a
Sodium and potassium should be added after 48 hours. cumulative loss of 10-15% in the first week of life. Failure
Glucose infusion should be maintained at 4-6 mg/kg/ to lose weight in the first week of life would be an indicator
min. 10% dextrose may be used in babies >1250 g and 5- of excessive fluid administration. However, excessive
7.5% dextrose in babies with birth weight <1250 g. weight loss (>3% in 24 hr) in the first 5-7 days or later
would be non-physiological and would merit correction
Intravenous fluid therapy: Indications for starting IV fluid
with fluid therapy.
therapy include birth weight less than 1200 g or gestation
<30 wk, respiratory distress, feed intolerance, hemo Clinical examination: The usual physical signs of
dynamic instability, gastrointestinal malformations (like dehydration are unreliable in neonates. Infants with 10%
tracheoesophgeal fistula, duodenal or ileal atresia, (100 mL/kg) dehydration may have sunken eyes and
anorectal malformation, etc.) or any other severe illness fontanel, cold and clammy skin, poor skin turgor and
precluding oral feeding. Peripheral intravenous line is the oliguria. Infants with 15% (150 mL/kg) or more
most common intravenous access method used to provide dehydration would have signs of shock (hypotension,
fluid therapy. In neonates 22-24 gauze cannula is inserted tachycardia and weak pulses) in addition to the above
in peripheral veins on hands, antecubital fossa, feet or features. Dehydration would merit correction of fluid and
ankle. Fluid requirement is calculated based on birth electrolyte status gradually over the next 24 hours.
weight, day of life and current fluid balance.
Urine output, specific gravity: The capacity of the newborn
Risks of IV fluid therapy include local infection,
kidney to either concentrate or dilute urine is limited and
systemic infection, phlebitis, accidental fluid overload and
estimation of urine specific gravity would be useful to
extravasation. Because IV fluid therapy is a major risk
guide fluid therapy. The acceptable range for urine output
factor for nosocomial infection, all asepsis precautions
would be 1-3 mL/kg/hr, for specific gravity between
must be followed during insertion of IV cannula or
1.005-1.012.
administering fluids. Administration of hypertonic and
irritant medications like sodium bicarbonate and calcium Biochemical tests: Serum sodium and plasma osmolality
gluconate should be minimized to prevent extravasation. are helpful but not always essential in the assessment of
Oral feeds should be started at the earliest possible the hydration status in an infant. Serum sodium values
opportunity when clinical condition of neonate improves should be maintained between 135-145 mEq/L. Blood
and IV fluid should be stopped when oral feeds constitute gases are not needed routinely for fluid management.
about two-thirds of daily fluid requirement. IV sites However, they are useful in the acid base management of
should be inspected frequently to detect evidence of patients with poor tissue perfusion and shock.
extravasation. Hypoperfusion is associated with metabolic acidosis.
Mother
All mothers can provide KMC, irrespective of age, parity,
education, culture and religion. The mother must be
willing to provide KMC. The mother should be free from
serious illness to be able to provide KMC. She should
receive adequate diet and supplements recommended by
her physician. She should maintain good hygiene. Mother
would need family's cooperation to deal with her
conventional responsibilities of household chores till the
baby requires KMC.
122 Essential Pediatrics
Initiation of KMC care to continuous KMC (Figs 7.22A and B). Sessions that
Counseling: When baby is ready for KMC, arrange a time last less than one hour should be avoided because frequent
that is convenient to the mother and her baby. The first handling may be stressful for the baby. The length of skin-
few sessions are important and require extended to-skin contact should be gradually increased up to
interaction. Demonstrate to her the KMC procedure in a 24 hours a day, interrupted only for changing diapers.
caring, gentle manner and with patience. Answer her When the baby does not require intensive care, she should
queries and allay her anxieties. Encourage her to bring be transferred to the postnatal ward where KMC should
her mother/mother in law, husband or any other member be continued.
of the family. It helps in building positive attitude of the The mother can sleep with baby in kangroo position in
family and ensuring family support to the mother which reclined or semi-recumbent position about 15 degrees
is particularly crucial for post-discharge home-based from horizontal. This can be done with an adjustable bed
KMC. It is helpful that the mother starting KMC interacts or with pillows on an ordinary bed. A comfortable chair
with someone already practising KMC for her baby. with an adjustable back may be used for resting during
the day.
Mother's clothing: KMC can be provided using any front-
open, light dress as per the local culture. KMC works well
When to Stop KMC
with blouse and sari, gown or shawl. Suitable apparel that
can retain the baby for extended period of time can be KMC is continued till the baby finds it comfortable and
adapted locally. cosy. KMC is unnecessary once the baby attains a weight
of 2500 g and a gestation of 37 weeks. A baby who, upon
Baby’s clothing: Baby is dressed with cap, socks, nappy,
and front-open sleeveless shirt. being put in the kangaroo position, tends to wriggle out,
pulls limbs out, or cries/fusses, is not in need of KMC
KMC Procedure any more.
Figs 7.2QA and B: Kansaroo mother care being provided in Breastfeeding is most convenient and time saving. It
postnatal ward reduces the risk of cancer of breast and ovary.
Breastfeeding is the most effective way of shedding extra
Proteins: The protein content of breast milk is low (0.9-1.1 weight that mother has put on during pregnancy.
g/dL) as the baby cannot effectively metabolize a high
protein load. Most of the protein is lactalbumin and Breast Milk—Where and How it is Produced
lactoglobulin (60%), which is easily digested. Human milk
contains amino acids like taurine and cysteine which are
Anatomy
necessary for neurotransmission and neuromodulation. The breast is made up of glandular tissue, supporting
These are lacking in cow's milk and formula. tissue and fat (Fig. 7.23). The glandular tissue consists of
small clusters of sac-like spaces which produce milk.
Fats: Breast milk is rich in polyunsaturated fatty acids,
Around each sac is a basket-like array of muscle cells
necessary for the myelination of the nervous system. It
known as myoepithelial cells. Milk produced in the alveoli
also contains omega 2 and omega 6 (very long chain fatty
is carried along 20 small tubes or ducts towards the nipple.
acids) which are important for the formation of
Before reaching the nipple, the ducts widen to form 10-15
prostaglandins and cholesterol, required as a base for
lactiferous sinuses which store milk. The lactiferous
steroid hormones.
sinuses lie beneath the circle of dark skin around the nipple
Vitamins and minerals: The quantity and bioavailability of called the areola.
vitamins and minerals is sufficient for the needs of the The areola and nipples are extremely sensitive as they
baby in the first 6 months of life. are supplied by a rich network of nerve endings. On the
124 Essential Pediatrics
{s
...................J Oxytocin makes maintenance of this reflex. Even a single supplemental
Muscle cells < them contract feeding would interfere with successful breast milk
production.
Milk secreting I Prolactin makes
cells
{:
1 them secrete milk Oxytocin reflex (milk ejection reflex): Oxytocin is a hormone
produced by the posterior pituitary. It is responsible for
Ducts contraction of the milk from the glands into the lactiferous
Lactiferous f Milk collects
sinuses and the lactiferous ducts. This hormone is
sinuses ^here produced in response to stimulation to the nerve endings
in the nipple by suckling as well as by the thought, sight,
Nipple or sound of the baby (Figs 7.24B and C).
Since this reflex is affected by the mother's emotions, a
Areola relaxed, confident attitude helps the milk ejection reflex.
On the other hand, tension and lack of confidence hinder
Montgomery's glands
the milk flow.
This stresses the importance of a supportive health
professional or a relative to reassure the mother and help
Alveoli her gain confidence so that she can successfully breast
Supporting tissue
and fat feed her baby.
Fig. 7.23: Anatomy of breast Factors which Lessen Milk Production
• Dummies, pacifiers, bottles. Studies have revealed that
even one or two supplemental feed would hinder
areola are small swellings of glands which produce an
successful breastfeeding.
oily fluid to keep the nipple skin soft. Since the lactiferous
• Giving things like sugar water, gripe water, honey,
sinuses lie beneath the areola, a baby must suck at the
breast milk substitutes or formula, either as prelacteal
nipple and areola (gum line of the baby should rest at the
(before establishment of breastfeeding) feeds or
junction of areola and rest of breast tissue in order to exert
supplemental (at any time later) feeds.
pressure on lactiferous sinuses) to draw out the milk.
The glandular tissue is responsible for production of • Painful breast conditions like sore or cracked nipples
and congested breast.
milk. The fat and the supporting tissue are responsible
• Lack of night feeding, as it interferes with prolactin
for the size of the breast; hence a mother can produce
reflex
enough milk despite small size of the breast.
• Inadequate emptying of breast such as when sick or
Physiology small baby is unable to suck on the mother's breast,
and mother does not manually express breast milk.
Milk is produced as a result of the interaction between
hormones and reflexes. During pregnancy and lactation Reflexes in the Baby
the glandular tissue is stimulated to produce milk due to
A baby is born with certain reflexes which help the baby
various hormonal influences. Two hormones come into
to feed. These include rooting, sucking and swallowing
play during lactation.
reflexes.
Prolactin reflex (milk secretion reflex): Prolactin produced
The rooting reflex: When the mother holds her baby and
by the anterior pituitary gland is responsible for milk
her breast touches the baby's upper lip, cheek or the side
secretion by the alveolar epithelial cells (Fig. 7.24A). When
of the mouth, the baby opens her or his mouth and
the baby sucks, the nerve ending in the nipple carry
searches for the nipple with an open mouth. This is called
message to the anterior pituitary which in turn release
rooting reflex. This reflex helps the baby to find the nipple
prolactin and that acts on the alveolar glands in the breast
and helps in proper attachment to the breast.
to stimulate milk secretion.
This cycle from stimulation to secretion is called the The suckling reflex: This reflex which is very strong
prolactin reflex or the milk secretion reflex. The more the immediately after birth helps the baby draw out milk from
baby sucks at the breast, the greater is the milk production. the mother's breast. The sucking action consists of:
The earlier the baby is put to the breast, the sooner this • Drawing in the nipple and areola to form an elongated
reflex is initiated. The greater the demand, more is the teat inside the mouth.
milk produced. It is, therefore, important for mothers to • Pressing the stretched nipple and areola with the jaw
feed early, frequently and completely empty the breasts and tongue against the palate (which is sensitive for
at each feed and ensure that the baby is properly attached the suckling action).
to the breast. Since prolactin is produced during night • Drawing milk from the lactiferous sinuses by wave
time, breastfeeding during night is very important for like peristaltic movement of the tongue on the
Newborn Infants 125
Positioning
• Position of the mother: The mother can take any position
that is comfortable to her and her baby. She could sit or
lie down. Her back should be well supported and she
should not be leaning on her baby (Figs 7.25A to C).
Effective suckling
• Baby suckles slowly and pauses in between to swallow.
One may be able to see the movement of throat bones
and muscles and hear the gulping sound indicating that
baby is swallowing milk.
• Baby's cheeks are full and not hollow or retracting
during sucking.
Problems in Breastfeeding
Inverted nipples: Flat or short nipples which protract well
(become prominent or pull out easily) do not cause
difficulty in breastfeeding. Inverted or retracted nipples
sometimes make attachment to the breast difficult. These
mothers need additional support to feed their babies.
Treatment is started after birth of the baby. The nipple is
manually stretched and rolled out several times a day. A
pump or a plastic syringe is used to draw out the nipple
and the baby is then put to the breast (Fig. 7.27). Figs 7.Q5A to C: Different postures of feeding
127
Express one breast until the flow of milk slows and milk
only drips out, and then express the other breast until the
milk only drips. Alternate between breasts 5 or 6 times,
for at least 20 to 30 minutes. Stop expressing when the
milk no longer flows but drips from the start.
Step 1: Massage the breasts Low birth weight (LBW) refers to infants with a birth
gently toward the nipples weight less than 2500 g. Low birth weight infants have
higher morbidity and mortality. A baby's LBW is either
the result of preterm birth (before 37 completed weeks of
gestation) or due to intrauterine growth restriction (IUGR)
or both. IUGR is similar to malnutrition and may be
present in both term and preterm infants. Neonates
affected by IUGR are usually undernourished and have
loose skin folds on the face and in the gluteal region (Fig.
7.30), absence of subcutaneous fat and peeling of skin.
Step 2: Place the thumb and
index finger opposite each
other just outside the dark
circle around the nipple
Definitions
under her nipple and areola. Place her thumb on top of
Prematurity: Gestational age <37 completed weeks
the breast at least 4 cm from the tip of the nipple, and the
first finger on the under side of the breast opposite the Low birth weight: Birth weight < 2500 g
thumb. Compress and release the breast tissue between IUGR (Intrauterinegrowth restriction): It is a deviation from
her fingers and thumb a few times. If the milk does not an expected fetal growth pattern. IUGR can result from
appear she should reposition her thumb and finger closer any adverse factor that affects the normal growth potential
to the nipple and compress and release the breast as before. of the fetus. There are two patterns of IUGR:
Compress and release all the way around the breast, • Symmetric: When insult on the fetal growth occurs early.
keeping her fingers the same distance from the nipple. The size of the head, body weight and length are equally
Newborn Infants 129
Management
Small for gestational age (SGA): It is a statistical definition
• Strict adherence to asepsis
and denotes an infant whose weight is less than 2 standard
• Hand washing
deviations or less than the tenth percentile of the
• Minimal handling of babies
population norms (plotted on a growth chart).
• Low threshold for suspicion of sepsis, adequate and
appropriate use of antibiotics
Special Requirements and Issues
• Decreasing exposure to adults/other children with
Besides the pathologies that can affect all neonates communicable diseases particularly respiratory.
irrespective of weight and gestation, additional compli
cation occur in LBW which require special care and Metabolic Derangements
management. Problems
• Low hepatic glycogen stores with rapid depletion in
Resuscitation stress places these infants at increased risk of hypo
Problems glycemia.
• Compromised intrauterine environment with higher • Immature glucose homeostatic mechanisms in prema
chances of perinatal asphyxia ture babies can also lead to decreased inability to utilize
• Preterm babies have immature lungs that may be more glucose and resultant hyperglycemia, especially during
difficult to ventilate and are also more vulnerable to stressful periods like infection.
injury by positive-pressure ventilation. • Early onset hypocalcemia: presenting within 3 days of
• Immature blood vessels in the brain are prone to life and is usually asymptomatic, detected on investi
hemorrhage gation. It is especially seen in premature babies, infants
• Thin skin and a large surface area, which contribute to of diabetic mothers and those with birth asphyxia.
rapid heat loss • Late onset hypocalcemia presents as classical neonatal
• Increased risk of hypovolemic shock caused by small tetany, jitteriness and seizures. Feeds with higher
blood volume phosphate load such as cow's milk and some formulae,
130 Essential Pediatrics
result in hyperphosphatemia with subsequent hypo of hyperosmolar solutions, avoiding high pressures
calcemia. during ventilation and treating any bleeding diathesis.
Treatment is essentially supportive and management
Management of later complications such as hydrocephalus.
This has been discussed in appropriate sections. • Retinopathy of prematurity: Growth of retinal vessels
occurs from the optic disc to the periphery from 18
Jaundice weeks of gestation till term. Any injury to these vessels
Problems due to the still developing vessels of preterm retina
• Larger RBC volume for body weight when subjected to the premature transition of postnatal
• Immaturity of hepatic enzymes and hepatic excretory life especially high oxygen saturation as may be used
capacity during resuscitation, undergo pathological prolifera
• Immature blood brain barrier-increased risk for tion resulting in retinal damage with vision loss if left
bilirubin encephalopathy untreated. This complication can be decreased with
rational use of oxygen, maintaining a SpO, between 85-
Management
95% and regular screening for early detection and
This has been discussed in section on jaundice.
treatment.
• Hearing damage: While not restricted to preterm infants
Hematological Abnormality
in occurrence due to their immature systems, effect of
Problems hypoxia and renotoxic drugs is enhanced leading to a
• Polycythemia: Placental insufficiency with intrauterine frequent occurrence of sensorineural hearing loss
hypoxia leads to stimulation of erythropoiesis and especially after long and eventful NICU stay. Adjust
resultant polycythemia, especially seen in IUGR babies. ment of doses according to gestational age, checking
Polycythemia (>65% hematocrit) produces hyper drug levels and routine screening for early detection
viscosity with decreased organ perfusion. Manifes can minimize this complication.
tations include jitteriness, respiratory distress, cardiac • Osteopenia of prematurity: Low calcium, phosphorus and
failure, feeding intolerance, hypoglycemia, hypocal Vitamin D levels predispose premature babies to
cemia and hyperbilirubinemia. osteopenia and rickets early in neonatal period unless
• Anemia: Accelarated destruction of fetal RBCs, low extra supplementation is given. All VLBW babies
reticulocyte count and inadequate response of the bone should be started on 200 mg/kg of calcium, 100 mg/
marrow to erythropoietin cause anemia of premaurity. kg of phosphorus and 400 IU of vitamin D as oral or
Low iron stores, higher incidence of sepsis and frequent parenteral supplementation.
blood sampling in LBW babies further predisposes to • Respiratory distress syndrome: This has been described
risk of severe anemia. in detail later.
Management
Associated Conditions
• Treatmen t of polycythemia: Symptomatic infants or those
with Hct > 75% require partial exchange transfusion. Problem
For others, management includes increasing the fluid An IUGR birth itself might be an indication of a preexisting
intake. problem leading to such occurrence. Examples include
• Anemia: intrauterine infections and chromosomal anomalies which
- Iron supplementation: All LBW babies should be result in IUGR babies. These usually constitute a subgroup
started of 2-3 mg /kg of iron from 2 months till 2 of IUGR babies known as symmetrical IUGR; cause of
years of age. growth restriction is due to conditions other than
- Minimal sampling and quantification of amount nutritional deficiency and onset occurs early in fetal life
removed with proportionate restriction of head and body unlike
- Transfusions as per institution protocol. the nutritionally restricted IUGR with onset in third
trimester and sparing of head growth.
Immature Organ Systems in Preterms Management
Problem and management • According to diagnosis.
• Intraventricular hemorrhage: Preterms have a fragile
highly vascular collection of vessels near the lateral
Long Hospital Stay
ventricle of brain. Respiratory distress, mechanical Requirement for frequent monitoring and aggressive
ventilation, vigorous resuscitation, etc. can cause intervention in such high risk babies results in their
rupture of these vessels leading to adverse neurological separation from parents at birth, decreased contact and
sequelae. Preventive measures include minimal and high expenditure. It is an emotionally and financially
gentle handling, avoiding rapid changes in trying time for all families. Keeping parents involved in
intravascular volume such as rapid boluses or infusion decision making with counseling sessions directed at their
Newborn infants 131
concerns helps greatly in management and the final 1. Though majority of these infants are born at term, a
outcome. significant proportion are born premature with
inadequate feeding skills. They might not be able to
Discharge and Follow Up breastfeed and hence would require other methods of
• Screening tests before discharge or on follow up include feeding such as spoon or gastric tube feeding.
those for ROP detection and auditory brainstem evoked 2. They are prone to have significant illnesses in the first
response (ABER). few weeks of life, the underlying condition often
• Nutrition supplements including multivitamins, iron, precludes enteral feeding.
calcium and vitamin D are started. 3. Preterm infants have higher fluid requirements in the
• Immunization with BCG, Hep B and OPV given. Many first few days of life due to excessive insensible water
institutes prefer to delay immunization of Hep B and loss.
BCG till baby is 2 kg by weight. 4. Since intrauterine accretion occurs mainly in the later
• Weight gain should be consistently demonstrated for part of the third trimester, preterm infants (particularly
few days before discharge. Weight, length and head those born before 32 weeks of gestation) have low body
circumference should be noted at discharge and plotted stores of various nutrients at birth which necessitates
on a growth chart which can be used in follow up to supplementation in the postnatal period.
determine if growth is adequate. 5. Because of the gut immaturity, they are more likely to
• Baby should be feeding well; if on alternate feeding experience feed intolerance necessitating adequate
technique like paladai feeding the mother should be monitoring and treatment.
confident regarding its details.
Methods
• Absence of danger signs and completion of treatment
like IV antibiotics; if baby is being discharged on oral Direct and exclusive breastfeeding is the ideal method for
medication then parents should be well educated feeding a LBW infant. However, because of the various
regarding how to administer it and other details limitations, not all LBW infants would be able to accept
regarding it. breastfeeding at least in the initial few days after birth.
• Methods of temperature regulation, either KMC These infants have to be fed by either spoon/paladai or
practice or other methods should be well known to intragastric tube (gavage feeding); those babies who
parents and practised during hospital stay under cannot accept oral feeds by even these methods would
supervision. require intravenous fluids.
• All danger signs explained in detail to parents with The appropriate method of feeding in a given LBW
information regarding whom and where to contact infant is decided based upon the following factors:
clearly highlighted. • Whether the infant is sick or not and
- History of difficulty in feeding • Feeding ability of the infant (which depends upon the
- Movement only when stimulated gestational maturity).
- Temperature below 35-5°C or 37-5°C or more
- Respiratory rate over 60 breaths per minute Level of Sickness
- Severe chest indrawing It is essential to categorize LBW infants into two major
- History of convulsions groups, sick and healthy, before deciding the initial method
• Follow up within 3-7 days of discharge to ensure the of feeding.
baby has been adpted well to home environment.
Detailed follow up discussed elsewhere. Sick infants: This group constitutes infants with respiratory
distress requiring assisted ventilation, shock, seizures,
symptomatic hypoglycemia, electrolyte abnormalities,
FEEDING OF LBW BABIES____________________________
renal/cardiac failure, surgical conditions of gastro
Nutritional management influences immediate survival intestinal tract, necrotizing enterocolitis (NEC), hydrops,
as well as subsequent growth and development of low etc. These infants are usually started on intravenous (IV)
birth weight (LBW) infants. Early nutrition could also fluids. Enteral feeds should be initiated as soon as they
influence the long-term neurodevelopmental outcomes— are hemodynamically stable with the choice of feeding
Malnutrition at a vulnerable period of brain development method based on the infants' gestation and clinical
has been shown to have deleterious effects in experimental condition (see below).
animals. It is important to realize that enteral feeding is
Term infants with normal birth weight require minimal important even for sick neonates. Oral feeds should not
assistance for feeding in the immediate postnatal period. be delayed in them without any valid reason. Even infants
They are able to feed directly from mothers' breast. In with respiratory distress and/or on assisted ventilation
contrast, feeding of LBW infants is relatively difficult can be started on enteral feeds once the acute phase is
because of the following limitations: over and the infants' color, saturation and perfusion have
132 Essential Pediatrics
improved. Similarly, sepsis (unless associated with shock/ their feeding skills and also improves the milk secretion
sclerema/NEC) is not a contraindication for enteral in their mothers (Non-nutritive sucking).
feeding. Figures 7.32A and B show the method of paladai and
intragastric tube feeding in babies.
Healthy LBW infants: Enteral feeding should be initiated
immediately after birth in healthy LBW infants with the Progression of Oral Feeds
appropriate feeding method determined by their oral
All LBW infants, irrespective of their gestation and birth
feeding skills and gestation.
weight, should ultimately be able to feed directly from
Feeding Ability the mothers' breast. For preterm LBW infants started on
IV fluids/OG tube/paladai feeding, the steps of progres
Breastfeeding requires effective sucking, swallowing and
sion to direct and exclusive breastfeeding are summarized
a proper coordination between suck/swallow and
in Fig. 7.33.
breathing. These complex skills mature with increasing
Term LBW infants started on IV fluids (because of their
gestation. A mature sucking pattern that can adequately
sickness) can be put on the breast once they are
express milk from the breast is not present until 32-34
hemodynamically stable.
weeks gestation; the coordination between suck/swallow
and breathing is not fully achieved until 37 weeks of Choice of Milk
gestation. The maturation of oral feeding skills and the
All LBW infants, irrespective of their initial feeding
choice of initial feeding method at different gestational
method should receive only breast milk. This can be
ages are summarized in Table 7.17.
ensured by giving expressed breast milk (mothers' own
milk) for those infants fed by paladai or gastric tube.
Table 7.17: Maturation of oral feeding skills and the choice of
initial feeding method in LBW infants Expressed breast milk (EBM): All mothers should be
Gestational age counseled and supported in expressing their own milk
for feeding their preterm infants. Expression should
< 28 weeks ideally be initiated within hours of delivery so that the
infant gets the benefits of feeding colostrum. Thereafter,
it should be done 2-3 hourly so that the infant is
exclusively breastfed and lactation is maintained in the
28-31 weeks mother. Expressed breast milk can be stored for about 6
hours at room temperature and for 24 hours in refrigerator.
The steps of breast milk expression are given in Fig. 7.29.
Nutritional Supplementation
LBW infants, especially those who are born preterm,
require supplementation of various nutrients to meet their
high demands. Since the requirements of VLBW infants
differ significantly from those with birth weights of 1500-
2499 g, supplementation regimes for these two groups
Figs 7.32A and B: (A) Paladai feeding,- (B) Gavage feeding have been discussed separately.
134 Essential Pediatrics
Infants on IV fluids*
hemodynamically stable
^ If accepting well
i
Put them on mother's breast before each feed
Observe for good attachment and effective sucking
Fig. 7.33: Progression of oral feeding in preterm LBW infants. (IV, intravenous,- OG, oro-gastric tube; PMA, postmenstrual age; NNS, non
nutritive sucking) * Term and near-term sick infants started on IV fluids can be initiated on breastfeeding once they are hemodynamically stable
Supplementation for Infants with of vitamin D is met usually by de novo synthesis in the
Birth Weights of 1500-2499 g skin following exposure to sunlight and hence no
These infants are more likely to be born at term or near supplementation is required. However, because LBW
term gestation (>34 weeks) and are more likely to have infants are more at risk of osteopenia than healthy term
adequate body stores of most nutrients. Therefore, they infants, most neonatal units tend to supplement vitamin
do not require multi-nutrient supplementation (unlike D in the dose of 200-400 IU/day (Table 7.18).
VLBW infants). However, vitamin D and iron might still
have to be supplemented in them. While iron supple Supplementation in VLBW Infants
mentation is mandatory for all infants, supplementation These infants who are usually born before 32-34 weeks
of vitamin D is contentious because of the paucity of the gestation have inadequate body stores of most of the
data regarding its levels and deficiency status in different nutrients. Since expressed breast milk has inadequate
populations. Some would argue that the daily requirement amounts of protein, energy, calcium, phosphorus, trace
Newborn infants 135
elements (iron, zinc) and vitamins D, E and K, it is often Two types of growth charts are commonly used for
not able to meet the daily recommended intakes of these growth monitoring in preterm infants: intrauterine and
infants. Hence, these infants need multi-nutrient postnatal growth charts. Of these, the postnatal growth
supplementation till they reach term gestation (40 weeks, chart is preferred because it is a more realistic
i.e. until the expected date of delivery). The following representation of the true postnatal growth (than an
nutrients have to be added to the expressed breast milk intrauterine growth chart) and also shows the initial
in them: weight loss that occurs in the first two weeks of life. The
1. Calcium and phosphorus (140-160 mg/kg/d and 70- two postnatal charts that are most commonly used for
80 mg/kg/d respectively for infants on EBM) growth monitoring of preterm VLBW infants are: Wright's
2. Vitamin D (400 IU/day), vitamin B complex and zinc and Ehrenkranz' charts. Once the preterm LBW infants
(about 0.5 mg/day)-usually in the form of multivitamin reach term gestation (40 weeks), WHO growth charts
drops should be used for growth monitoring.
3. Folate (about 50 mcg/kg/day)
4. Iron (2 mg/kg/day) Management of Inadequate Weight Gain
Multi-nutrient supplementation can be ensured by one Inadequate weight gain is a common and pertinent
of the following methods: problem in LBW infants. It starts at the time of initial
1. Supplementing individual nutrients, e.g. calcium, admission and continues after discharge resulting in
phosphorus, vitamins, etc. These supplements should failure to thrive and wasting in the first year of life. The
be added at different times in the day to avoid abnormal common causes are summarized in Table 7.19.
increase in the osmolality.
2. By fortification of expressed breast milk with human
milk fortifiers (HMF): Fortification increases the Table 7.19: Causes of inadequate weight gain
nutrient content of the milk without compromising its 1. Inadequate intake
other beneficial effects. Experimental studies have Breastfed infants:
shown that the use of fortified human milk results in Incorrect feeding method (improper positioning/
net nutrient retention that approaches or is greater than attachment)*
expected intrauterine rates of accretion in preterm Less frequent breastfeeding, not feeding in the night
hours*
infants. Preterm VLBW infants fed fortified human milk
Infants on spoon/paladai feeds:
do not require any supplementation other than iron.
Incorrect method of feeding* (e.g. excess spilling)
Fortification or supplementation of minerals and
Incorrect measurement/calculation
vitamins should be continued only till term gestation (40 Infrequent feeding*
weeks) in VLBW infants; after this period, only vitamin D Not fortifying the milk in VLBW infants
and iron needs to be supplemented (similar to infants with 2. Increased demands
birth weights of >1500 g). Illnesses such as hypothermia/cold stress*,
bronchopulmonary dysplasia
Growth Monitoring of LBW Infants Medications such as corticosteroids
Regular growth monitoring helps in assessing the ’Common causes
nutritional status and adequacy of feeding in LBW infants;
it also identifies those infants with inadequate weight gain.
All LBW infants should be weighed daily till the time
Management of inadequate weight gain consists of the
of discharge from the hospital. Other anthropometric
following steps:
parameters such as length and head circumference should
1. Proper counseling of mothers and ensuring adequate
be recorded weekly.
support for breastfeeding their infants; includes
Both term and preterm LBW infants tend to lose weight
assessment of positioning/attachment, managing sore/
(about 10% and 15% respectively) in the first 7 days of
flat nipple, etc.
life; they regain their birth weight by 10-14 days.
2. Explaining the frequency and timing of both breast
Thereafter, the weight gain should be at least 15-20 g/
feeding and spoon/paladai feeds: Infrequent feeding is
kg/day till a weight of 2-2.5 kg is reached. After this, a
one of the commonest causes of inadequate weight gain.
gain of 20 to 30 g/day is considered appropriate.
Mothers should be properly counseled regarding the
Grozvth charts: Using a growth chart is a simple but frequency and the importance of night feeds. A time
effective way to monitor the growth. Serial plotting of table where mother can fill the timing and amount of
weight and other anthropometric indicators in the growth feeding is very helpful in ensuring frequent feeding.
chart allows the individual infant's growth to be compared 3. Giving EBM by spoon/paladai feeds after breastfeeding
with a reference standard. It helps in early identification also helps in preterm infants who tire out easily while
of growth faltering in these infants. sucking from the breast.
136 Essential Pediatrics
4. Proper demonstration of the correct method of environments of the home or the hospital. The infection is
expression of milk and paladai feeding: It is important often transmitted through the hands of the care-
to observe how the mother gives paladai feeds; the providers. The presentation is that of septicemia,
technique and amount of spillage should be noted. This pneumonia or meningitis. The predisposing factors
should be followed by a practical demonstration of the include LBW, lack of breastfeeding, poor cord care,
proper procedure. superficial infections (pyoderma, umbilical sepsis),
5. Initiating fortification of breast milk when indicated aspiration of feeds, and disruption of skin integrity with
needle pricks and use of intravenous fluids.
6. If these measures are not successful, increase either the
a. Energy (calorie) content of milk by adding MCT oil, When to Suspect NNS?
corn starch, etc. Infants on formula feeds can be given
The manifestations of NNS are often vague and ill-
concentrated feeds (by reconstituting 1 scoop in 25
defined, and, therefore, demand a high index of suspicion
mL of water), OR
for early diagnosis. A common and early but non-specific
b. Feed volume - to 200 mL/kg/day.
manifestation is an alteration in the established feeding
behavior. The baby, who had been active and sucking
Suggested reading
normally, gradually or suddenly refuses to suck and
1. Nutrition. In: Edmond K, Bahl R (Eds). Optimal feeding of low- becomes lethargic, inactive or unresponsive. Poor cry,
birth-weight infants—Technical Review. World Health Organi
hypothermia, abdominal distension, vomiting and apneic
zation 2006; p42.
spells are other common manifestations. Diarrhea is
2. Sankar MJ, Agarwal R et al. Feeding of low birth weight infants.
uncommon. Fast breathing, chest retractions and grunt
Indian J Pediatr 2008;75:459-69.
indicate pneumonia. Most cases of meningitis do not
have any distinct clinical picture per se, making it
NEONATAL SEPSIS mandatory to suspect meningitis in practically all cases
suspected of sepsis. Presence of excessive or high-pitched
When pathogenic organisms gain access into the blood
crying, fever, seizures, blank look, neck retraction or
stream, they may cause an overwhelming infection
bulging anterior fontanel are highly suggestive of
without much localization (septicemia), or may get
meningitis. Shock, bleeding, sclerema and renal failure
predominantly localized to the lung (causing pneumonia)
are indicators of overwhelming sepsis.
or the meninges (causing meningitis). Systemic bacterial
A host of conditions like hypothermia, hyperthermia,
infections are known by the generic term neonatal sepsis
hypoglycemia, hypoxia, late metabolic acidosis, conges
(NNS), which incorporates septicemia, pneumonia and
tive heart failure, and even a simple condition like nasal
meningitis of the newborn.
block may mimic sepsis. A careful clinical examination
NNS is one of the most important morbidities seen at
and relevant investigations are necessary to differentiate
the community and facility levels. It is also the most
these conditions from NNS.
important cause of neonatal deaths in the community. If
diagnosed early and treated aggressively with antibiotics
Investigations
and, equally importantly, with good supportive care, it is
possible to save most cases of neonatal sepsis. No investigation is required as a prerequisite to start
treatment in a clinically obvious case. Blood culture is of
help in guiding therapy. A panel of tests consisting of total
Etiology
leukocyte count (TLC), absolute neutrophil count (ANC),
Escherichia coli, Staphylococcus aureus and Klebsiella sp. are immature to total neutrophil ratio (I/T ratio), CRP and
responsible for most cases of neonatal sepsis. micro ESR constitutes a useful sepsis screen for clinically
doubtful cases. Sepsis screen is considered positive if two
Early vs Late Sepsis of these parameters are positive. Value of sepsis screen is
Early-onset sepsis (EOS) (less than 72 hr) infections are more for exclusion of diagnosis of NNS. The diagnosis of
caused by organisms prevalent in the maternal genital tract sepsis can be reasonably excluded if two screens 12-24 hr
or in the delivery area. The predisposing factors include apart are negative.
low birth weight (LBW), prolonged rupture of membranes,
foul smelling liquor, multiple per vaginum examinations, Blood Culture
maternal fever, difficult or prolonged labor and aspiration Blood culture should be taken before starting antimicrobial
of meconium. EOS manifests frequently as pneumonia and therapy. After cleaning with alcohol, povidone-iodine and
less commonly as septicemia or meningitis. again alcohol, a specimen of 0.5 to 1.0 ml of blood can be
Late-onset sepsis (LOS) (greater than 72 hr) infections taken in a small culture media bottle containing 5 to 10 ml
are caused by the organisms thriving in the external of the liquid broth.
Newborn infants 137
Lumbar Puncture (LP) and 10 on day 7). Peak value is 15 mm at the end of 1st
1. LP should be performed in all cases suspected of NNS hour during neonatal period. High mESR is a specific
test but it has only moderate sensitivity. The value is
except in asymptomatic babies being investigated for
spuriously high in neonates with hemolysis and low in
maternal risk factors.
babies with disseminated consumptive coagulopathy.
2. Table 7.20 depicts the normal CSF parameters in
neonates.
Treatment
Institution of prompt treatment is essential for ensuring
Table 7.20: Normal CSF examination in neonates optimum outcome of neonates with sepsis who often reach
[(mean (range) ]
the health care facilities late and in a critical condition.
Supportive care and antibiotics are the two equally
important components of treatment. It should be realized
that antibiotics take at least 12 to 24 hours to show any
effect and it is the supportive care that makes the difference
between life and death early in the hospital course.
Supportive Care
Good supportive care plays a vital role in management of
sick babies. Meticulous attention is required to various
Indirect Markers of Neonatal Infection
aspects of it.
1. TLC: There is a wide range of normal TLC, from 8000 • Provide warmth; ensure consistently normal tempe
to 20,000 per cu mm and high counts are often of no rature (36.5°C-37.5°C). Kangaroo mother care (KMC)
value. Neonatal sepsis is associated with leukopenia is a useful modality to maintain temperature of small
(TLC < 5000/cu mm). and sick babies.
2. ANC: ANC includes both immature and mature neutro • Start oxygen by hood or mask, if cyanosed or grunting.
phils. ANC is obtained by doing a differential leukocyte Provide bag and mask ventilation with oxygen if
count on a stained smear or preferably by the automatic breathing is inadequate. Instilling normal saline drops
Coulter counter (after correction for nucleated red cells). in nostrils may help clear the nasal block.
ANC below 1800 per cubic mm is believed to be the • Assess peripheral perfusion by palpating peripheral
best predictor of sepsis, while neutrophilia does not pulses, assessing capillary refill time (CRT) (normal less
correlate well. than 2-3 seconds), and skin color. Serial measurement
3. I/T ratio: An I/T ratio of over 0.2 is a highly sensitive of urine output is helpful for this purpose. Infuse
marker of NNS. It is obtained by examining the normal saline or Ringer lactate 10 ml/kg over 5-10
peripheral blood smear, counting the immature and
minutes, if perfusion is poor as evidenced by CRT of
mature neutrophils separately. A mature neutrophil has
more than 3 seconds. Repeat the same dose 1-2 times
segmented nucleus and the segments are connected by
over the next 30-45 minutes, if perfusion continues to
characteristic thin filamentous strands. In contrast, the
be poor. Dopamine and dobutamine may be required
nucleus of a band cell is indented by more than one to maintain normal perfusion in sick babies.
half of its breadth giving a uniform diameter (band • Start intravenous line. If hypoglycemia is suspected,
like configuration or a lobulated appearance) in which infuse glucose (10%) 2 ml/kg stat. Do not use glucose
the isthmus between the lobules is broad enough to boluses routinely. Provide maintenance fluid,
reveal two distinct margins with nuclear material electrolytes and glucose (4-6 mg/kg/min). Add
between them. Occasionally, metamyelocytes, which potassium to IV fluids once normal flow of urine is
are less mature neutrophils than bands, may also spill documented.
into peripheral blood. The nucleus of a metamyelocyte • Ensuring optimal nutrition is extremely helpful in sick
shows only marginal identation. All bands and other babies. Enteral feeds should be initiated early if there
cell forms which are less mature than bands are is no abdominal distension and baby is hemodyna
classified as immature neutrophils. mically stable. Feed mother's milk. Consider parenteral
4. C-reactive protein (CRP): A concentration above 1 mg/ nutrition, if available.
dL would indicate NNS. • Administer vitamin K 1 mg intramuscularly.
5. Micro ESR: mESR is obtained by collecting capillary • Transfuse packed cells, if baby has a low hematocrit
blood in a standard preheparinized microhematocrit (less than 35-40%). Do not use blood/plasma
glass tube (75 mm length, internal diameter 1.1 mm, transfusion on routine basis for 'boosting' immunity.
outer diameter 1.5 mm), placing it vertically and
reading the fall in the red cell column after one hour.
Approach to Antimicrobial Therapy
The normal value (mm 1st hour) is equal to the Antimicrobial therapy constitutes the mainstay of
postnatal day of life plus 3 mm (thus it is 5 on day 2 treatment of sepsis. In a seriously sick neonate suspected
138 Essentia! Pediatrics
Empiric therapy when etiologic agent is not known: The Adjunct Therapy
empiric therapy of NNS should cover the major causative Exchange blood transfusion (EBT): EBT using fresh whole
pathogens while awaiting reports of culture studies. Since blood in sick infected babies in the presence of sclerema,
the antimicrobial spectrum and susceptibility profile is disseminated coagulation, hyperbilirubinemia or rapid
different in different newborn services, there cannot be a clinical deterioration has been shown to be effective. Since
universal recommendation of a single empiric regimen. the candidate babies are likely to be unstable, it is
Antibiotics are often used in neonates on the slightest important to monitor them carefully during the procedure.
suspicion of sepsis because of the grave and fulminant
nature of neonatal sepsis. But unbridled overuse of Intravenous immunoglobulin (IVIG): The use of IVIG as a
antibiotics is associated with the serious risk of emergence prophylaxis or in treatment of NNS is not recommended.
of resistant strains of pathogens. Most newborn units in It has doubtful beneficial immune-enhancement effect and
the country are facing the problem of overwhelming may be associated with harmful side effects.
resistance to commonly used antibiotics including third
generation cephalosporins. Rational use of antibiotics is,
Monitoring
therefore, the responsibility of every physician. Intensive care and monitoring is the key determinant of
Each treating unit should adopt a suitable policy. Based improved survival of neonates. The elements of
on changes in the spectrum of etiologic agents and the monitoring in sepsis are not different from those in other
antibiotics sensitivity pattern, the choice of antibiotics lifethreatening conditions, and enable detection of compli
must be periodically reviewed and modified. Table 7.21 cations at the earliest in order to ensure timely inter
provides possible regimen of empiric antibiotics. vention. The periodicity of documenting the various
parameters should be individualized.
Therapy after an etiologic agent is known: Antimicrobial
therapy can be made specific once a positive culture and
Prognosis
sensitivity report is available. However, this would be
known only after 2-3 days. Even in best institutions well The outcome depends upon weight and maturity of the
over 50% blood cultures are negative. infant, type of etiologic agent, its antibiotic senstivity
pattern; and adequacy of specific and supportive therapy.
The early-onset septicemia carries adverse outcome. The
Table 7.21: Initial antibiotic therapy (individualized and later reported mortality rates in neonatal sepsis in various
modified as per the clinical course and culture reports) studies from India ranges between 45-58%. The institution
Clinical situation Septicemia and Meningitis of sepsis screen for early detection of infection, judicious
pneumonia and early antimicrobial therapy, close monitoring of vital
First line signs and intensive supportive care are the most crucial
Community-acquired; Ampicillin or Cefotaxime factors responsible for a better outcome.
resistant strains unlikely penicillin and
and gentamicin gentamicin Suggested readings
Second line Sankar MJ, Agarwal R, Deorari AK, Paul VK. Sepsis in the newborn.
Hospital-acquired or Ampicillin or Cefotaxime Indian J Pediatr. 2008 Mar;75(3):261-6.
when there is a low to cloxacillin and
moderate probability of and amikacin
resistant strains amikacin NECROTIZING ENTEROCOLITIS
Pathogenesis: Several factors are implicated. intravascular coagulation and even anuria. There are frank
1. Mucosal injury: This is attributed to (i) ischemic damage signs of peritonitis with abdominal wall redness. Pneumo
to the intestinal mucosal barrier, as a result of fetal peritoneum is present in abdominal X-ray.
distress, perinatal asphyxia, respiratory distress
Management: All oral feeding should be withheld. A
syndrome -hypothermia, vascular spasm or following
nasogastric tube is inserted to relieve distension and
exchange transfusion for hyperbilirubinemia, (ii)
aspirate stomach contents. Fluids and electrolytes in
diarrhea and
adequate quantities should be administered. Parenteral
(iii) bacterial infections of the injured gut with E. coli,
alimentation may be administered to provide nutrition.
Klebsiella, Pseudomonas or Salmonella. More recently,
The blood, cerebrospinal fluid, urine and stools are
infection with clostridia, C. perfringens and C. butyricum
cultured. Shock is managed by replacement of fluids and
have been incriminated. Stasis of intestinal contents
use of vasopressor agents. Plasma and platelet transfusion
favors bacterial overgrowth.
are used to prevent bleeding tendency.
2. Formula feeding: Almost all patients of neonatal necrotiz
Perforation is suggested if there is free intra-abdominal
ing enterocolitis are artificially fed prior to the onset of
gas and liver dullness is obliterated. Surgical intervention
illness. Breast milk appears to be protective for NEC. It
is necessary in these cases.
appears that there must be a substrate in the formula
feed which facilitates gas production in the intestinal Sequelae: Intestinal strictures may be left in survivors.
flora. Poor systemic and gastrointestinal immunological These manifest with bloody stools, vomiting and abdo
protection against bacterial infections in the preterm minal distention. Shortened bowel leads to malabsorption.
babies predisposes them to infection of the gut.
POST-RESUSCITATION MANAGEMENT
Clinical features: The illness usually develops after the first
OF ASPHYXIATED NEONATES
week of life. The course may be very fulminant with death
occurring in a few hours, mortality rate being around Perinatal Asphyxia
40-50%. Clinical manifestations may be described in three Perinatal asphyxia is an insult to the fetus or newborn
stages: due to a lack of oxygen (hypoxia) and/or a lack of per
Stage 1: Suspected NEC: Unstable temperature, apnea, fusion (ischemia) to various organs. It is often associated
bradycardia, lethargy, mild abdominal distension, with tissue lactic acidosis and hypercarbia.
vomiting. In stage IB, blood is present in stools. X-ray There is no universally accepted definition of perinatal
shows mild intestinal distension in stage 1A and IB. asphyxia. The American Academy of Pediatrics Commit
Stage 2: Clinical signs as above. Bowel sounds are tee on Fetus and Newborn has suggested essential criteria
diminished with or without abdominal tenderness. In (Tables 7.22 and 7.23) of defining a case of perinatal
more severe cases of this stage (2B), there may be metabolic asphyxia.
acidosis and mild thrombocytopenia. Pneumatosis
intestinalis (gas in intestinal wall) and dilatation of Table 7.22: Essential criteria for perinatal asphyxia
intestines are seen on abdominal X-ray (Fig. 7.34).
• Prolonged metabolic or mixed academia (pH <7.0) on an
Stage 3: In addition to the above, the infant has low blood
umbilical arterial blood sample
pressure, bradycardia, apnea, acidosis, disseminated • Persistence of apgar score of 0-3 for >5 min
• Neurological manifestations, e.g. seizures, coma, hypo
tonia or hypoxic ischemic encephalopathy (HIE) in the
immediate neonatal period
• Evidence of multiorgan dysfunction in the immediate
neonatal period
In the absence of such quantification it is better to use between various arteries. Two areas frequently involved
the term 'neonatal depression', which refers to a condition are the posterior white matter, involving the occipital
of the infant in the immediate postnatal period radiation at trigone and anteriorly around the foramen of
(approximately 1st hour) without making any association Munro. Relative sparing of the cerebral cortex is seen due
with objective evidence. to its rich supply of arteries. Long-term sequels include
National Neonatology Forum of India (NNF) and WHO spastic diplegia and quadriplegia (lower limbs > upper
use an Apgar of 0-3 and 4-7, at 1 minute, to define severe limbs) and visual impairment. Posthemorrhagic infarcts
and moderate birth asphyxia respectively (1985). For the are usually associated with severe intraventricular bleeds
community settings NNF defines asphyxia as absence of and result from venous infarction due to occlusion of
cry at 1 minute and severe asphyxia as absent or medullary and terminal veins by the large bleed. Other
inadequate breathing at five minutes. lesions include small infarcts secondary to blocking of end
arteries resulting in porencephaly, hydrancephaly or
Neuropathology multicystic encephalomalacia.
These differ according to gestation (Table 7.24) and are of
Diagnosis and Approach
the following main types:
Hypoxia is an evolving process that starts at the onset of
Table 7.24: Neurological patterns of hypoxic ischemic the insult and continues after resuscitation and thereafter
encephalopathy (HIE) manifests in form of sequelae. Management thus depends
Premature newborns on which point in this evolution it is detected; with the
preventive approach beginning in the prenatal period and
Selective subcortical neuronal necrosis
then continuing in the form of a long follow up much after
Periventricular leukomalacia
Focal and multifocal ischemic necrosis the stabilization of the initial condition.
Periventricular hemorrhage infarction
Antenatal Assessment
Term neivborn
Meticulous antenatal check up with early detection and
Selective cortical neuronal necrosis
management of high risk mothers such as those with
Status marmoratus of basal ganglia and thalamus
diabetes, hypertension, or bad obstetric history help both
Parasagittal cerebral injury
Focal and multifocal ischemic cerebral necrosis reduce complications and allow the mother and the
treating doctor to prepare adequately.
Perinatal Assessment
Term
Anticipating problems and being prepared for inter
Selective neuronal necrosis involves cerebral cortex,
vention require rigorous monitoring during labor which
hippocampus, basal ganglia, cerebellum and anterior horn
may include, depending on availability of resources, the
cells of spinal cord. Seen predominantly in term infants
following—fetal movement, non-stress test, fetal bio
and depending on site, this manifests clinically as diminis
physical profile, fetal heart rate alternation, and fetal acid-
hed consciousness, seizures, and abnormalities of feeding,
base status.
breathing, etc. Status marmoratus is a variant of selective
Fetal heart rate monitoring clinically or by tococardio-
neuronal necrosis involving only basal ganglia and thala
graphy helps detect fetal tachycardia (>160) or the more
mus, having long term sequelae such as choreoathetosis, worrisome fetal bradycardia (<120). Normal beat-to-beat
spastic quadriparesis and retardation. Focal necroses are variability is 6-25 beats per minute. Most ominous are late
commonly thromboembolic and involve the left middle deceleration (a slowing of heart beginning 15-30 seconds
cerebral artery. Parasagittal area serves as the watershed after onset of uterine contractions and returning to baseline
area for many arteries and hence is vulnerable to ischemia after contraction ends) and combination of loss of
resulting in proximal limb weakness (upper > lower) that variability with the various types of deceleration.
later may develop into spastic quadriparesis. Fetal scalp pH < 7.0 or base deficit > 12 is an evidence
of significant and prolonged intrauterine asphyxia and are
Preterm
indications of urgent delivery. Meconium passage
Selective neuronal necrosis is rare in preterms; diencepha suggests fetal hypoxia though 10-20% of normal preg
lic neuronal necrosis restricted to thalamus and brainstem nancy and 25-50% of uncomplicated postdated pregnan
with or without hypothalamus and lateral geniculate body cies may also have meconium-stained liquor. Fetal nails
is seen. Hypoxia and acidosis followed by hyperoxia and cord staining indicate > 4 to 6 hrs of exposure.
demonstrates a unique pattern of injury involving pontine
nucleus and subiculum of the hippocampus. Delivery Room
Periventricular leukomalacia (PVL) results from HIE Prevention of heat loss and rapid establishment of effective
insult leading to coagulative necrosis and infarction of ventilation and circulation are the cornerstones to neonatal
periventricular white matter that is the watershed area resuscitation. The details of resuscitation have been
Newborn Infants 141
discussed previously. Hyperthermia should also be Involvement of other systems, most commonly renal
avoided as it may lead to further neurological damage. and cardiac, significantly add to the clinical picture and
Other conditions that may be considered in the delivery point to substantial perinatal insult.
room and thereafter include: the effect of maternal drugs
or anesthesia; acute blood loss; acute intracranial bleeding; Management of Hypoxic-ischemic Injury
CNS malformation; neuromuscular disease; cardiopul Initial management includes effective resuscitation at the
monary disease; mechanical impediments to ventilation; delivery room followed by supportive care under frequent
and infection (including septic shock and hypotension). monitoring. The aim is to keep all parameters within
normal range except for fluids, which may be restricted in
Postnatal Assessment case of syndrome of inappropriate antidiuretic hormone
Risk factors noted in ante and intrapartum period along (SIADH).
with post delivery resuscitation, Apgar and neurological 1. Temperature: Even though hypothermia has been
examination help in diagnosis of most cases. Laboratory recently investigated for its neuroprotective actions
methods help quantify the damage and can predict presently recommended temperature remains the
outcome to some extent. thermoneutral zone for the baby.
A wide spectrum of clinical manifestations is seen 2. Oxygen (PaOJ: Both hypoxia and hyperoxia can
depending on the severity of injury. These manifestations damage neurons; hence percent O, saturation (SpOJ
change over time and are clinically noted in babies of or preferably arterial oxygen levels should be moni
gestational age >36 weeks by classification on the basis of tored and kept in normal range.
Sarnat stages of HIE (1976). This helps both note the 3. Carbon-dioxide (PaCO:): Hypercarbia causes cerebral
evolution of the state and predict outcome. No baby in acidosis and vasodilatation, which leads to shunting
stage 1 has a poor outcome, in stage 2, 20-40% may have of blood away from compromised areas (steal pheno
adverse outcome while stage 3 has a universally poor menon) increasing infarct size. Hypocapnia of <25 mm
outcome (Table 7.25). Hg decreases cerebral perfusion and can cause
In acute severe HIE the sequence seen is: infarction. Both should be avoided and this requires
• During 1st 12 hrs—Evidence of bilateral hemispheric blood gas monitoring.
dysfunction with decreased consciousness. 4. Perfusion: Cerebral perfusion pressure (CPP) reflects
• Between 12-24 hrs—apparent improvement in level of systemic blood pressure in a pressure passive manner.
consciousness but with associated worsening of other Hence to maintain the desired range of CPP a systemic
aspects such as seizures or apnea. mean arterial pressure of 45-50 mm Hg (term), 35-40
• During the first 3 days of life—signs of brainstem (1-2 kg weight) and 30-35 mmHg (< 1 kg weight) is
dysfunction worsening like ophthalmoplegia, bulbar required. Blood pressure measurement should be taken
involvement and arrest may occur. in all babies. A central venous pressure of 5-8 mm Hg
• After 3-4 days—if patient survives, gradual improve in term and 3-5 mm Hg in preterm babies is ideal. Free
ment in the neurological status occurs. Persistent water administration should be restricted. In case of
sequelae that commonly remain include dullness, poor perfusion, bolus administration should be done
feeding problems, obstructive apnea and abnormal slowly and along with monitoring to avoid over
muscle tone. hydration. Judicious use of pressors can help maintain
Milder presentations include hyper alert states with adequate BP. Hyperviscosity due to a hematocrit of 65
jitteriness, excessive crying, exaggerated Moro and or more should be corrected by partial exchange with
hyperreflexia. normal saline.
5. Glucose: Levels between 75-100 mg/dl are recom abnormal but EEG shows no seizure activity, tapering of
mended. Higher levels enhance cerebral edema and phenobarbitone may still be tried. If EEG shows seizure
compromise perfusion, while hypoglycemia potentiates activity, reevaluation is done at 3 months.
excitotoxic damage. Hypoglycemia is commonly seen
in asphyxiated infants and must be regularly monitored Prognosis
and rigorously corrected. Seizures caused by hypo The following predict a poor outcome:
glycemia should not be used for Sarnat classification. • Lack of spontaneous respiratory effort within 20-30
6. Metabolic profile: Hypocalcemia and electrolyte minutes of birth is associated with almost uniform
disturbances should be regularly looked for till mortality
stabilization of baby and corrected as indicated. • Sarnat stage 3
7. Cerebral edema: Intracranial pressure (ICP) can be • Abnormal neurological findings persisting beyond the
estimated by measuring the vertical distance between first 7-10 days of life
the anterior fontanel and the heart at the point that the • Oliguria (<lml/kg/day) during the first 36 hours
midportion of the fontanel flattens when the baby is • Interictal burst suppression or isoelectrical pattern on
tilted up. (Normal = 50 mm H20 or lower). The main EEG.
cause of edema is cytotoxic injury and treatment • Persistent hypodensities on CT after 1 month of injury.
directed at reducing the edema per se has not shown Thus all these babies should have regular follow up
to be useful. However factors enhancing it should be with monitoring of neuro developmental milestones to
prevented. detect any deficits early and to intervene effectively.
8. Seizures: 20-50% of infants with HIE develop seizures
during day 1 or 2. Seizures are commonly focal or Suggested reading
multifocal. Metabolic disturbances such as hypo Agarwal R, Jain A, Deorari AK, Paul VK. Post-resuscitation management
glycemia, hypocalcemia and hyponatremia must be of asphyxiated neonates. Indian J Pediatr 2008; 75:175-80.
ruled out. Seizures may be intractable initially but
usually burn themselves out by 48 hours. Major RESPIRATORY DISTRESS
differential diagnosis includes pyridoxine deficiency
Respiratory distress in the neonate is common problem
and drug toxicity. Subtle seizures lasting short durations
and when severe, it can be a serious neonatal emergency.
need not be treated.
It can be due to respiratory (Table 7.26) and non-
Once the baby is seizure free for 3-4 days anti
respiratory causes (Table 7.27). Early recognition and
convulsants are stopped in the same order as they were
prompt treatment is essential to improve outcome.
started, except phenobarbitone. Phenobarbitone is
stopped at discharge if neurological examination is Approach
normal and baby is feeding well on breast. If neuro
Respiratory distress in a neonate can be recognized by the
logical examination is not normal, then phenobarbitone
presence of varying combinations of tachypnea
is continued until one month. At one month if baby is
(RR>60/min), chest retractions, grunting, flaring of alae
normal neurologically, phenobarbitone is tapered off
nasi and cyanosis. Severity of distress can be assessed by
over a couple of days. If neurological function is
Table 7.27: Non-pulmonary causes of rapid breathing respiratory distress within the first 24 hours, the most
likely cause is meconium aspiration syndrome (MAS). A
Cardiac CHF, congenital heart disease.
term baby with uncomplicated birth developing tachy
Metabolic Hypothermia, hypoglycemia, metabolic
acidosis. pnea in the first few hours of birth is likely to have transient
CNS Asphyxia, cerebral edema, hemorrhage. tachypnea of newborn. Presence of suprasternal recessions
Chest wall Asphyxiating thoracic dystrophy, Werdnig with or without stridor indicates upper airway
problem Hoffman disease. obstruction.
CHF: congestive heart failure, CNS: central nervous system
Respiratory Distress Syndrome (RDS) or
Hyaline Membrane Disease (HMD)
using the respiratory distress score (Table 7.28). The RDS is common in preterm babies less than 34 weeks of
gestation, age at onset, severity of distress and presence gestation. The overall incidence is 10-15% but can be as
of associated clinical features help in arriving at a high as 80% in neonates <28 weeks. In addition to
diagnosis. It should be noted that chest retractions are prematurity, asphyxia, acidosis, maternal diabetes and
mild or absent in respiratory distress due to non- cesarean section can increase the risk of RDS.
respiratory causes.
Etiopathogenesis
Cardiac diseases: Cardiac etiology for respiratory distress
In RDS, the basic abnormality is surfactant deficiency.
should be suspected if a neonate with distress has cyanosis
Surfactant is a lipoprotein containing phospholipids like
or hepatomegaly. Congenital heart disease and cardiac
phosphatydylcholine and phosphatydylglycerol and
arrhythmias can present as congestive cardiac failure in
proteins. Surfactant is produced by type II alveolar cells
the neonatal period. Transposition of great vessels (TGV)
of lungs and helps reduce surface tension in the alveoli.
and hypoplastic left heart syndrome usually present on
In the absence of surfactant, surface tension increases and
day one with progressive distress. Most other cardiac
alveoli tend to collapse during expiration. During
conditions present after the first week of life. A preterm
inspiration more negative pressure is needed to keep
neonate having a systolic murmur with tachypnea and
alveoli patent. There is inadequate oxygenation and
hepatomegaly is likely to have patent ductus arteriosus
increased work of breathing. Hypoxemia and acidosis
(PDA).
result in pulmonary vasoconstriction and right to left
Metabolic causes: Metabolic acidosis is one of the common shunting across the foramen ovale. This worsens the
causes of tachypnea in a neonate. Sepsis, asphyxia, hypoxemia and the neonate eventually goes into
diarrhea and dehydration can predispose a neonate to respiratory failure. Ischemic damage to the alveoli causes
develop metabolic acidosis. These neonates usually have transudation of proteins into the alveoli. Surfactant
tachypnea and minimal distress. production starts around 20 weeks of life and peak at 35
weeks gestation. Therefore any neonate less than 35 weeks
CNS causes: Neonates with birth asphyxia, cerebral
is prone to develop RDS.
hemorrhage, or meningitis can present with tachypnea
and respiratory distress. These neonates are usually Clinical Features
lethargic with poor neonatal reflexes.
Respiratory distress usually occurs within the first 6 hours
Respiratory causes: All respiratory diseases listed in Table of life. Clinical features include tachypnea, retractions,
7.26 can occur both in preterm and term babies. However, grunting, cyanosis, and decreased air entry. Diagnosis can
if a preterm baby has respiratory distress within the first be confirmed by chest X-ray. Radiological features include
few hours of life the most likely cause is respiratory reticulogranular pattern, ground glass opacity, low lung
distress syndrome (RDS). Similarly if a term baby born to volume, air bronchogram (Fig. 7.35), and white out lungs
a mother with meconium stained liquor develops in severe disease.
Prevention of RDS
Administration of antenatal steroids to mothers in preterm
labor (<35 wk) has been a major breakthrough in
management of preterm infants. Antenatal steroids are
effective in decreasing RDS, intraventricular hemorrhage
Fig. 7.35: Moderate to severe hyaline membrane disease: note and mortality in these neonates (Table 7.29).
homosenous opacification of lungs obscuring heart borders and
presence of air bronchogram (arrows)
Table 7.29: Antenatal corticosteroids in preterm labor
Prenatal diagnosis can be made by determining the Benefits
lecithia lecithin/sphingomyelin (L/S) ratio in the amniotic • 50% reduction in the incidence of respiratory distress
fluid. L/S ratio > 2.0 indicates adequate lung maturity. A syndrome
simple bedside test, the shake test, can be done on the • 50% reduction in the incidence of intraventricular
amniotic fluid or gastric aspirate to determine lung hemorrhage (IVH)
maturity. The gastric or amniotic fluid is mixed with • 40% reduction in mortality
absolute alcohol, shaken for 15 secs and allowed to settle. Indications
Bubbles are formed in the presence of adequate surfactant • All women with preterm labor between 24 and 34 weeks
indicating extent of lung maturity. of gestation
Contraindication
Management
• Clinical chorioamnionitis
Neonates suspected to have RDS need to be cared for in
• Eclampsia
neonatal intensive care unit with IV fluids, and oxygen.
[Maternal hypertension and diabetes mellitus are not
Mild to moderate RDS can be managed with continuous contraindications. Careful monitoring and management
positive airway pressure (CPAP). CPAP is a non invasive of hypertension and hyperglycemia should be ensured]
modality of support where a continuous distending
Drug regimens
pressure (5-7 cm of water) is applied at nostril level to
keep the alveoli open in a spontaneously breathing baby. • Inj. Betamethasone 12 mg IM every 24 hours, 2 doses
(preferred)
This is an excellent modality of respiratory support which
• Inj. Dexamethasone 6 mg IM every 12 hours, 4 doses
minimizes lung injury and other complications such as
(only if betamethasone cannot be arranged)
air leak and sepsis. Preterm babies developing severe RDS
• Maximum effect is seen between 24 h and 7 days of
often require mechanical ventilation in form of synchro administration of antenatal steroids. However, benefits
nized intermittent mandatory ventilation (SIMV). Preterm still accrue beyond these time limits.
babies are at risk of lung injury by excessive pressure and
One should avoid multiple courses of antenatal steroids, if
high oxygen. High saturations of oxygen (above 95%) can the tvometi remain undelivered after the first course.
produce retinopathy of prematurity (ROP) which can
blind the infant.
RDS has generally a good prognosis if managed Meconium Aspiration Syndrome (MAS)
appropriately. Survival is as high as 90% in very low birth Meconium staining of liquor occur in 10-14% of
weight babies (<1500 g). In the absence of ventilatory pregnancies. Neonates born through meconium stained
support, most neonates with severe disease will die. liquor can aspirate the meconium into the lungs and
develop respiratory distress. This is known as meconium resulting in right to left shunt across the foramen ovale
aspiration syndrome (MAS). Aspiration of meconium can and/or ductus. The disease is more common in term and
occur in utero, during birth or immediately after birth. post-term babies and occurs as a result of persistent
Thin meconium can cause chemical pneumonitis. Thick hypoxia and acidosis. Hypoxia and hypercarbia cause
meconium aspiration can block the large and small airway pulmonary vasoconstriction. This increases pulmonary
causing areas of atelectasis and emphysema which can vascular pressure and results in right to left shunting.
progress to develop air leak syndromes like pneumo Common causes include asphyxia, respiratory distress
thorax. Presence of atelectasis and emphysema can cause due to MAS, RDS, diaphragmatic hernia, etc. Primary
ventilation perfusion mismatch in these babies that can pulmonary hypertension can also occur because of an
progress to respiratory failure. abnormal pulmonary vasculature secondary to chronic
intrauterine hypoxia.
Clinical Features and Course The neonate usually presents with severe respiratory
MAS usually occurs in term or post term babies and small distress and cyanosis. It is often difficult to differentiate
for dates babies. These babies usually develop respiratory PPHN from cyanotic congenital heart disease. Echo
distress in the first few hours of life, that often deteriorates cardiography helps in ruling out congenital heart disease
in next 24-48 hours. If untreated, distress can progress to and may demonstrate right to left shunt across the foramen
respiratory failure. Complications include pneumothorax, ovale.
other air leak syndromes (pneumopericardium, pneumo Ventilatory support is mandatory. Nitric oxide, a
mediastinum) and persistent pulmonary hypertension. pulmonary vasodilator, may help. Prognosis is poor even
Chest X-ray shows bilateral heterogeneous opacities, areas with ventilatory support.
of hyperexpansion and atelectesis and air leak (Fig. 7.36).
Pneumonia
Pneumonia is a common cause of respiratory distress in
both term and preterm babies and is caused by bacteria
such a E. coli, S. aureus and K. pneumoniae. Neonatal
pneumonia may be due to aspiration or occasionally due
to viral or fungal infection. Though group B streptococcal
pneumonia is common in the West, it is uncommon in
India.
The neonate has features suggestive of sepsis in addition
to respiratory distress. Chest X-ray shows pneumonia (Fig.
7.37), blood counts are raised and blood culture may be
positive. Treatment includes supportive care and specific
antibiotic therapy. Ampicillin or cloxacillin with genta
micin is usually used. If the pneumonia is due to hospital
acquired infection, antibiotics like cephalosporins with
Management
Clinical course in these babies can be complicated by
severe pulmonary hypertension, which is a difficult
condition to treat. IV fluids and oxygen are needed for
mild distress and ventilatory support for severe disease.
A good supportive care in terms of maintenance of normal
body temperature, blood glucose and calcium level,
ensuring analgesia and avoiding unnecessary fiddling
pays good dividends. With ventilatory support, 60-70%
neonates survive, but in the absence of ventilatory support,
mortality is high in severe disease.
amikacin may have to be used. Survival is 60-70%, if treated increased permeability causing leakage of water and
early with appropriate antibiotics. protein. In later stages there is fibrosis and cellular
hyperplasia. Severe lung damage leads to respiratory
Transient Tachypnea of Newborn (TTN) failure. These babies continue to require prolonged oxygen
Transient tachypnea of the newborn is a benign self- therapy.
limiting disease occurring usually in term neonates and
Pneumothorax
is due to delayed clearance of lung fluid. These babies
have tachypnea with minimal or no respiratory distress. Presence of air in the pleural cavity (pneumothorax) is
Chest X-ray may show hyperexpanded lung fields, most common in babies with meconium aspiration
prominent vascular marking and prominent interlobar syndrome and those being ventilated (Fig. 7.39). Transillu
fissure (Fig. 7.38). Oxygen treatment is often adequate. mination of the chest can help in diagnosis. Needle
Prognosis is excellent. aspiration or chest tube drainage is a life saving procedure
in this situation.
Surgical Problems
Tracheo-esophageal fistula (TEF) should be suspected in
any neonate with excessive frothing. Diagnosis can be
confirmed by a plain X-ray with a red rubber catheter (not
Fig. 7.39: Tension pneumothorax on right side displacing
infant feeding tube); the catheter generally stops at 10th mediastinum and pushing the diaphragm down
thoracic vertebrae in presence of TEF.
Diaphragmatic hernia should be suspected in any
neonates who has severe respiratory distress and has a Apnea
scaphoid abdomen. This condition can be detected during Apnea may be defined as cessation of respiration for 20
antenatal ultrasonography. Chest X-ray shows presence seconds with or without bradycardia and cyanosis or for
of bowel loops in the thoracic cavity. shorter periods if it is associated with cyanosis or
bradycardia. Apnea is a common problem in preterm
Chronic Lung Disease (CLD) or neonates. It could be central, obstructive or mixed.
Bronchopulmonary Dysplasia (BPD)
Apnea of prematurity occurs in preterm neonates
Diagnosis is suspected when a preterm neonate continues between the 2nd to 5th days of life and is because of the
to have respiratory distress and remains oxygen or immaturity of the developing brain. Central apnea can
ventilator dependent for a long time. Criteria for diagnosis also occur because of pathological causes like sepsis,
are oxygen requirement beyond 36 weeks post metabolic problems (hypoglycemia, hypocalcemia),
conceptional age or beyond 28 days of life. CLD occurs temperature instability, respiratory distress, anemia and
because of barotrauma and oxygen toxicity that causes polycythemia. Obstructive apnea can occur because of
damage to the alveolar cells, interstitium and blood block to the airway by secretion, improper positioning,
vessels. Inflammatory mediators are released and there is etc.
Newborn Infants 147
Treatment is supportive and involves correction of in the third week of life, which may persist into the 2nd to
underlying cause. Drugs used include aminophylline and 3rd month of life in a few babies. This increased frequency
caffeine. Prognosis is good in apnea of prematurity. In of jaundice in breastfed babies is not related to
other cases it depends on the underlying cause. characteristics of breast milk but rather to inadequate
breastfeeding (breastfeedingjaundice). Ensuring optimum
Suggested readings breastfeeding would help decrease this kind of jaundice.
1. Bhutani VK. Differential diagnosis of neonatal respiratory
disorders. In: Intensive of the Fetus and Neonate. Ed Spitzer AR. Breast Milk Jaundice
Mosby Year Book 1996; 494-505.
2. Greenough A, Roberton MRC. Respiratory distress syndrome. In:
Approximately 2-4% of exclusively breastfed term babies
Neonatal Respiratory Disorders. Eds Greenough A, Roberton NRC, have jaundice in excess of 10 mg/dL beyond third-fourth
Milner AD. Arnold 1996; 238-279. weeks of life. These babies should be investigated for
3. Singh M, Deorari AK. Pneumonia in newborn babies. Indian J prolonged jaundice. A diagnosis of breast milk jaundice
Pediatr 1995; 62: 293-306.
should be considered if this is unconjugated (not staining
nappies); and other causes for prolongation such as
JAUNDICE...................................................................................
continuing hemolysis, extravasated blood, G6PD defi
Jaundice is an important problem in the first week of life. ciency and hypothyroidism have been ruled out. Mothers
It is a cause of concern for the physician and a source of should be advised to continue breastfeeding at frequent
anxiety for the parents. High bilirubin levels may be toxic intervals and STB levels usually decline over a period of
to the developing central nervous system and may cause time. Some babies may require phototherapy. Breast
neurological impairment even in term newborns. Nearly feeding should not be stopped either for cessation or
60% of term newborn becomes visibly jaundiced in the treatment of breast milk jaundice.
first week of life. In most cases, it is benign and no
Clinical Quantification
intervention is required. Approximately 5-10 % of them
have clinically significant jaundice mandating the use of Originally described by Kramer, dermal staining of bili
phototherapy or other therapeutic options. rubin may be used as a clinical guide to the level of jaun
dice. Dermal staining in newborn progresses in a cephalo
Physiological Versus Pathological Jaundice caudal direction. The newborn should be examined in a
Physiological jaundice represents physiological imma good daylight. The skin of forehead, chest, abdomen,
turity of the neonates to handle increased bilirubin thighs, legs, palms and soles should be blanched with
production. Visible jaundice usually appears between 24- digital pressure and the underlying color of skin and
72 hours of age. Serum total bilirubin (STB) level usually subcutaneous tissue should be noted (Fig. 7.40). STB levels
peaks by 3 days of age and then falls in term neonates. are approximately 4-6 mg/dL (zone 1), 6-8 mg/dL (zone
STB levels are below the designated cut-offs for photo 2), 8-12 mg/dL (zone 3), 12-14 mg/dL (zone 4) and >15
therapy. It does not require any treatment. mg/dL (zone 5). In general, the estimation of STB levels
Pathological jaundice is referred to as an elevation of
STB levels to the extent where treatment of jaundice is
more likely to result into benefit than harm. There is no
clear cut demarcation between pathological and physio
logical jaundice. STB levels have been arbitrarily defined
as pathological if it exceeds 5 mg/dL on first day, 10 mg/
dL on second day, or 12-13 mg/dl thereafter in term
babies. Such jaundice warrants investigation for a cause
and therapeutic interventions such as phototherapy.
Appearance of jaundice within 24 hours, STB levels above
the expected normal range, presence of clinical jaundice
beyond 3 weeks and conjugated bilirubin (dark urine
staining the nappy) would be categorized under this
category.
Breastfeeding Jaundice
Exclusively breastfed infants have a different pattern of
physiological jaundice as compared to artificially-fed
babies. Jaundice in breast-fed babies usually appears
between 24-72 hours of age, peaks by 5-15 days of life
and disappears by the third week of life. One-third of all Fig. 7.40: Dermal zones for estimation of serum total bilirubin
breastfed babies are detected to have mild clinical jaundice levels
148 Essential Pediatrics
by dermal zones is unreliable particularly at higher STB Risk Factors for development of severe hyperbilirubinemia
levels, after phototherapy and when it is carried out by 1. Pre-discharge STB in the high-risk zone.
an inexperienced observer. STB can be assessed nonin- 2. Jaundice observed in the first 24 h.
vasively by a transcutaneous handheld device. Trans- 3. Blood group incompatibility with positive direct
cutaneous bilirubinometry is useful to identify antiglobulin test (DCT), other known hemolytic disease
significantly jaundiced neonates and helps decrease the (e.g. G6PD deficiency).
need for frequent lab estimation of STB. 4. Gestational age 35-36 weeks.
5. Previous sibling received phototherapy.
Measurement of Bilirubin Levels 6. Cephalohematoma or significant bruising.
Pathological Jaundice
Term and Near Term Neonates
The American Academy of Pediatrics (AAP) has laid down Fig. 7.41: Guidelines for phototherapy in hospitalized infants of 35
or more weeks’ gestation. Infants at lower risk (> 38 wk and well)
criteria for managing babies with elevated serum bilirubin.
— Infants at medium risk (> 38 wk + risk factors or 35-37 6/7wk and
Guidelines for phototherapy and exchange transfusion are
well) Infants at higher risk (35-37 6/7 wk + risk factors)
provided in Figs 7.41 and 7.42 respectively. Both the
figures have age in hours on the X-axis and STB levels on
Y-axis. There are three curves on each figure representing
three risk categories of babies defined by gestation and
other risk factors.
Preterm Neonates
Table 7.30 provides cut-offs for exchange transfusion and
phototherapy in preterm neonates below 35 weeks of
gestation.
Adapted from Halamek LP, Stevenson DK. Neonatal Jaundice. In Fanroff AA, Martin RJ (Eds): Neonatal Perinatal Medicine.
Diseases of the fetus and Infant. 7ed. St Louis, Mosby Year Book 2002. pp 1335.
1. Treatment decisions are based on serum total bilirubin (STB).
2. Gestation is more important than birth weight of the baby in deciding need for phototherapy or exchange transfusion. A
higher cutoff can be used for a small for date baby.
3. Postnatal age should also be considered when deciding for treatment. Jaundice appearing on first day of life is more likely to
need treatment than that appearing later.
4. Sick baby refers to presence of asphyxia, hypothermia, sepsis, acidosis, hypoxia, hypercapnia and evidence of hemolysis.
150 Essential Pediatrics
CONGENITAL MALFORMATIONS
stenosis or covered anus, anocutaneous fistulae are cerebrospinal fluid, nerve roots and a dysplastic spinal
common in both sexes. Anovestibular fistula (low lesion) cord. There is a distinct line of demarcation between the
in females and anorectal agenesis with rectoprostatic skin and the protruding membranous sac. In contrast,
urethral fistula (high lesion) are common in male infants. meningocele is covered with only skin. The covering
Among the males with high or intermediate lesions, cannot be demarcated into two different areas of skin and
80% are rectovesical fistulae, but among the females with meninges. There may be no associated neurological deficit,
high defect, 80% have a rectovaginal fistula. There are but Arnold-Chiari malformation and congenital hydro
significant chances of associated anomalies in case of cephalus are often associated. Severe motor and sensory
higher anorectal anomalies. deficit are common and urinary and fecal incontinence
An X-ray film of the abdomen is obtained 12-24 hours are usually present. Meningomyelocele is operated only
after birth, with the baby being kept in an inverted if there is no paralysis of lower limbs and if there is no
position. A lateral picture of the pelvis should be obtained bladder/bowel involvement.
to define whether the rectal pouch is above or below a
line drawn from the pubis to the coccyx. Abdominal ultra Cleft Lip and Cleft Palate
sound should be done to detect associated urinary tract Cleft lip is recognized readily (Fig. 7.45), but a careful
anomalies. Intravenous pyelogram and micturating cysto- inspection of the oral cavity is necessary to identify cleft
urethrogram should also be done to exclude palate. A cleft of the soft palate can be easily missed unless
vesiocoureteral reflux. Meconium may be passed from the baby is examined carefully. Ventricular septal defect
vagina and unless a careful examination of the perineum is a common associated anomaly with cleft palate.
is done, the diagnosis of anorectal anomaly may be missed In Pierre-Robin syndrome, cleft palate is associated with
in female infants. Urinary infection often supervenes in retracted jaw (micrognathia) and large tongue, with a
rectovesical fistulae. tendency for glossoptosis. In these cases, tongue should
Treatment is surgical. Prognosis is better with low be stabilized early in life by surgery to maintain an
defects. About 80 to 90% of patients become continents adequate airway. Feeding is difficult in cases of cleft palate.
after surgery for low defects. More than two-thirds of For the first few days, gavage feeding or spoon-feeding
patients are incontinent after surgery of high defects. may be done. Bottle feeding may be tried with a soft nipple
with rubber flange, which close the cleft and help the baby
Neural Tube Defects in sucking. If this is not successful, palatal prosthesis may
Anencephaly: Anencephaly is due to a defect in the be used. The baby should be kept under constant
development of neural axis and is not compatible with surveillance for maintaining nutrition and adequate
life. growth and development. These babies are prone to
Encephalocele: In encephalocele, the brain and/or its develop otitis media and should be carefully watched and
coverings herniate through a defect in the skull. treated as and when required. Despite successful repair
of cleft palate, residual speech defects may be present,
Congenital hydrocephalus: Congenital hydropcephalus is necessitating help of a speech therapist.
due to occlusion of aqueduct of sylvius or basal cisterns.
This usually follows intrauterine infections such as Management: Management of cleft palate requires a team
toxoplasmosis, rubella, cytomegalovirus and syphilis, but effort involving a pediatrician, a plastic surgeon,
may also be the result of a congenital malformation of the
aqueduct, Dandy-Walker syndrome (posterior fossa cyst
and a defect of cerebellar vermis), Arnold-Chiari
malformation (displacement of brainstem and cerebellum
in the spinal canal) or multiple congenital malformations
of the nervous system.
Diagnosis should be suspected if the head circum
ference increases rapidly (more than 1 cm in a fortnight
during the first three months). CT or MRI scan should be
done to confirm the diagnosis. The type of dilatation of
ventricles indicates the site of obstruction. Isolated
aqueductal stenosis has better prognosis.
Treatment should be directed at the specific cause if
amenable to therapy and surgical intervention such as
ventriculocaval or ventriculoperioneal shunt. Infection of
shunt is common.
orthodontist, ENT specialist and speech therapist. Cleft 1. To make a correct assessment of the baby.
lip is repaired in the neonatal period. Operation for cleft 2. To make sure that there is a genuine indication for
palate is generally deferred until the second year. referral. One should explain the condition and reasons
for transport to the family.
Diaphragmatic Hernia 3. One should correct hypothermia before transporting,
Diaphragmatic hernia occurs because of failure of closure since it may even worsen on the way.
of the pleuroperitoneal membrane. This allows intestinal 4. One should stabilize the baby as much as possible.
loops to ascend to the thorax that compress the developing 5. A precise note should be written providing details of
lung and can result in pulmonary hypoplasia (Fig. 7.46). the baby's condition, need for referral and treatment
These babies can present at any time after birth. At birth a given to the baby.
baby may be suspected to have diaphragmatic hernia if 6. The mother should be encouraged to accompany the
there is respiratory distress and a scaphoid abdomen. Bag baby. In case she cannot accompany immediately, she
and mask ventilation should be avoided in these babies. should be encouraged to reach the facility at the earliest.
Surgical repair after stabilization is the treatment of choice. 7. A doctor/nurse/dai/health worker should accompany
the baby, if feasible, to provide care en route.
8. One should ensure warmth on the way:
the accompanying members in this modality of care cognitive and motor functions are still evolving at 12
within minutes, months corrected age and the period of acquisition of
f. If intravenous fluids are being provided, one should developmental milestone is variable. Also, some neuro
make sure that the attendants know how many drops logic abnormalities that are identified in the first year of
of infusion are to be given every minute; they should life are transient or improve whereas findings in other
also be explained how to close the regulator to stop children may worsen over time. By 18-24 months correc
the infusion once the bottle empties. ted age the environmental factors begin to exert a stronger
10. One should take the baby to the nearest referral facility influence on test results, cognitive and motor abilities
(inform them in advance on phone or otherwise), by diverge, language and reasoning skills are developing and
the shortest route, using the fastest possible and there is improved prediction to early school age
affordable mode of transport. performance. Standard follow-up for many multicenter
networks is currently at 18-24 months corrected age. The
FOLLOW-UP OF HIGH RISK NEONATES correction for gestational immaturity at birth should be
done till 24 months age.
Improved perinatal and neonatal care has resulted in
improved survival of many sick and small neonates who
What should be Done at Follow-Up?
are at-risk for long-term morbidities such as growth
failure, developmental delay and visual/hearing 1. Assessment of feeding and dietary counseling: Parents
problems. A proper and appropriate follow-up program should be asked about the infants' diet and offered
would help in prevention, early detection and appropriate dietary counseling at each visit. Breastfeeding
management of these problems, thereby ensuring frequency and adequacy should be assessed. The
disability and morbidity free survival. amount, dilution and mode of feeding should be noted
if supplemental feeding is given. It is also important to
Who Needs Follow-Up Care? record the duration of exclusive breastfeeding. If a baby
Table 7.31 lists the cohort of high risk infants who require is not gaining adequate weight on exclusive breast
follow up services. feeding, take care of any illness or maternal problems
which may interfere with feeding and milk output. If
poor weight gain persists despite all measures to
Table 7.31: High risk neonates who need follow-up care improve breast milk output supplementation can be
1. Babies with <1800 g birth weight and/or gestation <35 considered. Complementary feeding should be started
weeks at 6 months corrected age. Initially, semisolids should
2. Small for date (<3rd centile) and large for date (>97th be advised in accordance with the local cultural
centile) practices.
3. Perinatal asphyxia-Apgar score 3 or less at 5 min and/
2. Growth monitoring: Growth (including weight, head
or hypoxic ischemic encephalopathy
circumference, mid-arm circumference and length)
4. Mechanical ventilation for more than 24 hours
5. Metabolic problems—symptomatic hypoglycemia and should be monitored and plotted on an appropriate
hypocalcemia growth chart at each visit.
6. Seizures 3. Developmental assessment: Assessment of developmental
7. Infections-meningitis and/or culture positive sepsis milestones should be done according to the corrected
8. Shock requiring inotropic/vasopressor support age. The milestones should be assessed in four domains
9. Infants born to HIV-positive mothers
—gross motor, fine motor, language, and personal-
10. Hyperbilirubinemia > 20 mg/dl or requirement of ex
social. Infants who lag behind in any domain should
change transfusion
undergo a formal developmental evaluation by a
11. Major malformations
clinical psychologist using tests such as Developmental
assessment of Indian Infant II (DASII II). Age appro
When to Follow Up priate stimulation should be provided to these babies.
The following should be the follow-up schedule: 4. Immunization: Immunization should be ensured
• 2 weeks after discharge according to chronological age. Parents should be
• At 6, 10, 14 weeks of postnatal age offered the option of using additional vaccines such as
• At 3, 6, 9,12 and 18 months of corrected age and then 6 Hemophilus influenzae B, typhoid, MMR.
monthly.
The influence of environmental factors on performance 5. Ongoing problems: Ongoing morbidities such as
is less at 12 months corrected age and biomedical issues diarrhea, pneumonia occur more frequently in these
such as oxygen supplementation for chronic lung disease babies and should require appropriate treatment.
have resolved. By 12 months corrected age the cognitive 6. Neurological assessment: Muscle tone should be assessed,
and language assessment can also be done. However, any asymmetry between the extremities should also be
Newborn Infants 155
of life and normal levels of serum calcium are regained EFFECT OF MATERNAL CONDITIONS
by day 3 of life. ON FETUS AND NEONATES
and opposing effects of human placental proactin, Hypothyroidism during pregnancy is not a significant
progesterone and cortisol. This is how latent diabetes in problem and treatment with replacement doses of thyroid
the mother may become apparent diabetes during hormone is usually well tolerated and easily titrated.
pregnancy. Excess maternal glucose and amino acids Hypothyroidism has occurred in fetus whose mothers
provide the substrate for increased synthesis of protein, have inadvertently received radioactive iodine during
lipids and glycogen in the fetus. Most part of the large pregnancy. There is currently no reliable method for
fetal size is due to the accumulation of fat. (Intrauterine diagnosing hypothyroidism in utero.
growth retardation observed in some infants of diabetic
mothers may be due to maternal placental vascular Maternal Immunologic Diseases
insufficiency).
Autoimmune diseases are characterized by an immune
The basic mechanism of hypoglycemia in these cases is
attack on tissues of the body in the apparent absence of
diminished production of glucose and increased removal
active infection. Symptoms arise from the resulting
by insulin. The cause of hypocalcemia is not clear but is
impairment of cell or organ function. The autoantibody
probably due to diminished production of parathormone.
mediated diseases can have direct consequences on the
Hypomagnesemia as seen in infants of the diabetic mother
fetus and neonate because the antibodies are usually of
may be due to increased losses of magnesium in the urine
the immunoglobulin G (IgG) type, which are transported
of diabetic mothers. Hyperbilirubinemia may be due to
across the placenta to the fetal circulation. Diseases in this
the breakdown of hemoglobin from collection of blood in
class include myasthenia gravis, Goodpasture syndrome,
cephalohematoma which is usual in the delivery of large
Graves' disease, antiphospholipid antibody syndrome
babies. Since insulin blocks induction of enzyme system,
(APS), immune thrombocytopenic purpura (ITP), and
this may explain lower production of surfactant. This
systemic lupus erythematosus (SLE).
along with higher risk of preterm deliveries explains
higher risk of respiratory distress syndrome. Increased APS is an autoimmune disease associated with
smooth muscles in pulmonary arteries may explain thrombophilia and recurrent pregnancy loss. Anti
persistent pulmonary hypertension. Infants of diabetic phospholipid antibodies and APS are usually seen in
mothers have one to nine percent incidence of diabetes in association with SLE and other rheumatic diseases.
later life. Vasculopathy, infarction, and thrombosis have been
identified in placentas from women who had failed
Hypertensive Disorder of Pregnancy pregnancies and APS. Treatment trials have focused on
immunomodulation (e.g. corticosteroids and intravenous
Hypertension during the pregnancy causes uterine
immune globulin [IVIG]) and anticoagulation (e.g. low-
vasculature remodeling and activation of rennin-
dose aspirin, heparin, low-molecular weight heparin).
angiotensin system. Preeclampsia-eclampsia is severe
form of pregnancy induced hypertension. The funda ITP in pregnant women usually induces moderate
mental abnormality recognized in preeclampsia-eclampsia thrombocytopenia in the fetus or the newborn. The
is uteroplacental ischemia. The following complications frequency of intracranial hemorrhage has been estimated
are likely to occur during pregnancy of a hypertensive to be about 1% and is less frequent in autoimmune
mother. thrombocytopenia than in neonatal allo-immune thrombo
1. Intrauterine growth retardation. cytopenia (10%). No significant correlation has been
2. Increased perinatal mortality. observed between neonatal thrombocytopenia and
3. Increased incidence of spontaneous and/or iatrogenic maternal platelet autoantibodies. The history of a previous
prematurity. infant who had thrombocytopenia is the only important
4. Respiratory depression of the fetus due to the use of factor in estimating the risk of fetal thrombocytopenia.
sedatives. After birth, thrombocytopenia in the neonate usually
worsens during the first days of life. Postnatal
Disorder of Thyroid Functions during Pregnancy management typically involves observation when the
Hyperthyroidism occurs in approximately 0.2% of platelet count is greater than 20 x 103/pL (20 x 10VL) in a
pregnancies and results in significant increase in the child who exhibits no clinical bleeding. For infants who
prevalence of low-birth-weight delivery and a trend have evidence of hemorrhage, single-donor irradiated
toward higher neonatal mortality. Most common cause platelets may be administered to control bleeding, even
of thyrotoxicosis (85% of cases) in women of child bearing though the platelet count may not show a sustained
age is Graves disease. Pathogenesis of Graves disease is increase. In addition, the infant may benefit from an
not fully understood but it probably represent an infusion of IVIG.
overlapping spectrum of disorders that are characterized Neonatal lupus erythematosus is a model of passively
by production of polyclonal antibodies. Measurement of acquired autoimmunity in which immune abnormalities
thyroid-stimulating antibodies (TSAbs) is useful in in the mother lead to the production of anti-SSA/Ro-SSB/
predicting whether the fetus will be affected. La antibodies that cross the placenta and presumably
158 Essential Pediatrics
injure fetal tissue. The most serious manifestation is Table 7.33: Maternal disorders and possible adverse
damage to the cardiac conducting system that results in effects on the fetus
congenital heart block (CHB), which is usually third
degree. No serologic profile is unique to mothers of
affected children, but compared with mothers of healthy
children, anti-SSA/Ro antibodies are usually of high titer.
For the fetus in whom a block is identified, there are
several guidelines for treatment, but no definitive app
roach. If the fetus has been in complete block for more
than 3 weeks and there is no sign of myocardial dysfunc
tion or hydrops, it might be prudent to monitor with
frequent echocardiograms and not institute any medi
cation. For incomplete blocks, very recently identified
blocks, or complete blocks associated with dysfunction
or hydrops, 4 mg daily of maternal dexamethasone is a
reasonable consideration. Children (affected or unaffec
ted) whose mothers have anti-SSA/Ro or SSB/La anti
bodies do not appear to have an increased risk of develop
ing systemic rheumatic diseases during adolescence and
early adulthood.
should be minimized. The benefits of medication to the Drugs listed in Table 7.35 are known to be or suspected
mother must always be carefully weighed against the risk to be teratogenic when given during the first trimester of
to the fetus. pregnancy.
8 Immunity and Immunization
The word 'immunity' (Latin immunis) means the state of monocyte-macrophage and neutrophil activities by
protection from infectious disease. The immune system inducing their adherence to vascular endothelial cells,
has evolved as defence system to protect animals from extravasation and chemotaxis at the site of inflammation.
invading microorganisms and malignant disorders. It first Activation of the classical pathway results in low levels
recognizes a microorganism or any other foreign material, of C4, C2 and C3; activation of alternative pathway is
discriminates it from self, and then mounts an appropriate characterized by reduced levels of C3 and normal levels
response to eliminate it. Two broad categories of immune of C4 and C2.
system act in concert to eliminate microorganisms: innate Cellular components of the innate immune system
immune system and adaptive immune system. The former comprise of mononuclear phagocytic cells (polymor
is primitive, non-specific, has no memory and provides phonuclear leukocytes, macrophages and NK cells). They
the first line of defense against infections. The adaptive ingest extracellular material by phagocytosis, which fuses
immune system is highly evolved, specific and has with the lysosomes, forming phagolysosomes. Activation
memory characterized by a rapid rise in immune response of myeloperoxidase in phagolysosomes results in
that serves to eliminate the microorganism. production of superoxide that oxidizes and inactivates
microbial proteins. In the presence of chlorine, superoxide
INNATE IMMUNE SYSTEM forms another toxic compound, hypochlorous acid.
160
Immunity and Immunization 161
infections, while those with deficiency of the later consequential airway compromise. Therapy with
components (C5-C9) have predilection for Neisserial adrenaline and hydrocortisone is usually of no benefit.
infections. Systemic lupus erythematosus may occur in
individuals with C2/C4 deficiency. A deficiency of the Intravenous Immunoglobulin
Cl esterase inhibitor is associated with hereditary Intravenous immunoglobulin (IVIG) is pooled normal
angioneurotic edema, characterized by sudden appear intact polyspecific IgG derived from the plasma of healthy
ance of recurrent swellings in the body. donors who have been subjected to strict screening
procedures. Each batch of IVIG represents a donor pool
Miscellaneous
of 4000-8000 individuals such that the repertoire of
Hyper IgE Syndrome antibodies is representative of the population at large.
This is characterized by recurrent 'cold' staphylococcal Most IVIG preparations contain 90% monomeric IgG with
abscesses (involving the skin, joints and lungs) and only small amounts of IgA and IgM. Ideally, the IgG
markedly elevated serum IgE concentrations (usually subclass distribution of IVIG should be the same as in nor
mal plasma, but this is dependent on the manufacturing
>2000 IU/ml). Inheritance is variable; an autosomal
process. For instance, some IVIG preparations do not
dominant pattern is sometimes seen.
contain the IgG3 subclass in adequate quantities.
Mannan Binding Lectin Deficiency IVIG is the treatment of choice for Kawasaki disease,
This is a dominantly inherited, relatively common disorder autoimmune demyelinating polyradiculoneuropathy and
characterized by recurrent respiratory infections in early idiopathic thrombocytopenic purpura. The dose is 2 g/
kg given as single or divided infusions. In idiopathic
childhood; the degree of immunodeficiency is never
thrombocytopenic purpura, however, much lower doses
profound. Most patients remain asymptomatic throughout
have also been found to be equally effective.
life.
IVIG is also used as replacement therapy in various
TREATMENT OF PRIMARY forms of hypogammaglobulinemia. The recommended
IMMUNODEFICIENCY DISORDERS dose is 0.4-0.6 g/kg every 3^ weeks. Its use can also be
considered in selected cases of severe myasthenia gravis,
Bone marrow transplantation is the treatment of choice autoimmune neutropenia, neonatal alloimmune and
for most forms of significant cellular immunodeficiency autoimmune thrombocytopenia, lupus crisis, dermato-
(e.g. SCID, Wiskott Aldrich syndrome, hyper IgM myositis not responding to conventional steroid therapy
syndrome). For it to succeed, the procedure should be and certain vasculitides. IVIG has been used for
done in early infancy. However, it cannot be done in prophylaxis and treatment of neonatal sepsis in low birth
children with ataxia-telengiectasia. Children with X-linked weight babies but the results are equivocal. Use of IVIG
agamma-globulinemia and common variable immuno for treatment of sepsis in older children is even more
deficiency need to be administered 3-4 weekly injections controversial.
of IV immunoglobulin (IVIG). This treatment is very Administration of IVIG can be associated with several
expensive but it can result in an almost normal lifespan. side effects. The infusion must be started very slowly
While children with IgA deficiency usually do not require (initially a drop per minute) and the child monitored for
any specific therapy, those with IgG2 subclass deficiency allergic reactions, which may include anaphylaxis. The
may require monthly replacement IVIG therapy. Prophy infusion rate can be slowed, or even discontinued, if the
lactic therapy with antimicrobials (usually cotrimoxazole) child develops chills or rigors. Long term risks include
is required for some children with IgGl and IgG3 those of transfusion transmitted infections. The risk of
deficiency. acute renal failure is negligible with current iso-osmolar
Long-term cotrimoxazole and itraconazole prophylaxis preparations.
has greatly improved the management of chronic
granulomatous disease. Interferon gamma is also an Suggested reading
important, albeit expensive, modality of treatment for this 1. Ochs HD, Smith CIE, Puck JM. Primary immunodeficiency dis
condition. In some children with CGD, bone marrow eases: A molecular and genetic approach. Oxford University Press,
London, 1999.
transplantation may be required. While there is no specific
2. Singh S, Bansal A. Transient hypogammaglobulinemia of infancy:
therapy for complement deficiencies, infusion of plasma twelve years' experience from Northern India. Ped Asthma All
may be used in life threatening situations. For Cl esterase Immunol 2005; 18: 77-81.
inhibitor deficiency, prophylactic danazol or stanozolol 3. Parslow TG, Sittes DP, Terr Al, Imboden JB. Medical Immunol
ogy, 10th edn. New York: Lange Medical Books. 2001.
therapy results in significant improvement, but injections
4. Burnouf T, Radosevich M. Reducing the risk of infection from
of synthetic Cl esterase inhibitor may be required plasma products: specific preventative strategies. Blood Rev 2000;
whenever there is laryngeal involvement and 14: 94-110.
164 Essential Pediatrics
adjuvants in the diphtheria pertussis tetanus (DPT) With live vaccines, usually a single dose is sufficient to
vaccine. induce immunity; OPV is an exception where multiple
If a large number of susceptible individuals are doses are required because infection of intestinal mucosa
simultaneously protected from a particular infectious is required. Storage and transportation conditions are
disease by immunization at the same point of time, the critical to the potency of live vaccines.
transmission chain of the infectious agent can be broken,
thus decreasing the risk of disease in the unimmunized Killed Vaccines
children as well. This is called the herd effect of The chief advantage with killed vaccines is the stability of
immunization. Vaccines that protect only against disease these vaccines. However, the immunity induced is usually
(e.g. diphtheria) have a lower herd effect than vaccines not permanent and multiple doses, including booster
that protect against both disease and infection (e.g. measles doses, are required to ensure prolonged protection. Most
and OPV). Vaccines that have low protective efficacy (e.g. killed bacterial and some killed viral vaccines (like
pertussis and typhoid) will similarly have no significant influenza) are associated with significant local and
herd effect. The herd effect is utilized as one of the systemic reactions.
strategies for eradication of poliovirus, and may be used
to interrupt transmission in measles epidemics. Toxoids
Toxoids are modified toxins that, if well purified, are non
TYPES OF VACCINES toxic to the recipient. Primary immunization is in form of
Vaccines may consist of live attenuated organism, killed multiple divided doses in order to decrease the adverse
or inactivated organism, modified toxins or toxoids, or effects at each administration, and to provide high
subunits of antigens. Some examples of each of these are antibody titres that occur with repeated exposure to the
same antigen. Booster doses are required to sustain the
listed in Table 8.3.
protection.
Live Vaccines
Subunit Vaccines
These vaccines actually infect the recipient but do not
cause disease because the potency of the organism has Other non replicating antigens include capsular
been attenuated. If residual maternal antibody is present polysaccharide and viral or bacterial subunits. Capsular
in the infant's serum, it may neutralize the organism before polysaccharides are carbohydrate antigens that elicit
infection occurs, thus interrupting the "take" of a vaccine; humoral response by stimulating B cells directly, without
hence, vaccines like measles and measles, mumps, rubella modulation by helper T cells. Hence, there is no
(MMR) are administered beyond 9 months of age. BCG immunological memory, and the antibodies produced are
and oral poliovirus vaccine (OPV) are exceptions as the of the IgM class alone, rather than an IgG response.
maternally derived immunity does not interfere with the
PRINCIPLES OF IMMUNIZATION
vaccine "take". There is no interference with response to
BCG because it induces cell mediated immunity which is A good vaccine is one that is easy to administer, induces
not transferred from mother to fetus; hence, it may be permanent immunity, is free of toxic substances, has
given shortly after birth. OPV infects the gut mucosa and minimal side effects, is easy to produce and is stable at
residual maternal antibody does not interrupt this different environmental conditions. The choice of a vaccine
infection. for any immunization program depends on the utility or
necessity in terms of prevalence and severity of disease it hepatitis A and typhoid are stored in the middle racks;
helps prevent, efficacy, and safety profile. The timing of while hepatitis B, varicella and diluents are stored in the
administration depends on the age at which the disease is lower racks.
anticipated and feasibility. Basic principles of immuni
zation are listed in Table 8.4. BCG VACCINE
VACCINE STORAGE AND COLD CHAIN The Bacillus Calmette Guerin (BCG) vaccine continues to
be the only effective vaccine against tuberculosis.
The potency of a vaccine is maintained by cold chain, Currently several strains are in use; the common ones
which refers to the proper system of transporting, storing, include Copenhagen (Danish 1331) and Pasteur. The
and distributing vaccines at the recommended tempera Danish 1331 strain was being produced in India at Guindy,
tures from the point of manufacture to the point at which Tamil Nadu till recently.
they are administered. Maintenance of appropriate The protective efficacy of the BCG vaccine is variable.
temperature is critical to the viability and potency of a Its efficacy against severe forms of tuberculosis like miliary
vaccine. While BCG, OPV and measles are very sensitive tuberculosis and tubercular meningitis is about 50-80%,
to heat and can be frozen without harm, vaccines like but protection against development of pulmonary
tetanus toxoid are less sensitive to heat and may in fact be tuberculosis is less than 50%. BCG does not protect against
damaged by freezing. Other vaccines that must not be other mycobacterial diseases like leprosy. BCG induces
frozen include DT, DPT, Td, hepatitis B, hepatitis A, primarily cell mediated immunity, and there is no
Hemophilus influenza b, and whole cell killed typhoid interference by maternal antibody. It is usually adminis
vaccine. In the refrigerator, OPV vials are stored in the tered at or soon after birth to provide early protection and
freezer compartment (0 to -4°C). In the main compartment to utilize the opportunity of the infant being available;
(4-10°C) BCG, measles and MMR are kept in the top rack some believe that the adverse events are also less frequent
(below the freezer); other vaccines like DPT, DT, TT, in neonatal period.
Immunity and Immunization 167
The vaccine is supplied in the form of a lyophilized or Once administered, the vaccine viruses reach the
freeze dried powder, in a vacuum-sealed dark-colored intestines where they must establish an infection of the
multidose vial. The vaccine is reconstituted with sterile mucosal cells to elicit an immune response; this is termed
normal saline. Any unused vaccine must be discarded the "take" of the vaccine virus. Theoretically, one dose
after 4 hours, otherwise bacterial contamination may should suffice, but due to various reasons like inter
occur. The vaccine is extremely sensitive to light and heat. ruptions in the cold chain, interference due to intestinal
The cold chain should be maintained at all points in transit. infection with other enteroviruses, or the presence of
In the lyophilized form the vaccine remains potent for up diarrhea that causes excretion of the virus before it can
to a year at 2-8°C, but the potency drops rapidly after attach to the mucosal cells, 'take' rates may be variable
reconstitution. and several doses may be required. Seroconversion rates
Each dose of the vaccine contains 0.1 to 0.4 million live after 3 doses of OPV are 73%, 90% and 70% for serotypes
viable bacilli. The recommended volume is 0.1 ml at all 1,2 and 3. Hence the number of doses should be increased
ages. Conventionally, the vaccine is administered on the to decrease the frequency of vaccine failure. For this reason
convex aspect of the left shoulder at the insertion of the the IAP recommends five doses in infancy and two booster
deltoid, to allow for easy identification of the BCG scar. doses at 15-18 months and again at 5 years. The first dose
The intradermal route should be used to raise a wheal of OPV may be administered to the neonate, three doses
about 5 mm. Subcutaneous administrations may cause are given 4 weeks apart along with DPT at 6, 10 and 14
lymphadenopathy. At the injection site, BCG bacilli weeks, and the opportunity for measles immunization at
multiply and form a papule at about 2-3 weeks, which 9 months can be utilized for OPV administration, too. In
enlarges to 4-8 mm size at 5-6 weeks; this papule ulcerates addition to the routine OPV doses, "pulse polio" doses
and then heals by scarring at around 6-12 weeks. Adverse on every National Immunization Day (NID) and sub-
effects include persistent ulcer with delayed healing, National Immunisation Day (sNID) until the age of 5 years
ipsilateral axillary or cervical lymphadenopathy, and are also mandatory.
rarely, abscess and sinus formation. Children with severe Where poliovirus circulation is intensive, paralytic
deficiencies in cellular immunity may develop dissemi poliomyelitis is a disease almost exclusively seen in infants
nated BCG disease. Majority of children will show a and children, and adults are immune. Simultaneous
positive reaction to tuberculin test 4 to 12 weeks after administration of OPV to all susceptible infants and
immunization. children interferes with the circulation of the wild polio
Children who are tuberculin positive have an accele virus in the community. In order that no wild poliovirus
rated and enhanced response to BCG administration, and remains in circulation, NIDs are organized each year for
this 'BCG" test has been used by some as a diagnostic test this purpose. Organization of such mass campaigns is one
for tuberculosis. Although it is considered more sensitive of the 4 key strategies for eradication of polio; the others
than tuberculin test, it is associated with the risk of severe are maintaining high routine infant immunization
reactions like ulceration, and is used rarely. coverage with OPV, organization of mop-up campaigns in
event of an outbreak, and maintaining a sensitive system
of surveillance for acute flaccid paralysis (AFP).
POLIOMYELITIS VACCINES
The vaccine contains magnesium chloride as a
Two types of vaccines are available worldwide for preven stabilizing agent, and is therefore stable for 3-4 months at
tion of poliomyelitis, the live attenuated oral poliovirus 4-8°C and for 1-2 years at -20°C; the potency is decreased
vaccine (OPV) developed by Salk and the inactivated or with temperature fluctuations, especially to above 8°C.
killed poliovirus vaccine (IPV) developed by Sabin. Both Vaccine potency can be effectively monitored with the
vaccines are available as trivalent preparations containing vaccine vial monitor (VVM), displayed on the label of the
the three types of poliovirus, and both, when used as vial.
recommended, provide good protection from paralytic Breastfeeding and mild diarrhea are not contra
poliomyelitis as well as control of the disease in the indications for the administration of OPV. OPV is an
community. excellent vaccine and is the vaccine of choice for the
eradication of poliovirus in developing countries like
Oral Polio Vaccine (OPV)
India, where it should continue to be used till wild
The OPV is a suspension of over 105-106 median cell poliovirus circulation ceases. However, OPV (especially
culture infectious doses of the attenuated poliovirus types the type 2 strain) is associated with the risk of vaccine
1,2 and 3 in each liquid dose, which is two drops in India, associated paralytic poliomyelitis (VAPP), which occurs
and 0.5 ml in some countries like the USA. OPV has also in 1 in a few million vaccines, resulting in 250-800 cases
been formulated as a monovalent vaccine (mOPV). The every year globally. The emergence of outbreaks caused
mOPV type 1 vaccine has been used in India for the first by vaccine-derived virus is a relatively recent pheno
time in specific areas where surveillance showed PI wild menon, and has been seen in the Dominican Republic,
virus transmission in 2005. Egypt, Haiti, Madagascar and the Philippines. It is a virus
168 Essential Pediatrics
that has mutated from the original Sabin strain by more do not give immunization with OPV due to fear of side
than 1% and reverted to neurovirulence. Two types of effects and neither give IPV due to non-affordability. The
vaccine-derived poliovirus (VDPV) have been recognized: advantage of combining use of IPV and OPV is that the
iVDPV (i for immunodeficient), which is isolated from risk of VAPP is extremely low as the child receives OPV
immunodeficient individuals and cVDPV (c for circula at the time when he/she is protected against VAPP by
ting), which is isolated from outbreaks and has similar maternal antibodies, and subsequently, he/she is
epidemiological and biological characteristics as the wild protected from VAPP by IPV. An all IPV schedule would
viruses. keep the child at a small risk for VAPP through exposure
to the OPV virus through contacts/ environment before
Inactivated Polio Vaccine (IPV) he/ she receives his/her first dose of IPV. Hence, the
IPV is a suspension of formaldehyde killed and purified combined OPV and IPV schedule strives to provide the
poliovirus grown in monkey kidney or human diploid cell best protection to an individual child while not deviating
culture. The potency is measured by 'D' antigen content. from the national immunization policies.
Currently used IPV vaccines have enhanced potency IAP recommends that the birth dose of OPV and all
compared to previously used IPVs, and contain 40D, 8D doses on the NIDs be given to the child. Hence, a child
and 32D units of the types 1, 2 and 3 polioviruses should receive OPV at birth, OPV and IPV at 6,10 and 14
respectively. The vaccine is highly immunogenic; it weeks, OPV and IPV at 15-18 months, OPV at 5 years,
produces excellent humoral immunity, and also induces and OPV on all NID's and SNID's. A child less than 5
local pharyngeal and, possibly, intestinal immunity as years of age who has completed primary immunization
well. Seroconversion is seen in 90-95% cases when 2 doses with OPV may be offered IPV as catch up vaccination as
of the vaccine are given 2 months apart beyond 2 months three doses; 2 doses at 2 month interval followed by a third
age, while 3 doses, given beyond 6 weeks age and only 4 dose 6 months after the first dose. OPV need not be given
weeks apart, are associated with seroconversion in 99% with these IPV doses, but should be given with the first
cases. Hence the vaccine can be given in 3 doses along and 2nd boosters of DTP and on all NID's and SNID's.
with DTP beginning at 6 weeks age, without decrease in IPV is the vaccine of choice in patients with immuno
seroconversion or increase in side effects. Since IPV deficiency including symptomatic HIV, and in siblings and
induces only low levels of immunity (via secretary IgA) close contacts of such patients; OPV should be avoided
in the gut, IPV is less reliable in control of spread of wild especially in patients with B cell immunodeficiency. The
virus. However, observations from use of the vaccine in primary immunization and first IPV booster are as
the USA and other developed countries indicate that IPV discussed above; a second booster dose of IPV at 5 years
has excellent herd effect. IPV is also very safe. The vaccine is also recommended. Once poliovirus eradication is
is administered intramuscularly in 0.5 ml volume, singly achieved, the country should switch to IPV usage and OPV
or as a combination (available with DTaP/ Hib in India). use should be discontinued.
The recommendations of the polio eradication commit
tee of the Indian Academy of pediatrics (IAP) highlight DIPHTHERIA VACCINE
the potential utility of IPV in two key areas; firstly, to curb
Natural immunity to diphtheria is often acquired through
wild virus transmission in UP and Bihar, and secondly,
apparent or inapparent infections. However, even
to switch to IPV DPT combination in polio free states in
apparent infections may not confer protection against
preparation for the post polio eradication era.
subsequent infections. Maternal antibodies protect the
IAPCOI had previously recommended use of IPV in infant against disease and also interfere with immune
conjunction with OPV in children after one to one response to vaccination for several weeks after birth.
discussion with parents; IAPCOI now recommends Hence vaccination beginning some weeks after birth is
offering additional use of IPV with OPV in all children required, in multiple doses to ensure protection. Diph
who can afford the vaccine. Recommending wider use of theria antitoxin titre of >0.1 IU/ml is said to be associated
IPV is in view of the excellent immunogenicity, efficacy with protection from disease.
and safety of IPV and the inevitability of switch to IPV in Diphtheria vaccine is a toxoid vaccine, containing the
the post polio eradication era. The IAPCOI recommends diphtheria toxin (DT) that has been modified and adsorbed
continued use of OPV in concordance with the govern onto aluminium hydroxide, which acts as an adjuvant. It
ment policy of using OPV for polio eradication, evidence has been in use for about six decades as a combination
to suggest that mucosal immunity (as measured by stool vaccine with tetanus toxoid (TT) and whole cell killed per
excretion of virus after monovalent OPV1 challenge) is tussis vaccine as DTPw. The quantity of toxoid contained
superior with combination of OPV and IPV as compared in a vaccine is expressed as its limit of flocculation (Lf)
to IPV alone, and to avoid confusion in the minds of content. Each dose of the vaccine contains 20-30 Lf of DT,
parents whose children receive only IPV about the efficacy 5-25 Lf of TT and >4 IU of whole cell pertussis in 0.5 mL
and safety of OPV. The latter may adversely influence the volume. The vaccine should be stored at 2-8°C. It is
turn-up for OPV on NID's; there might be individuals who administered intramuscularly in the anterolateral thigh.
Immunity and Immunization 169
Common adverse effects include fever, local pain and include immediate anaphylaxis, or the development of
induration; rarely, incessant crying and encephalopathy encephalopathy lasting >24 hours within 7 days of
are seen. All adverse effects are related chiefly to the vaccination. If a child develops persistent inconsolable
pertussis component. crying lasting more than 3 hours, hypotensive-hypo-
Primary immunization requires 3 doses to be given resposive episode, or hyperpyrexia (temperature > 40.5°C)
4-8 weeks apart; in our country this is carried out at 6,10 within 48 hours of DTPw administration, or febrile or
and 14 weeks. After 3 doses, antitoxin response to DT and afebrile seizures within 72 hours of DTPw administration,
TT is seen in over 95%, but protective efficacy against parents should be counseled about risk of recurrence of
pertussis is lower at about 70-90%. Immunization does these adverse events with further doses of the vaccine. If
not eliminate Corynebacterium diphtheritic from the skin or such an event recurs after a subsequent dose, the vaccine
nasopharynx. is contraindicated in the future.
Booster doses of DTP are required to achieve a protec DT contains the same doses of diphtheria and tetanus
tive antibody titer of 0.1 IU/ml which confers protection toxoids as DTP, but is devoid of the pertussis component.
against diphtheria in the first decade of life. Immunity It is indicated for immunization of individuals with a
following primary immunization with DTP or one booster known contraindication to DTP, such as progressive
wanes over the next 6-12 years. IAPCOI recommends a neurological disease or encephalopathy lasting more than
total of 5 doses of DTP vaccine; three in infancy as part of 24 hours within 7 days of administration of DTP
primary immunization and two booster doses at 18 previously. It is recommended for use up to the age of 7
months and 5 years. If given beyond 7 years of age, years, beyond which Td must be used, as described below.
primary immunization or booster doses should be in the
form of Td or Tdap, which contains smaller amounts of Acellular Pertussis Vaccine (DTPa)
diphtheria toxoid (2 Lf) and acellular pertussis vaccine. The suspicion that the active pertussis toxin and endotoxin
are responsible for the high incidence of adverse events
PERTUSSIS VACCINE associated with DTPw administration led to the develop
Pertussis is an important cause of childhood morbidity ment of various types of purified acellular pertusssis
and mortality in children and remains endemic all over vaccine DTPa. The available DTPa vaccines contain
the world despite routine childhood immunization, inactivated pertussis toxin (PT) and one or more additional
affecting principally infants and, to a lesser extent, pertussis antigens, like filamentous hemagglutinin (FHA),
adolescents. Natural infections as well as immunization pertactin, fimbrial protein and a non-fimbrial protein.
induce immunity that lasts up to 10 years, necessitating Trials have demonstrated that these vaccines have similar
revaccination for continued protection. efficacy compared to DTPw vaccine, but are associated
The vaccine has been traditionally available as DTPw with significantly fewer systemic and local side effects.
or "triple antigen", as described above. For primary The PT component of these vaccines is > 4 IU (10-25 mg),
immunization, three doses of the vaccine are administered while the DT content is between 6.7-25 Lf in each 0.5 ml
at 6,10 and 14 weeks. However, the protective efficacy of dose.
pertussis vaccine is only 70-90%, even after three doses. The vaccine is not recommended for routine use in our
Immunity following primary immunization or booster country because of the high cost; the IAPCOI endorses
dose of pertussis vaccine wanes over next 6-12 years, the continued use of the DTPw in the National Program
making re-immunization essential for continued in India in view of its proven efficacy. The DTPa may be
production. administered to children when parents opt for it in view
The local (pain and redness) and systemic (fever) of the advantage of fewer side effects, or are reluctant to
reactions commonly seen with DTPw is chiefly because the administration of further doses of DTPw after an
of the pertussis component. The incidence of these adverse adverse effect with a previous dose. DTPa is absolutely
effects increases with the number of doses administered, contraindicated if a previous dose of DTPw or DTPa was
hence the vaccine is not used beyond 5 doses, and beyond associated with immediate anaphylaxis, or the develop
7 years of age. DTPw has also been rarely incriminated in ment of encephalopathy lasting >24 hours within 7 days
the induction of serious neurological complications, of vaccination. In case of anaphylaxis, all vaccines contain
though no conclusive evidence is available. No causal ing any of the three components of the vaccine are to be
relationship has been demonstrated between the adminis avoided in the future. Children who develop encephalo
tration of the vaccine and development of chronic pathy should receive DT instead of DTPw or DTPa.
neurological disease. The vaccine is relatively contrain
dicated in children with progressive neurological disease,
Reduced Antigen Acellular Pertussis Vaccine
but children with stable neurological diseases like
(Tdap) and Reduced Antigen Diphtheria Toxoid
Vaccine (Td)
developmental delay, cerebral palsy and idiopathic
epilepsy may be vaccinated. Absolute contraindications Both natural infection with pertussis and routine
to the administration of further doses of the vaccine immunization in infancy induce an immunity that wanes
170 Essential Pediatrics
by adolescence. This results in a second peak of the disease of Tdap followed by two doses of Td at 0,1 and 6 months.
associated morbidity in adolescence. Pertussis control is The IAPCOI recommends the use of DTPw or DTPa, and
unlikely to be achieved if adolescents and adults are not not Tdap, as second booster in children below 7 years of
protected against the disease, because they are the source age. Td may be used whenever TT is indicated in children
of infection to susceptible individuals. The availability of above 7 years of age.
Tdap offers the prospect of reducing disease burden in
the community. The rationale for its use is that the reduced TETANUS VACCINE
antigen content causes less severe adverse effects while
being sufficient to induce protective response in a In many developing countries including ours, neonatal
previously immunized individual (booster effect). tetanus remains an important cause of neonatal mortality.
Immunity against diphtheria wanes with time, too, and Using two dose tetanus toxoid (TT) to immunize pregnant
the only effective way to control the disease is through women or women of child bearing age is an important
immunization throughout life to provide constant strategy to reduce the incidence of this disease, because
protective antitoxin levels. While standard dose DT is IgG antibodies are passively transferred across the
recommended for primary immunization against diphthe placenta to the fetus and protect the newborn. The last
ria because of its superior immunogenicity and minimal dose of TT should have been received at least 2 weeks
reactogenicity, the adult preparation Td (or dT) containing prior to delivery. This constitutes passive immunization
a lower content of the toxoid is recommended in for the child. Since tetanus can occur at any age, primary
individuals 7 years of age or older, because it is adequately immunization is essential, for which three doses of the
immunogenic and reactogenicity is known to increase with vaccine (as DPT) are given one month apart. Boosters are
age. given at 18 months and at 5, 10 and 16 years of age. The
The available Tdap vaccine in India contains tetanus efficacy of TT vaccine varies between 80-100%. Tetanus
toxoid 5 Lf, diphtheria toxoid 2 Lf and three acellular antitoxin level of 0.01 IU/mL is considered the minimum
pertussis components namely, pertussis toxoid 8 pg, protective level in animals; in humans, the level of anti
filamentous hemagglutinin 8 pg and pertactin 2.5 pg. Td toxin required depends on the toxin load. For previously
contains 5 Lf of tetanus toxoid and 2 Lf of diphtheria unimmunized school children, 2 doses of TT given 1
toxoid. The reduced antigen diphtheria toxoid vaccine (Td) month are sufficient. TT should not be administered after
contains diphtheria toxoid 2 Lf and tetanus toxoid 5 Lf.
every injury if immunization is complete and last dose is
The contraindications to Tdap are serious allergic reaction
received within last 10 years. For previously immunized
to any component of the vaccine or history of encephalo
pregnant women, 1 dose of TT is sufficient if the second
pathy not attributable to an underlying cause within 7 days
pregnancy within the next 5 years, but would need to be
of administration of a vaccine with pertussis component.
administered 2 doses if the interval exceeds 5 years.
Td is not associated with significant adverse effects.
Tetanus toxin, which is highly toxic, is inactivated by
Tdap should be administered as a single dose at the
age of 10-12 years. The single booster dose of Tdap may formalin to make tetanus toxoid (TT), and adsorbed onto
be followed by Td boosters every 10 years. There is no aluminium salts to enhance its immunogenicity. TT
data at present to support repeat doses of Tdap. Tdap may vaccine contains 5 Lf of the toxoid. It is a heat stable vaccine
also be used as replacement for Td/TT booster in children that remains potent for a few weeks even at 37°C. Tetanus
above 10 years and adults of any age if they have not toxoid is administered with diphtheria toxoid and
received Tdap in the past and 5 years have elapsed since pertussis killed vaccine as a combination called DPT; DT,
the receipt of previous TT/Td vaccine. If less than 5 years Td and TT are also available.
have elapsed since Tdap administration, TT is not required Recommendations for routine tetanus prophylaxis in
for wound prophylaxis. Tdap is also used for primary wound management and indications of tetanus immuno
immunization of children above 7 years, using one dose globulin (TIG) are listed in Table 8.5.
For children < 7 years DTPw or DTPa may be given while TT or Td may be used in older children.
*TIG: Tetanus immunoglobulin (250 IU i/m)
**Yes if > 10 years since last dose
’’’Yes if > 5 years since last dose
Immunity and Immunization 171
incorporation of HB vaccine in the National Immunization in a dose of 0.5 mL in newborns, and 0.06 mL (32-48 IU)
Schedule in a phased manner. per kilogram body weight for all other ages. Following
The current HBV vaccine is a highly purified vaccine exposure, HBIG should be administered as soon as
produced by recombinant DNA techniques in yeast possible, preferably within 48 hours.
species. It contains aluminium salts as adjuvant. The
vaccine should be stored at 2-8°C and should not be RABIES VACCINE
frozen. The vaccine is administered intramuscularly in Rabies is endemic in India and 50% of the deaths
anterolateral thigh in children and in deltoid in adults. attributable to this disease occur in our country. Currently
The dose is 0.5 mL, containing 10 pg of antigenic three types of vaccines are available against the virus.
component, in children upto 19 years of age and 1 mL (20 Nerve tissue vaccines are no longer recommended because
pg) in older persons. It is recommended that the dose be of poor efficacy and high incidence of serious adverse
doubled in patients on hemodialysis, immunocompro effects, like neuroparalytic reactions. The purified duck
mised individuals and those with malignancies. Sero
embryo vaccine (PDEV) has been available for several
conversion rates are > 95% after three doses. An antibody
decades and continues to be used. It is free from myelin
titre of >10 mlU/mL is considered protective.
basic protein and considered safe for use. Its immuno
HB vaccine is given in three doses. It is known that genicity is comparable to modern tissue culture vaccines.
immunization at birth prevents horizontal transmission.
Modern tissue culture vaccines (MTCV) include purified
Immunization at birth, 1 and 6 months is considered ideal
chick embryo cell (PCEC) vaccine (Rabipur), human
in terms of its proven immunological efficacy. Attempts
diploid cell vaccine (HDCV) (Rabivax) and purified vero
at integrating HB vaccination into the National Schedule
cell vaccine (PVRV) (Verorab, Abhayrab). All tissue cell
without increasing number of contacts have led to trials
culture vaccines are equally efficacious and safe, and any
of other schedules which have been found to provide good
one of these may be used. The vaccine is stored at 2-8°C.
efficacy. Hence the vaccine may be given at birth, 1 month
Common adverse effects include local pain, swelling and
and 6 months of age, at birth, 6 weeks and 14 weeks of
induration. Systemic manifestations like fever, malaise,
age, or at birth, 6 weeks and 6 months of age. Where birth
abdominal pain and headache are less common and
dose has been missed, it may be given at 6,10 and 14 weeks
transient.
of age. Currently, there is no evidence to suggest that
In case of an animal bite, one should immediately clean
booster doses are required.
the wound thoroughly with soap, irrigate the wound with
Hepatitis B surface antigen (HBsAg) screening should
running water for 10 minutes, and then apply povidone
be offered to all pregnant women. If the mother is known
iodine, 70% alcohol or tincture iodine. All individuals
to be HBsAg negative, it is not essential that HB vaccine
should receive post exposure prophylaxis as detailed
be given to the newborn at birth, vaccination of the child
below. All patients with wound category III (WHO
may safely begin at 6 weeks. Where the mother's status is
recommendations) should also receive rabies immunoglo
not known, it is safer to vaccinate the newborn within a
bulin (RIG); these include all transdermal bites or scratches
few hours of birth. If the mother is known to be HBsAg
and contamination of mucous membranes with saliva (e.g.
positive, the child must receive the vaccine within a few
licks). RIG is not required in case of licks on intact or
hours of birth, along with Hepatitis B immunoglobulin
broken skin, nibbling of uncovered skin and minor
(HBIG) within 24 hours of birth. Administration of HBIG
scratches or abrasions without bleeding. Wound suturing
up to 5 days after birth may be effective. If HBIG has been
should be avoided. If suturing is essential for hemostasis,
administered, any of the schedules incorporating a birth
dose of the vaccine can be used. If HBIG is not adminis it should be done after administration of RIG.
tered, the baby should be immunized in an accelerated RIG provides passive immunity by immediately
schedule at 0, 1 and 2 months, along with an additional neutralizing the rabies viruses on contact so that neural
dose at 9-12 months. HBIG and HB vaccine should be infection is prevented. The dose of RIG is 20 U/kg for
administered at separate sites. human (HRIG) and 40 U/kg for equine (ERIG) immuno
Vaccination of older children and adults requires three globulin. RIG should be infiltrated in and around the
doses at 0, 1 and 6 months, where 0 refers to the date of wound; in case of large or multiple wounds, RIG may be
administration of the first dose. diluted with normal saline so as to infiltrate all wounded
HBIG provides immediate passive immunity and is areas. Any remaining immunoglobulin should be
used in circumstances where an acute exposure to HBsAg administered intramuscularly at a site away from vaccine
positive material has occurred. Concurrent use of HBIG site; usual sites include the deltoid and anterolateral thigh.
and HB vaccination, i.e. combined passive and active HRIG is very expensive and not available easily. ERIG is
immunization, results in 90% decrease in the risk of associated with a high risk of adverse effects including
transmission of HBV. Such circumstances include needle anaphylaxis; therefore skin testing is recommended before
stick injuries, sexual exposure, use of blood product not its use.
screened for HBV, etc. HBIG is administered intra There are various schedules for administration of rabies
muscularly at a site away from the site of HB vaccination, vaccine for post-exposure prophylaxis, using the
Immunity and Immunization 173
intramuscular and intradermal routes (Table 8.6). The are live attenuated vaccines derived from the Oka strain,
anterolateral thigh and deltoid region are preferred sites originally developed in Japan. The vaccine induces good
for intramuscular administration; the gluteal region cellular and humoral immune response and high (95-99%)
should not be used. The dose is 1 mL for all modern tissue protective efficacy which is long lasting.
culture vaccines except PVRV in which case the dose is The varicella vaccine is not recommended for universal
0.5 mL. The intradermal dose is one-fifth of the intra immunization in our country because of the benign nature
muscular dose. of the disease in children; it may be offered to children
In India, the Essen schedule or WHO standard schedule is from affording families on an individual basis after
most commonly practised. The Zagreb schedule induces discussion with parents. It is recommended for all children
an early immune response, but the long term efficacy is with chronic cardiac or pulmonary disease, immuno
poor if administered along with RIG. TRC-ID schedule is deficiency, HIV infection (with CD4 counts more than 15%
a cost effective and efficacious schedule that is now for age), leukemia (while disease is in remission and
approved for use in India, using either PCEC or PVRV, in chemotherapy has been discontinued at least 3-6
centers with adequate training and frequent use of the months back), and those on long-term salicylates or high
vaccine. dose steroids. Household contacts of immuno
Pre-exposure prophylaxis is offered to individuals at compromised children should also be immunized. It may
high risk of rabies due to contact with animals, e.g. vete be considered in children attending creches and day care
rinary doctors, wildlife workers, dog handlers, taxider facilties, and in adolescents who have not had varicella in
mists, postmen, animal laboratory workers, municipal the past or are known to be seronegative for varicella IgG.
workers etc. Three doses are recommended to be given It may be administered to household contacts of patients
intramuscularly on days 0, 7 and 21 or 28. A booster dose with varicella but the vaccine must be given within 72
is required after 1 year and every 5 years thereafter. In hours and the efficacy is not guaranteed. Susceptible
case of re-exposure after completed pre or post-exposure adolescents and adults should also be vaccinated if they
prophylaxis, two doses are recommended on days 0 and stay or work in an institutional setting, e.g. school, hospital
3. The intradermal schedule using MTCV is also accep or military establishment.
table; here the boosters are required yearly. The vaccine is administered subcutaneously or
Since human rabies immunoglobulin (HRIG) is intramuscularly in a dose of 0.5 ml (containing at least
required in addition to the vaccine for most animal bites, 1000 plaque forming units). Two doses of the vaccine are
and the availability, cost and knowledge regarding use of given 4-8 weeks apart in children older than 13 years.
HRIG is limited, IAPCOI recommends that pre-exposure Previously a single dose was considered sufficient in
prophylaxis against rabies be offered to all children at high children between 1 and 13 years of age, but the American
risk for rabies. Pre-exposure prophylaxis will obviate the Academy of Pediatrics now recommends two doses, as
need for use of HRIG and will restrict the number of post for older children, in view of increasing reports of
exposure doses to 2 on day 0 and day 3. breakthrough varicella following vaccination. However,
in the absence of sufficient data on changing epidemiology
of chicken pox, the IAPCOI continues to recommend
VARICELLA VACCINE
single dose of varicella vaccine in children aged below 13
Chicken pox (varicella) chiefly affects children and young years. The vaccine should not be administered to children
adults in whom it is usually a benign and self limiting below one year of age. The vaccine should be stored at 2-
infection. The disease may be associated with compli 8°C. It should be protected from light and used within 30
cations when it occurs in adults, pregnant women and minutes of reconstitution. Adverse reactions include fever,
immunocompromised individuals. The available vaccines rash and local pain, redness and swelling.
Table 8.6: Various schedules for administration of rabies vaccine for post-exposure prophylaxis*
* Day 0 refers to the day of administration of the first dose. Numbers indicate number of doses required on a particular day.
Where multiple doses are to be administered on the same day, different sites should be used.
** This additional dose is recommended for immunocompromised or severely malnourished patients.
174 Essential Pediatrics
Varicella zoster immunoglobulin (VZIG) provides intramuscularly or subcutaneously, in a dose of 0.5 mL,
passive immunity to non-immune individuals who are which contains 25 pg of the antigen. The vaccine should
exposed to varicella and are at significant risk of be stored at 2-8°C and should not be frozen. The vaccine
complications. Post-exposure prophylaxis is recommen is associated with mild adverse effects like local pain and
ded for susceptible contacts with significant exposure to swelling. The IAPCOI recommends the administration of
varicella or herpes zoster who are at risk for severe disease. the currently available Vi polysaccharide vaccine to all
This group includes pregnant women, neonates whose children every three years beginning by the age of 2 years
mother has developed varicella 5 days before or 2 days till age of 18 years.
after delivery and immunocompromised children and An oral vaccine has been developed recently, using the
adults. Post-exposure prophylaxis is best achieved by live attenuated Ty21a strain of S. typhi. This strain has a
administering varicella zoster immunoglobulin (VZIG) genetically stable mutation in the gal E gene; its reversion
now available as an IV preparation at a dose of 0.2-1 ml/ to virulence is unlikely. The vaccine acts by inducing local
kg (5-25 units/kg) of body weight, or 125 units/ 10 kg gut immunity; hence there is no immunological marker
body weight, within 96 hr of exposure. of its efficacy. Vaccine efficacy is 50-60% with the available
formulation, and is present within 7 days of primary
TYPHOID VACCINE immunization. Primary immunization consists of three
doses given on alternate days on an empty stomach. Since
Enteric fever is an important public health problem in our
the bacteria are inactivated by gastric acidity, the vaccine
country. Three types of typhoid vaccines have been
is available as enteric coated capsules which must be
developed, as described below. The efficacy of all vaccines
swallowed intact and not chewed or opened. For this
ranges between 50-70%.
reason the vaccine is suitable for use only in children above
The whole cell inactivated typhoid vaccines (TA/TAB)
6 years of age. Antibiotics are contraindicated between 3
are inexpensive vaccines that have been available for
days before to 7 days after the vaccine administration as
several decades as either a heat-killed phenol-preserved
their use may compromise the vaccine "take". The vaccine
vaccine or as an acetone-inactivated vaccine. The acetone-
should be stored at 2-8°C. Vaccination has to be repeated
inactivated vaccine is more immunogenic but is also
every 3-5 years. Currently the vaccine is not available in
associated with more adverse effects. Both vaccines
India.
contain 1000 million particles of inactivated whole cell
Salmonella typhi in each mL. The vaccine induces
HEPATITIS A VACCINE
antibodies against the cell wall somatic (O) antigen and
the flagellar (H) antigen. The antibody response can be Infection with hepatitis A (HA) virus is endemic in India,
used as indicative of response to the vaccine, but the same and is usually benign in children; among children who
may interfere with the interpretation of Widal test in acquire the infection below 5 years of age, 50-85% have
vaccinated individuals. The vaccine is safe and immuno non-specific manifestations like any viral illness. Disease
genic in children older than 6 months. Primary immuni severity, rate of complications and mortality are higher in
zation comprises of two doses given at least 4 weeks apart, those with underlying chronic liver disease, and in adults.
by the subcutaneous route. Dose is 0.25 mL in children Available HA vaccines are formalin inactivated
between 6 months-10 years, and 0.5 mL in an older vaccines derived from strains grown on human diploid
individual. Protective efficacy is 50-70%, and ensues 4 cell lines. Aluminium hydroxide is used as an adjuvant.
weeks after administration. Re-vaccination is required The vaccine is administered intramuscularly in two doses
every 2-3 years, and should be done preferably before 6 months apart; no boosters are required as immunity
the peak season. Adverse effects include fever, local pain appears to be long lasting. The vaccine has protective
and malaise; these are more common with the vaccine efficacy of 94-100%. Since maternal antibody may interfere
containing TA/TAB than with the pure S. typhi vaccine. with immune response to the vaccine, hence the vaccine
The vaccine should be stored at 2-8°C and should not be should be administered beyond 18 months of age. Local
frozen. Currently this vaccine is not available in our pain and induration are the adverse reactions commonly
country. noted. All available brands of hepatitis A vaccines have
The Vi capsular polysaccharide of S. typhi has an similar efficacy and safety.
important role in the virulence of the organism as it The HA vaccine is not recommended for universal
prevents phagocytosis and inhibits serum bactericidal immunization in our country because of the benign nature
action. The purified antigen is incorporated in the Vi of the disease in children; it may be offered to children
capsular polysaccharide vaccine, an unconjugated from high socio-economic strata on an individual basis
polysaccharide vaccine that can be used in children older after discussion with parents. It is recommended for all
than 2 years of age. The vaccine has an efficacy of 50- children with chronic liver disease who are seronegative
60%, seen after 2 weeks of administration. Vaccination for HA virus. It may be considered in children attending
elicits immune response in form of anti-Vi antibodies. A creches and day care facilities, in travelers from abroad
single dose is recommended to be administered either attending endemic areas, and in adolescents who have not
Immunity and Immunization 175
had viral hepatitis in the past or are known to be administered between ages 6-12 weeks and subsequent 2
seronegative for HA virus. It may be administered to doses at intervals of 4-8 weeks; vaccination should not be
household contacts of patients with HA virus infection initiated for infants aged >12 weeks, and all 3 doses should
but the vaccine must be given within 10 days of the index be administered before the age of 32 weeks.
case being infected. Vaccination should be postponed in infants with acute
gastroenteritis as it might compromise efficacy of the
ROTAVIRUS VACCINE ________ vaccine. Risks versus benefits of vaccination should be
considered while considering vaccination for infants with
Rotavirus is a major cause of diarrhea related morbidity chronic gastrointestinal disease, gut malformations,
and mortality in children worldwide. Rotavirus is an RNA previous intussusception and immunocompromised
virus with 7 serogroups (A-G), of which group A infants.
rotaviruses cause most human disease. Epidemiologic
studies from India indicate that rotavirus is responsible HEMOPHILUS INFLUENZA B VACCINE
for 6-45% of all childhood diarrheas that need hospitali
zation. The first clinically licensed rotavirus vaccine was Worldwide, hemophilus influenza type b (Hib) is an
Rotashield, a live oral tetravalent vaccine which was important cause of invasive infections like pneumonia,
withdrawn soon after its introduction in 1998 due to meningitis and bacteremia, especially in children below 2
occurrence of vaccine associated intussusception. years of age. A study of pathogens from six centers in India
Currently, two live oral vaccines, namely Rotarix and (the Invasive Bacterial Infections Study) showed that Hib
is an important cause of meningitis. Effective vaccines are
RotaTeq, are licensed and marketed worldwide, while a
available, and their incorporation into the immunization
vaccine based on Indian neonatal strains is undergoing
schedule of developed countries has resulted in a
clinical trials.
significant decline in morbidity and mortality attributable
Rotarix is a monovalent attenuated human rotavirus
to invasive disease due to Hib.
vaccine derived from human rotavirus strains, and
The capsular polysaccharide is the moiety used as the
contains the G1P1A(8) strain. It is administered orally in
antigen in the available vaccines. Since polysaccharide
a 2-dose schedule to infants at 2 and 4 months of age.
antigens are poorly immunogenic in children below 2
RotaTex is a human bovine reassortant vaccine and
years of age, it is conjugated to a protein antigen in order
consists of five reassortants between the bovine WC23
to enhance the immunogenicity. The PRP-T vaccine has
strain and human Gl, G2, G3, G4 and P1A(8) rotavirus
the tetanus toxoid as the conjugate, the Hb-OC has the
strains. It is administered orally in a three dose schedule
mutant CRM 197 diphtheria toxin, while PRP-OMP
at 2, 4 and 6 months. In trials conducted elsewhere, both
incorporates the outer membrane protein of meningo
vaccines have shown 85-98% efficacy against severe
coccus as conjugate. PRP-OMP is a more immunogenic
rotavirus gastroenteritis and have been demonstrated to
vaccine than the other two, but is not available in India.
be safe with no increased risk of intussusception as
Conjugate vaccines for hemophilus influenza containing
compared to placebo. Efficacy trials in developing
diphtheria toxoid do not contain enough toxoid to be a
countries of Africa and Asia are ongoing. Shedding of the
substitute for DTP or DT.
vaccine virus is observed in 10% of vaccinees with Rotateq
The IAP-COI recommends that Hib vaccine be adminis
and more than 50% of vaccinees with Rotarix. Simul
tered to all children; however, given the epidemiological
taneous administration of rotavirus vaccines with OPV
does not appear to affect adversely the efficacy of either profile of infections with Hib, unimmunized children
above 5 years of age should not receive the vaccine.
vaccine.
Vaccination is particularly recommended prior to
The morbidity and mortality burden of rotavirus in
splenectomy and in patients with sickle cell disease.
India is huge and an efficacious rotavirus vaccine is
required. However, given the tremendous diversity in Vaccination schedule depends on the age of the child
circulating strains of the virus and the lack of efficacy at the time immunization is initiated. Three doses are
studies from India, the results of efficacy trials of the recommended in a child below 6 months, 2 doses in a child
currently licensed for use vaccines cannot be extrapolated between 6-12 months, and one dose in a child aged
to India. The IAPCOI recommends that any decision to between 12-15 months; a booster should be administered
administer the vaccine be based on a one to one discussion in these children at 18 months of age. When immunization
with parents. is delayed beyond 15 months, one dose is considered
Vaccination should be strictly as per schedule; there is sufficient. Two doses of the vaccines should be at least 4
a potential risk of intussusception if vaccines are given to weeks apart. The vaccine is safe and immunogenic, and
older infants. The first dose of Rotarix can be given at 6 has a protective efficacy of over 95%.
weeks and no later than at 12 weeks; the interval between
PNEUMOCOCCAL VACCINE
the 2 doses should be at least 4 weeks, and two doses
should be completed by age 16 weeks, and no later than Worldwide, S. pneumoniae is responsible for 15-50% of all
by 24 weeks of age. The first dose of Rotateq should be episodes of community acquired pneumonia, 30-50% of
176 Essential Pediatrics
all cases of acute otitis media, and 50% of deaths due to is given in a dose of 0.5 ml intramuscularly, as three doses
pneumonia every year. Among 90 known serotypes of at 6, 10 andl4 weeks, with a booster at 15-18 months.
S. pneumoniae, 7 serotypes (14, 6, 19, 18, 9, 23 and 7) are Children between 6-12 months should be administered 2
responsible for 85% of invasive pneumococcal disease in doses 4-8 weeks apart and 1 booster at 15 -18 months,
the developed world. In India, it has been demonstrated those between 12-23 months get 2 doses 8 weeks apart;
that serotypes 6, 1, 19, 14, 4, 5, 45, 12, 7, 23 are the most while those between 2-5 years should receive a single
prevalent, and serotypes 1 and 5 account for 30% of dose.
invasive pneumococcal disease. The IAPCOI recommends administration of both PCV
Children under the age of 2 years are at greatest risk and PPV23 in all high-risk children who can afford the
for invasive pneumococcal disease (IPD). Children at high vaccine, because while PCV provides robust immune
risk for pneumococcal disease include those with response and immune memory, the PPV23 provides
congenital immunodeficiency, HIV, children on immuno expanded serotype coverage. Where the cost of PCV is a
suppressive therapy, organ transplant recipients, sickle limiting factor at least PPV23 should be given to high-
cell disease, asplenia or hyposplenia, chronic cardiac, liver, risk children >2 years of age. If affordable, PCV should be
or pulmonary disease (excluding asthma unless on high given first, in the schedule described above; for children
dose oral steroids), chronic renal failure, nephrotic over 5 years a single dose of PCV is recommended. In
syndrome, diabetes mellitus, and children with cerebro children aged >2 years, PPV 23 should also be given as a
spinal fistula or cochlear implants. Currently, two single dose. A gap of 2 months must be maintained
vaccines are available, the unconjugated pneumococcal between PCV and subsequent PPV 23. Only one repeat
polysaccharide vaccine and the conjugate vaccines. dose of PPV23 is recommended in high risk children; this
The unconjugated polysaccharide vaccine is a 23 valent may be given after 3-5 years if the child is less than 10
vaccine (PPV23). Since capsular polysaccharides stimulate years of age and after 5 years if child is aged more than 10
B cells directly independent of T cell stimulation, the years.
vaccine is poorly immunogenic below the age of 2 yrs,
MENINGOCOCCAL VACCINE
and immunological memory is low. The vaccine does not
reduce nasopharyngeal carriage of S. pneumoniae; Neisseria meningitides is a major cause of bacterial menin
therefore, it does not provide herd immunity. Its efficacy gitis accounting for 30-40% of cases in children below 15
against prevention of IPD in the high-risk population is years. Endemic cases and severe meningococcal disease
less than 70%. The vaccine is administered intramuscularly are primarily seen in children and adolescents; attack rates
in a dose of 0.5 mL; more than two life time doses should are highest in infants between 3-12 months of age. Even
not be given. with treatment, case fatality rates are high (5-15%). The
Pneumococcal conjugate vaccine (PCV) is available as infection is usually due to serogroups A, B, C, Y and W135;
a 7 valent pneumococcal conjugate vaccine (PCV7) serogroup A (and sometimes C) may cause epidemics. In
containing 7 polysaccharide antigens linked to a protein India endemic cases are chiefly due to serogroup B.
carrier. These antigens are from serotypes (4, 6B, 9V, 14, Infection results in serogroup specific immunity.
18C, 19F and 23) that account for 85% of invasive disease Two types of vaccines have been developed: the
in USA, where efficacy trials demonstrated >95% unconjugated polysaccharide vaccines and a conjugate
reduction in IPD and 30% reduction in pneumonia. A herd group C vaccine. Unconjugated vaccines contain group
^ effect results from reduction in nasopharyngeal carriage specific capsular polysaccharides, which, like other poly
I of S. pneumoniae; a significant decline in pneumococcal saccharide vaccines, are T cell independent and do not
[51 disease has been seen in unvaccinated contacts of the induce immunological memory, and are not very immun
i] vaccinees after introduction of the vaccine in the ogenic below 2 year of age. Bivalent (containing group A
I immunization program of developed nations. The current and C) and tetravalent (containing groups A, C, Y and
™ PCV7 covers only 55% of pneumococcal serotypes W135) vaccines are available.
prevalent in India. Conjugated vaccines with broader The meningococcal vaccine is indicated in close contacts
serotype vaccines should be available in future. of patients with meningococcal disease (as an adjunct to
Since pneumococcus is a cause of significant morbidity chemoprophylaxis), certain high risk groups (complement
and mortality in children (especially those <2 years), the deficiency, sickle cell anemia, asplenia, before splenec
IAPCOI recommends the use of the currently available tomy), during disease outbreaks (when caused by a sero
conjugate pneumococcal vaccine (PCV7) after one to one group included in the vaccine), and before travel to the
discussion with parents in healthy children aged <2 years; high endemicity belt in Africa.
vaccination of healthy children >2 years is likely to be The vaccine is administered in a dose of 0.5 ml intra
associated with less benefits due to the low risk of invasive muscularly or subcutaneously in a single dose. If required,
pneumococcal disease in these children. There is no data revaccination may be considered after 3-5 years. Fever
to support the use of pneumococcal vaccine in healthy and pain at injection site are the commonly reported
children aged >5 years, and it should not be given. PCV adverse events. The vaccine is not recommended for
Immunity and Immunization 177
universal immunization in India. During epidemics, hemagglutinin and neuraminidase), with frequent
children above 2 years of age may be administered the mutations due to antigenic drifts and antigenic shifts,
vaccine. If the vaccine is given to younger children (e.g. resulting in frequent changes in the strains in circulation.
close household contact), protective efficacy is likely to Since the available vaccines elicit a strain specific humoral
be low. immune response, this is the only vaccine whose compo
The conjugated group C vaccine has been marketed in sition has to be altered yearly according to the expectation
some countries where group C is the most common isolate of the prevalent strain in the next peak season.
in meningococcal disease. Three doses of the vaccine are Influenza vaccines are inactivated vaccines derived
administered 4-8 weeks apart in children below 6 months, from viruses grown in embryonated hen's eggs, and are
while 2 doses suffice for 6-12 months age and 1 dose is of three types. Whole virus vaccines that were available
enough in older children. previously were associated with significant adverse
effects, especially in children; hence they are no longer
JAPANESE B ENCEPHALITIS VACCINE used. Split product vaccines are produced from detergent
treated highly purified influenza viruses. Surface antigen
Japanese encephalitis is an important cause of viral
vaccines are subunit vaccines containing the purified
encephalitis in our country; being responsible for 2000-
antigens hemagglutinin and neuraminidase. Current
3000 cases and 500-600 deaths annually. In absence of
vaccines are highly immunogenic and associated with
specific therapy, vaccination remains the most important
minimal adverse events. The vaccines are usually trivalent,
control measure, and is indicated in all children between
containing two influenza A subtypes and one influenza B
1-15 years of age residing in highly endemic areas like
strain. The composition of the vaccine is reviewed by the
Andhra Pradesh, Uttar Pradesh and Karnataka. It should
WHO six-monthly to update antigens contained in the
also be given to visitors to endemic areas if duration of
vaccine based on the prevalent circulating strains.
stay is expected to be more than 4 weeks. Three types of The vaccine is recommended for use in high risk
vaccine are available, the mouse brain-derived inactivated children, including those with chronic cardiac or pul
vaccine, the cell culture-derived inactivated vaccine and monary disease, immunodeficiency, HIV infection, sickle
the cell culture-derived live attenuated vaccine. cell disease, diabetes mellitus, systemic lupus erythema
The mouse brain-derived vaccine is an inactivated tosus, long-term aspirin therapy, and children with severe
vaccine administered subcutaneously in a dose of 0.5 ml for asthma who frequently require oral corticosteroids.
children between 1-3 years and 1 ml in an older child. Pri Primary immunization requires two doses to be given in
mary immunization consists of 3 doses; the second and children between 6 months and 8 years of age, while a
third doses are given 7 and 30 days after the first dose. single dose suffices in older children. Revaccination is
Booster doses are to be administered at 1 year after primary required annually; the dose should be given prior to the
immunization and every 3 years subsequently. Common peak influenza season. The vaccine is administered
adverse events include fever, malaise and local tenderness intramuscularly, in a dose of 0.25 ml in children < 3 years
and redness. Reports of a temporal relationship of vacci and 0.5 ml in an older child.
nation to acute encephalitis and anaphylactic reactions in
recipients have resulted in decline in usage of this vaccine. HUMAN PAPILLOMA VIRUS (HPV) VACCINE
An inactivated vaccine derived from primary hamster
Cervical cancer is the second most common cancer and
kidney cell line was popular in China, but its use was the leading cause of cancer related deaths in women.
discontinued following availability of the live cell culture Cervical cancer is almost always caused by persistent
derived vaccine. The cell culture derived live vaccine is infection with oncogenic human papillomavirus (HPV).
based on a stable neuro-attenuated strain of JE virus, the Among 100 known serotypes of HPV, about 20 are
SA-14-14-2, which was first used in China and is currently oncogenic, with serotypes 16 and 18 being associated with
in use in Nepal and South Korea. The vaccine has high 70% cases of invasive cervical cancer. Additionally,
efficacy; initial studies demonstrated 80% efficacy with oncogenic serotypes of HPV may have a causal role in the
one dose and 98% with two doses, but recent studies pathogenesis of anal, vulvar, vaginal, penile and
suggest efficacy of upto 99% even with a single dose. The oropharyngeal cancers. Nononcogenic HPV serotypes 6
vaccine is administered in a dose of 0.5 ml subcutaneously. and 11 cause 90% of anogenital warts.
Other than anaphylaxis, there are no reported serious The available vaccines against HPV are self-assembling
adverse events. The vaccine has been used in pilot projects virus like particles (VLP) constituted of recombinant LI,
initiated by the Government of India in hyperendemic the major capsid protein of HPV. Since these do not contain
districts of Uttar Pradesh, West Bengal, Assam and any nucleic acid, these empty capsids are non-infectious
Karnataka, and found to be safe. but capable of eliciting a host immune response. VLP
based vaccines prevent more than 90% new infections with
INFLUENZA VACCINE _____ ____
the serotypes included in the vaccines. The vaccines do
The influenza virus has three antigenic types (A, B and C) not protect against serotypes with which infection has
and several subtypes (based on the surface antigens already occurred before vaccination.
178 Essential Pediatrics
Two vaccines are currently licensed; these include vaccine and not as a vaccine against a sexually transmitted
Gardasil, a quadrivalent vaccine active against HPV infection (STI). The dose is 0.5 mL intramuscular in the
strains 6, 11, 16 and 18, and Cervarix, a bivalent vaccine deltoid. The recommended age for initiation of vaccination
targeting only HPV 16 and 18. Clinical trials with both is 10-12 years, while catch up vaccination may be
vaccines have shown good efficacy against types 16, 18 permitted up to 26 years of age. Gardasil is given in three
related CIN grades 2 and 3 and adenocarcinoma in situ doses at 0, 2 and 6 months (with a minimum interval of 4
(AIS), and Gardasil is also effective in preventing vaccine weeks between 1st and 2nd dose, and 12 weeks between
type related genital warts, vaginal intraepithelial neoplasia the second and third dose), while Cervarix is given at 0,1
and vulvar intraepithelial neoplasia. Persistent protection and 6 months. Both vaccines are contraindicated in
for up to 5 years has been demonstrated, as also a good patients with history of hypersensitivity to any vaccine
response to booster immunization. Local adverse effects and should be avoided in pregnancy. The vaccines may
with both vaccines include mild to moderate pain at the have a lower immunogenicity and efficacy in immuno
injection site, and swelling and erythema; systemic compromised hosts. At present boosters are not recom
adverse effects such as fever are rare. No serious adverse mended.
events following immunization have been attributable to
the vaccines. RECOMMENDATIONS OF THE INDIAN ACADEMY OF
The vaccine is of public health importance in a country PEDIATRICS COMMITTEE ON IMMUNIZATION
like India where compliance with routine screening for (IAPCOI)
cervical cancer is low and several women are diagnosed
The IAPCOI endorses and fully supports the National
with the cancer every year. However, several issues
immunization program, but recommends additional
pertaining to the vaccine remain unresolved. The duration
vaccines for children to meet the immunization needs of
of protection provided, and hence, the ideal age at
our population. The Academy also suggests certain
vaccination and need of booster doses, if any, are not
optional vaccines that may be administered after
known. The vaccine is not expected to be effective in
discussion with parents regarding their utility and costs.
women already persistently infected with the virus. Any
The IAPCOI categorizes the childhood vaccines as listed
cross protection against other strains is likely to be modest.
in Table 8.7. The differences in the national immunization
Socio-cultural issues related to the vaccine being protective
program and the recommendations of the IAP are
against a sexually transmitted disease may limit its
highlighted in Table 8.8.
acceptability. Importantly, immunization status should
not create a false complacency resulting in a decline in
COMBINATION VACCINES
routine screening for cervical cancer, especially when
routine immunization has not been ensured, because this With the advent of several new vaccines, a child needs to
may result in a paradoxical rise in cervical cancer related be administered more than twenty antigens to avail
mortality. Screening programs should therefore continue protection against vaccine preventable diseases. The ideal
as per recommendations. vaccine, as proposed by the CVI, would be one that shall
The IAPCOI recommends that the HPV vaccines should provide all indicated antigens in a single dose, shall be
be offered to all females who can afford the vaccine, given administered preferably orally, shall be heat stable, shall
prior to sexual debut, as a cervical cancer preventing be effective if administered soon after birth, and shall be
Table 8.8: Comparison of the National Immunization Program with the recommendations of the
Indian Academy of Pediatrics (IAP) Committee on Immunization
BCG Bacillus Calmette Guerin vaccine; OPV oral poliovirus vaccine; Hep B hepatitis B vaccine; DTPw diphtheria toxoid, tetanus
toxoid, whole cell killed pertussis vaccine; DTPa diphtheria toxoid, tetanus toxoid, acellular pertussis vaccine; Hib hemophilus b
vaccine; Bl 1st booster dose; MMR measles, mumps and rubella vaccine; B2 2nd booster dose; DT diphtheria toxoid with
tetanus toxoid; TT tetanus toxoid; Td tetanus toxoid with reduced dose diphtheria; Tdap tetanus toxoid with reduced dose
diphtheria and pertussis vaccine; PCV7 pneumococcal heptavalent conjugate vaccine
* OPV + Inactivated polio vaccine (IPV) where affordable
‘ May be given at 6 months of age
** Revaccination required every 3 years
"‘Give a second dose after 1 month if there is no clear history of prior immunization with DTP
# The second dose of MMR may be given any time 8 weeks after the first dose
##Give a second dose after 1 month if there is no clear history of prior immunization with DTP/DT/TT
affordable to families of all economic strata. While such a zation, higher compliance to the immunization schedule
vaccine remains a dream, ongoing research is addressing and enhanced immunization coverage, less need for
these needs of simplification and expansion of the immuni storage space and an overall decrease in expense on
zation program through a variety of combination vaccines. packaging, handing and transportation of vaccines.
A combination vaccine consists of 2 or more separate The concept of combination vaccines is not novel; those
immunogens that have been physically combined in a in common use include DTP, DT or Td, OPV, IPV and
single preparation. These immunogens may be antigens MMR. Combination vaccines that have been recently
or serotypes of the same pathogen (e.g. trivalent polio licensed as well as those in final stages of development
vaccine) or different pathogens (e.g. DTP vaccine). This are listed in Table 8.9.
concept is distinct from simultaneous vaccination, which There are several challenges in the development of
implies the administration of multiple physically separate combination vaccines. The antigens combined together in
vaccines, at the same time, at separate sites or by different a vaccine should be compatible with each other, should
routes. not interfere with each other's immunological 'take'
Studies on the diversity of antigen receptors indicate (relevant especially for live viral vaccines) and should be
that the immune system of an infant can respond to a large indicated at the same time in the immunization schedule.
number of antigens simultaneously. There is no evidence Some antigens may require an adjuvant to be present in
that the efficacy of any currently recommended vaccine the combination. The total volume of the vaccine thus
is altered by its concurrent administration with another produced should not be excessive, and the final product
vaccine recommended for administration at the same age. should be stable for at least 18-24 months. Before
There are several benefits of combining vaccines. Use of recommending a particular combination vaccine, its
combination vaccines shall mean a decrease in the number efficacy should be evaluated in clinical trials, and its
of injections for a child resulting in decreased pain and inclusion into the immunization program of a country
local adverse effects, fewer visits required for immuni should follow a cost benefit analysis.
180 Essential Pediatrics
Table 8.9: Combination vaccines for use in children and infants, recently introduced or in final stages of development
Combination Vaccines of the Future glycoproteins can be used to bring the antigens into
With advances in molecular technology, it is likely that antigen presenting cells the same way as they mediate
combination vaccines in the future shall be based on infection with influenza virus. Thus IRIV may be used as
genomic technology, in form of either pox virus based or an alternative adjuvant for multivalent vaccines, e.g.
virosome based vaccines. The pox virus genome can be influenza A and B, hepatitis A, tetanus and diphtheria
manipulated to incorporate genes for multiple foreign vaccines, which are alum precipitated products.
antigens, suggesting the possibility of its modification into
Suggested reading
a multivalent vaccine candidate. Immunopotentiating
reconstituted influenza virosomes (IRIV) are liposomes 1. IAP Committee on Immunization (IAPCOI). Consensus Recom
mendations on Immunization, 2008. Indian Pediatrics 2008; 45:635-
that contain glycoproteins hemagglutinin and neura
648.
minidase and can be used as carriers for multiple antigens, 2. Vaccination- Present status and future challenges, Guest Ed Dutta
which can be covalently attached to the liposomes. The AK. Indian J Pediatr 2007; 74: SS No. 2.
9 Infections and Infestations
FEVER Etiopathogenesis
Fever may be caused by multiple causes including
Fever is a controlled increase in body temperature over infection, vaccines, biologic agents, tissue injury,
the normal values for an individual. The normal body malignancy, drugs, autoimmune diseases, granulomatous
temperature in children is higher as compared to adults, diseases, metabolic disorders (gout) and genetic disorders
exhibits a normal circadian diurnal variation and varies such as familial Mediterranean fever. All these insults
between 36.1°C to 37.8°C (97°F-100°F) on rectal measure result in the production of endogenous pyrogens, such as
ment. There is a normal diurnal variation in the body interleukin (IL)-l, IL-6, tumor necrosis factor (TNF)-a,
temperature; it is lowest between 0 and 0600 hours and interferon-P and interferon-y and lipid mediators such
maximum between 1700 and 1900 hours. as prostaglandin E2, which alter the temperature set point
in the anterior hypothalamus leading to elevation in body
Measurement and Definition temperature. In contrast to fever, the high body tempe
rature in heat illness is due to increased heat production or
The core body temperature can be measured at several
reduced heat loss, with the hypothalamic set point being
sites including the oral cavity, axilla, rectum, ear canal
normal. Here, the core temperatures can rise to beyond
and over the temporal artery. The rectal method is the
106°F. Common causes of heat illness are hyperthy
most accurate method for measurement of temperature
roidism, anhidrotic ectodermal dysplasia, drugs such as
and fever is defined as rectal temperature of more than
38°C or 100.4°F. However, measurement of rectal tempe anticholinergics and phenothiazines, heat stroke and
rature is not always possible in clinical practice. In children malignant hyperthermia.
below the age of 4-5 years, axillary temperature may be Evaluation of a Febrile Patient
used if taken correctly. The axillary temperature is on an
average 0.5-1 °C or 1-2°F lower than the rectal tempe Fever is a symptom and not a disease; hence, evaluation
rature. Fever, if measured in the axilla, is defined as for cause is important. If temperatures are very high, heat
temperature more than 37.2°C or 99°F. In infants below illness should be suspected. It is useful to classify fevers
the age of 3 months, if the axillary method shows fever, as short duration fevers and prolonged fevers as etiology
rectal temperatures should be measured as this is of and management strategies differ. The pattern of fever is
serious concern and mandates investigations as discussed only sometimes useful in arriving at a diagnosis.
later. Intermittent fevers are characteristic of malaria; biphasic
In children above the age of 4-5 years, the oral method fevers are seen in illnesses such as dengue and lepto
is suitable. The oral temperature is on an average 0.5-TF spirosis; and periodic fevers (fever syndromes with
or 0.25-0.5°C lower than rectal temperature. Fever as regular periodicity) are seen in cyclic neutropenia, PFAPA
measured in the oral cavity is defined as temperature more syndrome (periodic fever, adenopathy, pharyngitis,
than 37.5°C or 99.5°F. aphthous ulcers) and hyperimmunoglobulin (Ig) D
Both mercury and electronic thermometers are syndromes.
available. The electronic thermometers take only 30
Management
seconds for recording temperature, are convenient to use
but are subject to calibration errors. The mercury Fever is a symptom and, therefore, treatment of the
thermometers take 2-4 minutes to record temperature, are underlying cause is important. Treatment of fever per se
cheaper and especially suitable for home use where may not always be needed. Fever has been shown to
regular calibration of electronic thermometers is not improve the immunologic response to certain infections
possible. The infrared thermometers used for measure in experimental models; whether this is clinically
ment of ear/temporal artery temperatures are very quick significant is unknown. However, fever may be associated
and closely approximate rectal temperatures but are with adverse effects such as paradoxical suppression of
expensive. immune response, increased insensible water losses,
181
182 Essential Pediatrics
cardiopulmonary stress and triggering febrile seizures in ineffective. External cooling is needed with ice water
predisposed patients. sponging, cooling blankets, cold water enemas and gastric
Reduction of fever should be a priority in patients with washes. At the same time, measures should be taken to
past/family history of febrile seizures, those critically ill, correct the underlying condition.
those with cardiorespiratory failure, those with disturbed
fluid and electrolyte balance, or with temperature exceed Suggested reading
ing 40°C (104°F). For the rest, treatment should be 1. Lorin MI. Fever: pathogenesis and treatment. In: Feigin RD, Cherry
individualized; parental counseling is important. JD, eds. Textbook of Pediatric Infectious Diseases, 4th edn.
Philadelphia, WB Saunders, 89-94
The two commonly used drugs for antipyresis in
2. Crocetti M, Moghbeli N, Serwint J. Fever phobia revisited: Have
children are paracetamol and ibuprofen. Other agents such parental misconceptions about fever changed in 20 years?
as aspirin, nimesulide and mefenamic acid are associated Pediatrics 2001; 107: 1241-6
with high incidence of adverse effects and are better
avoided. Ibuprofen decreases fever at the same rate as SHORT DURATION FEVERS
paracetamol, the nadir with ibuprofen is slightly lower
and duration of action is longer (6 hr) as compared to Short duration fevers lasting for less than 5-7 days are
paracetamol (4 hr). However, the risk of side effects such one of the most common reasons for pediatric outpatient
as acute renal failure and gastrointestinal bleeding is visits. The overwhelming majority are due to viral
theoretically higher with ibuprofen (not substantiated by infections. Of greater concern are fevers without localizing
observational studies). Conversely, the consequences of signs/without focus in children below the age of 3 years
paracetamol overdose (hepatic failure) are more sinister (especially below 3 months) as they may indicate an
than those with ibuprofen (renal failure, neurological underlying serious bacterial infection (SBI). Since H.
depression). Considering all factors, it is reasonable to use influenzae and S. pneumoniae are important causes of SBI
paracetamol at a dose of 15 mg/kg every 4 hours (max. 5- the algorithms suggested here may change with increasing
6 doses/day) as the first-line drug for fever management. immunization with H. influenzae and S. pneumoniae
It is reasonable to shift to ibuprofen in those patients who vaccines.
have not adequately responded to paracetamol, at a dose
of 10 mg/kg every 6 hr. There is no evidence at present to Fever without Focus in Less than 1 Month
support alternating or combined use of paracetamol and Fever in a neonate (< 1 month of age) is generally a medi
ibuprofen. cal emergency. This is because of (i) 5-15% risk of serious
Tepid water sponging may be used as a complementary bacterial infection such as sepsis, bacteremia, urinary tract
method to drug therapy in bringing down fever quickly infections, pneumonia, enteritis and bacterial meningitis,
in some children. (ii) neonates may look well and still have serious bacterial
Heat illness is a medical emergency. The high tempe infection and (iii) the implications of missing or delaying
ratures can cause irreversible organ damage and should diagnosis of sepsis are serious.
be brought down quickly. Since the hypothalamic set point A detailed clinical assessment should be performed
is not altered, non-steroidal anti-inflammatory drugs, (Fig. 9.1). A toxic neonate is at high risk of serious bacterial
which act by reducing prostaglandin production, are infections and should be treated aggressively. The patient
Fig. 9.1 : Evaluation of fever in a patient less than 3-months-old; CSF cerebrospinal fluid;
TLC total leukocyte count; CRP C reactive protein
Infections and Infestations 183
The risk of serious bacterial infections decreases with Systemic onset juvenile rheumatoid arthritis, Kawasaki
advancing age and in this age group it is 5%. A child disease, systemic lupus erythematosus, inflammatory bowel
disease, polyarteritis nodosa
presenting with fever without focus should be assessed
completely. Detailed history is taken about vaccination, Malignancies
history of sick contacts in family and the condition of the
Leukemia, lymphoma, Langerhan cell histiocytosis
child when fever is down. If the patient looks toxic, he
should be hospitalized and undergo appropriate
evaluation and treatment. In a non-toxic child with fever
Approach to FUO
less than 39°C, one can merely observe. In children with
fever more than 39°C, the risk of bacteremia is higher and The first step is to identify sick patients who need
it is recommended to do a leukocyte count and examine stabilization and urgent referral to a tertiary care centre.
smear for malarial parasite. If the leukocyte count is Subsequently all attempts should be made to reach an
>15,000/cu mm, blood culture should be sent and the etiologic diagnosis. A detailed history is of paramount
patient administered IV ceftriaxone on either an inpatient importance. History should include
or outpatient basis. If the count is less than 15,000/cu mm, • Whether and how fever was documented (it is not
observation is continued. Most patients with a febrile uncommon to find children with history of prolonged
illness shall develop a focus in the next 1-2 days. fever not to have fever documented by a thermometer)
184 Essential Pediatrics
Complications Prevention
Secondary bacterial infections of the skin lesions may Prevention against varicella with the live attenuated
occur, occasionally resulting in necrotizing fascitis. varicella vaccine and use of varicella zoster immune
Infections and Infestations 187
State P1 P3 Total
• CO
Bihar 232
Uttar Pradesh 56 241 297
Delhi 4 1 5
Maharashtra 0 2 2
Haryana 0 2 2
Orissa 1 1 2
Andhra Pradesh 0 1 1
Madhya Pradesh 0 1 1
Rajasthan 0 2 2
Assam 1 0 1
Punjab 1 0 1
West Bengal 1 1 2
Uttrakhand 1 0 1
Total 68 481 549
Fig. 9.2 : Cases of poliomyelitis reported from India in 2008. P1 poliovirus type 1, P3 poliovirus type 3
illness. It invades local lymphoid tissue, enters the followed by rapid onset of flaccid paralysis that is usu
bloodstream and invades certain nerve cells. It may ally complete within 72 hours.
damage or destroy the nerve cells.
Polio encephalitis is characterized by irritability, delirium
Clinical Features and loss of consciousness; seizures may occur. The
paralysis may be of the upper motor neuron type.
In 90-95% of infected individuals, poliovirus infection is
inapparent. In the remaining 5-10% of individuals infected There are 3 types of paralytic poliomyelitis.
by poliovirus, one of the following syndromes may occur. Spinal paralytic poliomyelitis is the most common form of
Abortive polio occurs in 4-8% of infections and is paralytic poliomyelitis, accounting for approximately 80%
characterized by a minor illness with low grade fever, sore cases. It results from a lower motor neuron lesion of the
throat, vomiting, abdominal pain, loss of appetite and anterior horn cells of the spinal cord and affects the
malaise. Recovery is rapid and complete; there is no muscles of the legs, arms and/or trunk. Severe cases may
paralysis. It cannot be distinguished from other viral develop quadriplegia and paralysis of the trunk, abdo
minal and thoracic muscles. The affected muscles are
infections.
floppy and reflexes are diminished. The sense of pain and
Non-paralytic aseptic meningitis occurs in 1-2% of infections, touch are normal. Paralysis is often asymmetrical, affecting
with headache, neck, back, and leg stiffness several days legs more often than arms. Paralytic manifestation in
after a prodrome similar to abortive polio. Recovery occurs extremities begins proximally and progresses to involve
within 2-10 days. distal muscle groups (i.e. descending paralysis). Residual
flaccid paralysis is usually present after 60 days.
Paralytic poliomyelitis occurs in 0.5-1% of infections.
Symptoms occur in two phases, minor and major, Bulbar polio accounts for 2% cases and results from a cra
separated by several days without symptoms. The minor nial nerve lesion, resulting in respiratory insufficiency and
phase consists of symptoms similar to those of abortive difficulty in swallowing, eating or speaking.
poliomyelitis. The major phase of illness begins with Bulbospinal polio accounts for 20% cases and is a
muscle pain, spasms and the return of fever. This is combination of spinal paralytic and bulbar polio.
190 Essential Pediatrics
Depending on the strain of poliovirus, the ratio between maintained with pillows, rolled towels or sand bags. Warm
subclinical and clinical infections is estimated to range moist fomentations can be given with soft towels, dipped
between 100:1 and 1000:1. Older children and adults run in warm water to relieve pain and spasms (Sister Kenny's
a greater risk of developing paralytic illness. The case- treatment). Analgesics can also be given to relieve pain
fatality rate ranges between 2-20% among persons who and fever. All the joints of affected limb/limbs should be
do develop the paralytic form of the disease. However, if moved through their passive range of movements, 2-3
there is bulbar or respiratory involvement, the case-fatality times/day for 10 times at each joint, to prevent joint
rate may be as high as 40%. stiffness. This helps to stimulate proprioceptive impulses
from muscles and tendons thus helping improvement in
Residual Paralysis muscle power.
As the acute phase of illness (0-4 weeks) subsides, the As the acute phase of illness subsides, recovery in
recovery begins in paralyzed muscles. The extent of muscle power is helped by giving physiotherapy, helping
recovery is variable ranging from mild to severe residual ambulation and prevention of deformities. Some children
paresis at 60 days, depending upon the extent of damage require orthosis at some stage for ambulation. Others with
caused to the neurons by the virus. Maximum neurological fixed deformities and contractures require orthopedic
recovery takes place in the first 6 months of the illness; intervention.
slow recovery continues up to two years. After two years, Vaccines
no more recovery is expected and the child is said to have
The available vaccines and the recommended schedule
post polio residual paralysis, which persists throughout life.
are discussed in chapter 8.
Diagnosis
Eradication of Polio
The diagnosis is based on the history and the characteris
Eradication is possible because polio affects only man,
tic clinical manifestations of asymmetric flaccid paraly
immunity is lifelong, a safe vaccine is available and there
sis. Stool examination is recommended in every case of acute
are no carriers or reservoirs of the infection. The strategies
flaccid paralysis (AFP). Virus can be detected from onset
for achieving this goal are:
to 8 or more weeks after paralysis; the highest probability
of detection is during the first 2 weeks after onset of Attaining High Routine Immunization
paralysis. Examination of the cerebrospinal fluid (cell count,
Immunize every child aged <1 year with at least three
gram stain, protein and glucose) is useful in eliminating
doses of oral poliovirus vaccine (OPV).
other conditions that cause AFP. Current serologic tests
cannot differentiate between wild and vaccine virus National Immunization Days (NIDs)
strains. Collection of blood specimens for culture or
On these days, under the Pulse Polio Immunization (PPI)
serology is not recommended.
program, additional OPV doses are administered to every
Differential Diagnosis child <5-year-old. The aim of NIDs/PPI is to "flood" the
community with OPV within a very short period, thereby
The two diseases most commonly confused with polio are
interrupting transmission of virus throughout the
Guillain-Barre syndrome and transverse myelitis. Other community. Intensification of the PPI program is accom
conditions with a presentation similar to those of paralytic plished by the addition of extra immunization rounds,
poliomyelitis include traumatic neuritis, less frequently, adding a house-to-house "search and vaccinate"
meningitis /encephalitis, as well as illnesses produced by component in addition to providing vaccine at a fixed post.
a variety of toxins (diphtheria, botulism). The number of PPI rounds conducted during any
particular year is determined by the extent of poliovirus
Treatment
transmission in the state/district.
Treatment should be early and appropriate to the stage
B and degree of paralysis. Children with bulbospinal polio Mopping-up immunization
W and respiratory paralysis require hospitalization. In acute When poliovirus transmission is reduced to well-defined
51 stage children with isolated limb/limbs paralysis can be and focal geographic areas, intensive house-to-house,
jm managed at home. They should be advised complete rest, child-to-child immunization campaigns are conducted
■ proper positioning of the affected limb and passive range over a period of days to break the final chains of virus
of movement at the joints. Massage and intramuscular transmission.
injection should be avoided during acute phase of illness.
Frequent change of the posture of the patient is must. The Acute Flaccid Paralysis Surveillance
child should be made to lie on firm bed and maintain limbs Under the Global Polio Eradication Initiative, surveillance
in neutral position. The child should lie with trunk and for polio is conducted through investigation of patients
hip straight with slight flexion (5-10°) at knees and feet at with AFP. AFP surveillance helps to detect reliable areas
right angle at the ankle joint. This position can be where poliovirus transmission is occurring.
Infections and Infestations 191
Acute flaccid paralysis (AFP) is defined as sudden on of cases of both post-transfusion and community-acquired
set of weakness and floppiness in any part of the body in hepatitis are not identified as being caused by hepatitis
a child <15-year old or paralysis in a person of any age in A-E, investigators have sought to identify other poten
whom polio is suspected. In other parts of the world, at tially hepatotropic viral agents, including hepatitis G virus,
least one case of AFP (excluding polio) occurs annually TT virus and SEN virus.
for every 100,000 children less than 15-years of age
(background AFP rate). The non-polio causes of AFP HEPATITIS A
account for this background rate. Sensitive surveillance
Hepatitis A is caused by infection with the hepatitis A vi
will detect a background AFP rate of 1/100,000 children.
rus (HAV), a nonenveloped RNA virus, first identified by
In our country, where the incidence of conditions such as
electron microscopy in 1973. It is classified within the ge
traumatic neuritis and AFP caused by other non-polio
nus hepatovirus of the picornavirus family. In humans, a
enteroviruses is very high, the background non-polio AFP
single serotype of HAV exists. HAV infection induces life
rate is higher.
long protection against reinfection. HAV is extremely re
The Ministry of Health & Family Welfare, Government
sistant to degradation by environmental conditions, a
of India issued an official instruction that all health
property that allows its maintenance and spread within
facilities, clinicians and other practitioners are required
populations. In developing countries with poor environ
to notify AFP cases immediately to the District Immuni
mental hygienic conditions, nearly all children are infected
zation Officer (DIO), by the fastest available means. All
with HAV before 9-years of age. It is spread via the fecal
cases with AFP should be reported and their stools must
oral route through contaminated food and water, and
be collected within 14 days of onset. If it is not possible to
person-to-person spread under poor sanitary conditions.
collect stool specimens within 14 days, the specimens
Infections occur early in life in areas where HAV is highly
should still be collected up to 60 days after onset of
endemic.
paralysis. Upon verification that the case meets the AFP
case definition, the DIO initiates the case investigation. Clinical Features
As part of the investigations two stool samples are
The course of hepatitis A is extremely variable. The
collected from the child at a minimum interval of 24-hr. A
severity of the disease increases with age at time of
sixty day follow-up is done between the 60th and 90th
infection. The course of acute hepatitis A can be divided
day in certain categories of AFP cases to determine the
into four clinical phases:
presence/absence of residual paralysis. The presence of
residual paralysis at this time is further evidence that the • Incubation or preclinical period ranging from 10 to 50 days
cause of paralysis is likely to be due to poliovirus. (median 30 days), during which the patient remains
An AFP case is "confirmed" as polio only by the asymptomatic despite active replication of the virus.
isolation of wild poliovirus from any stool specimen. An • Prodromal or pre-icteric phase ranging from several days
AFP case is classified as "non-polio AFP" if wild poliovirus to more than a week, characterized by symptoms like
is not isolated from adequate stool specimens. If stool loss of appetite, fatigue, abdominal pain, nausea and
specimens are inadequate, final classification of the AFP vomiting, fever, diarrhea, dark urine and pale stools.
case as either non-polio AFP or compatible with polio will Children generally belong to this group.
depend on the results of the 60-day examination. If the • Icteric phase, during which jaundice develops at total
60-day follow-up examination shows no residual bilirubin levels exceeding 2-4 mg/dl. The icteric phase
weakness, the case is classified as non-polio AFP. generally begins within 10 days of the initial symptoms.
Fever improves after the first few days of jaundice. The
Suggested reading mortality rate is low (0.2% patients with jaundice) and
1. National Polio Surveillance Project. Available at: http:// the disease resolves.
www.npspindia.org/index.asp
• Convalescent period, where resolution of the disease is
2. Poliomyelitis Eradication Field Guide, 3rd edn. Available at http:/
/www.paho.org/english/ad/fch/im FieldGuide_Polio.pdf slow, but patient recovery uneventful and complete.
3. Singhal T, Amdekar YK, Thacker N and Indian Academy of Occasionally, extensive necrosis of the liver occurs
Pediatrics. IAP Committee on immunization. Ind Pediatr 2007; 44: during the first 6-8 weeks of illness. In this case, high fever,
390-2. marked abdominal pain, vomiting, jaundice and the
development of hepatic encephalopathy associated with
VIRAL HEPATITIS
coma and seizures occur. These are the signs of fulminant
Hepatitis is a general term meaning inflammation of the hepatitis, leading to death in 70-90% of the patients. In
liver and can be caused by a variety of different viruses patients who survive, neither functional nor pathologic
such as hepatitis A, B, C, D and E. Hepatitis A and E are sequelae are common despite the widespread necrosis.
responsible for most of the water-borne (community Infection with HAV does not lead to chronic or persistent
acquired) hepatitis while B, C and D are responsible for hepatitis. Relapsing hepatitis occurs in 3-20% of patients
post-transfusion hepatitis. Since a considerable number 4 to 15 weeks after the initial symptoms have resolved.
192 Essential Pediatrics
In acute hepatitis A, the presence of anti-HAV IgM is rate ranges from 2 to 20%. In hyperendemic areas, HBV
detectable about 3 weeks after exposure, its titer increases infections occur mainly during infancy and early
over 4 to 6 weeks, then declines to non-detectable levels childhood. In Asia, perinatal transmission from HBsAg
within 6 months of infection. carrier mothers to their infants is a very important route
of transmission, leading to chronicity. Approximately 90%
Diagnosis of the infants of HBeAg seropositive carrier mothers
The specific diagnosis of acute hepatitis A is made by become HBsAg carriers, irrespective of a high or low
finding anti-HAV IgM in the serum of patients. As IgG HBsAg carrier rate in the population. In areas of low
anti-HAV persists lifelong after acute infection, detection endemicity, horizontal infection is the main route of
of IgG anti-HAV alone indicates past infection. Laboratory transmission.
evaluation of liver function includes estimation of total
and direct bilirubin, transaminases, alkaline phosphatase, Pathogenesis and Natural Course
prothrombin time, total protein and albumin. HBV has an incubation period of 2 to 6 months. Following
a primary HBV infection, the host may run an acute,
Immune Prophylaxis fulminant or chronic course.
The administration of immunoglobulin can reduce the
incidence of hepatitis A up to 90%, and it is most effective Acute and Fulminant Hepatitis
if given before exposure. Its use is declining, since there is Acute hepatitis is marked by symptoms similar to other
increasing use of HAV vaccines. Immunoglobulin G may acute hepatitis illnesses, i.e. fever, vomiting, jaundice and
be used for postexposure prophylaxis. If administered anorexia. Recovery is marked by hepatitis B surface
within two weeks of exposure it either prevents antibody (anti-HBs) seroconversion. Fulminant hepatitis
development of disease or reduces its severity. is heralded by pathologic mental status changes within 2
to 8 weeks after the initial symptoms in an otherwise
Active Immunization healthy child. About two-thirds of children with fulminant
Inactivated HAV vaccines are available that are safe, hepatitis B present in infancy.
highly immunogenic and provide long-term protection
from infection. The vaccine is highly effective and provides Chronic Infection
seroconversion rates of more than 99% when given as a Children with chronic HBV infection are mostly asympto
single primary immunization, followed by a booster dose matic. They are generally active and grow well. Although
6 months later. liver damage is usually mild during childhood, serious
sequelae, including cirrhosis and hepatocellular
Treatment carcinoma, may develop insidiously at any age. An
As no specific treatment exists, prevention is the most immune-mediated process is the main mechanism for cell
effective approach against the disease. Therapy is damage. During acute exacerbations of chronic HBV
supportive and is aimed at maintaining adequate infections, CD8+ T lymphocytes are the predominant cells
nutrition. There is no evidence to suggest that restriction in the liver in the areas of piecemeal necrosis. Since HBeAg
of fats has any beneficial effect on the course of the disease. is an important marker reflecting active viral replication
Eggs, milk and butter may actually help provide a correct and infectivity, its clearance is used as a marker for the
caloric intake. Antiviral agents have no role because the success of antiviral therapy. Children with chronic HBV
hepatic injury appears to be immunopathologically infection are HBeAg seropositive at the initial stage of
mediated. Referral to a liver transplant centre is infection; this antigenemia can persist for years after
appropriate for patients with fulminant hepatitis A. primary infection (Fig. 9.3). Spontaneous clearance of
Temporary auxiliary liver transplantation for subacute HBeAg occurs gradually with increasing age. Viral
liver failure may be a way to promote native liver replication is reduced during this process. This process of
regeneration. HBeAg seroconversion takes place subclinically in most
individuals for a period of 2 to 7 years (Table 9.3). This
HEPATITIS B______ process is usually preceded by an elevation of
aminotransferases. After HBeAg clearance,
Hepatitis B virus is a 3.2 kb, circular, partially double aminotransferase levels return to normal levels and anti-
stranded DNA virus. HBV contains four open reading HBe develops. Long-term follow-up of HBsAg carrier
frames, which encode major structural and nonstructural children shows that the rate of HBsAg clearance is low
proteins for HBV. (0.6% annually), and occurs only after clearance of HBeAg.
During the early phase of infection, the amount of vi
Epidemiology of HBV Infection rus in the liver and blood is usually large, whereas the
HBV infection is prevalent in Asia, Africa, Southern liver damage is mostly mild. The host immune system
Europe and Latin America, where the HBsAg seropositive gradually recognizes the virus and starts to clear the virus.
Infections and infestations 193
third of cases; those most likely to respond have high ALT million infected persons. Children who received trans
activity and a greater histological activity index score in fusions of potentially contaminated blood products prior
the liver biopsy before treatment. Children younger than to the institution of routine screening have seroprevalence
6 years have an enhanced response to IFN(x2b treatment. rates upto 95%.
Side effects of IFN in children are flu-like symptoms,
headache, depression, loss of appetite, anemia, leukopenia Presentation
and thrombocytopenia. Promising results are emerging The mean incubation period of post-transfusion acute
using pegylated IFN in adults with chronic hepatitis B, HCV infection is 7 to 8 weeks, with a range of 2 to 26 weeks.
but data in children are lacking. Acute HCV is usually anicteric or subclinical and only
Lamivudine monotherapy for 1 year provides satis one-third of patients develop jaundice or symptoms.
factory results in children with chronic hepatitis B. Child Fulminant hepatic failure due to HCV is rare. In adults,
ren with higher pretreatment ALT levels and histologic 85% of patients exposed to HCV will develop chronic
activity index scores are most likely to respond to infection, of which approximately 10 to 20% develop
lamivudine. The medication is well tolerated, has minimal cirrhosis. In children, the course of HCV infection is
side effects and is easy to administer. However, the generally benign. Most children with acute hepatitis C are
development of resistant viral mutants (YMDD) limits the asymptomatic.
benefit of long-term monotherapy. Combinations of either When symptoms are present, they are often nonspecific
INFa2a or INFa2b with lamivudine have comparable (malaise, anorexia) or mild; jaundice is present in 25%.
effects and slightly better results than monotherapy in Most children exposed to HCV are at risk to become
children affected by chronic hepatitis. Other drugs chronically infected based on persistently detectable
including adefovir, entecavir and dipivoxil have serum anti-HCV antibodies and HCV RNA. Children with
documented clinical activity against wild and lamivudine chronic HCV infection may also remain asymptomatic.
resistant HBV, but needs to be further evaluated in Progression to decompensated liver disease in children is
children. rare. Biochemical markers such as serum alanine
aminotransferase (ALT) typically fluctuate in HCV
HEPATITIS C patients. Normal or only minimally increased ALT levels
are reported with chronic HCV infection, and serum ALT
Hepatitis C virus (HCV) was recognized in 1989 as a ma
levels can remain elevated despite anti-HCV sero-
jor cause of non-A, non-B hepatitis. HCV is an enveloped,
negativity. Liver histology shows portal lymphoid
single-stranded, positive-sense ribonucleic acid (RNA)
aggregates, bile duct injury and steatosis; necro-
virus, classified as an independent genus (Hepacivirus)
inflammatory activity is mild.
within the Flavivirus family. The HCV genome encodes
for a polyprotein, which undergoes proteolysis by viral Perinatal Transmission
and host-encoded proteases, resulting in the formation of
The rate of vertical transmission is approximately 5-6%,
the various HCV proteins. The HCV genome is organized
which is low compared to that for hepatitis B virus and
so that its 52 end encodes for the structural proteins includ
human immunodeficiency virus (HIV). High-titer mater
ing the core (or capsid) and envelope proteins (El and
nal viremia correlates with higher transmission rates.
E2), whereas the nonstructural (NS) or functional viral
proteins (NS2-NS5) are encoded by the larger subsequent Diagnosis
32 segment.
The diagnosis of HCV infection is based on detection of
Viral Variants antibodies against recombinant HCV antigens by enzyme
immunoassay or recombinant immunoblot assay or by
The HCV RNA-dependent RNA polymerase lacks proof
detection of HCV RNA using nucleic acid tests. Enzyme
reading ability, which results in HCV being genetically
immunoassay is limited by frequent false-positive results,
heterogeneous. Based on analysis of HCV sequences, six
particularly in patients with elevated globulin levels such
major HCV genotypes are recognized. HCV genotypes 1
as those with autoimmune hepatitis. Recombinant
and 2 are the most prevalent worldwide. HCV genotype
immunoblot assay detects HCV immunoglobulin IgG
3 is most common in Australia and the Indian sub
antibodies against synthetic HCV recombinant antigens
continent. The viral genotypic distribution in children
and synthetic peptides immobilized on a solid matrix.
generally parallels that reported regionally in adults. HCV
Recombinant immunoblot assays are less sensitive but
genotype 1 correlates with higher serum viral levels and
more specific than enzyme immunoassay in detecting anti-
a less favorable response to antiviral treatment.
HCV antibodies. Recombinant immunoblot assay is,
therefore, not recommended for initial HCV screening and
Epidemiology
are useful to confirm viral infection. Nucleic acid tests
The worldwide prevalence of HCV infection is directly detect circulating virus; two tests are currently
approximately 3%, which represents an estimated 170 used for the detection of HCV that rely on different
Infections and Infestations 195
amplification schemes, namely target and signal amplifi healthy chronic carrier state has been detected, and no
cation. Nucleic acid tests identify the presence of HCV recurrence of hepatitis E has been reported.
very early in the course of infection, and, therefore, are
used to diagnose infection even before the anti-HCV Diagnosis
antibodies have appeared. These tests are also necessary Laboratory evaluation of HEV is similar to that of HAV.
to detect HCV in infants born to infected mothers, in The antibody elevated in acute hepatitis E is IgM anti-
whom HCV antibodies may be of maternal origin and in HEV. The viral proteins pORF2 and pORF3 detected by
immunocompromised patients whose ability to produce enzyme immunoassay or ELISA form the basis for
HCV antibodies may be impaired. diagnosis. To confirm the results of these tests, Western
blot assays to detect IgM and IgG anti-HEV in serum can
Therapy be used, along with polymerase chain reaction tests for
Sustained virologic responses are achieved in only 8-35% the detection of HEV RNA in serum and stool and liver,
of patients given recombinant interferon monotherapy. and immune electron microscopy to visualize viral
However, significantly higher sustained virologic particles in feces. Antibodies to HEV (IgM and IgG)
responses are attained (30-40%) by combining interferon develop at the time symptoms occur, usually before the
with ribavirin at 15 mg/kg/d. Longer-acting pegylated development of jaundice. IgM anti-HEV titer declines
interferons have been subsequently developed based on rapidly during early convalescence, while IgG anti-HEV
the premise that more sustained drug levels would result persists for long duration and provides protection against
in greater antiviral activity. Several randomized clinical subsequent infections.
trials in adults verify considerably better virologic
responses (50-60%) with the use of pegylated interferons, Vaccines
particularly when given in conjunction with ribavirin. At present, there are no commercially available vaccines
However, in general, sustained virologic response rates for the prevention of hepatitis E.
in children treated with interferon alone (30-60%) appear
to be two- to threefold higher than in similarly treated Prevention
adults. Importantly, biochemical and virologic responses As with HAV good personal hygiene, high quality
have been accompanied by significant histologic improve standards for public water supplies and proper disposal
ment in all treated patients included in these trials, and of waste have resulted in a low prevalence of HEV
interferon has been well tolerated in children. infections in developed countries.
Treatment
HEPATITIS E
As no specific therapy is capable of altering the course of
Hepatitis E virus was first described in 1978 after an
acute hepatitis E infection, prevention is the most effective
epidemic affecting 52,000 individuals in Kashmir.
approach against the disease.
Hepatitis E is caused by infection with the hepatitis E virus
(HEV), a single-stranded RNA virus. The virion is
nonenveloped and with a diameter of 27-34 nm, is HEPATITIS DUE TO OTHER VIRUSES
composed entirely of viral protein and RNA. Just like HAV, Certain cases of post transfusion (10%) and community
HEV is transmitted from person-to-person via the fecal acquired hepatitis (20%) are of unknown origin. There are
oral route. It is usually transmitted through contaminated three viruses that have been potentially associated with
drinking water. Hepatitis E virus causes acute sporadic liver disease but no conclusive evidence exists to support
and epidemic viral hepatitis. Symptomatic HEV infection them as a cause for these cases. These viruses are HGV/GB
is most common in young adults aged 15-40 years and is virus C, TT virus and SEN virus. GB virus C (GBV-C), or
uncommon in children since it is mostly asymptomatic HGV, is a recently discovered enveloped RNA virus that
and anicteric. belongs to the Flavivirus family. GBV-C and HGV were
independently isolated and reported by two different
Presentation groups of researchers; they are 96% similar, indicating that
The incubation period following exposure to HEV ranges they are two genotypes of the same virus. This virus has a
from 3 to 8 weeks, with a mean of 40 days. The clinical predominant parenteral mode of transmission. It is found
presentation of hepatitis E is similar to hepatitis A. The throughout the world, with a high prevalence in both
severity of an HEV infection is generally greater than the healthy populations and in different patient groups. This
severity of an HAV infection. In pregnant women, the has called into question its actual role in acute or chronic
disease is particularly severe where mortality approaches hepatitis. The tissue tropism of HGV is also not clearly
20% with infections in the third trimester. Premature established, however, it may replicate in human
deliveries with high infant mortality up to 33% are mononuclear cells rather than in hepatocytes. Overall, most
observed. No evidence of chronic inflammation or of a infections are asymptomatic, and whether HGV is truly a
196 Essential Pediatrics
cause of 'non A to E' hepatitis is unlikely. TTV is a non The spread of dengue is attributed to expanding geo
enveloped single-stranded DNA virus. Although TTV is graphic distribution of the four dengue viruses and of their
found in patients with non A to E hepatitis, its overall preva mosquito vectors, the most important of which is the pre
lence has not been different between healthy individuals dominantly urban species Aedes aegypti. A rapid rise in
and patients with liver disease. It has both parenteral and urban populations is bringing ever greater numbers of
non-parenteral routes of transmission. The data available people into contact with this vector, especially in areas
for TTV does not support a significant role for this virus in that are favorable for mosquito breeding, e.g. where
children. SENV is a single-stranded DNA virus from the household water storage is common and where solid
Circovirus family that bears some similarity to TTV. The waste disposal services are inadequate.
prevalence of SENV infection is shown to increase with the
volume of transfused blood, supporting the parenteral Virus
mode of transmission. About 15% of SENV-infected Dengue fever and dengue hemorrhagic fever (DHF) are
patients develop acute non A to E hepatitis temporally
caused by infection due to any of the four serotypes of
related to the appearance of viremia, whereas the rest do
dengue viruses. Dengue viruses are arboviruses that
not. Several studies have documented a high prevalence of
belong to the family Flaviviridae. These viruses are
SENV infection in healthy individuals and those with acute
spherical particles approximately 50 nm in diameter.
or chronic liver disease, and have also suggested non-
Dengue RNA has approximately 11,000 nucleotides. The
parenteral transmission.
envelop protein bears epitopes that are unique to the
Suggested reading serotypes; the antibodies to these unique epitopes
neutralize by interfering with the entry of the virus into
1. Hsu EK, Murray KF. Hepatitis B and C in children. Nat Clin Pract
the cells. There are other epitopes that are shared between
Gastroenterol Hepatol 2008; 5: 311-20.
2. Price N, Boxall EH. Treatment of children persistently infected with dengue viruses (dengue subgroup antigens) and other
hepatitis B virus: seroconversion or suppression. J Antimicrob flaviviruses (group antigens).
Chemother 2007; 60: 1189-92. Four well-defined types of dengue virus have been
3. Koff RS. Review article: vaccination and viral hepatitis - current identified, called DENV-1, DENV-2, DENV-3 and DENV-
status and future prospects. Aliment Pharmacol Ther 2007; 26:
4, respectively; these have distinctive genetic structures.
1285-92.
4. Heller S, Valencia-Mayoral P. Treatment of viral hepatitis in Genotyping has been used to trace the movement of
children. Arch Med Res. 2007; 38: 702-10. dengue viruses between different geographic regions.
Transmission
DENGUE FEVER, DENGUE HEMORRHAGIC
FEVER, DENGUE SHOCK SYNDROME Dengue viruses are transmitted to humans through the
bites of infective female Aedes mosquitoes. Mosquitoes
Dengue fever is an acute febrile illness caused by viruses
generally acquire the virus while feeding on the blood of
belonging to the Flaviviridae family and is characterized
an infected person. After virus incubation for 8-10 days,
by biphasic fever, myalgia, arthralgia and rash. Dengue
an infected mosquito is capable, during probing and blood
hemorrhagic fever (DHF) is characterized by abnorma
feeding, of transmitting the virus, to susceptible indivi
lities in hemostasis and by marked leakage of plasma from
duals for the rest of its life. Infected female mosquitoes
the capillaries; the latter may lead to shock (dengue shock
may also transmit the virus to their offspring by transo-
syndrome).
varial (via the eggs) transmission, but the role of this in
Epidemiology sustaining transmission of virus to humans has not yet
been delineated.
The global prevalence of dengue has grown dramatically
Humans are the main amplifying host of the virus,
in recent decades. The disease is now endemic in more
although studies have shown that in some parts of the
than 100 countries in Africa, the Americas, the Eastern
world monkeys may become infected and perhaps serve
Mediterranean, South-east Asia and the Western Pacific.
South-east Asia and the Western Pacific are most seriously as a source of virus for uninfected mosquitoes. The virus
affected. Nearly 2.5 billion people are at risk from dengue. circulates in the blood of infected humans for two to seven
WHO currently estimates there may be 50 million cases days, at approximately the same time as they have fever;
of dengue infection worldwide every year. Aedes mosquitoes may acquire the virus when they feed
During epidemics of dengue, attack rates among on an individual during this period.
susceptibles are often 40-50%, but may reach 80-90%. An
estimated 500,000 cases of DHF require hospitalization Pathophysiology of the Infection and
each year, of whom a very large proportion are children. Its Consequences
At least 2.5% of cases die, although case fatality could be The major pathophysiologic changes that determine the se
twice as high. Without proper treatment, DHF case fatality verity of disease in DHF and differentiate it from dengue
rates can exceed 20%. With modern intensive supportive fever are plasma leakage and abnormal hemostasis leading
therapy, such rates are reduced to less than 1%. to rising hematocrit values, moderate to marked thrombo
Infections and Infestations 197
Asymptomatic Symptomatic
I
Dengue hemorrhagic fever
Undifferentiated fever _ ,
..... , . Dengue M
fever syndrome
1
(Vira syndrome)
*
No shock Dengue shock
syndrome
Without hemorrhage With unusual hemorrhage
In the hospital, all children without hypotension (DHF improvement. If there is no improvement in vital
grades I and II) should be given Ringer's lactate infusion parameters and hematocrit is rising, colloids 10 ml/kg are
at the rate of 7 ml/kg over one hour. After one hour if rapidly infused. If the hematocrit is falling without
hematocrit decreases and vital parameters improve, fluid improvement in vital parameters, blood is transfused
infusion rate should be decreased to 5 ml/kg over next presuming that lack of improvement is due to occult blood
hour and to 3 ml/kg/hour for 24-48 hours. When the loss (Fig. 9.6). Once improvement starts then fluid infusion
patient is stable as indicated by normal blood pressure, rate is gradually decreased. In addition to fluids, oxygen
satisfactory oral intake and urine output, the child can be should be administered to all patients in shock.
discharged (Fig. 9.5). For uncontrolled bleeding in DHF or DSS, the role of
If at one hour the hematocrit is rising and vital plasma or platelet infusion remains unclear. Infusion of
parameters do not show improvement, fluid infusion rate fresh frozen plasma and platelet concentrates may be
is increased to 10 ml/kg over next hour. In case of no beneficial in patients with disseminated intravascular
improvement fluid infusion rate is further increased to 15 coagulation.
ml/kg over the third hour. Patients showing no
improvement in vital parameters and hematocrit at end Monitoring
of 3 hours, should be treated with colloids or plasma In view of the rapid course in DHF and DSS, close
infusion (10 ml/kg) (Fig. 9.5). Once the hematocrit and monitoring of the patient is crucial in the first few hours
vital parameters are stable, the infusion rate is gradually of illness. Heart rate, respiratory rate, blood pressure and
reduced and discontinued over 24-48 hours. pulse pressure should be measured every 30 minutes until
In children with hypotension (DSS grade III) Ringer's the patient is stable and thereafter every 2-4 hours. Central
lactate solution, 10-20 ml/kg is infused over one hour or venous pressure monitoring is desirable in children who
as bolus if blood pressure is unrecordable (DSS grade IV). develop hypotension. Difficulties are often encountered
The bolus may be repeated twice if there is no in insertion of central lines in critically ill small children.
DHF I & II
»
RL 10 ml/kg/hr RL 5 ml/kg/hr
__ f
Assessment at two hours Further improvement
-*
No improvement RL 3 ml/kg/hr
Assessment at 3 hours
Discharge when stable for 24-48 hr
No improvement
J
Colloids 10 ml/kg/hr
No improvement
DSS
Assessment of shock
I '
Assessment
Improved No improvement
J 1
Gradually decrease RL Hematocrit increased Hematocrit decreased
infusion with monitoring,
as in Fig. 2
i 1
Colloids 10 ml/kg Blood transfusion
Assessment
Improved No improvement
i
Look for anemia, acidosis, myocardial dysfunction; treat accordingly
urban cycle involves A. aegypti and humans. In rural cycle Suggested reading
(seen in Africa) the disease is endemic with a small number 1. Griffin DE. Alphaviruses. In: MD, Howley PM. Fields Virology,
of cases occurring in most years. In urban areas, the Philadelphia 5th edn; Knipe. Phialadelphia: Lippincott Williams
outbreaks are sporadic and explosive with infection of a & Wilkins; 2007: 1047-8.
large population within weeks. In Asia, the virus may be 2. Ravi V. Reemergence of chikungunya virus in India. Indian J Med
Microbiol 2006; 24: 83-4.
maintained in urban cycle, with A. aegypti, or require
reinoculation before onset of epidemic. Outbreaks
HUMAN IMMUNODEFICIENCY VIRUS INFECTION
typically occur during the rainy season, associated with
the population density of the mosquito vector, which Human immunodeficiency virus (HIV) infection has
breeds in household containers and puddles with peak become an important contributor to childhood morbidity
activity in mid-morning and late afternoon. After an and mortality, especially in many developing countries.
epidemic, the disease typically vanishes for years, because
a large proportion of the population is immune. Epidemiology
The World Health Organization (WHO) estimated that
Clinical Features more than 38.6 million persons worldwide were living
The disease has a sudden onset, with an incubation pe with HIV infection at the end of 2007; 2.3 million of these
riod of 2-12 days. Infection is characterized by fever, head were children under 15 years of age. More than 90% of
ache, fatigue, nausea, vomiting, muscle pain, rash and joint HIV-infected individuals live in developing nations. Sub-
pain. Fever rises abruptly to 103-104°F and is accompa Saharan Africa accounts for nearly 90% of the world's total
nied by rigors. The acute phase lasts for 2-3 days. Joint population of HIV-infected children. India and Thailand
pain appears suddenly and is often very severe in inten dominate the epidemic in South-East Asia, with more
sity; the arthralgia/arthritis is polyarticular, migratory, recent expansion into Vietnam, China and Cambodia.
and predominantly affects the small joints of hands, wrist, Worldwide, it is estimated that 660,000 children,
ankle and feet, with less involvement of larger joints. including 270,000 children between 0 and 18 months of
Headache is present in 80% of cases. Photophobia and age require antiretroviral treatment, and that 4 million
retro-orbital pain may also occur. An itchy, transient HIV-infected and HIV-exposed infants and children
maculopapular rash appears 4-8 days later affecting the require cotrimoxazole prophylaxis from 6 weeks of age
trunk and limbs. Inguinal lymph nodes may be enlarged. to prevent Pneumocystis jiroveci pneumonia. Without
The joint pains may continue for many months after the access to antiretroviral therapy, 20% of vertically infected
illness. Fatalities are rare and associated with young age, children will progress to acquired immunodeficiency
thrombocytopenia and shock. syndrome (AIDS) or death in their first year of life and
more than half of HIV-infected children will die before
Diagnosis their fifth birthday.
fusion with the cell membrane allows entry of viral RNA in children. Approximately 10-20% of HIV-infected
into the cell cytoplasm. Viral DNA copies are then trans newborns in developed countries presented with a rapid
cribed from the virion RNA through viral reverse transcrip disease course, with onset of symptoms of AIDS during
tase enzyme activity, and duplication of the DNA copies the first few months of life and, if untreated, death from
produces double-stranded circular DNA. Because the HIV- AIDS-related complications by 4 years of age. In resource-
1 reverse transcriptase is error-prone, many mutations poor countries, >85% of the HIV-infected newborns may
arise, creating wide genetic variation in HIV-1 isolates even have such a rapidly progressing disease.
within an individual patient. The circular DNA is It has been suggested that if intrauterine infection
transported into the cell nucleus where it is integrated into coincides with the period of rapid expansion of CD4 cells
chromosomal DNA; this is called as the provirus. The in the fetus, it could effectively infect the majority of the
provirus can remain dormant for extended periods. body's immunocompetent cells. Most children in this
HIV-1 transcription is followed by translation. Acapsid group have a positive HIV-1 culture and/or detectable
polyprotein is cleaved to produce, among other products, virus in the plasma in the first 48 hours of life. This early
the virus-specific protease (plO). This enzyme is critical evidence of viral presence suggests that the newborn was
for HIV-1 assembly. The RNA genome is then incorpo infected in utero. In contrast to the viral load in adults,
rated into the newly formed viral capsid. As the new virus the viral load in infants stays high for at least the first 2
is formed, it buds through the cell membrane and is years of life.
released. The majority of perinatally infected newborns (60-80%)
HIV-2 is a rare cause of infection in children. It is most present with a second pattern that of a much slower
prevalent in Western and Southern Africa. If HIV-2 is progression of disease with a median survival time of 6
suspected, a specific test that detects antibody to HIV-2 years. Many patients in this group have a negative viral
peptides should be used. culture or PCR in the 1st week of life and are, therefore,
considered to be infected intrapartum. In a typical patient,
Transmission the viral load rapidly increases by 2-3 months of age
Transmission of HIV-1 occurs via sexual contact, (median 100,000 copies/mL) and then slowly declines over
parenteral exposure to blood, or vertical transmission from a period of 24 months. This observation can be explained
mother to child. The primary route of infection in the partially by the immaturity of the immune system in
pediatric population is vertical transmission. Most large newborns and infants. The third pattern of disease (i.e.
studies in the United States and Europe have documented long-term survivors) occurs in a small percentage (<5%)
mother-to-child transmission rates in untreated women of perinatally infected children who have minimal or no
between 12-30%. In contrast, transmission rates in Africa progression of disease with relatively normal CD4 counts
and Asia are higher, up to 50%. and very low viral loads for longer than 8 years.
Vertical transmission of HIV can occur during the HIV-infected children have changes in the immune
intrauterine or intrapartum periods, or through system that are similar to those in HIV-infected adults.
breastfeeding. Up to 30% of infected newborns are infected CD4 cell depletion may be less dramatic because infants
in utero. The highest percentages of HIV-infected children normally have a relative lymphocytosis. Therefore, for
acquire the virus intrapartum. Breastfeeding is an example, a value of 1,500 CD4 cells/mm3 in children <1
important route of transmission, especially in the year of age is indicative of severe CD4 depletion and is
developing countries. The risk factors for vertical comparable to <200 CD4 cells/mm3 in adults.
transmission include preterm delivery (<34 wk gestation), Lymphopenia is relatively rare in perinatally infected
a low maternal antenatal CD4 count, use of illicit drugs children and is usually only seen in older children or those
during pregnancy, >4 hours duration of ruptured with end-stage disease.
membranes and birth weight <2500 g. B-cell activation occurs in most children early in the
Transfusions of infected blood or blood products have infection as evidenced by hypergammaglobulinemia
accounted for a variable proportion of all pediatric AIDS associated with high levels of anti-HIV-1 antibody. This
cases. Heat treatment of factor VIII concentrate and HIV response may reflect both dysregulation of T-cell
antibody screening of donors has virtually eliminated HIV suppression of B-cell antibody synthesis and active CD4
transmission to children with hemophilia. Blood donor enhancement of B-lymphocyte humoral responses.
screening has dramatically reduced, but not eliminated, CD4 depletion and inadequate antibody responses lead
the risk of transfusion-associated HIV infection. Sexual to increased susceptibility to various infections and the
contact is a major route of transmission in the adolescent clinical manifestations vary with the severity of
population. immunodeficiency.
physical examination at birth is normal. Initial signs and swelling, lymphocytic interstitial pneumonitis (LIP) and
symptoms may be subtle and non-specific, such as early onset of progressive neurologic deterioration.
lymphadenopathy, hepatosplenomegaly, failure to thrive, The HIV classification system is used to categorize the
chronic or recurrent diarrhea, interstitial pneumonia, or stage of pediatric disease by using two parameters: clinical
oral thrush, and may be distinguishable from other causes status (Table 9.6) and degree of immunologic impairment
only by their persistence. Whereas systemic and (Table 9.7).
pulmonary findings are common in the United States and
Europe, chronic diarrhea, wasting, and severe
Opportunistic Infections
malnutrition predominate in Africa. Symptoms found Children with HIV infection and advanced or severe
more commonly in children than adults with HIV infection immunosuppression are susceptible to develop various
include recurrent bacterial infections, chronic parotid opportunistic infections. The important pathogens are
Table 9.6: WHO clinical staging of HIV/ AIDS for children with confirmed HIV infection
Clinical Stage 1
Asymptomatic Persistent generalized lymphadenopathy
Clinical Stage 2
Unexplained persistent hepatosplenomegaly Papular pruritic eruptions
Fungal nail infection Angular cheilitis
Lineal gingival erythema Extensive wart virus infection
Extensive molluscum contagiosum Recurrent oral ulceration
Unexplained persistent parotid enlargement Herpes zoster
Recurrent or chronic upper respiratory tract infections (otitis media, otorrhoea, sinusitis, tonsillitis)
Clinical Stage 3
Unexplained moderate malnutrition or wasting not adequately responding to standard therapy
Unexplained persistent diarrhoea (14 days or more)
Unexplained persistent fever (above 37.5° C intermittent or constant, for longer than one month)
Persistent oral candidiasis (after the first 6-8 weeks of life)
Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis or periodontitis
Lymph node or pulmonary tuberculosis
Severe, recurrent bacterial pneumonia
Symptomatic lymphoid interstitial pneumonitis
Chronic lung disease including bronchiectasis
Unexplained anemia (<8 g/dl), neutropenia (<0.5 x 109/L) or chronic thrombocytopenia (<50 x 109/L)
Clinical Stage 4
Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy
Pneumocystis pneumonia
Recurrent severe bacterial infections (e.g. empyema, pyomyositis, bone or joint infection, meningitis)
Chronic herpes simplex infection (orolabial, cutaneous >1 month duration or visceral at any site)
Esophageal candidiasis (or candidiasis of trachea, bronchi, lungs)
Extrapulmonary or disseminated TB
Kaposi sarcoma
Cytomegalovirus infection: retinitis or CMV infection affecting another organ, with onset at age >1 month
Central nervous system toxoplasmosis (after one month of life)
Extrapulmonary cryptococcosis (including meningitis)
HIV encephalopathy
Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidioidomycosis)
Disseminated non-tuberculous mycobacterial infection
Chronic cryptosporidiosis (with diarrhea)
Chronic isosporiasis
Cerebral or B cell non-Hodgkin lymphoma
Progressive multifocal leukoencephalopathy
Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy
Unexplained refers to where the condition is not explained by other causes
a Some additional conditions can also be included in regional classifications (e.g. reactivation of American trypanosomiasis in
Pneumocystis jiroveci, Cryptosporidium, cryptococcus, severe pneumonia can be managed as outpatients using a
isospora and CMV. second- or a third-generation cephalosporin or a
combination like- amoxicillin-clauvulanic acid. Since P.
P. jiroveci (previously P. carinii) pneumonia (PCP) is the
jiroveci pneumonia cannot be excluded at the outset in
opportunistic infection that led to the initial description
most HIV-infected children with severe respiratory
of AIDS. PCP is one of the commonest AIDS-defining
infections, cotrimoxazole should be added unless another
illnesses in children in the US and Europe. However, data
diagnosis has been definitively made.
regarding the incidence of PCP in children in other parts
The principles of supportive care of HIV-infected
of the world are scarce. The majority of the cases occur
children admitted with severe pneumonia are similar to
between 3rd and 6th months of life. Even if a child
those in non-HIV-infected children.
develops PCP while on prophylaxis, therapy may be
started with TMP/SMX. This is because the prophylaxis Tuberculosis is an important infection associated with HIV.
may have failed because of poor compliance, or unusual Co-existent TB and HIV infections accelerate the pro
pharmacokinetics. Untreated, PCP is universally fatal. gression of both the diseases. HIV-infected children are
With the use of appropriate therapy, the mortality more likely to have extrapulmonary and disseminated
decreases to less than 10%. The risk factors for mortality tuberculosis; the course is also likely to be more rapid.
are the severity of the episode, and the severity of the The overall risk of active TB in children infected with HIV
immunosuppression. is at least 5- to 10-fold higher than that in children not
Recurrent bacterial infections: In various studies from infected with HIV. All HIV-infected children with active
developing countries, up to 90% of HIV-infected children TB should receive anti tubercular therapy for 9-12 months.
had history of recurrent pneumonias. Initial episodes of A close follow-up is essential to diagnose non-response /
drug resistance early.
pneumonia often occur before the development of signi
ficant immunosuppression. As the immunosuppression Viral infections due to respiratory syncytial virus (RSV),
increases the frequency increases. The common pathogens influenza and parainfluenza viruses result in symptomatic
for community-acquired pneumonia in these children are disease more often in HIV-infected children in comparison
S. pneumoniae, H. influenzae and S. aureus. However, in to non-infected children. Infections with other viruses such
children with severe immunosuppression and in hospital- as adenovirus and measles virus are more likely to lead
acquired infections, gram negative organisms, such as, P. to serious sequelae than with the previously mentioned
aeruginosa gain importance. The clinical features of viruses. As RSV infections most often occur in children in
pneumonia in HIV-infected children are similar to those the first 2 years of life, during which many of these may
in uninfected children. However, in severely immuno not be severely immunocompromised, the severity of
compromised children, the signs may be subtle. The illness may not be different from the non-HIV-infected
response to therapy is usually slow, bacteremia is common children. In children with AIDS, disseminated CMV is a
and relapse rates are high. known opportunistic infection, but pneumonia caused by
The choice of appropriate therapy is based on the local this virus is rare. The principles of diagnosis and treatment
patterns of etiologies. In many settings, an appropriate of these infections in HIV-infected children are similar to
choice would be a combination of a broad-spectrum those in non-HIV-infected children.
cephalosporin and an aminoglycoside. In areas where a
large proportion of S. aureus isolates are resistant to Fungal infections usually present as a part of disseminated
antistaphylococcal antibiotics (MRSA), then the empiric disease in immunocompromised children. Pulmonary
inclusion of vancomycin, clindamycin, linezolid, or other candidiasis should be suspected in any sick HIV-infected
drugs to which community-acquired MRSA is usually child with lower respiratory tract infection that does not
susceptible should be considered. Children with non- respond to common therapies.
206 Essential Pediatrics
Lymphoid Interstitial Pneumonitis (LIP) of malabsorption with partial villous atrophy not
LIP is recognized as a distinctive marker for pediatric HIV associated with a specific pathogen, is probably the result
infection and is included as a Class B condition in the of direct HIV infection of the gut.
revised criteria for AIDS in children. In absence of Chronic liver inflammation is relatively common in HIV
antiretroviral therapy, nearly 20% of HIV-infected children infected children. In some children, hepatitis caused by
developed LIP. The pathogenesis of LIP are not well CMV, hepatitis B or C viruses, or mycobacteria (MAC)
understood, but might include an exaggerated immuno may lead to liver failure and portal hypertension. It is
logic response to inhaled or circulating antigens, and/or important to recognize that several of the antiretroviral
primary infection of the lung with HIV or Epstein-Barr drugs such as didanosine, and protease inhibitors may
virus (EBV). also cause reversible elevation of transaminases.
Pancreatitis is uncommon in HIV infected children. This
LIP is characterized by nodule formation and diffuse
may be the result of drug therapy, e.g. didanosine, lami
infiltration of the alveolar septae by lymphocytes,
vudine, nevirapine or pentamidine. Rarely, opportunistic
plasmacytoid lymphocytes, plasma cells and immuno-
infections such as MAC or CMV may be responsible for
blasts. There is no involvement of the blood vessels or
acute pancreatitis.
destruction of the lung tissue. Children with LIP have a
relatively good prognosis compared to other children who
Neurologic Invovement
meet the surveillance definition of AIDS. LIP is usually
diagnosed in children with perinatally acquired HIV The incidence of central nervous system (CNS) involve
infection when they are older than 1-year of age, unlike ment in perinatally infected children may be more than
PCP. Most children with LIP are asymptomatic. Tachy 50% in developing countries but lower in developed
pnea, cough, wheezing and hypoxemia may be seen when countries, with a median onset at about one and a half
children present with more severe manifestations; years of age. The most common presentation is progressive
crepitations are uncommon. Clubbing is often present in encephalopathy with loss or plateau of developmental
advanced disease. These patients can progress to chronic milestones, cognitive deterioration, impaired brain growth
respiratory failure. Long standing LIP may be associated resulting in acquired microcephaly, and symmetric motor
with chronic bronchiectasis. The presence of a reticulo- dysfunction. CNS infections- meningitis due to bacterial
nodular pattern, with or without hilar lymphadenopathy pathogens, fungi such as Cryptococcus and a number of
that persists on chest radiograph for 2 months or more, or viruses may be responsible for clinical presentations that
is unresponsive to antimicrobial therapy is considered are indications for ICU admissions. CNS toxoplasmosis
presumptive evidence of LIP. Care should be taken to is exceedingly rare in young infants, but may occur in HIV-
exclude other possible etiologies. A definitive diagnosis infected adolescents; the overwhelming majority of these
is made on histopathology. cases have serum IgG antitoxoplasma antibodies as a
Early disease is managed conservatively. The effect of marker of infection. The management of these conditions
antiretrovirals on LIP is probably limited. Steroids are is similar to that in non HIV-infected children; the response
indicated if children with LIP have symptoms and signs rates and outcomes may be poorer.
of chronic pulmonary disease, clubbing and /or hypo
xemia. Treatment usually includes an initial 4- to 12-week Cardiovascular Involvement
course of prednisolone (2 mg/kg/d) followed by a
Cardiac abnormalities in HIV-infected children are
tapering dose, using oxygen saturation and clinical status
common, persistent, and often progressive; however, the
as a guide to improvement. This is then followed by
majority of these are sub-clinical. Left ventricular (LV)
chronic low dose prednisolone.
structure and function progressively may deteriorate in
the first 3 years of life, resulting in subsequent persistent
Gastrointestinal Disease
mild LV dysfunction and increased LV mass in HIV-
The pathologic changes in the gastrointestinal tract of infected children. Children with encephalopathy or other
children with AIDS are variable and can be clinically AIDS-defining conditions have the highest rate of adverse
significant. A variety of microbes can cause gastro cardiac outcomes. Resting sinus tachycardia is reported
intestinal disease, including bacteria (salmonella, in up to nearly two-thirds and marked sinus arrhythmia
campylobacter, Mycobacterium avium intracellulare in one-fifth of HIV-infected children. Gallop rhythm with
complex), protozoa (giardia, Cryptosporidium, isospora, tachypnea and hepatosplenomegaly appear to be the best
microsporidia), viruses (CMV, HSV, rotavirus), and clinical indicators of congestive heart failure (CHF) in HIV-
Candida. The protozoal infections are most severe and can infected children; anticongestive therapy is generally very
be protracted in children with severe immunosuppression. effective, especially when initiated early. Electro
Children with Cryptosporidium infestation can have cardiography and echocardiography are helpful in
severe diarrhea leading to hypovolemic shock; this may assessing cardiac function before the onset of clinical
merit admission to PICU. AIDS enteropathy, a syndrome symptoms.
Infections and Infestations 207
Renal Involvement or have stage 1 or 2 disease may receive ART if they have
Nephropathy is an unusual presenting symptom of HIV evidence of advanced or severe immunosupression.
infection, more commonly occurring in older symptomatic The availability of antiretroviral therapy has trans
children. Nephrotic syndrome is the most common mani formed HIV infection from a uniformly fatal condition to
festation, with edema, hypoalbuminemia, proteinuria and a chronic infection, where children can lead a near normal
life. The currently available therapy does not eradicate
azotemia with normal blood pressure. Polyuria, oliguria
the virus and cure the child; it rather suppresses the virus
and hematuria have been observed in some patients.
replication for extended periods. The 3 main groups of
Diagnosis drugs are nucleoside reverse transcriptase inhibitors
(NRTI), non-nucleoside reverse transcriptase inhibitors
All infants born to HIV-infected mothers test antibody-
(NNRTI) and protease inhibitors (PI). Highly active
positive at birth because of passive transfer of maternal
antiretroviral therapy (HAART) is a combination of 2
HIV antibody across the placenta. Most uninfected infants
NRTIs with a PI or a NNRTI. The details of the antiretro
lose maternal antibody between 6 and 12 months of age.
viral drugs are shown in Table 9.8.
As a small proportion of uninfected infants continue to
have maternal HIV antibody in the blood up to 18 months Cotrimoxazole Prophylaxis
of age, positive IgG antibody tests cannot be used to make
In resource-limited settings, cotrimoxazole prophylaxis is
a definitive diagnosis of HIV infection in infants younger
recommended for all HIV exposed infants starting at 4-6
than this age. In a child older than 18 months of age,
weeks of age (or at first encounter with the health care
demonstration of IgG antibody to HIV by a repeatedly
system) and continued until HIV infection can be exclu
reactive enzyme immunoassay (EIA) and confirmatory ded. Cotrimoxazole is also recommended for HIV-exposed
test (e.g., Western blot or immunofluorescence assay) can breastfeeding children of any age, and cotrimoxazole
establish the diagnosis of HIV infection. Although prophylaxis should be continued until HIV infection can
serologic diagnostic tests were the most commonly used be excluded by HIV antibody testing (beyond 18 months
in the past, tests that allow for earlier definitive diagnosis of age) or virological testing (before 18 months of age) at
in children have replaced antibody assays as the tests of least six weeks after complete ceszation of breastfeeding.
choice for the diagnosis of HIV infection in infants. All children younger than one year of age documented
Specific viral diagnostic assays, such as HIV DNA or to be living with HIV should receive cotrimoxazole
RNA PCR, HIV culture, or HIV p24 antigen immune prophylaxis regardless of symptoms or CD4 percentage.
dissociated p24 (ICD-p24), are essential for diagnosis of After one year of age, initiation of cotrimoxazole prophy
young infants born to HIV infected mothers. By 6 months laxis is recommended for symptomatic children (WHO
of age, the HIV culture and/or PCR identifies all infected clinical stages 2, 3 or 4 for HIV disease) or children with
infants, who are not having any continued exposure due CD4 <25%. All children who begin cotrimoxazole prophy
to breastfeeding. HIV DNA PCR is the preferred virologic laxis (irrespective of whether cotrimoxazole was initiated
assay in developed countries. Plasma HIV RNA assays in the first year of life or after that) should continue until
may be more sensitive than DNA PCR for early the age of five years, when they can be reassessed.
diagnosis, but data are limited. HIV culture has similar
sensitivity to HIV DNA PCR; however, it is more Nutrition
technically complex and expensive, and results are often It is important to provide adequate nutrition to HIV-
not available for 2—1 week compared to 2-3 days with PCR. infected children. Many of these children have failure to
The p24 antigen assay is less sensitive than the other thrive. These children will need nutritional rehabilitation.
virologic tests. Figure 9.7 shows the suggested algorithm In addition, micronutrients like zinc may be useful.
for diagnosis of HIV infection in infants.
Immunization
Management
The vaccines that are recommended in the national
The management of HIV infected child includes antiretro schedule can be administered to HIV infected children
viral therapy, prophylaxis and treatment of opportunistic except that symptomatic HIV infected children should not
infections and common infections, adequate nutrition and be given OPV and BCG.
immunization.
Prevention of Mother to Child Transmission (MTCT)
Antiretroviral Therapy The risk of MTCT can be reduced to under 2% by interven
Decisions about antiretroviral therapy for pediatric HIV- tions that include antiretroviral (ARV) prophylaxis given
infected patients are based on the magnitude of viral rep to women during pregnancy and labor and to the infant in
lication (i.e. viral load), CD4 lymphocyte count or percent the first weeks of life, obstetrical interventions including
age, and clinical condition. A child who has WHO stage 3 elective cesarean delivery (prior to the onset of labor and
or 4 clinical disease should receive ART irrespective of rupture of membranes), and complete avoidance of
the immunologic stage. Children who are asymptomatic breastfeeding.
208 Essential Pediatrics
Delivery
HIV-exposed infant
HIV + pregnant woman
(breastfed and non-breastfed)
Fig. 9.7 : HIV diagnosis in children below the age of 18 months with DNA-PCR
Antiretroviral Drug Regimens for Omission of the Sd-NVP for the mother may be
Treating Pregnant Women considered for women who receive at least four weeks of
Recommended regimen for pregnant women with AZT before delivery. When Sd-NVP is used to prevent
indication for antiretroviral therapy (ART) is combination MTCT, either alone or in combination with AZT, the
of zidovudine (AZT), lamivudine (3TC) and nevirapine rationale of giving AZT and 3TC intrapartum and for
(NVP) in antepartum, intrapartum and postpartum pe seven days postpartum is to prevent resistance to NVP.
riod. The recommended regimen for pregnant women
who are not eligible for ART, but for preventing MTCT is: ARV Regimens for Infants Born to HIV Positive
• Antepartum: AZT starting at 28 weeks of pregnancy Mothers
• Intrapartum: A combination of single dose (Sd) NVP, The recommended regimen for infants is Sd-NVP + AZT
AZT and 3TC for one week. When delivery occurs within two hours of
• Postpartum: A combination of AZT and 3TC for 7 days. a woman taking Sd-NVP, the infant should receive Sd-
The recommended treatment for pregnant women in NVP immediately after delivery and AZT for four weeks.
labor and who have not received ART is: If the mother receives less than four weeks of antenatal
• Intrapartum: A combination of Sd-NVP, AZT and 3TC ART, then four weeks rather than one week of AZT is
• Postpartum: A combination of AZT and 3TC x 7 weeks recommended for the infant.
Infections and Infestations 209
milk, the presence of mastitis and low maternal CD4+ T the occurrence of tuberculosis disease. Approximately 40%
cell count. Exclusive breastfeeding has been reported to of infected children less than 1 year of age if left untreated
carry a lower risk of HIV transmission than mixed feeding. develop radiologically significant lymphadenopathy or
According to current UN recommendations (WHO, 2001) segmental lesions compared with 24% of children between
when replacement feeding is acceptable, feasible, affordable, 1-10 years and 16% of children 11-15 years of age. In India,
sustainable and safe, avoidance of all breastfeeding by HIV- over 100,000 children die from tuberculosis every year.
infected mothers is recommended. Otherwise, exclusive The important reasons for a recent worldwide increase
breastfeeding is recommended during the first months of in childhood tuberculosis include inadequate treatment
life. WHO recommends that the transition between facilities for tuberculosis, inadequate facilities to prevent
exclusive breastfeeding and early cessation of breastfeed tuberculosis infection in children, HIV pandemic, and
ing should be kept as short as possible, "early and abrupt emergence of drug resistance with nearly 170,000 children
cessation" bearing in mind that mixed feeding during this dying of it every year. Due to improved standard of living
period carries a 70% greater risk of MTCT. Replacement and better sanitation, the incidence of tuberculosis has
feeding should be given by katori spoon. steadily declined in the affluent and highly developed
countries. However, it is still a major public health problem
Suggested reading in the economically underprivileged countries of Asia,
1. WHO/UN AIDS. AIDS epidemic update Dec 2007. Africa and South America.
2. WHO. Antiretroviral therapy of HIV infection in infants and
children in resource-limited settings: towards universal access. Epidemiology
WHO 2006.
Agent
All patients of pulmonary tuberculosis and most cases of
COMMON BACTERIAL INFECTIONS
extrapulmonary disease are caused by human type strain
of Mycobacterium tuberculosis. A few cases of extra
TUBERCULOSIS
pulmonary illness particularly the tubercular lymph
Tuberculosis is a chronic infectious disease caused by adenitis may be due to the bovine strain.
Mycobacterium tuberculosis. Tuberculosis still is one of the
deadliest diseases in the world killing nearly 2 million Reservoir of Infection
people every year. More than ninety percent of all The infection is spread by the tuberculous patient, who
tuberculosis cases occur in the developing countries, discharges tubercle bacilli in his sputum or nasopharyn
where limited resources are available for optimal geal secretions during bouts of coughing or sneezing, etc.
treatment. Tuberculosis continues to be an important Such patients are open or infective cases. In the pediatric
cause of morbidity and mortality for children worldwide. age groups, few infections may also occur by the
transplacental route (congenital tuberculosis).
Magnitude of the Problem
Since most children acquire the organism from adults in Mode of Infection
their surroundings, the epidemiology of childhood The usual mode of infection is through inhalation of
tuberculosis follows that in adults. Because of the difficulty droplets of infected secretions. The infected sputum
of confirming the diagnosis the global burden of childhood spitted carelessly by open cases of tuberculosis dries up
tuberculosis in the world is unclear. Another important and the tubercle bacilli are resuspended in the dust and
reason is that children do not make a significant air. This may be a source of infection through breathing.
contribution to the spread of tuberculosis. Several Infection through ingestion of infected material is rare.
estimates make use of an arbitrary calculation assigning Rarely infection may be transmitted through skin, mucous
10% of the tuberculosis burden to children. Tuberculosis membrane or transplacentally.
infection and disease among children are much more
Hj prevalent in developing countries, where resources for Host Factors
W control are scarce. It is estimated that in developing
Cl countries the annual risk of tuberculosis infection in Age: No age is exempt from tuberculosis. Tubercle bacilli
are not transferred across the healthy placenta but the fetus
I children is 2-5%. The estimated lifetime risk of developing
may be infected from the infected placenta. Frequency of
■ tuberculosis disease for a young child infected with M.
infection with tubercle bacilli increases progressively as
tuberculosis as indicated by positive tuberculin test is about
the child grows in age. As discussed above, an infant is
10%. About 5% of those infected are likely to develop
more likely to develop disease after an infection compared
disease in the first year after infection and the remaining
with an older child.
5% during their lifetime. These rates increase about six
fold in HIV infected individuals. Nearly 8-20% of the Sex: The adolescent children especially the girls are more
deaths caused by tuberculosis occur in children. The age prone to develop active tuberculosis disease during
of the child at acquisition of infection has a great effect on puberty.
Infections and Infestations 211
microbiologic evidence in the majority of children with be seen in about 50% children. Meningitis may occur in
pulmonary tuberculosis. The onset of symptoms is 20-30% of cases.
generally insidious, but may be relatively acute in miliary
Pleural effusion follows the rupture of a subpleural focus
tuberculosis.
into the pleural cavity. The pleura may also be infected
Primary infection usually passes off unrecognized. Asymp by hematogenous spread from the primary focus. The
tomatic infection is defined as infection associated with effusion usually occurs because of hypersensitivity to
tuberculin hypersensitivity and a positive tuberculin test tuberculoproteins. If the sensitivity is high, there is
but with no striking clinical or roentgenographic mani significant pleural effusion along with fever and chest pain
festations. on affected side. Minor effusions associated with the rup
Most symptoms in children with primary complex ture of primary foci are usually not detected. Tuberculous
(PPC) are constitutional in the form of mild fever, anorexia, effusion is uncommon in children younger than 5-years
weight loss, decreased activity. Cough is an inconsistent of age, is more common in boys, and is rarely associated
symptom and may be absent even in advanced disease. with segmental lesion and miliary tuberculosis. The onset
Irritating dry cough can be a symptom of bronchial and may be insidious or acute with rise in temperature, cough,
tracheal compression due to enlarged lymph nodes. In dyspnea and pleuritic pain on the affected side. There is
some children, the lymph nodes continue to enlarge even usually no expectoration. Pain in chest may disappear once
after resolutions of parenchymal infiltrate. This may lead the fluid separates the inflamed pleural surfaces; this may
to compression of neighboring regional bronchus. The be replaced by some discomfort. Increase in effusion may
PPC may be picked up accidentally during evaluation of make breathing shallow and difficult. The clinical findings
intercurrent infections. depend on the amount of fluid in the pleural cavity. In
early stages, a pleural rub may be present. Early signs
Progressive primary disease (PPD) is the result of the
include decreased chest wall movement, impairment of
progression of primary disease. Children with PPD may
percussion note and diminished air entry on the affected
present with high-grade fever and cough. Expectoration
side. As the fluid collection increases, the signs of pleural
of sputum and hemoptysis are usually associated with
effusion become more definite.
advanced disease and development of cavity or ulceration
of the bronchus. Abnormal chest signs consist mainly of
dullness, decreased air entry and crepitations. Cavitating
Extrathoracic Tuberculosis
pulmonary tuberculosis is uncommon. The most common forms of extrathoracic disease in
Children with endobronchial tuberculosis may present children include tuberculosis of the superficial lymph
with fever, troublesome cough (with or without expecto nodes (scrofula) and the central nervous system. Other
ration). Dyspnea, wheezing and cyanosis maybe present. rare forms of extrathoracic disease in children include
Occasionally, the child may be misdiagnosed as asthma. osteoarticular, abdominal, gastrointestinal, genitourinary,
In a wheezing child less than 2- yr-old, the possibility of cutaneous and congenital disease.
endobronchial tuberculosis should always be considered.
TB of the superficial lymph nodes can be associated with
Partial compression of the airway can lead to emphysema.
drinking unpasteurized cow's milk or can be caused by
Features of collapse may be present if a large airway is
extension of primary lesions of the upper lung fields or
completely compressed.
abdomen leading to involvement of the supraclavicular,
Miliary tuberculosis is an illness characterized by heavy
anterior cervical, tonsillar and submandibular nodes.
hematogenous spread and progressive development of
Although lymph nodes may become fixed to surrounding
innumerable small foci throughout the body. The disease
tissues, low grade fever may be the only systemic
is most common in infants and young children. The onset
symptom. A primary focus is visible radiologically only
of illness is often sudden. The clinical manifestations
30 to 70% of the time. Tuberculin skin test results usually
depend on the numbers of disseminated organisms and
are reactive. Although spontaneous resolution may occur,
the involved organs. The child may have high-grade fever,
untreated lymphadenitis frequently progresses to
I which is quite unlike other forms of tuberculosis. The child
caseating necrosis, capsular rupture, and spread to
•1 may also have dyspnea and cyanosis. There are hardly
adjacent nodes and overlying skin, resulting in a draining
Si any pulmonary findings but fine crepitations and rhonchi
sinus tract that may require surgical removal.
I may be present. These findings may occasionally be
^ confused with other acute respiratory infections of Central nervous system disease is the most serious compli
childhood. The illness may be severe, with the child having cation of tuberculosis in children and arises from the for
high fever, rigors and alteration of sensorium. In addition, mation of a caseous lesion in the cerebral cortex or me
these children may have lymphadenopathy and ninges that results from occult lymphohematogenous
hepatosplenomegaly. The other presentation of miliary spread. Infants and young children are likely to experi
tuberculosis may be insidious with the child appearing ence a rapid progression to hydrocephalus, seizures and
unwell, febrile and losing weight. Choroid tubercles may cerebral edema. In older children, signs and symptoms
Infections and Infestations 213
progress over the course of several weeks, beginning with weightage is given to laboratory tests, i.e. demonstration
fever, headache, irritability and drowsiness. The disease of acid fast bacilli, tubercles on histology, suggestive
advances with symptoms of lethargy, vomiting, nuchal radiology and tuberculin test >10 mm induration. These
rigidity, seizures, hypertonia and focal signs. The final scoring systems are not used routinely.
stage of disease is marked by coma, hypertension,
decerebrate and decorticate posturing, and death. Rapid Laboratory Tests
confirmation of tuberculous meningitis can be difficult The diagnostic tests for pulmonary tuberculosis can be
because of the wide variability in cerebrospinal char divided into 2 categories: (a) demonstration or isolation
acteristics, nonreactive tuberculin skin tests in 40% and of M. tuberculosis or one of its components; (b) demons
normal chest radiographs in 50%. Because improved tration of host's response to exposure to M. tuberculosis.
outcomes are associated with early treatment, empiric
antituberculous therapy should be considered for any Demonstration of M. tuberculosis or
child with basilar meningitis, hydrocephalus or cranial its components
nerve involvement that has no other apparent cause. M. tuberculosis can be demonstrated by (i) Ziehl Neelson
Tuberculosis of abdomen is often due to hematogenous (ZN) staining, (ii) special stains, (iii) cultures,
spread from the primary focus in the lungs. It may, (iv) polymerase chain reaction and (v) other methods. The
however, be secondary to swallowing of the infected above methods can be used on sputum, gastric lavage,
sputum by a patient with pulmonary lesions. Primary bronchoscopic lavage fluid, or pleural fluid. The best
tuberculosis of the intestines due to ingestion of the food specimen for demonstration of M. tuberculosis in children
contaminated by tubercle bacilli is relatively less common is the early morning gastric aspirate obtained by using a
in India as the milk is generally boiled before use. nasogastric tube before the child arises. The yield of M.
Patients with abdominal tuberculosis may remain tuberculosis on ZN stain is less than 20% and depends on
asymptomatic initially. Symptomatic patients show extent of pulmonary disease and number of specimen
evidence of tuberculous toxemia and may present with tested. For better results 3 consecutive specimen of gastric
colicky abdominal pain, vomiting and constipation. The aspiration are recommended. If a delay in the processing
abdomen feels characteristically doughy. The abdominal of specimen is expected the GA should be neutralized with
wall is not rigid but appears tense, so that the abdominal sodium bicarbonate for higher yield.
viscera cannot be palpated satisfactorily. The rolled up
omentum and enlarged lymph nodes may appear as Culture
irregular nodular masses with ascites. The liver and spleen
Lowenstein- Jensen (LJ) medium is the most widely used
are often enlarged. Histological examination of the liver
medium for determination of characteristic features of
may show granulomatous hepatitis and fatty change.
colonial morphology, growth rate and pigment produc
Diagnosis tion. Though the culture technique is simple, 7-10 week
of incubation may be necessary for detection of organisms.
The diagnosis of tuberculosis in children is usually based
Microscopic examination of thin layer culture plate may
on clinical signs and symptoms, chest roentgenogram,
lead to detection of microcolonies of M. tuberculosis as early
tuberculin testing and history of contact with adult
as after 7 days. The yield of culture of gastric aspirate
patients. Clinical features may be nonspecific and chest
varies from 30-50% in children with tuberculosis.
radiograph and Mantoux test are difficult to interpret. In
Excessively long period required for isolation of M.
addition, these do not give conclusive evidence for the
tuberculosis by conventional culture techniques has led to
disease. Although demonstration of mycobacterium in
the development of other techniques for culture such as
various clinical specimens remains gold standard, this is
BACTEC radiometric assay, Septichek AFB system and
often not possible in children due to the pauci-bacillary
mycobacterial growth indicator tube system.
nature of the illness.
A history of contact with an infective case contact is defined
Polymerase Chain Reaction (PCR)
as any child who lives in a household with an adult taking
antitubercular therapy or has taken such therapy in past PCR is the most commonly used technique of nucleic acid
2-years. A history of contact is available in less than one- amplification, for diagnosis of tuberculosis. The PCR may
third of the patients. Contacts can often be traced to be used to (i) diagnose tuberculosis rapidly by identifying
maidservant, cook, domestic aid or gardener in case of DNA from M. tuberculosis in clinical samples that are
tuberculous children from well-to-do families with healthy negative by microscopic examination; (ii) determine
parents. Tracing of contact is important not only for rapidly whether acid-fast organisms identified by micro
confirming the diagnosis but also for protection of other scopic examination in clinical specimens are M. tuberculo
vulnerable children from the disease. sis or atypical mycobacteria; and (iii) identify the pres
Various scoring systems have been developed for ence of genetic modifications known to be associated with
diagnosis of tuberculosis. In these scoring system more resistance of some antimycobacterial agents. The most
214 Essential Pediatrics
Serodiagnosis
In absence of good diagnostic method for childhood
tuberculosis, a lot of interest has been generated in
serodiagnosis. ELISA has been used in children to detect
antibodies to various purified or complex antigens of M. Fig. 9.8 : X ray film of PPC showing left hilar adenopathy with ill
tuberculosis. Despite a large number of studies published, defined parenchymal lesion
serology has found little place in the routine diagnosis of
tuberculosis in children, even though it is rapid and does predilection of involvement of apical or posterior
not require specimen from the site of disease. Sensitivity segments of upper lobe or superior segment of lower lobe
(Fig. 9.9). There may be features of collapse as well (Fig.
and specificity depend on the antigen used, gold standard
9.10). Bronchiectasis may occur in PPD because of (i)
for the diagnosis, and the type of tubercular infection. At
destruction and fibrosis of lung parenchymal resulting in
present, serodiagnosis does not have any role in diagnosis
retraction and irreversible bronchial dilatation, and (ii)
of childhood pulmonary tuberculosis.
cicatricial bronchostenosis secondary to localized
endobronchial infection resulting in obstructive
Methods to Diagnose Latent Tuberculosis Infection
pneumonitis and distal bronchiectasis. In children,
Till date, tuberculin skin test was the only method to cavitary disease is uncommon and occurs rarely in
diagnose latent tuberculosis infection. Recently, a new test children.
QuantiFERON®-TB test (QFT) was approved by the Food
and Drug Administration as an aid for detecting latent
M. tuberculosis infection. This is an in vitro diagnostic aid
that measures a component of cell-mediated immune
reactivity to M. tuberculosis, and is based on the quanti
fication of interferon-gamma (IFN-gamma) released from
sensitized lymphocytes in whole blood incubated
overnight with purified protein derivative (PPD) from M.
tuberculosis and control antigens. Similarly, another in vitro
test- ELISPOT is also available for diagnosis of latent
infection.
Radiology
Chest radiograph has an important role in diagnosis of
^ childhood tuberculosis, especially pulmonary tuber-
I culosis. In extra-pulmonary tuberculosis, presence of
1 lesions on chest radiograph supports diagnosis.
Pleural effusion may occur with or without lung lesion consolidation and atelectasis are non-specific. Contrast
(Fig. 9.11). In miliary tuberculosis, there are multiple enhanced MRI is emerging as a very useful technique for
lesions of size 2-5 mm (Fig. 9.12). Occasionally, the chest diagnosing CNS tuberculosis, as it demonstrates the
radiograph may be normal and lymphadenopathy may localized lesions, meningeal enhancement and the brain
be detected on computed tomography (CT), which is not stem lesions.
evident radiographically. In addition, CT features such as
Tuberculosis Skin Test
low attenuation lymph nodes with peripheral enhance
ment, lymph node calcification, branching centrilobular The tuberculin skin test (Mantoux text) is the test most
nodules and miliary nodules are helpful in suggesting the commonly used for establishing the diagnosis of
diagnosis in cases where the radiograph is normal or tuberculosis in children. Although currently available
equivocal. Other features such as segmental or lobar tuberculin skin test antigens are not 100 percent sensitive
or specific, no better diagnostic test is widely available.
The positive and negative predictive values of the
tuberculin skin test are affected significantly by a number
of factors. Infection with M. tuberculosis produces a
delayed-type hypersensitivity reaction to specific
antigenic components of the bacilli. All PPD lots are bio
assayed to demonstrate equal potency. Thus, the standard
test dose of a commercially available preparation is
defined as the dose of that product that is biologically
equivalent to 5 TU of PPD-S or 2 TU of tuberculin PPD
RT23. The reaction to tuberculin typically begins 5 to 6
hours after the patient receives the injection and reaches
maximal induration at 48 to 72 hours. In some individuals,
the reaction may peak after 72 hours. In these instances,
the tuberculin skin test should be measured again and
interpretation of the test should be based on the larger,
later reading. Rarely, vesiculation and necrosis may occur.
In these cases, repeat tuberculin testing should be avoided.
Variability of the tuberculin skin test may be reduced by
giving careful attention to details of administration and
reading. A one-quarter to one-half inch, 26-gauge needle
and tuberculin syringe are used to inject 0.1 mL of PPD
intradermally into the volar aspect of the forearm. Forty-
Fig. 9.11: Showing massive pleural effusion on left side eight to seventy-two hours after the injection is given, the
216 Essential Pediatrics
diameter of induration should be measured transversely Table 9.10: Interpretation of Mantoux test
to the long axis of the forearm and recorded in millimeters.
Size of induration Interpretation
A trained health care professional should read all skin
tests. A non-reactive tuberculin skin test does not exclude <10 mm Negative; no active disease
latent or active tuberculosis. Numerous factors can
5-10 mm Borderline; consider positive in
diminish tuberculin reactivity, resulting in a false-negative immunocompromised host; contact with
reaction. Numerous factors also have been associated with adult patient with sputum AFB positive
false positive tuberculin reactions and decreased tuberculosis
tuberculin test specificity (Table 9.9). Because some
>10 mm Positive; suggests disease in presence of
antigens in PPD are shared with other mycobacteria and
clinical features
Bacille Calmette-Guerin (BCG), false-positive reactions can
occur in children who have been infected with other
mycobacterium or have received BCG vaccination. No
reliable method for distinguishing BCG-induced cross Histopathology
reactivity from reactivity secondary to mycobacterial Lymph nodes, liver and other tissues may be examined
infection exists. Although BCG vaccination of older for histological evidence of tuberculosis by fine needle
children or adults results in greater initial and more aspiration cytology (FNAC).
persistent cross-reactivity, most of these individuals lose
cross-reactivity within 10 years of receiving the vacci Diagnostic Algorithm for Tuberculosis
nation. Interpretation of tuberculin skin test reactions is The diagnosis of tuberculosis disease in children continues
based on risk of infection and progression to disease (Table to be challenging. Even in the advanced nations, the
9.10). diagnosis is most often made by combination of a positive
tuberculin skin test, chest radiograph, physical
BCG test examination and history of contact with adult patient with
An accelerated response after injection of the vaccine is tuberculosis. Newer diagnostic methods such as PCR,
observed in individuals suffering from tuberculosis. An chromatography and serodiagnosis have not given
induration of more than 5-6 mm after 3 days of BCG encouraging results. Newer staining and culture methods
vaccine is considered a positive reaction. The Indian have found their place in the management of tuberculosis.
Academy of Pediatrics does not recommend BCG test for There is a need to develop better techniques for diagnosis
diagnosis of tuberculosis. of tuberculosis in children. The suggested algorithm for
Table 9.9: Causes of false positive and false negative Mantoux test
diagnosis of pulmonary tuberculosis is given in of large number of treatment trials for children and con
Fig. 9.13. cern about the development of resistance to anti
tuberculosis drugs. Short-course chemotherapy, with the
Treatment treatment duration as short as 6 months, has become the
The principles of therapy in children with tuberculosis are standard practice. Intermittent regimens have been
similar to that of adults. documented to be as effective as daily regimen in the
paediatric population.
Commonly Used Drugs in Childhood Tuberculosis The major problem in inclusion of children in Directly
The drugs used for treatment of tuberculosis in children Observed Treatment Short course (DOTS) program has
are given in Table 9.11. been a difficulty in demonstration of AFB and classi
fication of different clinical manifestations according to
Drug Regimens categories described for adults. There have been efforts
During the last few years, changes have occurred in the to develop classification of different types of childhood
therapeutic approach to childhood tuberculosis as a result tuberculosis into 3 categories similar to those for adults.
Pulmonary TB suspect
• Fever and/or cough > 3 weeks
• +/- Loss of weight / No weight gain
• H/o contact with suspected or diagnosed case of active TB
Sputum examination
............... r—“—
Q Symptoms persist
Fig. 9.13: Diagnostic algorithm for pediatric tuberculosis (TB). CXR Chest X-ray, Mx Mantoux/tuberculin test
Recently a consensus statement jointly prepared by Indian transmission in a newborn with multiple focus of infection.
Academy of Pediatrics and Revised National Tuberculosis It is difficult to differentiate between congenital and
Control Program (RNTCP) has also proposed a classi postnatally acquired tuberculosis.
fication of different types of tuberculosis in children into Infants born to mothers with active tuberculosis should
three categories. be screened for evidence of disease by a thorough physical
Table 9.12 gives standardized categories given by WHO examination, tuberculin test and X-ray film of chest. If
along with suggested clinical condition in children. physical examination and investigations are negative for
disease, the infant should be started on isoniazid
Corticosteroids prophylaxis at doses of 5 mg/kg/day for 6 months. After
Corticosteroids, in addition to antitubercular drugs, are three months, the patients should be examined for
useful in treatment of patients with CNS tuberculosis and evidence of infection and a repeat tuberculin test is done.
occasionally pulmonary tuberculosis. These are useful in If tuberculin test is negative, the infant can be immunized
settings where the host inflammatory reaction contributes with BCG and INH can be stopped. If tuberculin test is
significantly to tissue damage. Short courses of cortico positive but the infant is asymptomatic, INH prophylaxis
steroids are indicated in children with endobronchial is continued for another 3 months.
tuberculosis that causes localized emphysema, segmental Infants with congenital tuberculosis should be treated
pulmonary lesions or respiratory distress. Some children with four drugs (isoniazid, rifampicin, pyrazinamide,
with severe miliary tuberculosis may show dramatic streptomycin) in the intensive phase followed by two
improvement with corticosteroids if alveolocapillary block drugs (isoniazid, rifampicin) during maintenance phase
is present. Significant improvement in symptoms can for next 4 months.
occur in children with tuberculous pleural effusion. The
most commonly used medication is prednisolone, at doses Management of a Child in Contact
of 1-2 mg/kg/day for 4-6 weeks. with an Adult with Tuberculosis
Nearly one-third of children (aged less than 5 years) in
Management of an Infant born
contact with adults with active tuberculosis disease may
to Mother with Tuberculosis
have evidence of tuberculosis infection. The infection was
Congenital tuberculosis is rare. The fetus may be infected more commonly associated with younger age, severe
either by hematogenously through umbilical vessels or malnutrition, absence of BCG vaccination, contact with
through ingestion of infected amniotic fluid. In the former an adult who was sputum positive and exposure to
situation, there will be primary focus in liver and in latter environmental tobacco smoke. It is suggested that children
it will be in lungs. It is difficult to find the route of below 5 years of age in contact with adult patients with
sputum positive tuberculosis should receive 6 months of at risk of developing drug resistant tuberculosis: children
isoniazid prophylaxis. It is mandatory to screen all in contact with adult patients who have proven drug
children in the household of an adult patient with sputum resistant tuberculosis, children with tuberculosis getting
positive tuberculosis for evidence of tuberculosis. antituberculosis drugs but not responding and children
who respond to antituberculosis drugs in the beginning
Monitoring of Therapy and then show deterioration. Appearance of new lymph
Response to treatment can be judged by using the nodes on treatment, persistence of shadow or isolated non
following criteria: clinical, radiological, bacteriological, clearance of X-ray film of the chest should not be
and laboratory test. considered indicator of drug resistant tuberculosis.
epithelial cells and liberates serous and fibrinous material the fluorescent antibody technique may be used to iden
which forms a grayish white pseudomembrane which tify diphtheria bacilli.
bleeds on being dislodged. The surrounding tissue is Nasal diphtheria should be differentiated from foreign
inflamed and edematous. body nose or congenital syphilis. Faucial diphtheria
The organs principally affected by the exotoxin include should be differentiated from acute streptococcal
the heart, kidney and myocardium. membranous tonsillitis (patients have high fever but are
less toxic and the membrane is confined to the tonsils),
Clinical Features viral (adenovirus) membranous tonsillitis (high fever, sore
The onset is generally acute with fever, malaise and throat, membranous tonsillitis with normal leukocyte
headache. The child has a toxic look. Shock may occur count, self limited course of 4-8 days), herpetic tonsillitis/
due to myocarditis or adrenal insufficiency. aphthous stomatitis (extremely painful condition that
The local manifestations depend on the site of responds to levimasole), thrush (moniliasis), infectious
involvement. mononucleosis (generalized rash, lymphadenopathy,
abnormal lymphocytosis, positive Paul Bunnel test),
Nasal Diphtheria agranulocytosis and leukemia. Laryngeal diphtheria
This is characterized by unilateral/bilateral sero- should be differentiated from croup, acute epiglottitis,
sanguinous discharge from the nose and excoriation of laryngotracheobronchitis, retropharyngeal abscess,
upper lip. The child does not look too sick. peritonsillar abscess and bronchopneumonia.
cultured on Bordet-Gengou medium, which is often multiplies in the reticuloendothelial system and after
positive in the catarrhal and paroxysmal stage. Rapid tests incubation period varying from 7-14 days spills into the
like direct fluorescent antibody and counter immuno- bloodstream and is widely disseminated, especially to
electrophoresis exist but are not available routinely. Other liver, spleen, bone marrow, gallbladder and the Peyers
conditions that present with prolonged episodes of patches of the terminal ileum. This spill marks the onset
spasmodic cough include adenoviral infection, endobron of clinical manifestations of enteric fever. Infection leads
chial tuberculosis, inhaled foreign body and reactive to both local and systemic immune responses, which are,
airway disease. however, inadequate to prevent relapse or reinfection.
beta lactams such as cefixime or ceftriaxone as compared In summary, blood culture is the most important
to quinolones and azithromycin. investigation in diagnosis of enteric fever. The blood
culture is 100% specific, gives information on antimicrobial
Carrier State susceptibility of the isolate, is cost effective in the long
Although 5-10% adult patients may shed salmonella in run and is particularly important as other diagnostic
stool following an acute attack for up to 3 months, only 1- methods are suboptimal.
4% excrete bacilli for more than 1 year. These individuals
are potential sources of infection for family members and Treatment
contacts and for the community if they are in occupations
Indications for Inpatient Treatment
that involve food-processing. There is no data on carrier
prevalence in children and routine examination of stool Most cases of enteric fever can be managed at home with
following recovery from enteric fever is not recommended. oral antibiotics and advice to seek medical follow up in
case of failure to respond to therapy or development of
Diagnosis complications. Children with persistent vomiting, inability
Leukocyte counts may be normal to low with absolute to take orally, severe diarrhea or abdominal distension
eosinopenia and neutrophilic predominance. Anemia and usually require intravenous antibiotics therapy and
thrombocytopenia may occur in advanced illness. There intravenous fluids, necessitating admission to hospital.
may be mild elevation of transaminases to 2-3 times
normal. The gold standard for diagnosis is blood culture. Antimicrobial Susceptibility
The sensitivity is greatest in the first week at around 90% The antimicrobial sensitivity of S. typhi/paratyphi has
but drops to 40% in the 4th week. Its overall sensitivity is shown changes over the decades. Though resistance to
60%, which reduces to 20^0% after antibiotics. Salmonella chloramphenicol was first noted soon after its first use in
is an easy organism to culture and use of bile broth media the 1940's, it was not until 1972 that chloramphenicol-
and automated culture systems such as BACTEC improve resistant typhoid fever became a major problem. Multi
recovery. Sufficient blood should be collected (10 ml in Drug Resistant typhoid fever (MDRTF) became a common
adults and 5 ml in children) and a blood: media ratio of occurrence by the end of 1990s, with emergence of S. typhi
1:5 should be maintained. The use of clot culture methods simultaneously resistant to all the drugs that were used as
does not significantly improve recovery rates. Bone first-line treatment (chloramphenicol, trimethoprim,
marrow cultures have higher yield as compared to sulfamethoxazole and ampicillin). Fluoroquinolones were
peripheral blood cultures as salmonella is a pathogen of introduced in the late 1980's and early 1990's and produced
the reticuloendothelial system and should be done when very good results initially, but the past decade has seen a
patients present in later stages of the illness. Owing to progressive increase in the minimum inhibitory concen
very low recovery rates, stool cultures and urine cultures trations (MIC) of ciprofloxacin in S. typhi and paratyphi.
are not recommended. Antimicrobial susceptibility testing Since the current MICs are still below the standard
of the isolate is important in the era of multidrug susceptibility breakpoint, laboratories continue to report
resistance. bacteria as sensitive to fluoroquinolones, but the use of
The Widal test has been in use for around 100 years fluoroquinolones in this scenario is associated with a high
for the serological diagnosis of typhoid. It detects presence incidence of clinical failure because drug levels needed to
of IgG and IgM antibodies to H (flagellar antigen) of S. kill organisms with such high MICs are not achieved with
enterica var typhi and paratyphi A and B, and O (somatic standard doses, and often, even with highest tolerated
antigen) common to typhi and paratyphi A and B. Anti O doses. Resistance to nalidixic acid has been suggested as a
titers are both IgG and IgM that rise and decline early, surrogate marker for high ciprofloxacin MICs that predict
while anti H are primarily IgG that rise and decline late in fluoroquinolone failure. Hence resistance to nalidixic acid
course of the disease. The conventional method of may be used to guide antibiotic therapy, especially where
interpretation of the Widal test has been to demonstrate MIC testing is not available (i.e. if resistance to nalidixic acid
fourfold rise in antibody titers in two samples. Since this is present, quinolones should not be used or, if used, high
is often not practical, a single titer of at least 1: 160 for doses should be given, irrespective of the results of
both O and H is considered positive. Even with this ciprofloxacin/ofloxacin sensitivity). Alongside the recent
compromise, the Widal test has several limitations. rise in resistance to quinolones, there has been some return
Sensitivity is low in the first week of illness and in patients in sensitivity to first-line antibiotics such as chlorampheni
treated with prior antibiotics. Specificity is low owing to col, cotrimoxazole and ampicillin. However, concerns of
anamnestic reactions, prior vaccination, cross reactivity toxicity and inconsistent reports of sensitivity preclude
with other Enterobacteriaceae and subclinical infections in their widespread use.
endemic areas. Other tests such as Tubex and Typhidot Currently, third-generation cephalosporins such as
that detect IgM antibodies against typhoid have not ceftriaxone and cefixime are the first-line agents for
proven to be superior to the Widal test. therapy of enteric fever. Azithromycin is a new drug that
224 Essential Pediatrics
is being used as an alternative agent. Often there is (ampicillin, chloramphenicol and cotrimoxazole), it is
discordance between in vitro and in vivo susceptibility in prudent to continue with ceftriaxone alone rather than
S. enterica; salmonella may show in vitro susceptibility to change because the older drugs do not offer any advantage
aminoglycosides and second-generation cephalosporins, over ceftriaxone. If cultures are negative and
but good in vivo responses may not be seen; therefore, these defervescence has not occurred by day 7, a thorough
drugs should not be used to treat enteric fever. search for alternative etiology for fever should be made
and ceftriaxone continued. There is no role for changing
Choice for Empirical Therapy the antimicrobial agent or adding another drug, since
Where enteric fever is clinically suspected but cultures ceftriaxone resistance is currently anecdotal.
have not been sent for, reports are awaited or are sterile,
Therapy of Relapses
empirical therapy may be started. Choice for empirical
therapy is guided by various factors including the severity Relapse rates vary with the type of drug and are most
of the illness, inpatient/outpatient therapy, presence of common with beta lactams (ceftriaxone, cefixime)
complications and local sensitivity patterns. especially if shorter duration of therapy is used. Usually
For uncomplicated enteric fever, oral cefixime in a dose relapses may be satisfactorily treated with the same drug
of 20 mg/kg/day is the drug of choice, both for sensitive as used for primary therapy but for at appropriate dose
and multidrug resistant S. typhi. In areas where nalidixic and duration. However, if the isolate is nalidixic acid
acid resistance is infrequent (rare at the moment in India), sensitive and fluoroquinolones were not used for primary
fluoroquinolones may still be considered the drugs of therapy, they should be used for treatment of the relapse.
choice; however, if both nalidixic acid resistance and Azithromycin is likely to be a promising agent for this
resistance to other drugs (like amoxicillin, chloram purpose.
phenicol, cotrimoxazole) are widespread, the only options Therapy of Carriers
are oral cefixime or azithromycin. If the local resistance
The carrier state is uncommon in children and testing for
pattern is unknown, chances of failure are likely to be least
chronic carriage 3 months after an episode of enteric fever
if either cefixime or azithromycin is used.
is not routinely recommended in children. However, if
Azithromycin (10-20 mg/kg/day) is a good second
chronic carriage is demonstrated, treatment with
choice agent; chloramphenicol (50 mg/kg/day), amoxi
amoxicillin (100 mg/kg/d) with probenecid (30 mg/kg/
cillin and cotrimoxazole are other second-line agents.
d) or cotrimoxazole (10 mg/kg/d) for 6-12 weeks is
Clinical efficacy is more or less the same with all these
recommended. If the strain is nalidixic acid sensitive,
drugs with each drug having its own advantages and
quinolones for 28 days is a better option.
limitations. The choice of medication depends on
individual preference, experience, and level of comfort Prevention
and cost considerations. Once culture results are available,
therapy can be modified. There is no data at present to The most effective and desirable method for preventing
support use of combination therapy in enteric fever. enteric fever is by improving hygiene and sanitation. This
For severe illness and where complications are present, will yield additional dividends of reduction in the burden
intravenous ceftriaxone and cefotaxime are used in a dose of other water-borne illnesses as well. Since this is unlikely
of 100 mg/kg/day. In patients with history of penicillin in the near future in developing countries, vaccination is
or cephalosporin allergy, aztreonam, chloramphenicol (in a major preventive strategy, as detailed in chapter 8.
higher than usual doses) or cotrimoxazole (in higher than
Suggested reading
usual doses) are used as second-line agents. Parenteral
1. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever.
treatment is continued until defervescence has occurred,
N Eng J Med 2002; 347: 1770-82.
oral intake has improved and complications resolved. 2. Kundu R, Ganguly N, Ghosh TK, Yewale VN, Shah RC, Shah NK;
Thereafter, therapy can be switched to oral cefixime to IAP Task Force. Report: management of enteric fever in children.
complete a total duration of 14 days. Other oral drugs that Indian Pediatr 2006; 43: 884-7.
may be used for switch over therapy include cefpodoxime, 3. Kundu R, Ganguly N, Ghosh TK, Yewale VN, Shah RC, Shah NK;
IAP Task Force. Report: diagnosis of enteric fever in children.
azithromycin, cotrimoxazole and amoxicillin. However,
Indian Pediatr 2006; 43: 875-83.
the experience with cefpodoxime is limited, and the other
agents require switch to a different class of antimicrobials
leptospirosis _____ _____________
than cephalosporins.
If cultures are positive and show nalidixic acid Leptospirosis is an emerging zoonotic disease of
sensitivity, therapy should be changed to ciprofloxacin at worldwide distribution, caused by spirochetes of the
a dose of 20 mg/kg/day as quinolones are associated with genus Leptospira. The infection has a broad spectrum of
faster defervescence and lower relapse rates as compared clinical manifestations, varying from an influenza-like
to ceftriaxone. If cultures are positive and show nalidixic mild acute febrile illness with headache and severe
acid resistance as well as sensitivity to other drugs muscular pain, to severe leptospirosis causing jaundice,
Infections and Infestations 225
renal failure, and severe hemorrhagic manifestations like develop aseptic meningitis or uveitis with recurrence of
pulmonary hemorrhage with respiratory distress, fever. Encephalitis, cranial nerve palsies, paralysis and
myocarditis with arrhythmias, meningitis and papilledema are rare manifestations. Central nervous
meningoencephalitis. system abnormalities usually normalize within 1 week;
Most cases of leptospirosis occur in tropical and mortality is rare.
subtropical countries. While rats are the principal source
Icteric leptospirosis (Weil's syndrome): This is the most severe
of human infection, dogs, cats, livestock and wild animals
form of leptospirosis, characterized by jaundice, renal
are other important animal reservoirs. Infected animals
dysfunction, hemorrhagic diathesis and high mortality.
may excrete spirochete in urine for several weeks. The
Initial symptoms same as anicteric leptospirosis but after
survival of excreted organisms depends on the moisture
1-2 weeks, hepatic, renal and vascular dysfunction
content and temperature of the soil. Humans acquire
develops. Hepatomegaly and tenderness in right upper
infection after getting exposure to water or soil conta
quadrant are usually detected. Splenomegaly found in
minated with rat urine. Agricultural workers, veterina
20% of cases. Renal failure may develop, often during the
rians, meat handlers, rodent control workers and
second week of illness. All patients have abnormal urinary
laboratory personnel are at higher risk of getting infected
finding on urinalysis in the form of hematuria, proteinuria
because of occupational exposure.
and casts. Azotemia is common, often associated with
oliguria or anuria. Hemorrhagic manifestations are rare
Pathogenesis
but when present, may include epistaxis, hemoptysis and
Leptospira enter the body through abrasions and cuts in gastrointestinal and adrenal hemorrhage. Transient
skin or through mucus membranes, and spread to all thrombocytopenia may occur. Mortality is 5-15%.
organs hematogenously. The organisms damage the
endothelial lining of small blood vessels, with leakage and Diagnosis
extravasation of blood cells, hemorrhage, and ischemic
The diagnosis is established by serologic testing and by
damage to various organs including liver, kidneys,
isolation of infecting organism. Serologic tests for
meninges and muscles.
leptospira are microscopic agglutination test (MAT), read
by dark-field microscopy for agglutination, and titers are
Clinical Features
determined. Enzyme-linked immunosorbant assay
Human infection with Leptospira may range from methods, including an IgM-specific dot ELISA test, have
asymptomatic infection to a severe multiorgan involve also been developed. Leptospira can be isolated from
ment which is often fatal. Symptomatic infection is a blood and/or CSF during the first 10 days of illness and
relatively mild and anicteric febrile illness in over 70% of from urine for several weeks beginning at around 1 week.
patients; about 20% present as aseptic meningitis, while Warthin-Starry silver staining and immunoflouroscent
severe leptospirosis with hepatorenal dysfunction (Weil's and immunohistochemical methods permit identification
disease) develops in 5-10% of individuals. The incubation of leptospira in infected tissue or body fluids. Spirochete
period is usually 1-2 weeks. may also be demonstrated by phase contrast or dark-field
The illness is often biphasic. In the initial or septicemic microscopy, but these are insensitive.
phase lasting 2-7 days, fever and non-specific symptoms
predominate, and organisms may be isolated from blood, Treatment
cerebrospinal fluid and other involved tissues. After a brief
Treatment should be initiated as early as possible. For a
asymptomatic phase, the second phase, called the immune
severe case of leptospirosis, parentral penicillin G (6-8
or leptospiruric phase, becomes manifest wherein
million U/m2/24 hr q 4 hr IV for 7 days) is the drug of
Leptospira localize to various tissues to cause tissue specific
choice. Tetracycline oral or IV (10-20 mg/kg/24 hr q 6hr)
signs and symptoms. In this phase, circulating auto
can be used as an alternative for patients allergic to
antibodies to Leptospira are present; organisms can no more
penicillin.
be isolated from blood or CSF but persist in tissues like
kidneys and aqueous humor.
TETANUS
Anicteric leptospirosis: Onset is abrupt with high grade fever
with rigors and chills, lethargy, severe myalgia, headache, Tetanus is caused by the bacterium Clostridium tetani, a
nausea, vomiting. Patient may have conjunctival suffusion spore forming, anerobic, gram-positive motile bacillus,
with photophobia and orbital pain, generalized lymph found in human and animal feces. Its spores are
adenopathy and hepatosplenomegaly. Transient maculo widespread in the environment. The organism produces
papular erythematous rash may be seen in <10% cases. a potent neurotoxin tetanospasmin, under certain
Hypotension with bradycardia and circulatory collapse conditions, which leads to the clinical manifestations of
is rarely seen. Most patients become asymptomatic within the disease. Tetanus commonly occurs in areas where soil
one week. During the immune phase, some children may is cultivated, in rural areas, in warm climates, and during
226 Essential Pediatrics
summer months. According to WHO estimates, it most commonly when the umbilical cord is contaminated
contributes to almost 8% of vaccine preventable deaths. at the time of cutting after delivery Symptoms usually
appear by the third day after birth, never in the first two
Pathogenesis days of life and rarely after the age of two weeks. Excessive
C. tetnni is a noninvasive organism. The spores of the unexplained crying followed by refusal of feeds and
organism remain nonpathogenic in soil or contaminated apathy are the common initial symptoms. The baby
tissues until conditions are favorable for transformation develops progressive feeding difficulty, becomes rigid,
into vegetative form. Transformation occurs in the develops paralysis, and may develop opisthotonic
presence of locally decreased oxygen reduction potential, posturing and experience painful spasms. The mouth is
typically in devitalized tissue, in the presence of a foreign kept slightly open due to pull and spasm of the neck (Fig.
body, trauma and crush injury and suppurative infections. 9.14). Reflex spasm of the masseter makes feeding painful.
Two types of toxins are produced by the organism, Pharyngeal muscles go into spasm and cause dysphagia
tetanolysin and tetanospasmin. and choking, lockjaw or reflex trismus followed by spasms
of limbs. There is generalized rigidity and opisthotonus
Tetanolysin is a hemolytic toxin, which potentiates
in extension. Spasm of larynx and respiratory muscles are
infection, but does not contribute to the disease process
characteristically induced by stimuli such as touch, noise
per se. Tetanospasmin, a 150 kDa protein coded by a
and bright light, resulting in episodes of apnea and
plasmid, is the main toxin responsible for the manifes
cyanosis. Constipation persists until the spasms are
tations of the disease. It binds to the neuromuscular
relieved. Intercurrent infections, dehydration and acidosis
junction at the site of injury, and undergoes retrograde
may complicate the clinical picture. It has a very high case
axonal transport to reach the presynaptic nerve terminal
fatality rate of 70 to 100%.
where it prevents the release of inhibitory neuro
transmitters glycine and GABA. In a normal state, these
transmitters prevent release of acetylcholine from
excitatory neurons thus inhibiting muscle contraction. In
the presence of the toxin, these inhibitory impulses are
prevented, leading to uncontrolled contraction of muscles.
Clinical Features
Tetanus mainly affects the unimmunized and partly
immunized individuals. The disease may occur in various
forms: neonatal, generalized, localized, and cephalic. The
most common forms are generalized and neonatal tetanus.
large number or sufficient density to be of importance. by invading the bloodstream weeks or even years later.
Resting habits of the mosquito are important for planning This intermittent release of schizonts in case of P. vivax
control measures. Mosquitoes usually breed in edges of and P. ovale may last for 2-3 years and for P. malariae for
streams, water tanks, pits, cisterns and overhead tanks. 10-20 years. The first exoerythrocytic cycle or the hepatic
A. stephensi breed in wells, cisterns, fountains and phase is asymptomatic and constitutes the incubation
overhead tanks, A. fluviatilis in moving water and A. period. This cycle lasts at least 10 days (1-2 weeks for
sundaicus in brackish water. Breeding sites such as falciparum infection).
burrowed pits, pools, ponds, marshy areas and
unregulated irrigation channels are conducive to mosquito Erythrocytic Phase
breeding and spread of malaria. Mosquitoes thrive best After replication in the liver (exoerythrocytic schizogony),
in temperature between 20-30 ° C, relative humidity 60% the parasites undergo asexual multiplication in the
and in areas with good rainfall. The peak transmission erythrocytes (erythrocytic schizogony). In erythrocytes,
season of malaria is between July and November. Malaria parasites develop into ring forms, mature trophozoites and
is uncommon at altitudes over 2000 m above sea level. then multinucleated schizonts, which rupture and release
more merozoites. Repeated cycles of erythrocyte invasion
Prevalence of Malaria in the Community and rupture lead to chills, fever, headache, fatigue,
A number of indices are used to estimate the prevalence nonspecific symptoms and, with severe malaria, signs of
of malaria in the community. Splenic index is the prevalence organ dysfunction (Table 9.13).
of malaria in the community as measured by the rate of A key feature of the life cycle of P. falciparum is
palpable spleen in children between the ages of 2-10 year. cytoadherence, whereby erythrocytes infected with mature
If less than 10% of children have palpable spleen, the parasites adhere to endothelial cells in the microvascula
incidence of malaria is considered low; hyperendemic ture. This process is presumably advantageous to the para
areas show palpable spleens in >50% and holoendemic in site, since it prevents the passage of abnormal erythrocytes
>75%. Parasite rate is percentage of children between 2-10 through the spleen. High concentrations of P. falciparum
years of age who show malarial parasites in blood films. infected erythrocytes in the microvasculature and a
Proportionate case rate is an index that measures the number complex interplay of host and parasite factors lead to the
of cases diagnosed with clinical malaria for every 100 manifestations of severe malaria, including cerebral
patients reporting to the health facility. malaria, noncardiogenic pulmonary edema and renal
failure. Because of the ability of mature P. falciparum
Life Cycle of the Parasite organisms in the erythrocytic stage to adhere to endothe
The life cycle of the malarial parasite involves two hosts. lial cells, only ring forms circulate (except in very severe
infections), and levels of peripheral parasitemia maybe low
Hepatic or Tissue Phase despite substantial infection. Termination of the erythro
When an infectious mosquito bites a human, it injects cytic schizogony does not necessarily terminate the infec
sporozoites, which circulate and invade hepatocytes and tion with malaria because merozoites of P. vivax, but not
reticuloendothelial tissues within 30 minutes of the bite. those of P. falciparum, may go into exoerythrocytic schizo
During hepatic infection, P. vivax produces 2000-15000 gony after the erythrocytic cycle. This explains why rela
merozoites and P. falciparum produces 40000 merozoites pses are frequent after vivax but not falciparum malaria.
by repeated divisions. These merozoites are released and
invade erythrocytes at end of the hepatic phase. In
Sexual Reproduction
infection due to P. vivax and P. ovale, a dormant stage After several stages of schizogony, some parasites develop
(hypnozoite) can persist in the liver and cause relapses into gametocytes, which may be taken up by mosquitoes,
Table 9.13: Characteristics of severe malaria; features associated with a poor prognosis
in which sexual reproduction and further development being of IgM type. The complement system, however, is
of the parasites lead to the generation of a new set of not involved. Schizont-infested erythrocytes are phago-
infectious sporozoites. The gametocytes are ingested by cytosed rapidly if they have been sensitized with specific
an Anopheles mosquito during a blood meal. Only the anti-malarial (opsonin) antibody. Antibodies against the
gametocyte forms survive in the stomach of the mosquito; toxins of malarial parasite protect the host from the toxic
all other stages are destroyed. The parasites' multiplication products of P. falciparum. Antimalarial antibodies and
in the mosquito is known as the sporogonic cycle. While malarial antigens in maternal blood may be transmitted
in the mosquito's stomach, fertilization of female gametes transplacentally to the fetus. While the former protect the
generates motile and elongated zygotes (ookinetes) that newborn of the immune mother from malaria, antigens
invade the midgut wall and develop into oocysts (resting or antigen-antibody complexes help the infant to acquire
stage). These oocysts grow, rupture and release sporo immunity against malaria.
zoites, which make their way to the mosquito's salivary
glands. Inoculation of the sporozoites into a new human Immune Evasion by the Parasite
host perpetuates the malaria life cycle. Though the parasite stimulates antimalarial antibodies in
the host, yet the infection may continue for long periods
Pathophysiology due to the ability of the malarial parasites to survive in
Innate Resistance the host. The reasons for the survival of the parasites
include: (i) antibodies against the parasite may promote
In countries where malaria is endemic, a large number of
their survival instead of destruction; (ii) the infection may
people suffer from the infection but a proportion of them
impair antibody synthesis; (iii) handling and processing
are relatively immune, even though they are exposed to
of the antigens by macrophages is impaired, and (iv)
the similar environment. Some individuals are vulnerable
sporozoites, schizonts and gametocytes are not destroyed
to infection with one species of plasmodium but not to
by immune defences of the host.
the other, due to the differences in genetic constitution of
the species. The natural capacity of the host to resist Immunopathology
infection with malaria is called the innate resistance, and Some pathological lesions in malaria are explained as
this may be due to differences in the surface receptor, being due to immunological mechanisms. Anemia is
intraerythrocytic factors or yet unknown causes. disproportionate to the damage to red blood cells by the
Differences in the cell membrane determine whether a parasites. It is due to the formation of autoantibodies to
merozoite can attach to the surface receptors or the cell the erythrocytes and immune binding or adherence of the
membrane and invade the cells. Epidemiologic obser circulating malaria antigen-antibody complexes to
vations suggest that patients with sickle cell trait, uninfected erythrocytes. Hemolysis associated with
thalassemia and glucose-6-phosphate dehydrogenase blackwater fever is attributed to drug hypersensitivity.
deficiency are relatively immune to malaria. It has been Damage to the kidneys is of two types: (i) acute transient
postulated that intraerythrocytic factors may (i) resist lesions in which proteinuria develops a week or two after
penetration of red cells by merozoites, (ii) impede the infection and responds to antimalarial treatment. Renal
development of merozoites and (iii) assist in their removal biopsy shows immune complex deposits in the glomeruli.
by the reticuloendothelial system. Homozygotes of sickle Proteinuria and immunological abnormalities disappear
cell disease are not protected from malaria but in 4-6 weeks, (ii) chronic progressive nephritic syndrome
heterozygotes are immune. Variations in HLA frequency observed secondary to P. malariae infections (quartan
may also determine the prevalence of malaria. malaria). Glomerular lesions are due to deposits of the
soluble immune complexes in the basement membrane
Acquired Resistance to Malaria of the glomerular capillaries.
Sporozoites injected into the host localize to the liver cells The spleen plays an important part in defence against
within a few minutes. Apparently, there is no immuno malaria. The spleen is enlarged in malaria and returns to
logical defense against the naturally transmitted normal as infection is controlled. Splenomegaly due to
sporozoites in the blood or in the liver cells. Immuno malaria is associated with elevated levels of IgM and
logical defences start operating when merozoites invade lymphocytosis in peripheral blood, bone marrow and liver
erythrocytes. The first response to malarial infection is sinusoids. Splenectomy results in relapse of the latent
infection.
phagocytosis in the spleen or the hyperplastic reticulo
endothelial cells. Cell-mediated immunity has an important Cerebral malaria occurs frequently in the preschool
role in protection, through activated macrophages that children, but is relatively rare in those with protein-energy
attack the parasitized erythrocytes. As host defences malnutrition. Histopathological studies show plugging of
develop sufficiently, the parasite level falls abruptly and the cerebral capillaries with infected erythrocytes,
a crisis occurs with defervescence of temperature. hemorrhages and deposition of fibrin in the vessels.
Following infection, serum immunoglobulins are Changes may be due to mechanical factors, altered
elevated, with most protective antibodies against merozoites capillary permeability and intravascular coagulation.
230 Essential Pediatrics
Autoimmunity in malaria: Autoantibodies are increasingly urine may occur. Convulsions usually occur even though
observed in patients living in the endemic zones. The the fever is only moderately high. The diagnosis of cerebral
circulating antiglobulins may be produced in response to malaria should be considered seriously in the endemic
the circulating malarial immune complexes. Antinuclear zones if the consciousness does not return soon in a febrile
antibodies are probably cross-reacting antibodies induced patient who develops convulsions. The children look pale.
by the malarial DNA. Presence of these antibodies may During fever they appear flushed and sweat freely.
be due to the release of the cross-reacting antigens, or
alteration of the host tissue. As the parasite may have Clinical Pattern in Endemic Zones
similar antigens as in the host, presence of these serological
The clinical profile of malaria from the highly endemic
abnormalities should be interpreted with caution in areas
zones is atypical. Since these patients have already some
endemic for malaria.
degree of tolerance to malaria, the parasitemia is minimal
Immunosuppressive Effects and symptoms are generally mild. The patient may appear
restless and pale. Appetite is poor and temperature rises
Individuals infected with malaria respond poorly to the
only occasionally. After some time, the inherited immunity
other antigens, e.g. tetanus toxoid. Collagen vascular
may diminish and as these patients are continuously
disorders such as rheumatoid arthritis and lupus are
exposed to heavy doses of infection with plasmodia and
uncommon in malarial endemic zones. Measles and
have poor immunological defence, a severe clinical disease
toxoplasmosis are generally more virulent. It is proposed
may then occur. At this stage, the patient may even die of
that the immunological effects of malaria might allow
cerebral malaria. After several episodes of malaria, some
Epstein-Barr virus to give rise to lymphoproliferative
degree of tolerance again develops and then the clinical
disorders.
picture becomes mild, with low grade fever, easy
Clinical Features fatigability and irritability. The liver and spleen are
enlarged. During this phase the patient may succumb to
The incubation period of malaria varies between 9 and 30
associated malnutrition, anemia and intercurrent bacterial
days, being the least for P. falciparum and longest for P.
infections. Patients in highly endemic zones may develop
malariae infections. The onset of the disease is not as
chronic malaria in which the liver and spleen are markedly
characteristic as is believed, especially in infections with
enlarged. They look wasted and pale with either no fever
P. falciparum. The onset of the disease is sudden with fever,
or only a moderate elevation of temperature.
headache, loss of appetite, lassitude and pain in the limbs.
The fever may be continuous or remittent for several days
Relapse
before it becomes classically intermittent. The illness, then,
is characterized by a cold stage (chills and rigors with Relapse is defined as the recrudescence of fever after a
headache, nausea, malaise and anorexia); hot stage (dry period which is greater than the normal periodicity of
flushed skin, rapid respiration and marked thirst); and malarial fever. Relapses are rare in falciparum malaria as
sweating stage (temperature falls by crisis). There is no fever the plasmodia do not go into the exoerythrocytic phase
for 24-48 hr, and subsequently the fever depends on the after the erythrocytic schizogony. These are however,
type of malarial parasite causing the infection. The fever frequent in vivax malaria because they can start
occurs on alternate days in falciparum and vivax malaria, erythrocytic schizogony, resulting in relapse of the clinical
and on the fourth day with P. malariae infection. Several illness.
paroxysm of fever may occur more or less regularly in a
primary attack of malaria. Complications
Table 9.14: Comparison of peripheral blood smear examination and rapid diagnostic tests for malaria
Peripheral smear Rapid diagnostic tests
Format Slides with blood smear Test strip
Equipment Microscope Kit only
Training Trained microscopist 'Anyone with a little training'
Test duration 20-60 minutes or more 5-30 minutes
Test result Direct visualization of the parasites Color changes on antibody coated lines
Capability Detects and differentiates all Detects malaria antigens (PfHRP2/ PMA/pLDH) from
plasmodia at different stages asexual and/or sexual forms of the parasite
Detection threshold 5-10 parasites/pL of blood 100-500/pL for P. falciparum, higher for non-falciparum
Species differentiation Possible Cannot differentiate among non-falciparum species; mixed
infections of P. falciparum and non-falciparum appear as
P. falciparum
Quantification Possible Not possible
Differentiation Possible Not possible
between sexual
and asexual stages
Disadvantages Availability of equipment and Unpredictable efficiency at low and very high parasitemia;
skilled microscopists, particularly cross reactions among plasmodial species and with auto
at remote areas and odd hours antibodies; persistence of antigens
Status Gold standard Not yet approved by the FDA
takes approximately 15 min, and results are visually in Polymerase chain reaction (PCR) has been found to be highly
terpreted. The presence of a positive control line verifies sensitive and specific for detecting all species of malaria,
that the test strip is functional (Fig. 9.15). The test remains particularly in cases of low level parasitemia and mixed
positive for 1-3 weeks after treatment. infections. The PCR test is reportedly 10-fold more
sensitive than microscopy. The PCR test has also been
Negative found useful in unraveling the diagnosis of malaria in
cases of undiagnosed fever. Antibodies to the asexual blood
stages appear a few days after malarial infection, increase
P. vivax in titer over the next few weeks, and persist for months or
years in semi-immune patients in endemic areas, where
re-infection is frequent. In non-immune patients,
I I I P. falciparum antibodies fall more rapidly after treatment for a single
infection and are undetectable in 3-6 months. These
Fig. 9.15: OptiMAL test for rapid diagnosis of malaria. Expected
antibodies can be detected by immunofluorescence or
reaction patterns on the OptiMAL test strip for a negative patient, a enzyme immunoassay. Fluorescent antibody technique,
patient with P. vivax malaria, and a patient with P. falciparum malaria. which detects species-specific IgG antibodies, may remain
positive for several months after cure of the illness. It is
useful in epidemiological surveys, for screening potential
Two other rapid diagnosis tests are available; these are blood donors and occasionally for providing evidence of
based on the histidine rich protein 2 of P. falciparum recent infection in non-immunes. Intraleukocytic malaria
(PfHRP2), a water soluble protein expressed on RBC pigment has been suggested as a measure of disease
membrane of P. falciparum, and pan-specific Plasmodium severity. Floivcytometry and automated hematology
aldolase (PMA), a parasite glycolytic enzyme produced analyzers have been found to be useful in indicating a
by all species. One test utilises PfHRP2 alone, while an diagnosis of malaria during routine blood counts. In cases
other test uses both PfHRP2 and PMA. Hence the former of malaria, abnormal cell clusters and small particles with
can only detect P. falciparum, with a detection limit of >40- DNA fluorescence, probably free malarial parasites, have
100 parasites/pL. The latter test is positive in presence of been seen on automated hematology analyzers and it is
any of the four species, with differentiation possible suggested that malaria can be suspected based on the
between P. falciparum and non-falciparum species (but scatter plots produced on the analyzer.
differentiation between the 3 non-falciparum species is not
possible). The detection limit of this test is higher for non Other investigations including complete blood counts, and
falciparum species than for P. falciparum. These tests do blood levels of glucose, bilirubin, urea, creatinine,
not provide any indication of parasite viability, unlike the transaminases, prothrombin time, urinalysis may be done
as required.
LDH based test.
Infections and Infestations 233
Drug categories
Schizonticidal drugs (used for Chloroquine, amodiaquine, quinine, pyrimethamine, trimethoprim, proguanil,
clinical and parasitological cure) sulfa-pyrimethamine, mefloquine, halofantrine, artemisinine and its derivatives
Gametocytocidal and antirelapse drugs Primaquine, 8-aminoquinoline group
Practice followed
Microscopy or Rapid diagnostic kit test (RDK) Clinical malaria (No microscopy or RDK)
P. vivax positive P. falciparum positive Low risk area High risk area
Chloroquine 25 mg /kg over 3 days 25 mg /kg over 3 days 25 mg/kg over 25 mg/kg over 3 days
3 days
Primaquine (contra 0.25 mg/kg/day 0.75 mg/kg on day 1 0.75 mg/kg on day 1
indicated in pregnant x 14 days under
woman and infants) medical supervision
(to prevent relapse)
Artesunate sulfa- 4 mg/kg/day of
pyrimethamine artesunate daily x
(Artesunate-based 3 days + 25 mg/
combination kg of sulphadoxine
therapy, ACT)* or sulphalene +
1.25 mg/ kg of
pyrimethamine on
day 1
Treatment categories
• Drugs for first-line treatment: Given to clinical or confirmed malaria, e.g. chloroquine
• Drugs for second-line treatment: Given to treatment failure, severe and complicated malaria, pregnant women, and travelers,
e.g. Artesunate + sulpha pyrimethamine (artesunate-based combination therapy, ACT) combination, quinine
• Mass treatment: Recommended in epidemics
• Indications for alternative /second-line antimalarial drug (artesunate-sulfa-pyrimethamine (ACT) combination)
• The area/PHC showing a treatment failure more than 10% (both early and late treatment failure) to chloroquine in the
minimum sample of 30 cases
• Suspected resistance: If despite full treatment, with no history of vomiting or diarrhea, patient does not respond within
72 hours parasitologically
• In areas with high disease burden, high proportion of P. falciparum, inadequate facilities for laboratory diagnosis, inaccessibility
and relatively poor communication facilities and the presence of P. falciparum chloroquine resistant pockets, based on clinical
diagnosis of malaria by a trained medical officers or trained paramedical personnel after excluding other common causes of
fever.
Artesunate tablets should not be administered as monotherapy; primaquine may not be given with ACT combination as artesunate
reduces gametocyte carriage.
234 Essential Pediatrics
Dispensing the correct drugs of assured quality (first dose Table 9.16: Investigations to detect complications of
may be given preferably by dispenser), and ensuring severe malaria
patient compliance are important. The classical
Blood
manifestations of malaria may not occur, especially in
children; hence, any case of fever in the endemic areas Parasite count
during transmission season maybe considered as malaria. Blood glucose level
Complete hemogram (hemoglobin estimation, white cell
Management of Severe Malaria count and platelet count)
Although most cases of P. falciparum malaria in patients Blood group determination and cross match
presenting to health services are uncomplicated, up to 10% Blood gas analysis
become severe and life threatening malaria, principally
Serum electrolyte estimation
because of delays in diagnosis and inadequate treatment.
Blood urea and creatinine level
In severe disease, the clinical spectrum, complications and
management in children considerably differ from those Blood culture
in adults. Complications such as multiple convulsions, Coagulation indices
Kussmaul's breathing (indicating metabolic acidosis) and Estimation of serum/plasma levels of liver enzymes
severe anemia are more common in children than in CSF
adults; while jaundice, a common complication in adults
with severe malaria, is rarely seen in children, and renal Microscopic examination including cell count
failure and pulmonary edema occur even more infre Estimation of CSF levels of glucose and protein (to exclude
quently than in adults. other infections of the central nervous system)
Urine
Immediate Management
Determination of specific gravity
The initial stabilization of the patient involves the use of
advanced life support techniques. The key steps include Microscopic examination including cell count
the following: Chest X-ray
• Assessment of airway, breathing and circulation and Evidence of pulmonary edema or pneumonia
intervention as required.
• Diagnosis and treatment of hypoglycemia and other
dyselectrolytemias (Table 9.16) Table 9.17: Criteria for admission of patients with severe
• Assessment of vital and consciousness (Glassgow malaria to ICU
Coma Scale)
Acidosis Base excess <-8
• Assessment of hydration.
Parasitaemia Endemic areas: >20%
• Management of unconsciousness patients should
Non-endemic areas: >10%
include placement of nasogastric tube and emptying
Coma Glasgow Coma scale < 8
of gastric contents (to prevent aspiration), urinary
catheterization (to measure urine output), and Hypoglycemia Blood glucose level < 2.2 mmol/1
placement of central vascualr access (to measure Renal dysfunction Urine output < 0.5 ml/kg/hr
central venous pressure) and lumbar puncture (LP), Pulmonary edema
should be performed to rule out acute bacterial
meningitis (Table 9.16); LP should be deferred if signs
of raised intracranial pressure are present. Quinine: Quinine can be administered intravenously, intra
Criteria for admission to the intensive care unit are muscularly or orally, but only the parenteral routes are
outlined in Table 9.17. recommended in the presence of severe malaria. Quinine
dihydrochloride salts are used parentally as the first line
Anti-malarial Therapy of treatment in most parts of the world. It acts on the
Treatment with effective anti-malarial agents is the only mature trophozoite stages only. Quinine has 85%
therapeutic intervention that has been shown to reduce bioavailability when given intramuscularly, even in young
mortality in severe malaria. Anti-malarial agents should children but the intramuscular route is avoided in view
be administered parenterally to patients with severe of the associated pain. A loading dose of intravenous
malaria, since gastrointestinal absorption may be erratic. quinine allows for parasiticidal concentrations to be
In a life-threatening situation such as severe malaria, all achieved quickly. It reduces fever clearance time and para
efforts should be directed to ensure that effective levels site clearance time (Table 9.18). Once the child is able to
of these drugs are attained in patients. The cinchona take orally, parenteral quinine is substituted with oral
alkaloids (e.g. quinine) or artemisinin derivatives are the quinine in a dose of 10 mg/kg/dose given 8 hourly to
usual drugs of choice in such a situation. complete 7 days of therapy with quinine.
infections and Infestations 235
Quinine has a strong stimulant effect on pancreatic Other anti-malarials: Other anti-malarial drugs such as
insulin secretion and leads to iatrogenic hypoglycemia. halofantrine, mefloquine, atavaquone, SP, doxycycline,
In the doses used for the treatment of malaria it does not and tetracycline are not recommended in severe and
appear to cause significant cardiotoxicity, but it is complicated malaria as primary treatment. Parasite
advisable to monitor the electrocardiogram while the resistance has developed to these drugs, when they are
loading dose is administered. Cinchonism (tinnitus, high- used alone. Mefloquine administered by the nasogastric
tone hearing impairment, nausea, dysphoria and route in patients with CM showed rapid but incomplete
vomiting) often leads to poor compliance with the seven- absorption suggesting that this route is unreliable in
day regime. Although quinine may cause contractions of patients with severe malaria. These anti-malarials may be
the pregnant uterus and has been associated with effects used in the latter stages of the management of severe
on the fetus, it remains the most widely used drug for the malaria to reduce the period of parenteral treatment,
treatment of severe malaria during pregnancy. improve compliance and cure, and prevent the develop
ment of resistance to the parenteral anti-malarials.
Quinidine: Quinidine, a d-isomer of quinine, is more
effective than quinine as an antimalarial but is also more Supportive Therapies
cardiotoxic. Systemic hypotension and significant QTc
Adjunct therapy may reduce mortality since over a third
prolongation are more commonly seen with quinidine. It
of the patients die within 12 hours of admission, before
is used mainly in the USA. It is rarely used in other parts
the antimalarials have had time to work. Supportive
of the world and except when quinine and artemisinin
therapy is aimed at reversal or termination of patho
derivatives are not available.
physiological mechanisms that lead to potentially fatal
Artemisinin derivatives: Artemether and artesunate are complications.
increasingly being used in the treatment of severe malaria.
Antibiotics: Blood cultures have detected bacteremia in 7—
Treatment is initiated with a loading dose that is followed
14% of patients admitted with severe malaria. Non
by a once-daily dose regimen. Such a schedule is more
typhoid Salmonella septicaemia is the most common co-
convenient than that used for the administration of
infection in children with severe malaria. In patients with
cinchona alkaloids. Artemisinin derivatives have the
a reduced level of consciousness, the differential diagno
advantage of clearing the parasitemia at a faster rate than
sis of meningitis must be entertained and broad-spectrum
that seen with quinine, because artemisinin and its
anti-microbial agents should be administered until the
derivatives are fatal for all stages of the parasite. However,
diagnosis can be excluded.
there is to date no difference in the efficacy and safety of
quinine and artemether, as shown by mortality or Anticonvulsants: Seizures are common in children with
frequency or severity of residual neurological sequelae. severe falciparum malaria, but occur less frequently in
The artemisinin derivatives have relatively few side- adults. The pathogenesis of seizures in severe malaria is not
effects, although severe allergic reactions have been clear, but they may be caused by the sequestration of
reported. The reticulocyte count may drop transiently in parasites in the brain, hypoglycemia, hyperpyrexia (in
the first week of treatment, although this does not appear children prone to febrile seizures), and sepsis or meningitis.
to aggravate the anemia associated with malaria. Seizures may not be detected clinically; particularly in
Artemisinin-induced neurotoxicity was detected in animal cerebral malaria. Prophylactic phenobarbitone is asso
models, although there have been no reports of neuro ciated with an increased risk of mortality in children. The
toxicity in human subjects. These compounds should be management of seizures should include correction of the
used in combination with other anti-malarials to prevent underlying cause, such as hypoglycemia. Anticonvulsants
the development of resistance. should be administered for seizures lasting more than five
236 Essential Pediatrics
minutes. Benzodiazepines are the most widely used and boluses of fluids that improve circulation. Children rarely
available anticonvulsants, but may cause respiratory develop pulmonary edema. Fluid administration should
depression. Other anticonvulsants, e.g. paraldehyde have be stopped and diuretics given if pulmonary edema is
less deleterious effects on respiration. With repeated or suspected. Monitoring the CVP is very helpful during the
prolonged seizures, phenytoin, phenobarbitone, fospheny- administration of fluids. There is no evidence to show that
toin, chlormethiazole and thiopentone have been used. fluid restriction improves the outcome in cerebral malaria.
These longer acting anticonvulsants require continued Electrolyte derangements, particularly hyponatremia
monitoring of vital signs for at least 4 hours after adminis are an important consideration in the choice of fluids to
tration. be administered. Isotonic (0.9%) saline is used to correct
hypovolemia. Maintenance fluids must contain sufficient
Blood transfusion and exchange transfusion: Blood transfusion
glucose to prevent hypoglycemia. When anemia is present,
is life-saving in severe malarial anemia. In malaria
blood transfusion should be considered as a therapeutic
endemic areas, children with hemoglobin concentration
intervention. Fresh blood improves acidosis and red cell
less than 4 g/dl or presence of respiratory distress or
deformability found in falciparum malaria. Hypocalcemia
parasitemia greater than 10%, with hemoglobin concen
(<2 mmol/1) should be managed with 0.3 ml/kg 10%
tration between 4 and 5 g/dl should receive blood
calcium gluconate administered intravenously over 30
transfusion. The role of loop diuretics in children during
minutes, while hypomagnesemia (<0.75 mmol/1 ) is
transfusion is not established. The clinical condition of
treated with 0.2 ml/kg 50% MgS04 administered
these individuals should be closely monitored to detect
intravenously over 30 minutes. Hypokalemia should be
the development of fluid overload. Small doses of loop
looked for and treated if present.
diuretics may avoid circulatory overload. Exchange
transfusion has been thought to benefit patients with high Inotropic support: Although shock (algid malaria) is rare,
parasite counts. The rationale is to remove infected red it is fatal. Dopamine appears to provide better inotropic
cells and thereby reduce the parasite burden, to reduce support than adrenaline.
antigen load, to remove parasite-derived toxins and
Hypoglycemia: Hypoglycemia is a common complication,
metabolites, and to correct anemia. In non-immune
particularly in children and pregnant women. Often, it
patients with severe falciparum malaria, indications for
cannot be detected clinically; hence frequent checking of
undertaking exchange transfusions include parasitemia
blood glucose levels is mandatory, particularly in patients
exceeding 30%, irrespective of clinical features, response
with impaired consciousness. Correction with 50%
to therapy or absence of poor prognostic features. It is
dextrose appears to be safe in adults, but this has not been
recommended that the procedure should be undertaken
established in children. Any blood sugar < 3 mmol/liter
even if parasitemia is above 10%, if the patient has features
should be treated with 5 ml/kg of 10% dextrose
suggestive of severe disease or if the individual has
intravenously.
demonstrated failure to respond to treatment after 12-24
hours or if poor prognostic factors such as advanced age, Raised intracranial pressure: Raised intracranial pressure
or presence of late-stage parasites (schizonts) in the (ICP) is frequent in children with cerebral malaria,
peripheral blood are present. Patients with anemia with especially in Africa. Recent studies from India suggest that
circulatory overload may benefit from an exchange brain swelling, is common in adults. The treatment of
transfusion. This procedure, justified by convention, raised ICP in malaria remains controversial. Mannitol may
should be attempted only in units that can supply reduce the ICP but with no effect in reducing sequelae or
pathogen-free compatible fresh blood and when facilities mortality.
for hemodynamic monitoring during and after the
Ventilation: Prompt endotracheal intubation by experien
procedure are available.
ced personnel and mechanical ventilation may be a life-
Dialysis: The indications for dialysis in acute renal failure saving procedure. Acute respiratory distress syndrome,
due to severe falciparum malaria are similar to other poor respiratory effort, aspiration pneumonia, acute
causes of renal failure. The mortality in acute renal failure pulmonary edema and deep coma may benefit from
without dialysis is 50-75%. Early diagnosis and treatment ventilatory support.
is important in preventing mortality. A rapidly rising
creatinine level is the most sensitive indicator of the need Therapies not Recommended
for dialysis. Peritoneal dialysis reduces mortality, but for the Treatment of Malaria
hemofiltration is even more effective and is associated with There are many therapies that have been tried in severe
an improved outcome. malaria, but there is insufficient evidence to recommend
their use.
Fluids: The role of fluids in severe falciparum malaria is
controversial and appears to be different in children as Antipyretics use remains controversial, since studies in pa
compared to adults. The fluid requirements must be tients with non-severe malaria showed that use of
assessed in each patient. Hypovolemia is corrected by antipyretics, e.g. paracetamol, (only) prolonged parasite
Infections and Infestations 237
Suggested reading
Prevalence
Management of severe malaria in children: proposed guidelines for the
United Kingdom. Maitland K, Nadel S, Pollard AJ, Williams TN, New Leishmaniasis is endemic in more than 60 countries
ton CRJC, Levin M. Br Med J 2005; 331: 337-43. worldwide, and is seen in all continents except Australia
238 Essentia! Pediatrics
and Antartica. Over 90% cases of visceral leishmaniasis The disease may begin insidiously and be
(VL) are seen in India, Bangladesh, Nepal, Sudan and asymptomatic initially, but usually runs a chronic course
Brazil, while cutaneous leishmaniasis is seen in that may be fatal without or despite treatment. Death
Afghanistan, Pakistan, Syria, Saudi Arabia, Algeria, Iran, usually occurs within 2 years in 75-95% cases, because of
Brazil, and Peru. In India, annually about 1-3 lakh cases severe secondary bacterial infections or gastrointestinal
of Kala-azar are reported, most often from Bihar and bleeding in advanced disease.
eastern UP.
Post Kala-azar Dermal Leishmaniasis (PKDL)
Disease Patterns Post-kala azar dermal leishmaniasis (PKDL) develops after
The disease is seen in three main patterns: visceral, resolution of visceral leishmaniasis and is seen in a small
cutaneous and mucocutaneous leishmaniasis. Other less percentage of patients in Africa and India. This is usually
common disease patterns include post-kala azar dermal due to infection by the L. donovani cluster. The time interval
leishmaniasis, leishmaniasis recidivans and diffuse to development of PKDL is variable; it usually occurs 1-
cutaneous leishmaniasis. The type of disease expressed 10 years after successful treatment of VL. Hypopigmented
depends both on the type of Leishmania species and on macular, maculo-papular or nodular skin lesions are seen
the zymodeme (electrophoretic isoenzyme pattern) first in the perioral area, chin and lips, and later appear
expressed on that species. Thus, one zymodeme may cause over the neck, extensor surfaces of the arms, trunk, and
visceral leishmaniasis while another zymodeme of the legs. Lesions spare the scalp, palms, soles, axillae and
same species may cause cutaneous leishmaniasis. perineum. Lepromatous leprosyis a close differential, but
peripheral nerves are spared. Skin lesions may persist for
Clinical Features
upto 20 years. These patients may act as chronic reservoir
Visceral Leishmaniasis of infection.
The incubation period is generally 3 to 8 months (range
Cutaneous Leishmaniasis
10 days-34 months). Features include high grade fever,
weight loss, hepatosplenomegaly, abdominal discomfort, This initially starts as a papule at the site of a sandfly bite,
lymphadenopathy, and pallor. Fever may be high or low which increases in size, crusts, and eventually ulcerates.
grade, remittent, intermittent or continuous; the 'double- The lesion may take 3-18 months to heal in over 90% of
rise' of temperature in a day (double quotidian), although cases. The incubation period is between 2 weeks to several
characteristic, is uncommon. There are no rigors and the months, with longer incubation period up to 3 years in
patient does not appear 'toxic'. Splenohepatomegaly, with Old World cases.
the spleen much larger than the liver, is usual. Spleen is
usually huge, firm, smooth and nontender and is palpable
Variations of Cutaneous Leishmaniasis
by the end of first month of illness. Moderate Leishmaniasis recidivans is characterized by tuberculoid
hepatomegaly is seen in over 80% of cases. Unlike African lesions developing around scars of healed cutaneous
VL, lymphadenopathy is infrequent in Indian VL (<5%). ulcers, revealing a low parasite count on biopsy. Infections
Hyperpigmentation of skin is characteristically a feature tend to be resistant to treatment.
of Indian VL and occurs in about two-thirds of patients in
Diffuse cutaneous leishmaniasis is a rare manifestation,
late stages of disease, affecting the face, hands and upper
wherein dissemination of skin lesions occurs over the face,
trunk. Progressive emaciation occurs in all cases of VL,
hands and feet, and lesions reveal high parasite numbers
though appetite is well preserved. Cough and diarrhea
due to poor cell-mediated immune response. This is more
are common. Bleeding manifestations in the form of
common in the New World Leishmania but also occurs
petechial hemorrhages, epistaxis and gum bleeding may
with L aethiopica in East Africa.
be seen. Pedal edema may occur due to hypoalbuminemia.
Jaundice is uncommon. Diminished cell mediated Mucocutaneous leishmaniasis is characterized by mucosal
immunity in VL may account for the high incidence of involvement of the nose, oral cavity and pharynx are seen,
secondary infections, mainly pneumonia, septicemia, causing difficulty with eating and an increased risk of
measles, tuberculosis, dysentry, otitis media and cancrum secondary infection which carries a significant mortality.
oris. Some cases of visceral leishmaniasis present This form of leishmaniasis has an incubation period of 1-
atypically and cases have been reported which involve 3 months, but may occur many years after the initial
the lungs, pleura, oral mucosa, larynx, esophagus, cutaneous ulcer has healed.
stomach, small intestine, skin and bone marrow.
Pancytopenia and hypergammaglobulinemia are Pathogenesis
characteristic. Anemia is attributed to autoimmune The protective immune response in VL is primarily cell
hemolysis, hypersplenism, ineffective erythropoiesis, co mediated immunity (CMI) which results in subclinical
existing nutritional deficiencies and gastrointestinal blood infection and spontaneous cure in majority of cases.
loss. Failure of CMI to develop leads to the clinical syndrome
infections and Infestations 239
of VL. For every case of VL, there are about 30 subclinical and a specificity of 86-94%. Some cross-reactivity is seen
infections. Malnutrition and F1IV predispose to clinical with leprosy, Chagas disease, malaria, and schisto
disease. somiasis, while a false negative test result may be seen in
Anti-leishmanial antibodies are not protective in nature. HIV. Immunochromatographic strip (dipstick ELISA)
The leishmanin skin test (Montenegro test) detects delayed- testing of blood from a finger prick for leishmanial anti-
type hypersensitivity to leishmanial antigens. The test is K39 antibody has been used successfully in field sero
negative during active VL and becomes positive 3-6 diagnosis with a sensitivity of 90-100 % (-93%) in
months after recovery. symptomatic patients, and a high specificity (90.6%). The
After infection, the organism lies exclusively intra- test uses a recombinant K-39 (rK39) antigen incorporated
cellularly, mainly inside macrophages as replicating into the strip. However, low sensitivity of the test has been
amastigotes. The outcome of infection depends on whether reported in studies from Sudan. Titers to rK39 decrease
the host mounts primarily a T-helper (Th)-l or Th2 following successful therapy and tend to rise in cases of
response. Studies suggest that the Thl response produces relapse, thus making it useful to recognize treatment
interferon c (IFNc), which mediates resistance, whilst Th2 failures. This test is useful in clinical management in
cells producing interleukin-4 confer susceptibility to resource-poor areas. Newer methods with high sensitivity
infection. In the Thl response, promastigotes attach to and specificity include the detection of Leishmania antigen
reticuloendothelial cells and Thl response activates and antibody in the urine.
macrophages leading to phagocytosis of promastigotes.
Napier's aldehyde test has been traditionally used as a non
Defective CMI correlates with increased suppressor cell
specific test for diagnosing kala-azar. It depends on the
activity and decreased production of IFN-y, interleukin-1
presence of increased levels of IgG and IgM in the blood.
and interleukin-2 by mononuclear cells. Host genetics
One or two drops of commercial formalin (40% formal
influence the type of immune response. Genes coding for
dehyde) are added to 1 mL of the serum in a test tube.
natural resistance associated macrophage protein 1
(NRAMP1), TNF or the major histocompatibility complex The serum becomes solid and opaque within 20 minutes
are thought to play a major role in the outcome of infection. in a strongly positive reaction and within 24 hours in a
Thus the interplay between the host-determined delayed- weakly positive test. Solidification without opacification
type hypersensitivity, antigen-specific T-cell reactivity is not diagnostic. The major limitation of the aldehyde test
and cytokine secretion, and the type and virulence of the is its poor sensitivity and specificity.
particular infecting Leishmania species determine what
Cutaneous Leishmaniasis
type of disease expression develops in the host.
Diagnosis is usually based on microscopic examination
Diagnosis of skin scrapings or biopsy specimens taken from the edge
Visceral Leishmaniasis of lesions. The method is rapid and low-cost, but has
limited sensitivity, especially in chronic lesions. Cultures
Demonstration of parasites: Diagnosis in visceral
of the lesions are more sensitive, but may become
leishmaniasis is usually based on microscopic detection
contaminated by bacterial and fungal elements in the
of amastigotes in smears of tissue aspirates or biopsy
biopsy specimen itself. Direct analysis of clinical
samples. Bone marrow aspirate or biopsy is frequently
specimens is better achieved by using PCR, which is rapid,
the tissue of choice with sensitivity between 55-97%.
with high specificity and sensitivity. Serology has limited
Lymph node aspirate smears (sensitivity 60%) or biopsy,
role because of the poor antibody response in cutaneous
liver biopsy (sensitivity 85%) and splenic aspirates
(sensitivity 97%) may also be used for diagnosis. Though leishmaniasis. The Montenegro (leishmanin) skin test has
splenic aspirate has the highest sensitivity, the procedure also been used which detects specific cutaneous delayed-
may result in life-threatening hemorrhage; the procedure type hypersensitivity to leishmania antigen. However, the
is contraindicated if the prothrombin time exceeds control test cannot be used to distinguish between current and
value by 5 seconds or more or platelet count is below past infection, and false positive results have been
40,000/mm3. reported in other skin infections.
Sometimes the parasite can be cultured from micro
scopy negative tissue samples on special media like Novy, Treatment
McNeal and Nicolle (NNN) medium or inoculated into Visceral Leishmaniasis
animals such as hamsters. Leishmania DNA can also be
Treatment of VL is largely based on pentavalent
detected in tissue aspirates and peripheral blood by
antimonials; however, increasing resistance to antimonials
polymerase chain reaction (PCR), with sensitivity of 70-
is a major problem, most evident in North Bihar, where
93% in peripheral blood. High sensitivities of even upto
the failure rate for this treatment is more than 50%.
the level of one parasite have been reported.
Pentavalent antimony [Sb (V)] can be given in the form of
Serological tests: Leishmania antibody may be detected by sodium stibogluconate [Sb (V) 100 mg/ml] or meglumine
the direct agglutination test with a sensitivity of 72-94% antimonate [Sb (V) 85 mg/ml]; both may be given
240 Essential Pediatrics
intravenously or intramuscularly with equal efficacy used in treatment-resistant cases of visceral leishmaniasis.
(Table 9.19). The dose of Sb (V) is 20 mg/kg for 28 days; Its use is limited by its substantial toxicity, including
however, a recent randomized trial showed a shorter, 10- hypotension, hypoglycemia, renal damage, injection
day course to be equally effective. IM injections are painful abscess, and diabetes, necessitating close inpatient
and better avoided. IV injections should be diluted 1:10 monitoring. Paromomycin (aminosidine) has been used
with 5% dextrose and infused slowly over 20 minutes. effectively in resistant cases in north Bihar. Though the
Adverse effects include vomiting, fatigue, arthralgia, drug is inexpensive, nephrotoxicity and ototoxicity are
myalgia, abdominal pain, elevated serum transaminases, concerns with its use. Sitamaquine, another oral agent, is
lipase and amylase levels, bone marrow depression, and currently being evaluated in phase II studies in our
ECG abnormalities, including non-specific ST and T-wave country and has been associated with a 50-67% cure rate.
changes and T-wave flattening or inversion. Rarely, there Imidazole and triazole drugs are not recommended for
may be prolongation of QTc. Weekly ECG monitoring is use in visceral leishmaniasis. Recommended treatment
recommended during therapy. Some recommend a regimens are summarized in Table 9.19.
maximum dose of 850 mg daily in order to minimize side
Supportive care: Severe anemia and thrombocytopenia may
effects such as arrhythmias; others, however, believe that
necessitate packed cell and platelet transfusion. The child
this might predispose to resistance. In some resistant cases,
should receive a nutritious diet, and co-existing nutritional
addition of IFNy to Sb (V) has been successful in inducing
deficiencies should be corrected. Concurrent infections
remission.
should be treated using appropriate antimicrobial agents.
Amphotericin B is an effective treatment used in Sb (V)-
resistant cases. It is toxic and requires admission to the Response to treatment: Fever, spleen size, hemoglobin, blood
hospital for a prolonged period. The main side effects cell counts, serum albumin, and body weight are
include fever, chills, thrombophlebitis, hypokalemia, and monitored for response to therapy. In most patients, the
renal failure. The alternative is to use the liposomal form, fever subsides within 7 days, blood counts and hemo
which is highly effective and less toxic, but continues to globin levels rise, the patient feels better, and spleen
be very expensive. Liposomal amphotericin B is currently becomes smaller within 2 weeks. Parasitological cure
the drug of choice for antimony resistant VL. Compared should be documented at the end of therapy by splenic or
to conventional amphotericin, its concentration in bone marrow aspiration. As relapses are common in this
reticuloendothelial cells is tenfold more, and it is ten times disease, patient should be followed for at least 6 months
less toxic. Recent studies using lower doses of this agent before a long term definite cure is pronounced. The spleen
show that it may be cost-effective even in resource poor may take 6 months to 1 year to regress completely. Relapse
areas with high antimonial resistance. is suggested by an increase of spleen size, a fall in
Miltefosine is the first effective orally active drug hemoglobin levels and should be confirmed by the
against leishmaniasis. Studies of treatment with this drug demonstration of parasites.
for 3 or 4 weeks have shown a cure rate of 95-100%; cure
rates at 6 months' follow-up are also comparable to Treatment of other Forms of Leishmaniasis
amphotericin B. It has the added benefit of a very good In PKDL, treatment is indicated only for those who have
safety profile; the chief adverse effects being gastro severe and prolonged disease. Pentavalent antimonials (2
intestinal side effects, which are frequent but mild. This month course) and liposomal amphotericin B are both
agent has the potential to be used in the treatment of effective.
patients as outpatients in resource-poor areas, though Cutaneous leishmaniasis in the Old World cutaneous
there are concerns about compliance and eventual leishmaniasis is not a life threatening disease and 90% of
resistance. patients heal spontaneously within 3-18 months.
Other effective drugs used in treating leishmaniasis Treatment of cutaneous leishmaniasis accelerates cure and
include pentamidine and paromomycin. Pentamidine is reduce scarring, which may improve cosmetic outcome.
Options include local or systemic treatment. Local local epidemiology. Where sandflies are mostly endophilic
treatment is preferred for Old World cutaneous leish (rest mostly indoors after feeding), spraying houses with
maniasis, small single lesions, lack of lymph node insecticide is effective, while use of treated and untreated
metastases and L mexicana lesions. New World lesions bed nets is effective where sandflies are endophagic (feed
except L mexicana, mucosal or lymph node involvement mainly indoors). Insecticide treatment of dogs and dog
and lesions refractory to local treatment are indications collars is useful where canines are important reservoirs.
for systemic treatment. Options of local treatment include In India, where anthroponotic transmission is important,
cryotherapy, local infrared heat lamps, paromomycin effective treatment of patients, especially those with PKDL
(aminosidine) ointment with methylbenzethonium (who may act as long-term reservoirs), has been found to
chloride, intralesional infiltration of the dermis and base be effective in controlling transmission when combined
of the lesion with pentavalent antimony and imiquimod with vector control.
in combination with meglumine antimonite. Systemic There is no effective vaccine for prevention of
treatment with antimonials in general requires a 20- day leishmaniasis. The safety and efficacy of live-attenuated
course. Pentamidine, meglumine antimonat, oral flucona and killed vaccines has been debated. Killed vaccines were
zole, ketoconazole, and oral miltefosine are other agents favoured in the 1990s because of safety problems with live
that have been studied. attenuated vaccines; however, recent advances in
Treatment of mucocutaneous leishmaniasis with manipulation of the Leishmania genome may make
antimonials is unsatisfactory; especially in severe disease.
development of a live attenuated vaccine more feasible.
Amphotericin B and liposomal amphotericin B have been
Recent approaches include working on recombinant DNA
used in difficult cases with success. Steroids may be used
derived antigen vaccines and protein or peptide-based
in cases where respiratory compromise is likely.
vaccines, made possible by the Leishmania Genome
Leishmania-HIV Coinfection Project. However, most vaccine research is targeted
against cutaneous leishmaniasis; any effectiveness against
VL may occur in HIV infected persons, either as an
visceral leishmaniasis is uncertain.
opportunistic infection or as a result of reactivation of
subclinical infection. A high index of suspicion is required Suggested reading
in patients with HIV with the typical presentations of
1. Piscopo TV, Azzopardi CM. Leishmaniasis.Postgrad Med J 2006;
visceral leishmaniasis such as pyrexia, pancytopenia and
82: 649-57.
hepatosplenomegaly. However, the presentation may be 2. Murray HW, Berman JD, Davies CR, et al. Advances in
atypical with prominent gastrointestinal or upper leishmaniasis. Lancet 2005; 366:1561-77.
respiratory tract involvement, and absence of hepato 3. Davies CR, Kaye P, Croft SL, et al. Leishmaniasis: new approaches
splenomegaly. Diagnosis is reached as for non-HIV to disease control. BMJ 2003;326:377-82.
patients except that the Leishmania antibody test (direct 4. Guerin PJ, Olliaro P, Sundar S, et al. Visceral leishmaniasis: current
status of control, diagnosis, and treatment, and a proposed research
agglutination test) is frequently negative. The main risk
and development agenda. Lancet Infect Dis 2002;2:494-501.
group is intravenous drug users where an anthroponotic 5. Herwaldt BL. Leishmaniasis. Lancet 1999; 354: 1191-9.
cycle is involved, with Leishmania organisms present in 6. Paredes R, Munoz J, Diaz I, et al. Symposium: Leishmaniasis in
used syringes being inoculated intravenously. HIV infection. J Postgrad Med 2003; 49:39-49.
In leishmania-HIV coinfection, the Leishmania
infection is often intractable, and is associated with a high AMEBIASIS
relapse rate. Visceral leishmaniasis in HIV infection is
Amebiasis is defined as infection with Entamoeba histo
being proposed for inclusion in the Centers for Disease
lytica. Clinical features of amebiasis due to E. histolytica
Control and Prevention CDC clinical category C for the
range from asymptomatic colonization to amebic
definition of AIDS as an indicator disease. Although
dysentery and invasive extraintestinal amebiasis, which
treatment of coinfection has not been adequately studied,
pentavalent antimonials are still used commonly. occurs most commonly in the form of liver abscess.
Meglumine antimonite, liposomal amphotericin and oral
Epidemiology
miltefosine have only been used in small studies.
Secondary prophylaxis, using pentavalent antimonials Amebiasis is associated with a high morbidity and
administered once every 28 days or liposomal ampho mortality and is a major public health problem globally,
tericin B every 21 days, prevents relapse and improves especially in Central and South America, Africa, and the
survival. Secondary prophylaxis should be continued at Indian subcontinent. Poverty, ignorance, overcrowding,
CD4 counts below 200/ml. Antiretroviral treatment has poor sanitation and malnutrition favor transmission. In
been effective in decreasing relapses of visceral developed countries, high-risk groups include travelers,
leishmaniasis. immigrants from areas of endemicity, and men who have
sex with men. Asymptomatic individuals account for
Prevention and Control almost 90% of the infections. Invasive disease with
Control of leishmaniasis involves controlling the source Entamoeba histolytica is a leading parasitic cause of human
of infection and eradicating the vector, and depends on mortality, causing 100,000 deaths every year globally.
242 Essential Pediatrics
E. histolytica is thought to infect 10% of the world's tenderness (seen in 80%), with watery, bloody or mucous
population, and 2-55% Indians. However, these may be diarrhea. Some may have only intermittent diarrhea
overestimates, because two morphologically identical, alternating with constipation. Fever is unusual.
genetically distinct but apparently nonpathogenic Occasionally fulminant amebic colitis may occur, with
Entameba species, namely E. dispar and E. moshkovskii, are profuse bloody diarrhea, fever, widespread abdominal
now being recognized as causing most of the asympto pain, diffuse tenderness and pronounced leukocytosis.
matic cases. Toxic megacolon, ameboma, cutaneous amebiasis and
The organism exists in nature as a cyst or a trophozoite. rectovaginal fistulae can occur as complications of
Cysts are oval or round, asymmetric with four nuclei, re intestinal amebiasis.
sistant to chlorination and low environmental tempera
tures, but susceptible to destruction with most Extraintestinal Amebiasis
disinfectants and to heating to 55°C. Asymptomatic Amebic liver abscess (ALA), seen in about 1% of infected
human cyst carriers are the principal reservoir of infection. individuals, is the most common extraintestinal
The infection is transmitted by feco-oral route by cysts of manifestation, and may occur months to years after
Entameba. The disease may occur months to years after infection. While some individuals may have concurrent
exposure. Humans are the only host. Young, immuno-
amebic colitis, more commonly there are no bowel
compromized and malnourished children are at a higher
symptoms. The child usually presents with fever with
risk of severe E. histolytica infection.
chills and rigors and right upper quadrant pain of acute
onset (<10 days). Examination reveals toxic appearance,
Pathogenesis
right upper quadrant tenderness and hepatomegaly;
Each ingested cyst excysts in the small intestine to produce jaundice is unusual (10-15%). Cough, along with dullness
eight trophozoites, that colonize the mucosa of the large or crepitations in the right lung base may be present. With
intestine. Trophozoites may cause tissue invasion and early diagnosis and therapy, the mortality from uncomp
destruction through several virulence factors, with little licated ALA is less than 1%. Complications include rupture
or no local inflammation, resulting in characteristic flask into the pleura, which has a relatively good prognosis,
shaped ulcers, seen commonly in cecum, transverse colon and rupture into the pericardium and superinfection with
and sigmoid colon. bacteria, which are more serious.
Extra-intestinal complications occur when trophozoites
invade the bloodstream and migrate through the portal
Investigations
circulation, to lodge usually in the liver. Amebic liver abscess
is usually single (95%) and more frequently involves the In all cases, the combination of serological tests with
right lobe of the liver (posterosuperior part) which receives detection of the parasite offers the best approach to
most of the blood draining the cecum and ascending colon. diagnosis.
Amebae are located at the periphery of abscess, while the
inside contains viscid necrotic tissue, which is sterile and Parasite Detection
devoid of any neutrophils. The abscess may regress, The most common microscopic techniques employed for
rupture or disseminate; transdiaphragmatic rupture may the identification of E. histolytica is direct saline (wet)
cause amebic empyema and pulmonary amebiasis. Rare mount of feces. The sample is examined within 1 hour of
extra-intestinal complications include amebic involvement collection to look for motile trophozoites. At least 3 stool
of peritoneum, pericardium, pleura, lungs, brain, genito specimens taken on consecutive days should be examined
urinary system and skin. because the test has poor sensitivity (<60%; -90% with 3
fresh samples). Stool contains plenty of erythrocytes but
Clinical Features
few leukocytes. Presence of ingested erythrocytes within
Asymptomatic Colonization trophozoites is pathognomic for E. histolytica, which is
Asymptomatic cyst passage is the most common mani otherwise indistinguishable from E. dispar. Patients with
festation of E. histolytica, accounting for 90% of human asymptomatic carriage generally have only cysts in the
infection. In most cases, the infection resolves spon fecal sample. Microscopy is a less sensitive method of
taneously, but uncommonly, these individuals may later identifying Entameba species than antigen detection tests;
present with amebic dysentery and other invasive specificity is also low due to misidentification of
manifestations. macrophages as trophozoites, polymorphonuclear cells as
cysts and other Entameba species such as E. dispar.
Dysentery/Amebic Colitis Various culture techniques for E. histolytica have been
After a variable incubaton period of weeks to months, available using fecal specimens, rectal biopsy specimens
about 10% individuals colonized with E. histolytica develop or liver abscess aspirates. However, it is not undertaken
symptomatic disease, in form of colitis or extraintestinal routinely in view of low sensitivity (50-70%) and technical
disease. Amebic colitis presents as abdominal pain or difficulties.
Infections and Infestations 243
therapeutic aspiration guided by CT in the treatment of in children and in travelers. G. lamblia is a flagellated
uncomplicated amebic liver abscess is controversial. Large protozoan that infects the duodenum and small intestine
amebic liver abscesses (>300 mL) may benefit from of humans and causes varied clinical manifestations.
aspiration with decrease in duration of hospital stay and Human infection may range from asymptomatic shedding
faster clinical improvement recovery when compared to of giardial cysts to symptomatic giardiasis, being
those managed medically alone. Abscess cavity resolves responsible for abdominal cramps, nausea, acute or
slowly over a period of several months. chronic diarrhea, with malabsorption and failure of
Aspiration is usually reserved for individuals in whom children to thrive.
diagnosis is uncertain (where pyogenic abscess or bacterial
superinfection is a concern), those who have not respon Epidemiology
ded to metronidazole therapy (persistent fever or The infection is endemic in developing countries with poor
abdominal pain after 4 days of treatment), individuals sanitation. In developed countries, the infection is
with large left lobe abscesses (because of the risk of rup common in institutional settings like daycare facilities and
ture into the pericardium), size more than 8-10 cm (sug sanitaria etc, or as localized outbreaks associated with
gesting impending rupture) and severely ill patients with contamination of drinking water with cysts. Breast milk
an accelerated clinical course and large abscesses suggest protects against giardiasis by virtue of the glycoconjugates
ing imminent rupture. Aspiration, percutaneous catheter and secretary IgA that it contains. Individuals with
drainage, or both, improve outcomes in the treatment of malnutrition, humoral immunodeficiencies and cystic
amebic empyema after liver abscess rupture, and fibrosis are particularly susceptible. Children appear to
percutaneous catheter (or, if necessary, surgical) drainage be more severely affected than adults.
could be lifesaving in the treatment of amebic pericarditis.
ALA rupture into the peritoneum is managed conser Pathogenesis
vatively, along with percutaneous catheter drainage for Giardia exists in two stages, cysts and trophozoites.
localized collections of fluid. Outside the human body it exists in the form of cysts. Cysts
Suggested reading are hardy, capable of surviving in cool, moist environ
ments for up to 2 months and in water that has been
1. Stanley SL. Amoebiasis.The Lancet 2003; 361:1025-1034.
2. Fotedar R, Stark D, Beebe N, Marriott D, Ellis J, Harkness J. routinely chlorinated, but are destroyed by boiling for 10
Laboratory diagnostic techniques for Entamoeba species. Clin minutes. Transmission of infection is through cysts, which
Microbiol Rev. 2007; 20: 511-32. may be ingested in contaminated water or food or spread
by direct person to person contact. Ingestion of 10-100
GIARDIASIS
cysts is sufficient for causing infection. Low pH of the
Giardiasis, caused by Giardia lamblia (also known as G. duodenum facilitates excystation and release of
intestinalis or G. duodenalis), is a major cause of diarrhea trophozoites. Trophozoites colonize the duodenum and
Infections and Infestations 245
proximal jejunum of the host, where they attach to the is strongly suspected but stool testing is negative,
intestinal brush border. A ventral disk on the concave duodenal aspirate or biopsy may yield high concentration
surface mediates the attachment of the protozoa to the of Giardia when fresh wet mount is examined for
intestinal wall, and also causes mechanical irritation and trophozoites. Where duodenal aspirate is negative,
damage to the microvilli of the small bowel mucosa. intestinal biopsy may be considered in presence of any
The host-microbial interactions that govern the outcome suggestive feature like lactose malabsorption or abnormal
of infection remain incompletely understood. Unlike radiographic findings (edema or segmentation in small
amebiasis, there are no invasive or locally destructive intestine), or a suggestive setting like absent secretory IgA
lesions. It is believed that the infection causes diarrhea or hypogammaglobulinemia.
via a combination of intestinal malabsorption and hyper
secretion. Giardia induce disruption of epithelial tight Treatment
junctions and enterocyte apoptosis, which activate T All symptomatic cases—acute and persistent diarrhea,
lymphocytes causing further enterocyte injury, resulting failure to thrive and malabsorption syndrome—require
in intestinal permeability and diffuse shortening of drug treatment. Asymptomatic cyst carriers are not treated
epithelial microvilli. These effects cause malabsorption except in specific situations like for outbreak control or
and maldigestion and, in addition, may facilitate the for prevention of spread from toddlers to immuno
development of chronic enteric disorders, including compromised family members. At present, treatment
inflammatory bowel disease, irritable bowel syndrome, options include the nitroimidazoles derivatives, especially
and allergies, via mechanisms that remain poorly metronidazole and tinidazole, and nitazoxanide.
understood. It has been incriminated for the reported Metronidazole is given in a dose of 15 mg /kg/ day for 5-
steatorrhea and decreased tryptic activity. Steatorrhea that 7 days; it has 80-90% efficacy and is inexpensive, but has
is often seen may occur due to pancreatic involvement, or frequent adverse effects and has to be given threee times
due to bacterial overgrowth in the duodenum and upper a day. Tinidazole has the advantage of high efficacy (>90%)
jejunum, and bile salt deconjugation liberating free bile and single dose treatment (50 mg/kg once), while
acids. nitazoxanide has high efficacy (80-90%), low incidence of
adverse effects and is available in suspension form.
Clinical Features Nitazoxanide is given for 3 days, in two doses, with the
The incubation period after ingestion of cysts is 1-2 weeks. dose depending on age (100 mg bid for 1-4 years, 200 mg
Most infections in both children and adults are bid for 4-12 years, 500 mg bid for >12 years). Second-line
asymptomatic. Symptomatic infections are more common in alternatives include albendazole, furazolidone, paromo
children than in adults, and usually take the form of acute mycin and quinacrine.
diarrhea with sudden onset of explosive, watery,
foulsmelling stools, along with nausea and anorexia; Suggested reading
others may also have abdominal distension, flatulence, 1. Kiser JD, Paulson CP, Brown C. Clinical inquiries. What's the most
epigastric cramps and mild fever. There is no blood or effective treatment for giardiasis? J Fam Pract 2008; 57: 270-2.
mucus in stools. The illness may last 3-4 days and is 2. Buret AG. Pathophysiology of enteric infections with Giardia
duodenalis. Parasite. 2008; 15: 261-5.
usually self-limiting in normal immunocompetent
3. Escobedo AA, Cimerman S. Giardiasis: a pharmacotherapy review.
children. Variable degree of malabsorption may occur. Expert Opin Pharmacother. 2007; 8: 1885-902.
Some patients may have a protracted course, with
persistent or recurrent mild to moderate symptoms such
AMEBIC MENINGOENCEPHALITIS ___
as brief episodes of loose foul smelling stools alternating
with constipation. Persistent diarrhea may be seen in 30- The term amebic meningoencephalitis refers to the
50% cases. A few children may develop chronic diarrhea, infection of the central nervous system by free-living
lactose and fat malabsorption and failure to thrive. amebae. The disease occurs in two clinical forms: primary
amebic meningoencephalitis (PAM) caused by Naegieria
Diagnosis fowleri and granulomatous amebic encephalitis (GAE)
Diagnosis of giardiasis is traditionally established by induced by amebae of spp. of Acanthamoeba and
microscopic examination of stools. At least three fresh Balamuthia. These organisms are ubiquitous, found in fresh
specimens of stools collected on alternate days should be and brackish water including ponds, lakes, wells, springs
examined to achieve sensitivity of 90%, because the and swimming pools. Infections have been reported
multiplication and passage of the giardial cysts is often throughout the world and are usually fatal.
intermittent. There is no blood or leucocytes in stools.
Enzyme immunoassay (EIA) and direct fluorescent Primary Amebic Meningoencephalitis (PAM)
antibody test for Giardia antigens in stools have been Naegieria fowleri causes a fulminating meningo
reported to have better sensitivity and require less encephalitis, mostly in children and healthy young adults
expertise than traditional microscopy. Where diagnosis who have a recent history of swimming in fresh water
246 Essentia! Pediatrics
lakes, pools and ponds, usually during hot summer could be useful for fast laboratory diagnosis. CT scan of
months. Rarely, infection may occur either by inhalation brain may reveal granulomatous lesions and ventricular
of air-borne cysts or by washing face in contaminated dilatation. Treatment has been attempted with flucona
water. The amebae enter the nose through contaminated zole, ketoconazole, sulfonamides and cotrimoxazole, but
water (or air), penetrate the nasal mucosa and the cribri prognosis is poor.
form plate and travel along the olfactory nerves to the
brain. Within the brain they provoke inflammation and Suggested reading
cause extensive destruction of tissue leading to a diffuse 1. Kaushal V, Chhina DK, Ram S, Singh G, Kaushal RK, Kumar R.
hemorrhagic necrotizing meningoencephalitis. The Primary amebic meningoencephalitis due to Naegieria fowleri. J
Assoc Phys India 2008: 56: 459-62.
incubation period ranges from 3 days to 2 weeks.
2. Ma P. Naegieria and acanthamoeba infection: Review. Rev Infect
Signs and symptoms are suggestive of acute pyogenic Dis 1990; 12: 490-504.
meningitis, including high grade fever, headache,
vomiting, seizures, altered sensorium, cranial nerve
palsies and signs of meningeal irriation. Disease
HELMINTHIC INFESTATIONS
progression is usually rapid; this along with the limited
awareness about the disease and consequent non
Helminthic infestations contribute to significant disease
institution of specific therapy, leads to death within 5-10
burden in children particularly in the underprivileged and
days; however, survivors have been reported occasionally.
in developing countries. Helminthiasis is caused by three
Microscopic demonstration of motile amebae in fresh
groups of worms, nematodes (roundworms), cestodes
cerebrospinal fluid is required for diagnosis. The organism
(tapeworms) and trematodes (flukes). All these groups
is seen in the CSF in the form of a 10-15 (J.m trophozoite
differ significantly in life cycle, mode of infection,
with nonprominent karyosome and a broad pseudopod.
pathogenesis and clinical manifestations and are
CSF evaluation is otherwise similar to that seen with acute
considered separately. Trematode infections are uncom
pyogenic meningitis with a high WBC count (usually in
mon in India and will not be considered further.
thousands) with a polymorphonuclear predominance, and
elevated proteins.
NEMATODES
Though PAM is rare, the disease has a grave prognosis
if treatment is delayed. Hence, infection with Naegieria Nematodes may be further classified as intestinal
must be considered in differential diagnosis of a patient nematodes and tissue nematodes.
with pyogenic meningitis presenting with history of
swimming in fresh water, non-specific cerebral edema on Intestinal Nematodes
CT, and no evidence of bacteria on Gram's stain, antigen Intestinal nematodes are the commonest type of helmin
detection assays and culture. A careful examination of CSF thic infestations. This group includes Ascaris lumbricoides
wet prepration is the key to the rapid diagnosis of Naegieria (roundworm), Enterobius vermicidaris (pinworm, thread
infection. A combination of high dose amphotericin B, worm), Ankylostoma duodenale (Old world hookworm)
rifampicin, and chloramphenicol has been employed for Nectar americanus (New world hookworm), Trichuris
therapy successfully in occasional patients. Good results trichura (whipworm) and Strongyloides stercoralis. These
have also been obtained with combinations of ampotericin infections are common where hygiene and sanitation are
B, fluconazole and rifampicin, and amphotericin B and poor and where there is improper disposal of sewage.
azithromycin.
Life Cycle
Granulomatous Amebic Encephalitis (GAE) Ascaris, Strongyloides, Necator and Ankylostoma inhabit the
This is an infection with Acanthamoeba species (and, rarely, small intestine, Enterobius is lodged in the cecum and
Balamuthia species) that is acquired through lung or skin Trichuris inhabits the large intestine. Eggs are released in
and spreads hematogenously. The infection is usually seen the feces with the exception of Enterobius where they are
in immunocompromised children like those with AIDS, released on the perianal skin. The eggs embryonate in the
SLE or post-renal transplant. Clinically, GAE runs a environment and become infective. In Ascaris, Enterobius
subacute or chronic course similar to tubercular meningi and Trichura, infection occurs by ingestion of embryonated
tis, and if untreated, is fatal. CSF examination reveals eggs. The larvae are released in the intestines and mature
motile trophozoites or cysts of Acanthamoeba, in addition into adult worms locally in case of trichuriasis and
to elevated proteins and lymphocytic leukocytosis. The enterobiasis, while in case of ascariasis they migrate
trophozoite of Acanthamoeba is 25-30 )j.m in size, with a through the intestinal wall, into the portal circulation, the
prominent karyosome and vacuolated cytoplasm. liver, heart, lungs, trachea, swallowed into the pharynx
A triplex real time TaqMan PCR assay for simultaneous and finally mature into adult worms in the small intestine.
identification of Acanthamoeba spp., Balamuthia In case of Necator, Ankylostoma and Strongyloides infection
mandriallaris, and N. fowleri has been developed and it occurs by penetration of the skin by filariform larvae
Infections and Infestations 247
cysticercosis, is the most prevalent infection of the brain Cysts in the brain parenchyma (parenchymal neuro-
worldwide and may be resposible for upto 20-50% of all cysticercosis) cause focal or generalized seizures and, less
seizures. commonly, headache, focal neurologic deficits, or
behavioral abnormality. Heavy cyst burden can cause
Pathogenesis encephalopathy with fever, headache, nausea, vomiting,
The life cycle of Taenia solium begins as a larva in pigs, altered mental status and seizures. Cysts in the
and human infection is acquired by ingestion of T. solium subarachnoid or ventricular spaces may cause meningeal
cysts in undercooked pork. The larvae attach to the human signs and symptoms, obstructive hydrocephalus or cranial
gut and grow into adult tapeworms. The adult tapeworm nerve palsies (by nerve entrapment); those located in the
sheds proglottids containing hundreds of tapeworm eggs spinal column can cause radicular pain or paresthesias.
into human feces. When ingested by pigs, these eggs Ocular cysts in the subretinal space or vitreous humor can
develop into larvae that invade the intestinal wall, enter impair vision by inflammation or through retinal
the bloodstream and lodge in various tissues to develop detachment, while those in the extraocular muscles may
into cysts. limit the range of eye movements. Skeletal muscle or
subcutaneous cysticercosis may be either asymptomatic
The eggs of beef tapeworm are not infectious to
or cause localized pain and nodules.
humans. Humans may ingest T. solium eggs, usually by
feco-oral transmission (via contamination of food by food Diagnosis
handlers with poor hand hygiene, or by ingestion of raw
The diagnosis of taeniasis is established by the
fruits or vegetables fertilized with contaminated human
demonstration of eggs or proglottids in the stools. Patients
waste), or sometimes through autoinfection (by reflux of
may pass motile segments of worms through anus.
eggs from intestine into the stomach by reverse peristalsis).
Diagnosis of neurocysticercosis is based on CT, with
Thus humans become dead-end hosts of the larval stage
or without contrast, or MRI of brain. Demonstration (by
of the parasite, and develop cysticercosis in various body
CT/MRI) of a solitary contrast-enhancing lesion less than
tissues. Ingestion of encysted pork does not directly cause
20 mm in diameter and producing no midline shift is
cysticercosis; rather, it causes an intestinal infection with
highly sensitive for neurocysticercosis; if the scolex is
the adult tapeworm and a human reservoir for T. solium
visible, it is pathognomonic for neurocysticercosis. Cystic,
eggs. Cysticercosis can occur in persons who do not eat
nonenhancing lesions suggest viable, nondegenerating
pork by feco-oral route described above. Infection with
cysts; cystic, enhancing lesions indicate degenerating cysts
adult tapeworm (taeniasis), on the other hand, is acquired
with some surrounding inflammation; and calcified cysts
by ingestion of undercooked pork or beef containing
suggest old cysts that have already died. MRI is superior
infectious cysticerci.
to CT in demonstrating spinal, brainstem, or intra
Initially the larvae become encysted, which helps viable ventricular lesions. Ocular or extraocular muscle cysti
cysts avoid initial host reaction and destruction by the host. cercosis can be picked up on CT or ultrasound, or by
This phase, which may last for 5-10 years, is often clinically dilated ophthalmologic examination.
silent except when cyst location or size causes signs or Detection of antibodies by enzyme-linked immunoblot
symptoms. Degenerating cysts release larval antigens that assay or enzyme-linked immunosorbent assay of the
produce a vigorous host response with release of serum or cerebrospinal fluid has a sensitivity of 65-98%
inflammatory mediators and surrounding edema. After and a specificity of 67-100%, varying with the cyst burden,
this phase, the encysted larvae degenearte entirely, die location, and phase of the infection; the immunoblot assay
and often calcify. Calcified cysts can produce symptoms is the preferred test.
by unclear mechanisms. Biopsy of the skin or muscle provides a definitive
diagnosis in ambiguous situations, and may be the
Clinical Features diagnostic method of choice for ocular, extraocular muscle,
B Infection with adult worm is mostly symptomatic, but or painful muscular/subcutaneous cysts.
H some children may have non-specific symptoms like
iJl nausea, abdominal pain and diarrhea. These patients may Treatment
m also develop cysticercosis through auto-infection. Infestation with the adult tapeworm (taeniasis) is treated
The clinical features of cysticercosis depend on the with praziquantel (5-10 mg/kg once) or niclosamide (50
location of the cysts and overall cyst burden. In about mg /kg once).
2 months, the larvae mature into cysticerci of about 2 mm Therapeutic options in neurocysticercosis include
to 2 cm size. Cysts can lodge in the brain, skeletal muscle, medications, surgery, or watchful waiting. The decision
subcutaneous tissues, spinal column and eyes. The two depends upon multiple factors, including symptoms and
sites associated with high morbidity are the brain, the most the location, number, stage, and size of cysts. Although
common (60-90 %) location for cysts, and the eye, the least active parenchymal lesions usually resolve spontaneously
common site (1-3 %). and thus may not require anticysticercal drugs, a meta
Infections and Infestations 249
analysis demontrates that cysticidal drug therapy is poor hygiene. The adult worm lives in the jejunum.
associated with reduced seizures and increased resolution Transmission is mainly feco-oral, but auto-infection may
of lesions in the brain parenchyma. Two effective also occur, such that one host may harbor upto thousands
anticysticercal drugs are available: albendazole (15 mg/ of adult worms. Symptoms are usually non-specific,
kg/day bid for 30 days) and praziquantel (50 mg/kg/day including mild abdominal discomfort and poor appetite;
tid for 30 days). Albendazole is more effective than some have linked growth retardation to H. nana infection.
praziquantel. A 7-day course of albendazole is perhaps The infection is a major cause of eosinophilia. The
as effective as a 14- or 28-day course, though longer diagnosis is based on the demonstration of characteristic
courses are preferred when more than a few lesions are eggs in stools. Treatment is with praziquantel (25 mg/kg
present. Massive infections generally are not treated with once) or niclosamide (50 mg /kg once, maximum 2 g).
antihelminthic medications because of the risk of an
overwhelming inflammatory response from degenerating Echinococcosis (Hydatid Disease)
cysts. This can be prevented by giving steroids for 2-3 Human echinococcosis is a common infestation caused
days before and during treatment. Watchful waiting is by larval stages of members of the genus Echinococcus, and
indicated for calcified cysts because they are already dead, is characterized by production of unilocular or multi-
hence children with seizures and calcified inactive lesions locular cysts in the lung and liver. Echinococcosis is
on CT do not require specific therapy apart from endemic in most contintents of the world, with hyper
anticonvulsants. The commonly used antiepileptics are endemic areas in Western China, North Africa, West Asia
phenytoin and carbamazepine, which should be continued and areas of South America.
for at least one year and then tapered or continued based
on symptoms. Pathogenesis
Treatment of subarachnoid and intraventricular Hydatidosis is a zoonosis caused by two Echinococcus
neurocysticercosis is complicated and risky. Cysts in these species, E. granulosus and E. mulilocularis. The parasite eggs
locations are usually managed surgically because medical are transmitted from members of the canine family like
treatment is associated with the risk of inflammation; dogs and wolves, to various wild and domestic animals
however, recent reports suggest that high-dose alben like sheep, cattle and goats, which act as intermediate
dazole (30 mg/kg/day) is associated with clearance of hosts. Humans are accidental hosts. Adult worm is a small
these cysts. A ventriculoperitoneal shunt should be placed tapeworm with 2-6 proglottids, which resides in the
in all patients with evidence of significant obstructive intestine of dog. Eggs from the adult worm are passed in
hydrocephalus. the stools that may contaminate the water and soil, and
Surgical removal of the cyst is considered the treatment also the fur coats of dogs. Ingestion of food or water
of choice for intraocular cysts; antihelminthic medication contaminated with eggs or direct contact with infected
should be avoided because therapy may induce inflam dogs may result in humans being infected accidentally.
mation that may threaten vision. Cysts in the extraocular Eggs hatch in the intestines to release larvae that penetrate
muscle may be treated with albendazole and steroids, or the intestinal mucosa, and traverse the venous or
surgically excised. Isolated skeletal muscle or subcuta lymphatic system to reach the liver, lungs and, less
neous cysticercosis requires no specific treatment unless commonly, other target organs.
it is painful, and then simple excision may suffice. In the target organs, larvae develop into characteristic
multiloculated fluid-filled cysts, called hydatid cysts. In
Suggested reading children lung cysts are common, whereas in adults cysts
1. Kraft R. Cysticercosis: an emerging parasitic disease Am Fam Phy are more commonly seen in the right lobe of the liver.
sician 2007; 76: 91-6. Other tissues that may be involved include bone, brain,
2. Castillo M. Imaging of neurocysticercosis. Semin Roengenol 2004; genitourinary tract, intestines and subcutaneous tissue.
39: 465-73.
A cyst has two walls; a thick lamellated layer supports an
3. Hawk MW, Shahlaie K, Kim KD, Theis JH. Neurocysticercosis: a
review. Surg Neurol 2005; 63: 123-32. inner germinal layer. From the inner aspect of the germinal
4. Singhi P, Ray M, Singhi S. Clinical spectrum of 500 children with layer multiple juvenile stage parasites or protoscolices may
neurocysticercosis and response to albendazole therapy. J Child be produced, which, in turn, may give rise to daughter
Neurol 2000; 15: 207-13. cysts within the primary cyst capsule. An outer tough
fibrous capsule is produced by host reaction to the
Hymenolepiasis organism. The fluid in a hepatic cyst is clear, colorless and
Infection with Hymenolepis nana, also known as the dwarf watery, but it may become thick and bile stained with
tapeworm, is very common in developing countries. Man treatment or with secondary bacterial infection. The cyst
acts as both definitive and intermediate host because the may keep on expanding over several years.
entire life cycle may be completed in human host; Life cycle of E. multilocularis is the same except that
however, rodents, ticks and fleas may serve as the rodents and mice serve as intermediate hosts. The
intermediate host. The infestation usually results form organism produces multilocular alveolar cysts with
250 Essential Pediatrics
exogeneous proliferation, progressively invading the liver of risk of infection and anaphylaxis. Antibody detection
parenchyma and other tissues of the body The cyst is not by ELISA is more sensitive but less specific. The test uses
confined to a single defined structure because the daughter partially purified antigens that cross-reacts with other
cysts bud externally, the cyst structures are poorly parasites such as cysticercosis and schistosomiasis.
demarcated from the target organ tissues, making surgical
removal difficult, and daughter cysts metastasize to Management
distant organs. The infection often mimics a malignancy.
Surgical excision has for long been considered the
Clinical Features treatment of chice. For simple and easily accessible cysts,
USG-or CT-guided percutaneous aspiration, instillation of
Symptoms depend on the target organ involved. Very
hypertonic saline or another scolicidal agent; and
often, liver cysts may regress spontaneously without
reaspiration after 15 minutes (PAIR) is now the preferred
becoming symptomatic. Otherwise, cysts may become
therapy. The risk of spillage with PAIR is minimal, and the
symptomatic after several years when significant mass
effect results in abdominal pain vomiting, increase in risk of anaphylaxis is further decreased by prophylactic
abdominal girth and a palpable mass; jaundice is rare. medical therapy beginning before PAIR and continuing for
Alveolar cysts have a more malignant course. Direct a month thereafter. PAIR, when combined with medical
spread of infected tissue may result in cysts in the therapy, results in shorter hospital stay and faster
peritoneal cavity, kidneys, adrenal gland or bones. Lung resolution of cyst compared to surgical excision. PAIR is
cyst may present with chest pain, cough, hemoptysis and contraindicated in pregnancy (where scolicidal therapy is
breathlessness. Involvement of the genitourinary tract may contraindicated) and in bile-stained cysts (wherein risk of
manifest as passage of cysts in the urine (hydatiduria) and biliary complications is high). The standard surgical
hematuria. Rupture or leakage from a hydatid cyst may approach is partial capsulectomy, drainage, and epiplo-
cause anaphylaxis, manifest as fever, itching and rash, and plasty, and remains the most frequent operative method.
results in dissemination of infectious scolices. Rare but Problems with this approach such as disease recurrence
potentially serious complications include compression of and a residual cavity have led to more radical operations
important structures in the central nervous system, bone, such as total pericystectomy. Laparoscopic and endoscopic
heart, eyes or genitourinary tract. approaches (endoscopic retrograde cholangiopancreato
graphy and sphincterotomy) have a role when the location
Diagnosis of the cyst or the patient's status does not permit more
Physical examination may reveal a palpable mass, radical approaches. In all approaches, care is taken to avoid
hepatomegaly or subcutaneous nodules. Ultrasonography spillage of cyst contents, which is associated with
is the most valuable tool in diagnosing echinococcal cysts. dissemination of infection and with risk of anaphylaxis.
Imaging findings of echinococcosis caused by E. granulosus Alveolar hydatidosis is difficult to remove, and require
are single, unilocular cyst or multiseptated cysts, showing more radical surgeries like partial hepatectomy.
"wheel-like", "rosette-like" or "honeycomb-like" appear Medical therapy alone may be attempted in patients
ances. There may be "snow-flakes" sign, reflecting free where surgery and PAIR are contraindicated. Albendazole
floating protoscoleces (hydatid-sand) within the cyst is also given both before and after percutaneous drainage
cavity. Degenerating cysts show wavy serpentine bands of hydatid cysts. Albendazole is administered in a dose
or floating membranes representing detached or ruptured of 15 mg/kg/day in two divided doses (maximum 800
membranes, or heterogeneous, solid-looking pseudo mg) for 2 weeks, repeated for 3-12 courses with 15 days
tumor with a "ball of wool sign". Dead cysts may show drug-free interval in-between two courses. The efficacy
calcified cyst wall. Imaging findings of Echinococcosis rate is 40-60%. Albendazole therapy is safe. Common side
caused by E. multilocularis are ill-defined infiltrating effects include elevated transaminases and abdominal
lesions of the liver parenchyma, consisting of multiple pain, and rarely, headache, abdominal distension or
small clustered cystic and solid components. On alopecia. The response to medical therapy is monitored
sonography, lesions are heterogeneous with indistinct by serial ultrasonography, which demonstrates a change
margins, showing "hailstorm appearance" or "vesicular in shape from spherical to elliptical or flat, progressive
or alveolar appearance". CT and MR imaging displays increase in echogenicity, and separation of membranes
multiple, irregular, ill-defined lesions. Multiple small
from the capsule (water lily sign).
round cysts with solid components or large lesions with
"geographical map"appearance may be seen, with
Suggested reading
frequent calcifications, appearing as peripheral calcifi
1. Czemak BV, Akhan O, Hiemetzberger R, Zelger B, Vogel W, Jaschke
cation or punctuate scattered calcific foci. Invasion into
W et al. Echinococcosis of the liver Abdom Imaging. 2008; 33:133-
the bile ducts, portal vein or hepatic vein may occur. Lung
43.
hydatid cyst is often apparent on a chest X-ray film. 2. Akhan O, Ozmen MN. Percutaneous treatment of liver hydatid
Diagnostic aspiration is generally contraindicated because cysts. Eur J Radiol 1999; 32: 76-85.
Diseases of Gastrointestinal
10 System and Liver
251
252 Essential Pediatrics
6. Site of lesion: In esophageal atresia (tracheo-esophageal vomiting. Metoclopramide and domperidone are useful
fistula) and stenotic lesions of the esophagus, the infant in vomiting because these increase gastric emptying.
has excessive frothing soon after birth. He may choke Ondansetron is increasingly used for intractable or
on attempted feeding. It may not be possible to pass a refractory vomiting. However, drug therapy is only
soft rubber catheter beyond the obstruction. The symptomatic and effort should be to identify the
swallowed milk is returned promptly, often relatively underlying cause. Symptomatic therapy of vomiting with
undigested and unchanged. In achalasia cardia, the phenothiazine without definitive assessment of the cause
vomiting is relieved on feeding in propped up position. of vomiting is never advisable.
Stomach: The child may vomit immediately or after
some hours. The infant may regurgitate soon after the Cyclical Vomiting Syndrome (CVS)
feed. Vomiting is not forceful. The milk is curdled but Children experience bouts or cycles of severe nausea and
is not bile stained. vomiting that last for hours or even days and alternate
Intestine: Vomitus is bile stained, greenish, if the with longer periods of no symptoms. CVS has no known
obstruction is beyond the ampulla of Vater. Feculent cause and each episode is similar to the previous ones.
vomiting suggests intestinal obstruction or paralytic The episodes tend to start at about the same time of day,
ileus. last the same length of time, and present the same
Vomiting due to central causes: There is generally no symptoms at the same level of intensity. Episodes can be
preceding cause. Vomiting is often sudden, unexpected severe enough to restraint the child to bed for days. The
and forceful. Persistent headache and signs of increased most common trigger is an infection, but emotional stress
intracranial pressure may be evident. or excitement, and other physical agents can also set off
episodes. Some patients may have a family history of
Management migraine. CVS is difficult to diagnose because there are
Most children vomit occasionally for trivial reasons. This no diagnostic tests. The condition is suspected by
need not cause undue alarm. Sips of cold, clear fluids are consistency and relapsing nature of symptoms and
better tolerated than the hot beverages like coffee and tea. excluding other organic causes. Patients are advised to
Carbonated beverages may increase vomiting. Children get enough rest and sleep. In cases of frequent and long-
with recurrent and persistent vomiting and associated lasting episodes, medications like propranolol,
features suggestive of an organic cause of vomiting should cyproheptadine and amitriptyline have been tried with
be evaluated properly and appropriate medical and limited success.
surgical remedial measures should be instituted.
Recurrent vomiting may cause failure to thrive.
Congenital Hypertrophic Pyloric Stenosis
Therefore, diet should be nutritious. Intravenous Hypertrophic pyloric stenosis is the commonest surgical
alimentation may be resorted to in case of persistent disorder of the stomach during infancy. This condition is
Diseases of Gastrointestinal System and Liver 253
five times more common in boys than in girls. The pylorus is not a substitute for surgery. However, if the diagnosis
is thickened and elongated and its lumen is narrowed due of stenosis is in doubt and pylorospasm is a possibility,
to hypertrophy of the circular muscle fibers of pylorus medical therapy with atropine, methyl nitrate,
(Fig. 10.2). metoclopramide and cisapride may be used.
associated complications, and initiate management. In thus provides therapeutic advantage and prompts weight
many of the cases, anemia may be present. Vomiting is a gain. Use of hypoallergenic formula in formula fed infants
symptom associated with many disorders. If vomitus is with vomiting help in cases of cow milk allergy.
bilious or associated with diarrhea, hepatosplenomegaly Positioning: Esophageal pH monitoring has demonstrated
or neurological features, other diagnosis should be that infants have significantly less GER when placed in
considered. Other differentials include duodenal atresia, the prone position than in the supine position. However,
intestinal malrotation and other gastrointestinal surgical prone positioning is associated with a higher rate of the
conditions, occasionally food allergies and intestinal sudden infant death syndrome (SIDS). Prone positioning
motility disorders. may be acceptable while the infant is awake, particularly
in the postprandial period. When prone positioning is
Investigations
necessary, it is particularly important that parents be
Radiography: The upper gastrointestinal barium series is advised not to use soft bedding, which increases the risk
neither sensitive nor specific for the diagnosis of GER, but of SIDS in infants placed prone. In children older than
is useful for the evaluation of the presence of anatomic one year, left lateral positioning during sleep and elevation
abnormalities, such as pyloric stenosis, malrotation and of the head end (25-45°) help in reducing GER.
annular pancreas in the vomiting infant, as well as hiatal
Lifestyle changes in the child and adolescent: Children and
hernia and esophageal stricture in the older child.
adolescents with GERD should avoid caffeine, chocolate
Scintigraphy: A nuclear scintiscan is performed by the oral and spicy foods that provoke symptoms. Obesity,
ingestion or instillation of technetium-labeled formula or exposure to tobacco smoke and alcohol are also associated
food into the stomach. Scintigraphy also provides with GER. The magnitude of additive benefit due to
information about gastric emptying. lifestyle changes in patients receiving pharmacological
therapy is exactly not known.
Esophageal pH monitoring: Esophageal pH monitoring is
widely used as an index of esophageal acid exposure (pH Pharmacotherapy
<4), measures the frequency and duration of episodes of Acid-suppressant therapy: Histamine-2 receptor antagonists
acid reflux. This test has been considered gold standard and proton pump inhibitors produce relief of symptoms
for diagnosis of GER. It helps establishing temporal and healing of esophagitis. Chronic antacid therapy is
association between acid reflux and frequently occurring generally not recommended, but commonly used for the
symptoms, and to assess the adequacy of therapy. short-term relief of intermittent symptoms of GER.
Intramural esophageal electrical impedance is a recently Prokinetic therapy: Cisapride reduces esophageal acid
developed test useful for detecting both acid and non-acid exposure and enhanced esophageal acid clearance
reflux by measuring the retrograde flows in the esophagus. resulting in improvement in frequency of symptoms and
esophageal histopathology. However, the use of cisapride
Endoscopy and biopsy: Endoscopy enables both visuali
is discouraged due to potential for serious cardiac
zation and biopsy of the esophageal epithelium. Endo
arrhythmias in patients receiving cisapride. Appropriate
scopy and biopsy can determine the presence and severity
patient selection and monitoring as well as proper use,
of esophagitis, strictures and Barrett's esophagus, as well
including correct dosage (0.2 mg/kg/dose QID) and
as exclude other disorders. A normal appearance of the
avoidance of co-administration of contraindicated
esophagus during endoscopy does not exclude
medications are important. Presently, mosapride is
histopathological esophagitis; subtle mucosal changes
gaining popularity in place of cisapride. Other prokinetic
such as erythema and pallor may be observed in the
agents like metoclopramide, domperidone and
absence of macroscopic esophagitis. Esophageal biopsy
bethanechol have not been shown to be effective in the
is recommended when endoscopy is performed to detect
treatment of GERD in children.
microscopic esophagitis and to exclude causes of
esophagitis other than GER. Surgical therapy: Surgery is considered for a small
proportion of patients with GERD with persistence of
Management symptoms on medical management or those unable to be
weaned from medical therapy. The Nissen fundoplication
Since most causes of GER are functional, reassurance is a
(a gastric wrap procedure) is the most popular of the many
major part of treatment. Conservative measures may
surgical procedures that have been used. The stomach is
include upright positioning at least in the first postprandial
wrapped and sutured 360° around the distal esophagus.
hour, elevating the head end of the bed, prone positioning
As the stomach distends, the pressure at the junction
(>6 months) and providing small frequent feeds thickened
compresses the distal esophagus.
with cereal.
GER persists into later childhood, long-term therapy with in infants, to walking on tiptoes, or tightening of buttocks
proton pumps inhibitors is required. Children with in older children. Abdominal pain and overflow incon
neurodevelopmental disabilities including cerebral palsy tinence (encopresis) may also be presenting symptoms in
have an increased prevalence of GER and high likelihood older children.
of developing long-term feeding disorders.
Evaluation
Suggested reading
A thorough history including family, psychological, school
1. North American Society for Pediatric Gastroenterology and
performance and medications is recommended as part of
Nutrition. Pediatric GE Reflux Clinical Practice Guidelines. J Pediatr
Gastroenterol Nutr 2001; 32: Suppl. 2, Sl-31. a complete evaluation of a child with constipation. History
2. Orenstein SR. Esophageal disorders in infants and children. Curr should include age of onset of symptoms; infants who fail
Opin Pediatr 1993; 5: 580-89. to pass meconium within first 48 hours of life are likely to
have Hirschsprungs disease than infants whose consti
Constipation pation began after being weaned from breast milk.
Constipation is defined as a delay or difficulty in defeca Physical examination for systemic abnormalities and
tion, present for 2 or more weeks and sufficient to cause perineal and anal abnormalities are must. At least one
significant distress to the patient. Constipation is digital examination of the anorectum is necessary to assess
characterized by infrequent bowel evacuations; hard, perianal sensation, anal tone, the size of the rectum, the
small feces, or difficult or painful defecation. Chronic presence of an anal wink, amount and consistency of stool
constipation is a source of anxiety for parents who worry and its location within the rectum. Children with rectal
that a serious disease may be causing the symptom. Only stenosis or Hirschsprung disease have tight anus,
a minority of children have an organic cause for distended abdomen and empty rectum.
constipation. In about 95% of children with constipation, An abdominal radiograph is not indicated to establish
no obvious anatomic, biochemical or physiologic the presence of fecal impaction if the rectal examination
abnormalities are identified. Many of these children have reveals the presence of large amounts of stool. Barium
functional constipation resulting from intentional enema is mandatory when constipation is since birth.
withholding of stool. In such children, an unpleasant event Barium enema, ano-rectal manometry and full thickness
may precipitate desire to withhold stool. A change of milk rectal biopsy (absence of ganglionic cells in Hirschsprung
formula, coercive toilet training or unpleasant toilet disease) may be required. In endemic areas, tests to rule
practices may lead to deliberate withholding. out hypothyroidism must be undertaken for all children
with constipation.
Causes
Constipation may be functional (non-organic) or organic. Management
Organic causes of constipation are listed below in Table The parents should be reassured of the benign nature of
10.2. simple constipation and the patient helped to develop
The normal stool frequency decreases from 4 or more normal bowel habits. Parents are encouraged to maintain
per day during infancy to once per day at 4 years of age. a consistent positive and supportive attitude in all aspects
Stool frequency of less that 3 times per week at any age is of treatment.
abnormal. Many children with constipation pass large,
hard stool and display stool withholding behavior, Rectal disimpaction of the hard fecoliths if present may be
characterized by stiffening of whole body and screaming performed by the oral route (mineral oil, polyethylene
glycol electrolyte solutions), the rectal route (phosphate
soda enemas, saline enemas, or mineral oil enemas,
Table 10.2: Organic causes of constipation suppositories—glycerin in infants and bisacodyl in older
Intestinal Hypothyroidism children). These interventions help in providing imme
Hirschsprung disease Panhypopituitarism diate relief, but need to be followed by maintenance
Anal/rectal stenosis therapy.
Neuromuscular
Anal fissure Once the fecal impaction is been removed, the treatment
Cerebral palsy
Anteriorly displaced Psychomotor retardation focuses on prevention of and recurrence of impaction. The
anal opening Spinal cord lesions goal is to achieve one soft stool per day and the minimum
Stricture Myotonic dystrophy acceptable is 3 or more stools per week with no pain or
Drugs Neuropathy or myopathy of soiling.
Narcotics GI tract
Vincristine Maintenance therapy has four components: fluid and dietary
Other causes
Psychotropics Low fibre diet interventions, toileting programmes, medication and
Metabolic / Endocrine Milk protein allergy follow up. Maintenance therapy consists of dietary
Cystic fibrosis interventions, behavioral modification, and laxatives to
256 Essential Pediatrics
assure that bowel movements occur at normal intervals The differential diagnosis in the neonatal period include
with good evacuation. Increasing fluid intake (at least 6- meconium plug syndrome, microcolon, hypothyroidism,
8 cups of per day), using high residue diets (whole wheat sepsis and cystic fibrosis. In neonatal period, plain
flour, fruit and vegetables) help in relieving the abdominal radiograph film reveals bowel distension with
constipation. Excessive milk drinking may worsen multiple air-fluid levels, and paucity of air in pelvis. A
constipation. barium enema usually shows the narrow aganglionic
bowel with dilated proximal bowel. However, a normal
Behavior modification and regular toilet habits are an
study does not exclude Hirschsprung disease. Rectal
important component of treatment. It may be supple
manometry helps in diagnosis in older infants. Rectal
mented with maintaining stool diary and reward system.
biopsy is the gold standard in diagnosing Hirschsprung
Child should be encouraged to use toilet regularly,
disease. Full thickness biopsy is ideal, but submucosal
without hurry or distractions.
biopsy also suffices in most cases. Recognition of the
When necessary, daily medication with mineral oil (a
absence of ganglionic cells in the myenteric and
lubricant) or magnesium hydroxide, lactulose, sorbitol, submucosal plexi is essential for the diagnosis. Hyper
polyethylene glycol (PEG) (osmotic laxatives), or a trophied nerves are observed in the aganglionic segment.
combination of lubricant and laxative is recommended.
All these agents are extensively studied and are effective The management is essentially surgical; the role of medical
and safe for long-term use. PEG 3350 appears to be management is restricted to stabilize the general condition
superior to other osmotic agents in palatability and of the child. Initially, a colostomy in the ganglionic bowel
acceptance by children. Phenolphthalein compounds are is performed to relieve the obstruction and allow the
better avoided. Lactulose solution 15 to 30 mL at breakfast dilated hypertrophied proximal bowel to return to normal.
relieves constipation. The medications can be weaned off Subsequently, definitive surgery is performed. This
consists of excision of the aganglionic segment with a
when the child has been regularly passing soft formed
"pull through" procedure enabling an anastomosis to be
stools for at least 6 months. Patience and persistence of
performed between the ganglionic colon and the anus.
the physician and care provider are the keys to success of
The most frequently performed surgeries are those
medical therapy. Consultation with a pediatric gastro
described by Swenson, Duhamel, Soave and Boley.
intestinal specialist becomes necessary when the therapy
Though the long-term bowel control is excellent, soiling
fails, when there is concern that an organic disease exists,
and constipation may occur in initial period. Use of
or when management is complex.
laparoscopes in neonatal colectomy has helped in rapid
recovery and less adhesions.
Suggested reading
Evaluation and Treatment of Constipation in Infants and Children: Rec Suggested reading
ommendations of the North American Society for Pediatric Rescoria FJ, Morrison AM, Engles D, et al. Hirschsprung disease:
Gastroenterology, Hepatology and Nutrition. J Pediatric Gastroenterol
Evaluation of mortality and long-term function in 260 cases. Arch Surg
and Nutr 2006; 43:el-el3.
1992; 127: 934-42.
Table 10.3: Causes of protuberant abdomen* Table 10.4: Causes of acute abdominal pain
Table 10.5: Causes of chronic and recurrent abdominal pain inflammation are important signs. The abdominal
Children <2-yr-old Children >2-yr-old examination should look for distension, tenderness,
organomegaly, any other mass, bowel sounds and bruit.
Colic Functional pain
Malabsorption Constipation A structured investigatory approach is needed in all cases.
Milk allergy Giardiasis It has a reassuring impact on the family and the child that
Rotational defects Intra-abdominal abscess the symptoms are being seriously considered. Children
Hirschsprung disease Lead poisoning with red flag symptoms and signs require more extensive
Esophagitis Pancreatitis investigations including endoscopy and contrast studies.
Abdominal migraine/
epilepsy Management: Organic causes should be excluded. The
Urolithiasis parents and child should be assured about absence of
major illness, once features of organic causes are absent.
Help of a child psychologist should be sought for
Chronic abdominal pain is defined as presence of at management is suspected psychiatric problem,
least three bouts of pain severe enough to affect activities maladaptive family and poor response to conservative
over a period of at least 3 months. The cause of pain may therapy. Patients with functional abdominal pain do not
be functional or organic (disease-based). Nearly 10% to need any medications. Hospitalization and drug therapy
15% of school-aged children experience recurring in such patients might reinforce the pain behavior. Unless
abdominal pain at some time. documented, therapy for helminthiasis, protozoal
The commonest cause of chronic abdominal pain in infections, H. pylori and acid-peptic disease is not useful.
older children is functional. The following features are Severe acute pain may be relieved by anticholinergic
clues to an organic cause: (i) localized pain in non- agents, but it should be used judiciously to avoid
periumbilical region; (ii) referred pain; (iii) pain awakens prolonged side effects.
the child from sleep; (iv) sudden onset of severe pain; (v)
high grade fever; (vi) dysuria; (vii) jaundice; (viii) Suggested reading
anorexia/weight loss; (ix) specific physical findings; and 1. McCollough M, Sharieff GQ. Abdominal pain in children. Pediatr
(x) reduced activity level. Clin N Am 2006;53:107-37.
2. Mittal SK, Verma IC. Abdominal pain in children. Indian J Pediatr
Functional abdominal pain is defined as abdominal pain 1994; 7: 1-15.
without demonstrable evidence of a pathologic condition,
such as an anatomic, metabolic, infectious, inflammatory Gastrointestinal Causes of Pain
or neoplastic disorder. The perception of recurrent Parasitic infestations: The usual helminthic infestations are
abdominal pain is the summation of sensory, emotional rarely responsible for abdominal pain; Giardia lamblia and
and cognitive input. Psychosocial stress, child's Entameba histolytica infestations are often incriminated. A
personality type and reinforcement of illness behavior bunch of roundworms may cause acute intestinal
within the family affect the pain intensity and quality. obstruction. Demonstration of the infestation does not by
Onset is usually between 4 and 14 years of age. There is itself establish the etiology of abdominal pain. Abdominal
no consistent duration, frequency or periodicity. The pain pain may recur even after treatment of the infestations.
is usually brief; pain-free intervals range from days to
weeks. When asked to point to the site of pain, the child Acute appendicitis: Acute appendicitis is rare in infancy but
usually places the entire hand over the umbilicus. There should be kept in mind in children and adolescents. There
is a tendency to under or over diagnose appendicitis and
is often no radiation to other sites. Examination and
have high negative laparotomy rates. The lumen of the
laboratory investigations do not disclose any abnormality.
appendix gets blocked (either by fecoliths or external
General approach to the child with recurrent abdominal pain: compression by surrounding structures) and intestinal
A complete history and physical examination are the most bacteria get a chance to flourish. This leads to edema of
important components of the evaluation of any patient the appendix that further acts as a constriction, thus
with recurrent abdominal pain. The history should focus hampering its blood supply. The inflammatory fluid leaks
on the timing of the pain; frequency; location; quality; out in the peritoneal cavity and produces pain. The
associated symptoms, such as diaphoresis, nausea, and increasing fluid and gas within the lumen of the appendix
dizziness; precipitating factors (recent viral illness, leads to its perforation. It has been estimated that if the
ingestion of certain foods, relation to stress and anxiety, inflammatory process goes unchecked, about 20% cases
relation to the menstrual cycle, and medication use). will perforate within 24 hours and the remaining 80% in
Systemic symptoms, such as weight loss, delayed linear 48 hours. The classical triad of right lower quadrant pain,
growth, delayed pubertal development, fever, rashes, and fever and vomiting does not occur in all cases. The patient
joint pain should be looked for. Family history for has moderate fever, vomiting at the onset, abdominal pain,
inflammatory bowel disease, peptic ulcer disease should distension and local tenderness over the McBurney's point
be asked for. Clubbing, rashes, arthritis, and perirectal in the right iliac fossa. Retrocecal appendicitis is difficult
Diseases of Gastrointestinal System and Liver 259
to diagnose clinically. Diarrhea and colicky abdominal intussusception. Air enema is used in some centers due
pain may be the only symptoms in these patients. to ease of administration and low radiation exposure when
Acute appendicitis is a clinical diagnosis, and no single done under fluoroscopy. Reduction by enema is not
investigation is confirmatory. Other possible causes and possible in ileoileal intussusception. Clinical signs of
associations (urinary tract infection) should be ruled out. peritonitis, perforation, or hypovolemic shock are clear
An erect X-ray abdomen may reveal calcification in the contraindications to enema and mandate surgical
appendix, deviation of spinal curvature to the right and a exploration. Prolonged symptoms (>24 hr), evidence of
dilated caecum and gas under diaphragm. In children obstruction such as air fluid levels on plain abdominal
below 2 years of age an X-ray examination is helpful in films, and ultrasonography findings of intestinal ischemia
the absence of reliable clinical signs. An ultrasound or trapped fluid are relative contraindications to perfor
examination may show a non-compressible appendix, ming enema. Surgical management of intussusception
peri-appendiceal fluid collection and a thickened carries very good outcome.
appendix. CT scan examination is also useful. Appendi-
Peptic ulcer: Peptic ulcer was believed to be infrequent in
cectomy at diagnosis is recommended.
children. Several well-documented series on peptic ulcer
Acute mesenteric lymphadenitis: The clinical features in childhood have been published. Most Indian studies
resemble acute appendicitis. There is history of preceding on recurrent abdominal pain do not find peptic ulcers as
respiratory or enteric disease possibly due to infection an important cause. Acute gastric ulceration may follow
with Yersinia pseudotuberculosis or Yersinia enterocolitica. intake of drugs such as aspirin, steroids, potassium
Pain is poorly localized and there is fever. In mesenteric chloride, toxins, stress (burns, intracranial lesions), sepsis
adenitis, area of tenderness shifts when the patient is rolled and shock. Helicobacter pylori has been implicated in the
from side to side but in appendicitis it is fixed. Treatment etiology of acute and chronic gastritis and duodenitis with
is symptomatic. ulcer formation. Zollinger Ellison syndrome associated
with increased production of gastric acid result in gastric
Obstructive lesions of the gut: Incomplete intestinal
and duodenal ulcer. Peptic ulcers may be primary or
obstruction as in tuberculosis of abdomen, intestinal
secondary to a severe underlying disease. The latter often
malrotation, Meckel's diverticulum, volvulus, diverti
require emergency surgery for perforation or hemorrhage.
culum and duplication of gut are occasionally responsible
In children with primary peptic ulcer, early symptoms are
also for recurrent abdominal pain, which is typically
mild but there is a high incidence of recurrent symptoms.
colicky. Abdominal distension and vomiting (bilious or
In early childhood, ulcer is more often gastric and
at times fecal, depending on the site of obstruction) are
hematemesis is the major presentation. Duodenal ulcer is
associated. Bowel sounds are loud and exaggerated. Plain
usually found in older children (>9 years). They complain
X-ray films of the abdomen reveal gas filled loops of the
of epigastric pain which may or may not have consistent
bowels and multiple air fluid levels. Ultrasonography of
relationship to meal. Pain is usually periumbilical and
abdomen should be done.
vomiting may be present. Diagnosis is confirmed by
Intussusception in infants: Intussusception presents as acute endoscopy. Most duodenal ulcers are localized on the
intestinal obstruction in infancy, mostly between 6-11 posterior wall of the duodenum.
months. Intermittent colicky abdominal pain, vomiting Treatment: The child is kept on a bland diet for a few
and bloody mucous stools (currant jelly), the classic triad days. Thereafter, a more liberal diet is permitted. Frequent
is encountered in only 20% to 40% of cases. History of small feeds are desirable. Use of antacids between meals
recent change of milk formula, upper respiratory tract and anticholinergic drugs is recommended. Most ulcers
infection, or vaccination may be present in a small heal in 3 to 4 weeks. H2 receptor antagonists or proton
proportion of patients. Severe colicky abdominal pain pump inhibitors (PPI) are used to reduce gastric acid
manifests as crying episodes and it may be associated with secretion. Although current evidence does not establish a
vomiting depending on the level of obstruction. A cause-effect relationship between infection and recurrent
sausage-shaped mass may be palpable usually in the right abdominal pain, symptomatic children with positive
quadrant of the abdomen; right iliac fossa may appear evidence of H. Pylori infection should be treated with
empty. Rectal examination may show the tip of the amoxicillin, clarithromycin and omeprazole for 1-2 weeks.
intussusceptum. Barium enema X-ray film shows cupping, Peptic ulcer may perforate in a few children. These require
as it is obstructed by the intussusceptum; the obstruction surgical closure. Blood transfusion may be required to
may be relieved following the procedure. Ultrasono maintain the hematocrit in case of bleeding peptic ulcers.
graphy may be useful.
Intussusception is a surgical emergency and the aim is Gastrointestinal allergy: Allergic response to specific foods
reduction of the obstructed bowel. Shock is treated and may cause diarrhea, nausea, vomiting and colicky
the patient is rehydrated. In intussusception of short abdominal pain. Allergy to cow's milk protein is not
duration, hydrostatic pressure of the barium enema (both unusual in the first few months of life. Babies could even
diagnostic and therapeutic) or saline enema usually relieve be sensitized in utero. Three main factors contribute to
260 Essential Pediatrics
the development of allergy, viz. genetic predisposition, subacute bacterial endocarditis, abdominal epilepsy,
allergen exposure and contributory factors such as hemolytic crisis in sickle cell disease and hereditary
immunologic defects, gastrointestinal disease, infection spherocytosis may be responsible for abdominal pain.
and non-specific irritants.
Metabolic causes: Lead poisoning, diabetic keto-acidosis,
Amebic liver abscess: Clinical manifestations include fever anaphylactoid purpura can also manifest with pain
with loss of appetite and right upper abdominal pain. abdomen. The treatment is directed at the specific cause.
Liver is enlarged and tender; jaundice is absent or minimal.
Metronidazole, 20 to 50 mg/kg/day in divided doses for DIARRHEA
7 days is effective in treatment.
Acute diarrhea is a leading cause of under-five mortality
Passive congestion of the liver: In congestive cardiac failure in India. Diarrhea is the passage of watery stools at least
and constrictive pericarditis, there is pain and tenderness three times in a 24 hour period. However, recent change
in the right hypochondrium. in the consistency of the stools is more important than the
frequency. Mothers usually know when their children
Choledochal cyst: There is a partial and intermittent
have diarrhea and provide useful working definitions in
obstruction to the flow of bile through the ampulla of
local situations.
Vater. The common bile duct is dilated into a cystic
enlargement. Patients have history of abdominal pain and Clinical Types of Diarrheal Diseases
jaundice intermittently. A cystic swelling may be felt in
Four clinical types of diarrhea can be recognized, each
the right upper quadrant of abdomen. The diagnosis is
reflecting the basic underlying pathology and altered
confirmed by ultrasonography and endoscopic retrograde
physiology:
cholangio-pancreatography (ERCP) or magnetic reso
• Acute watery diarrhea (including cholera) starts suddenly
nance cholangio-pancreatography (MRCP). Treatment is
surgical. and lasts several hours or days. The main danger is
dehydration; weight loss may occur if feeding is not
Acute pancreatitis: Acute pancreatitis may follow mumps, continued.
biliary tract disease, trauma, drugs, congenital anomalies • Acute bloody diarrhea (dysentery) is similar to acute
and generalized infections. Blunt abdominal trauma is an watery diarrhea, but associated with gross blood in
important cause of acute pancreatitis in childhood. It stool. The main dangers are intestinal damage, sepsis
should be suspected in patients with sudden severe and malnutrition; other complications, including
abdominal pain, tenderness in epigastrium or left upper dehydration, may also occur.
quadrant, vomiting, fever and extreme prostration. Serum • Persistent diarrhea starts as acute watery diarrhea and
and urinary amylase levels are elevated. Vigorous lasts 14 days or longer. The main danger is malnutrition
symptomatic and supportive, treatment is necessary. and serious non-intestinal infection; dehydration may
Mortality is 10 to 15% and complications including also occur.
pseudocyst occur in up-to 15%. Disease is generally self- • Diarrhea with severe malnutrition (marasmus or
limiting and supportive treatment is necessary. Surgical kwashiorkor) carries risk of severe systemic infection,
treatment is reserved for pancreatic abscess and necrotic dehydration, heart failure and vitamin and mineral
pancreatitis. deficiency.
The two main risks of diarrhea are malnutrition and
Disorders of genitourinary system: Acute glomerulo
death. While dehydration is the most common cause of
nephritis, acute pyelonephritis, acute cystourethritis,
death, several deaths occur as a result of malnutrition
urinary calculi, hydronephrosis, and ectopic kidney may
consequent to a series of diarrheal episodes. A child may
present with acute abdominal pain (Dietel's crisis).
lose almost as much water and electrolytes from the body
Abdominal pain in kidney disease is usually present in
during an episode of diarrhea as an adult, since the length
the back, flanks and lower abdomen. Pain due to ureteric
and surface area of intestinal mucosa of a child from where
calculi radiates along the course of ureters. Passage of
the diarrheal fluids are lost, are as large as in adults.
blood clots across the ureter may also cause clot colic.
However, loss of one liter of fluids from the body of a
Acute salpingitis, torsion of ovaries and hematocolpos
child weighing 7 kg (approximately 15% of body weight
should be considered in differential diagnosis of
loss) is much more hazardous than similar depletion from
abdominal pain in girls. Girls often suffer from severe
an adult of 70 kg weight (approximately 1.47% body
abdominal pain with each menstrual period, especially
weight loss). Significant dehydration disturbing the
around menarche. Torsion of testis is an acute surgical
balance of electrolytes and acid-base status of the body
emergency. It requires immediate intervention otherwise
permanent damage occurs. occurs in about 2 to 5% of all cases of diarrhea, and may
be fatal, if fluids and electrolytes are not replaced.
Causes of pain outside the abdomen: Basal pneumonia, While any infection is associated with higher morbidity
diaphragmatic pleurisy, rheumatic fever, pericarditis, and mortality in a malnourished child, diarrheal illnesses
Diseases of Gastrointestinal System and Liver 261
are important contributors to malnoutration. Diarrhea can How does Diarrhea Cause Significant Physiological
cause undernutrition and worsen milder forms of Disturbances in the Body?
malnutrition because: Approximately 60% of child's body weight is present in
• Impaired intestinal absorption causes loss of macro and two fluid compartments: the extracellular fluid (ECF) and
micronutrients (zinc); intracellular fluid (ICF). The extracellular compartment
• Urinary loss of specific nutrients occurs (vitamin A); includes circulating blood, intestinal fluid and secretions.
• There is increased catabolism due to infection; Diarrheal losses come from ECF and replacement fluids
• A child with diarrhea is often not hungry; should be of similar composition: relatively rich in sodium
• Mothers often make the mistake of not feeding the child with lower potassium. Kidneys regulate the electrolyte
enough food during diarrhea or even for some days content of the extracellular compartment by filtering, -
after recovery; and concentrating, diluting and reabsorbing fluids and
• Doctors often do not emphasize on the need for metabolites from the circulation. Functional ability of the
continued feeding during the diarrhea episodes. kidney of very young infants is not fully developed as
compared to older children.
What Causes Acute Diarrhea? Large amount of water and water soluble nutritive
Causative agents of acute diarrhea can now be identified substances such as electrolytes, metabolites and vitamins
in nearly 70-80% episodes of acute diarrhea in sophis are lost from the body during diarrhea episodes. Loss of
ticated laboratories. In India, rotavirus and enterotoxigenic water from the body causes a reduction or shrinkage in
E. coli account for nearly half the total diarrheal episodes the volume of extracellular compartment. In about half of
among children. Rotavirus is more frequently isolated in these cases, the concentration of sodium in the plasma or
children with severe disease than in mild cases. Cholera extracellular compartment remains nearly normal (about
accounts for 5-10% cases; it is endemic in some parts and 140 mEq/L). Since excessive sodium may be lost in the
may occur in outbreaks. The importance of cholera lies in stools in another 40 to 45% of cases, there is a relative
the rapidity with which severe dehydration may set in decline in the serum and ECF sodium level (hypo
within hours. Apart from enterotoxin producing E. coli natremia). Sodium is a major osmotic determinant of ECF.
(ETEC), which account for nearly 20% of childhood Therefore, the osmolality of ECF falls, causing movement
diarrhea, other forms of diarrheagenic E. coli are of water from the extracellular to intracellular compart
enteroinvasive (EIEC), enterohemorrhagic (EHEC), ment. This causes further shrinkage of the already reduced
attaching effacing E. coli or localized adherent (LA-EC), extracellular compartment volumes (Fig. 10.4).
diffusely adherent E. coli (DA-EC) and aggregative Skin turgor or elasticity is normally maintained by the
adherent E. coli (Agg-EC). EIEC and EHEC can cause presence of water and fat in the tissues. Shrinkage of
dysentery. EHEC is a cause of hemolytic uremic extracellular water in both hypo- and isonatremic types
syndrome. Shigella and Salmonella species are isolated in of dehydration impairs the skin elasticity. The skin appears
3-7% of childhood diarrheas. Shigella accounts for to be wrinkled like that of an old man. On pinching, it
majority of cases of dysentry. The other bacterial agents takes a few seconds for the skin fold to return to normal.
causing diarrhea include C. jejuni, Y. enterocolitica and A. In about 5% of diarrhea cases (especially if the child has
hydrophilia. E. histolytica accounts for nearly 5% of been given fluids with more salts), serum sodium levels
dysentery. Giardia lamblia rarely causes acute diarrhea. may be elevated to more than 150 mEq/L. In these
Intestinal helminthes do not usually cause of acute patients, the osmotic pressure of ECF is relatively higher.
diarrhea; their frequent presence in stools simply reflects Therefore, water comes from inside the cells to the
their high prevalence in the population. extracellular fluid and, therefore, partially masks loss of
262 Essential Pediatrics
skin turgor. The skin may appear soggy, doughy or Assess in the examination: (i) physical signs of
leathery. The physician is likely to erroneously under dehydration; (ii) nutritional status of the child; weight is
estimate a severe case of hypernatremic dehydration as the best parameter; and (iii) presence of pneumonia, otitis
mild dehydration unless he /she takes into account the media or other associated infections.
other more important sequelae of dehydration such as
circulatory or renal impairment. As the extracellular Clinical Approach to Etiologic Diagnosis
compartment is depleted, the blood volume is reduced. In rotavirus diarrhea, vomiting is an early feature and
This results in a weak, thready pulse and a fall in blood diarrhea is more severe. Most patients have mild to
pressure. Extremities appear cold. Because of low moderate fever. Norwalk virus infection occurs in slightly
hydrostatic pressure in the renal glomeruli, the filtration older infants and preschool children. Stools are large
of urine is reduced. This is ominous because poorly func and watery in secretory diarrhea due to infection with
tioning kidneys cannot regulate the metabolic derange toxigenic strains of E. coli or Vibrio cholerae. The fecal
ments. Urine flow is a good indicator of the severity of matter appears as curdy deposits. Vomiting is common
illness. In severe cases, renal failure may eventually set in cases of cholera. Fever, abdominal cramps and
tenesmus with passing of blood and mucus in stools
Diarrhea stools contain large amounts of potassium. indicate dysentery (colitis), often due to infection with
Therefore, the serum potassium level invariably falls if Shigella. Small amounts of blood in stools may be seen
diarrhea persists for more than a few days. This is more in infection with Shigella, Salmonella, Campylobacter or
pronounced in children with severe malnutrition. The invasive stains of E. coli. Infection of the gut with
affected children present with abdominal distension, Staphylococci, Candida albicans or Clostridium difficile
paralytic ileus and hypotonia of muscles. Electrocardio should be suspected in severe cases of diarrhea in very
gram may show ST depression and flat T waves. Since sick infants, who have received prolonged treatment with
intestinal secretions are alkaline and considerable broad spectrum antibiotics.
bicarbonate is lost in diarrheal stools, acidemia usually
accompanies the diarrheal dehydration. Patient in such Laboratory Investigations
cases remains asymptomatic till the base excess falls to 12 The large majority of acute diarrhea episodes can be
mMol/L. As the base excess falls below this level, the managed effectively even in absence of laboratory
breathing becomes deep and rapid (Kussmaul breathing). investigations:
To sum up, in early and mild cases of diarrhea, the child i. Stool microscopy: Fecal leukocyte counts of >10/hpf are
may be thirsty and slightly irritable. As the diarrhea suggested as an indicator of invasive diarrheas
continues and dehydration worsens, the child becomes requiring antibiotic therapy. However, the major
more irritable and develops a pinched look. The fontanele, problem is low specificity, being often positive in viral
if open, is depressed, the eyes appear sunken, and the diarrheas, where antibiotics are of no value.
tongue and the inner side of cheeks appear dry. Abdomen ii. Stool culture: This is of little value in routine
may become distended in hypokalemia. The child passes management of acute diarrhea. To identify cases for
urine at longer intervals. As acidosis worsens, the breath antibiotic especially infections with Shigella and V.
ing becomes deep and rapid. In extreme cases, the child cholerae, the presence of gross blood in stools and a
appears moribund, pulse appears to be weak and thready, cholera like clinical picture are more useful than
blood pressure falls and the quantity of urine passed is culture. E. coli is often reported on stool cultures but
markedly reduced. Children with severe dehydration may most laboratories lack the ability to identify whether
succumb rapidly, if they are not promptly treated. these are diarrheagenic or commensals.
iii. Blood gas estimations, serum electrolytes, renal
Assessment of Child with Diarrhea
function tests are not routinely indicated. These are
History performed only if the clinical condition of the child
A careful history should elicit whether the child has acute suggests acid-base imbalance, dyselectrolytemia or
watery diarrhea, dysentery or persistent diarrhea with or oliguria/ anuria.
without growth failure. Watery, large, frequent (one or iv. Tests for stool pH and reducing substances are not
more stools every 3 hours) stools indicate relatively greater indicated in acute diarrhea.
severity of illness. The following questions are important
to plan therapy: Did the child vomit during the preceding Physiological Basis for Management
6-8 hours? Did he pass urine during the same period? In most cases of acute diarrhea, electrolytes such as
What is the nature of fluids that the child has been taking? chloride and sodium besides water are actively secreted
Was the child receiving optimum feeding before the from the gut mucosa and are, thus, lost in stools.
illness? Has feeding been reduced or modified during Physiologists observed that while water and sodium were
diarrhea in a way that reduced the quantity of total energy being lost, nutrients such as glucose, amino acids and
intake or the quality of food consumed? dipeptides continued to be absorbed without difficulty in
Diseases of Gastrointestinal System and Liver 263
the majority of cases. The uptake of glucose and other Since 2004, based on the WHO/UNICEF and IAP
nutrients in the intestinal cells is an enzyme-mediated recommendations, the Government of India has adopted
active physiological process. The carrier mechanisms for the low osmolarity ORS as the single universal ORS to be
the transport of glucose and sodium across the cell used for all ages and all types of diarrhea. The low
membrane are interlinked. As glucose is absorbed, sodium osmolarity ORS is different from the previous ORS in
is also absorbed in the small gut, even though sodium is sodium content and osmolarity. The comparison between
being actively lost at the same time in stools of secretory the two ORS is given in Table 10.7. There were concerns
diarrheas due to the effects of the toxin elaborated by of hypernatremia when old WHO-ORS was used in
enterotoxigenic strains of Escherichia coli and Vibrio
cholerae. Sodium absorption also promotes absorption of
water. This is the physiological basis of oral rehydration
Table 10.7: Comparison between low osmolarity ORS and
therapy, which is a fascinating advance of modem
WHO-ORS
medicine and has probably saved more lives than any
other treatment modality. Ingredients of Concentration of various ingredients in
ORS solution ORS solution (mmol/L)
What is Oral Rehydration Therapy (ORT)? Low osmolarity WHO-ORS (old)
Oral rehydration therapy (ORT) today is at the core of ORS (new)
management of diarrhea. The term ORT includes (Table Sodium 75 90
10.6): Potassium 20 20
a. Complete oral rehydration salt (ORS) solution with Chloride 65 80
composition within the WHO recommended range; Citrate* 10 10
b. Solutions made from sugar and salt; Glucose 75 111
c. Food-based solutions; and * One mmol of citrate provides 3 mEq of base.
d. In presence of continued feeding, a variety or Oral rehydration solution (ORS) should preferably be given
with a teaspoon or consumed in small sips from a cup or
commonly available, culturally acceptable fluids
tumbler. A child with profuse vomiting is more likely to retain
irrespective of presence of glucose or without salt when
the fluid if it is consumed in small sips. Large gulps of fluids
the former are present. The term ORS for facilitating
stimulate gastrocolic reflex resulting in a quick passage of
understanding, refers to the complete oral rehydration stools and often vomiting.
salt mixture recommended by the WHO.
children with non-cholera diarrhea or with edema. The Treatment Plan A: Patients without
reduced osmolarity solution promotes water and sodium Physical Signs of Dehydration
absorption more efficiently than the old WHO-ORS. Meta
The mother should be educated to use increased amount
analysis of trials of reduced osmolarity ORS revealed
of culturally appropriate home available fluids (Table
reduced need of IV fluids, reduction in stool output, lower
10.6). In addition, they should be given ORS packets for
vomiting, and no significant hyponatremia. In addition,
use at home (Table 10.9). ORS is appropriate for both
no significant problems were observed in children with
prevention and treatment of dehydration. When ORS
acute cholera diarrhea. Similarly, no significant
packets are given to the mother at treatment center or by
hyponatremia was noticed in adults with cholera.
other health care providers, she is less likely to demand
or desire antidiarrheals. The mother should be asked to
Assessment of Severity of Dehydration
take the child to the health worker if the child does not
A child's dehydration status should be classified as no get better in 3 days or develops any of the following danger
dehydration, some dehydration or severe dehydration signs: many watery stools; repeated vomiting, marked
according to the WHO criteria (Table 10.8). thirst, eating or drinking poorly, fever, and blood in stool.
Treatment Plan B: Patients with Physical When is Oral Rehydration Therapy Ineffective?
Signs of Dehydration • High stool purge, more than 5 ml/kg body weight/ hour.
All cases with obvious signs of dehydration need to be • Persistent vomiting, greater than 3 vomitings per hour.
treated in a health center or hospital. However, oral fluid Children with less frequent vomiting tolerate ORS well.
therapy must be commenced promptly and continued • Incorrect preparation or administration of ORS solution;
during transport. The fluid therapy for dehydration has a very concentrated solution is unsafe due to high
three components: osmolality and a very dilute solution may be ineffective.
a. Correction of the existing water and electrolyte deficit • Abdominal distension and ileus.
as indicated by the presence of signs of dehydration • Glucose malabsorption: Rarely, and especially in
(rehydration therapy). undernourished patients, significant glucose
b. Replacement of ongoing losses due to continuing malabsorption may occur during acute diarrhea. The
diarrhea to prevent recurrence of dehydration use of ORS solution in such patients results in a marked
(maintenance therapy). increase in watery diarrhea with large amounts of
c. Provision of normal daily fluid requirements. glucose in the stools. The patient is very thirsty and
Deficit Replacement/Rehydration Therapy signs of dehydration do not improve, become worse or
reappear. When ORS solution is discontinued, the stool
Give 75 mL/kg of ORS in the first 4 hours. Use child's age
volume decreases. If this occurs, IV fluid should be used
only when you do not know the weight. Approximate fluid
for 24-28 hours, after which ORS solution can be tried
estimates for deficit replacement are given in the Table
again.
10.10.
• The approximate amount of ORS required (in mi) can also be calculated by multiplying the patient's weight (in kg) times 75.
• For infants under-6 months who are not breastfed, also give 100-200 ml clean water during this period.
• Encourage breastfeeding.
266 Essential Pediatrics
there is repeated vomiting or abdominal distension, give it is safe and desirable to continue feeding in acute
the fluids more slowly. If there is no improvement in diarrhea. Since children with diarrhea may develop
hydration after 3 hours, try to start IV fluids as early as protein-energy-malnutrition, the diet should be easily
possible. digestible and nutritionally balanced. Presence of
nutrients in the gut promotes absorption of sodium and
Monitoring water and hastens recovery of the intestinal epithelium
Reassess the child every 15-30 minutes until a strong because food in the intestine stimulates rapid cell turn over
radial pulse is present. If hydration is not improving, give and renewal of intestinal lining. More lives are lost because
the IV solution more rapidly. When the full amount of IV of unnecessary starvation in diarrhea. Following are the
fluid has been given, reassess the child's hydration status, recommendations on dietary management of acute diarrhea:
and
1. Children should continue to be fed during acute
• If signs of severe dehydration are still present, repeat
diarrhea because feeding is physiologically sound and
the IV fluid infusion as outlined earlier.
prevents or minimizes the deterioration of nutritional
• If the child is improving but still shows signs of some
status that normally accompanies such illness.
dehydration, discontinue IV treatment and give ORS
2. In acute diarrhea, breastfeeding should be continued
solution for 4 hours (as for Plan B). If the child is
uninterrupted even during rehydration with ORS.
normally breastfed, encourage the mother to continue
3. Optimally energy dense foods with the least bulk that
breastfeeding frequently.
are recommended for routine feeding and available in
• Observe the child for at least 6 hours before discharge,
the household should be offered during diarrhea, in
to confirm that the mother is able to maintain the child's
small quantities but frequently, at least once every 2-3
hydration by giving ORS solution.
hours.
Unique Problems in Infants Under 2 Months of Age 4. Staple foods do not provide optimal calories per unit
Breastfeeding must continue during the rehydration weight and these should be enriched with fats and oils
process, whenever the infant is able to suck. Complications or sugar, e.g. khichri with oil, rice with milk or curd
like septicemia, paralytic ileus, and severe electrolyte and sugar, mashed banana with milk or curd, mashed
disturbance are more likely in young infants with diarrhea potatoes with oil and lentil.
than at later ages. Diarrhea in these infants should be 5. Foods with high fiber content, e.g. coarse fruits and
ideally treated as inpatients by experienced physicians at vegetables should be avoided.
treatment centers with appropriate facilities. This allows 6. In non-breastfed infants, cow or buffalo milk can be
for careful assessment for need for systemic antibiotics given undiluted after correction of dehydration toge
and careful monitoring. ther with semisolid foods. Milk should not be diluted
with water during any phase of acute diarrhea.
Nutritional Management of Diarrhea Alternatively, milk cereal mixtures, e.g. dalia, sago,
A considerable quantity of nutrients is lost in the diarrheal milk-rice mixture, can be used.
stools. Appetite is impaired and food is often withheld 7. Routine lactose-free feeding, e.g. soy formula is not
from the child by the mother because of an erroneous belief required during acute diarrhea even when reducing
that rest to the bowel promotes early recovery. Some substances are detected in the stools. Lactose malabsorp
hydrolytic (disaccharidases) enzymes and absorptive tion meriting dietary modification is very uncommon in
mechanisms for glucose and amino acids may be partially acute diarrhea. It may be required in very few infants in
compromised during viral diarrhea. Transient carbo whom diarrhea persists beyond 8-10 days with progres
hydrate malabsorption may occur. Carbohydrates may sive weight loss and >1% reducing substances in stools.
pass unchanged in the lower gut, these raise intraluminal 8. During recovery, an intake of at least 125% of normal
osmotic pressure and draw water from the gut by osmosis RDA should be attempted with nutrient dense foods;
and increase the severity of diarrhea. Unabsorbed it should continue until the child reaches pre-illness
carbohydrates are also metabolized to short-chain fatty weight and ideally until the child achieves normal
acids by colonic bacteria and are then absorbed from the nutritional status, as measured by expected weight for
colon. These pathological changes are transient and do height or weight for age. This might take several weeks
not last for more than a few days in most cases. Therefore, or longer, depending on the degree of deficit.
Diseases of Gastrointestinal System and Liver 267
Fig 10.5: Algorithm for management of dysentery—*Disappearance of fever, less blood in stools, fewer stools, returns to normal activity
268 Essential Pediatrics
administration. Emphasis should be given for maintaining iii. Severe malnutrition (weight-for-length <70%, or
sanitation and hygiene. Three 'C's; clean hands, clean weight-for-age <60% of the WHO-growth medians or
container and clean environment are the key messages. the presence of pedal edema involving at least the feet).
Mother should be properly guided to avoid this risk by iv. Presence or suspicion of systemic infection.
concrete recommendations such as the use of clean
containers, avoiding exposure of food to dust, flies or Management
cockroaches. Hands should be washed and dried with Assess the child for signs of dehydration and give fluids
paper towel or clean towel and not by repeatedly used according to Treatment Plan A, B or C (for acute diarrhea),
towels, before administration of food to the baby. Water as appropriate. The mainstay of therapy of persistent diarrhea
given to the child or used for preparing feds should be is dietary management.
clean, potable, preferably boiled. Vegetables and fruits
should be washed and peeled before these are fed to the Dietary Algorithm for the Treatment of PD
child. Improvement of environment sanitation, good water The Initial Diet A
supply, adequate sewage disposal system and protection
[Reduced lactose diet; milk rice gruel, milk sooji gruel, rice with
of food from exposure to bacterial contamination are
curds, dalia]. Clinical trials at AIIMS have clearly shown
effective long-term strategies for control of all infectious
that reduced lactose diet is as well tolerated as totally
illnesses including diarrhea. These measures should be
lactose-free diet, without significantly increasing stool
sustained to achieve the desired goals.
output or increasing risk of dehydration (Table 10.13). Milk
Suggested reading
1. The Treatment of Diarrhea: A Manual for Physicians and Other Recommendations for Dietary Management
Senior Health Workers. WHO (2005). WHO/CDD/SER/80.2.
Infants aged less than 6 months: Persistent diarrhea occurs
2. Consensus Statement of IAP National Task Force: Status Report
on Management of Acute Diarrhea. Indian Pediatrics 2004; 41:335-
rarely in infants below 6 months who are exclusively
348.
breastfed. A breastfed infant could normally be passing
several soft or mushy stools each day. In such cases the
PERSISTENT DIARRHEA change in character of stools will be important. The princi
ples of treatment are summarized below:
Diarrhea that starts as an acute episode, and lasts at least i. Encourage exclusive breastfeeding.
14 days is said to be persistent (PD). This definition ii. Help mothers who are not breastfeeding to reestablish
excludes specific conditions like celiac disease, tropical lactation.
sprue, or other congenital, biochemical or metabolic iii. If only animal milk must be given, replace it with curds
disorders. The predominant causes of persistent diarrhea or a lactose-free milk formula (gives with a cup and
are listed below: spoon).
i. Persistent infection with one or more enteric iv. If required, cooked rice can be mixed with milk/curd/
lactose-free formula.
pathogens.
ii. Malabsorption particularly of carbohydrates and fat, Older infants and young children: Breastfeeding should be
due to a combination of malnutrition and enteric continued during PD. Breastfed infants continue to gain some
infection. weight even while passing abnormal stools for a few extra
iii. Infrequently, dietary protein intolerance. days after an acute episode of gastroenteritis. In the second
and later years, the breast milk output is less and optimal
Majority of patients with persistent diarrhea pass
feeding of a mixed diet is more important.
several loose stools daily but remain well hydrated.
Dehydration develops only in some patients because of
the high stool output or when oral intake is reduced due
to associated systemic infection. The major consequences
of PD are groivth faltering, worsening of malnutrition and
death during subsequent diarrheal or non-diarrheal illness.
Persistent diarrhea is more common in malnourished
infants and young children. The growth failure associated
with PD is not exclusively the result of malabsorption, it
also occurs due to inadequate energy intake during the
diarrheal episode. This results from anorexia associated
with the illness, faulty feeding practices and incorrect
advice by physicians. Nearly two-thirds of PD patients
*It can be substituted by cooked rice or sooji.
can be treated at home but it is better to hospitalize when
Preparation: Mix milk, sugar, rice together. Add boiled water
following are present: and mix well. Add oil. The feed can now be given to the
i. Age less than 4 months and not breastfed. child.
ii. Presence of dehydration.
270 Essential Pediatrics
cereal mixtures can be highly palatable, are consumed in The Third Diet C {Monosaccharide-based Diet)
large amounts, provide good quality proteins and some
Overall, 80-85% of patients with severe persistent diarrhea
micronutrients, and result in faster weight gain than milk-
will recover with sustained weight gain on the initial diet
free diets.
A or the second diet B. A small percentage may not tolerate
• If the patient is fed entirely on animal milk, the quantity
a moderate intake of the cereal in diet B. These children
should be reduced. Total elimination of animal milk is
are given the third diet (diet C) which contains only
not required routinely. Limit daily intake of milk to 50- glucose and a protein source as egg white or chicken or
60 mL/kg providing not more than 2 g of lactose/kg/ commercially available protein hydrolysates (Table 10.15).
day. To reduce lactose concentration in animal milk, Energy density is increased by adding oil to the diet.
do not dilute it with water as it reduces energy density
critically. Milk can be mixed with cereals, e.g. milk or
curd, rice gruel, milk soojii gruel, or dalia. Table 10.15: Diet C for persistent diarrhea
• Start feeding as soon as the child can eat. (Monosaccharide Based)
• Offer 6-7 feeds per day and a total daily energy intake
of 110 kcal/kg to begin with, increase energy intake
steadily, up to 150 kcal/kg over next two weeks if
required to achieve weight gain.
• Many children will eat poorly, until any serious
infection is treated for 24-48 hr. Use nasogastric feeding
initially in such situations.
consecutive days); (ii) adequate food intake; and (iii) Value of Laboratory Investigations
weight gain. Most children will lose weight in the initial
Patients with PD can be managed without elaborate labo
1-2 days, and then show steady weight gain, as associated
ratory tests using the algorithm outlined above with very
infections are treated and diarrhea subsides. They may high levels of success. Stool microscopy helps in identi
return home, but should be followed regularly to ensure fying trophozoites of E. histolytica and G. lamblia. Majority
continued weight gain and compliance with feeding
of patients who have cysts of E. histolytica are now known
advice. to have non-pathogenic E. dispar. Acid-fast staining with
modified Ziehl-Neelsen technique will identify Cyclospora,
Indications for Change from the Initial Diet (Diet A)
Isospora and Cryptosporidium. Large number of pus cells
to the Second Diet (Diet B) or Diet B to Diet C?
(>20/hpf) in stool suggests invasive diarrhea but a
In the absence of initial or hospital acquired systemic majority of patients with persistent diarrhea do not have
infection, the diet should be changed when there is these. Stools cultures for Salmonella and Shigella should
treatment failure, defined as: (i) a marked increase in stool be done if feasible. Isolation of E. coli is not helpful as most
frequency (usually more than 10 watery stools/day) any laboratories cannot characterize for virulence properties.
time after at least 48 h of initiating the diet; or (ii) return Stool pH and reducing substances help in determining
of signs of dehydration any time after initiating treatment; carbohydrate intolerance. In a non-hospital setting,
or (iii) a failure to establish weight gain by day 7. Unless detecting reducing substances is often difficult as tests
signs of treatment failure occur earlier, each diet should cannot be done promptly and several stools need to be
be given for a minimum period of 7 days. examined for sufficient sensitivity. It is, therefore, more
practical to use clinical criteria to decide a change in diet
Resumption of Regular Diet after Discharge
as discussed above. The fact that diet A has reduced lactose
Children discharged on diet B should be given small already assumes that some secondary lactose intolerance
quantities of milk as part of a mixed diet after 10 days. If exists in children with PD and malnutrition.
they have no signs suggestive of lactose intolerance
(diarrhea, vomiting, abdominal pain, abdominal Prognosis
distension, excessive flatulence) milk can be gradually Most patients with persistent diarrhea recover with the
increased over the next few days. A normal diet algorithmic approach outlined above. However 2-5%
appropriate for age can be resumed over the next week. patients may require parenteral nutrition and extensive
work up. These patients generally have high purge rates,
Recommendations for Antimicrobial Therapy in PD continue to loose weight, do not tolerate oral feeds and
Antimicrobial therapy in persistent diarrhea is indicated should be sent to specialized pediatric gastroenterology
in following situations: centers.
• In the presence of gross blood in stools or for specific
enteric pathogens against which such therapy is known CHRONIC DIARRHEA AND
to be beneficial, e.g. Shigella. Effective anti-shigella MALABSORPTION SYNDROMES
agents such as nalidixic acid or other quinolones should
Malabsorption syndromes are characterized by the
be given (see algorithm for dysentery).
association of chronic diarrhea, abdominal distension and
• Associated systemic infection—combination of paren
failure to thrive. Chronic diarrhea is the direct
teral penicillin or cephalosporin and aminoglycosides
consequence of malabsorption, which in turn results in
is usually appropriate.
malnutrition and failure to thrive. Chronic diarrhea has
• Severe malnutrition—use combination of penicillin or
to be differentiated from persistent diarrhea which is very
cephalosporin and an aminoglycoside as for associated
common. (Refer previous section). Chronic diarrhea here
systemic infection, even if uncertain about presence of
refers to primarily conditions associated with "abnormal
systemic infection
stools" which continues or recurrently occurs over several
• If possible, screen for urinary tract infection (UTI).
months. Dehydration is rare.
10-15% of children with PD and malnutrition require
Stools may be loose and bulky in celiac disease, greasy
antibiotics for associated lower UTI.
and yellowish in exocrine pancreatic insufficiency, as
• When group B salmonella are isolated in stool, treat
liquid as water and mistaken for urine in infants with
with systemic antibiotics only when there is a suspicion
congenital chloride diarrhea or passed noisily with flatus
of systemic infection.
in cases of sugar intolerance.
Additional drugs: Antimotility and antisecretory agents and Non-specific chronic diarrhea or toddler's diarrhea is
bile salt binding resins have not been shown to give any characterized by periods of frequent, heterogenous, often
significant clinical benefit when used to treat PD. mucus containing, foul smelling stools, often alternating
Probiotics have not been systematically evaluated for the with periods of normal stools and most importantly a
treatment of persistent diarrhea. normal state of nutrition.
272 Essential Pediatrics
Chronic diarrhea is differentiated into three major pathophysiologic reasons. Histologic changes in intestinal
pathophysiologic categories: impaired intraluminal digestion, malabsorption vary according to clinical conditions, these
intestinal malabsorption and fermentation (Tables 10.16 changes may be specific or non-specific.
to 10.18).
Diarrhea due to fermentation is liquid, acidic (pH less than
5.5) and often passed with flatus, and its volume is
Table 10.16: Chronic diarrhea due to impaired
variable, roughly proportionate to the amount of
intraluminal digestion
malabsorbed carbohydrate that has been ingested.
Impaired Conditions
digestion Evaluation of a child with chronic diarrhea: Work up of a child
All nutrients Cystic fibrosis, other pancreatic exocrine suspected to have chronic diarrhea and malabsorption
deficiencies. includes the following investigations:
Fat Isolated lipase or co-lipase deficiency, bile duct • Repeated stool examination especially for giardia;
atresia, interrupted enterohepatic circulation • Fecal fat excretion studies;
(e.g. ileal resection; Crohn's disease). • D-xylose test (blood levels and urinary excretion);
Proteins Congenital trypsinogen deficiency, congenital • Intestinal biopsy; and
enterokinase deficiency. • Specific tests, e.g. sweet chloride for cystic fibrosis;
exocrine pancreatic function tests; serology for celiac
disease; breath analysis for carbohydrate mal
Table 10.17: Chronic diarrhea due to intestinal malabsorption absorption.
resistant to oral iron supplementation are the commonest intestinal histopathologic abnormalities and also for
presentation. There may be associated dermatitis asymptomatic children with a condition associated with
herpetiformis, dental enamel hypoplasia, osteopenia, CD and characteristic histologic findings on small
delayed puberty, hepatitis (elevated liver enzymes), intestinal biopsy. A GFD for life remains the only
arthritis, and epilepsy. scientifically proven treatment available for symptomatic
individuals with CD. It is recommended that treatment
Diagnosis be started only after the diagnosis has been confirmed by
The initial work-up of these children involves complete intestinal biopsy. Even small amounts of gluten containing
hemogram, serum chemistry and tests measuring grains (wheat, rye and barley) ingested on a regular basis
intestinal absorption, such as d-xylose absorption, fecal lead to mucosal changes on intestinal biopsy and
fat excretion. Diagnostic evaluation specific to the CD persistence of clinical symptoms. Rice and maize are
include serological tests and histopathological changes in nontoxic and act as wheat substitutes. The clinical
intestinal mucosa. response to gluten withdrawal is dramatic. The growth
velocity improves rapidly. The major problem is of
Serological tests: Commercially available tests include anti-
noncompliance especially in teenagers. Most newly
gliadin IgA and IgG (AGA IgA and AGA IgG), anti-
diagnosed children will tolerate ingestion of lactose,
reticulin IgA (ARA), anti-endomysium IgA (EMA) and
particularly in moderate amounts; therefore, dietary
anti-tissue transglutaminase IgA (TTG) antibodies. Table
lactose restriction is not usually necessary. Young children
10.19 shows the efficacy of different antibodies used for
with more severe disease may benefit from an initial
diagnosing CD.
lactose-free diet.
Children with CD are to be monitored periodically for
Table 10.19: Sensitivity and specificity of the
assessment of symptoms, growth, physical examination
serological tests for CD
and adherence to a GFD. It is also recommended to
Antibodies Sensitivity (%) Specificity (%)
measure TTG or EMG after 6 months of treatment with a
AGA IgA 52-100 92-97 GFD to demonstrate a decrease in antibody titer as an
AGA IgG 52-100 50 indirect indicator of dietary adherence and recovery.
EMA 88-100 91-100
TTG 92-100 91-100 Suggested reading
Guideline for the Diagnosis and Treatment of Celiac Disease in Children:
Recommendations of the North American Society for Pediatric
Intestinal biopsy and histopathology: For confirmation of the Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroentero
Nutri 2005; 40: 1-19.
diagnosis of CD, intestinal biopsy is required in all cases.
As the histologic changes in CD may be patchy, it is Disaccharide Malabsorption
recommended that multiple biopsy specimens be obtained
from the second or more distal part of the duodenum. Pathophysiology
There is good evidence that villous atrophy is a Intestinal disaccharidases are located in the brush border
characteristic histopathologic feature of CD, but there can of epithelial cells of small intestinal mucosa. The
be infiltrative changes in the submucosa. The two superficially located enzyme is very vulnerable to damage
requirements mandatory for the diagnosis of celiac disease by a wide variety of agents. In the absence of these
are (i) villous atrophy with hyperplasia of the crypts and digestive enzymes, disaccharides are not hydrolyzed into
abnormal surface epithelium while the patient is eating simpler sugars and these pass unchanged into the lower
adequate amounts of gluten; and (ii) a full clinical and gut, where these draw water from the gut wall through
histological remission after withdrawal of gluten from the osmosis and cause catharsis. The unabsorbed sugar is
diet. A positive serological test that reverts to negative after fermented by colonic bacteria leading to production of H2,
treatment with a strict gluten-free diet (GFD) in such methane, C02 and low molecular weight organic acids.
cases is further supportive evidence for the diagnosis of H2 and C02 diffuse into the blood and are exhaled in
CD. In patients with selective IgA deficiency, serologic breath. The gases cause abdominal distension and frothy
diagnosis may become difficult as IgA antibodies will be character of loose stools. Older children with lactose
negative. So in patients who are strongly suspected to be deficiency may suffer from cramps on taking milk but may
CD, but regular IgA based marker is negative; IgA level not have diarrhea.
should be done. IgG antibody tests along with intestinal
biopsy are needed for the diagnosis of CD in these cases. Causes of Disaccharidases Deficiency
Congenital deficiency of disaccharidases is very rare.
Management Primary late onset deficiency of lactase is not uncommon
Treatment with a strict gluten-free diet (GFD) is recom in India and many Asian countries. A variety of conditions
mended for all symptomatic children with characteristic such as acute viral or bacterial gastroenteritis, protein
274 Essential Pediatrics
energy malnutrition, and prolonged use of drugs like The cystic fibrosis gene is on the chromosome 7 (at
neomycin, celiac disease, cow's milk protein intolerance 7ql3); there are more than 400 mutations at CF locus, of
and cystic fibrosis may cause secondary transient which Delta F508 (which denotes a single deletion at 508
deficiency of disaccharidases. position of the protein) is the commonest. The mutation
affects the gene's protein product, cystic fibrosis
Diagnosis transmembrane regulator (CFTR), which acts as a chloride
The diagnosis is based on (i) presence of more than 1/2 channel regulator and affects other aspects of
percent of reducing substance in the fresh stools (prior transmembrane movement of water and ions.
hydrolysis with HC1 is necessary before stools are tested CF is a syndrome of apparent exocrine gland dys
for the reducing substance); (ii) acidic stools (pH below function characterized by abnormality in mucus and
5.5) while the child is on a milk or diet containing electrolyte secretion leading to obstructive lesions in
offending carbohydrate; (iii) abnormal oral sugar tolerance multiple organs. Abnormal transmembrane transport of
test (blood glucose rise of less than 20 mg/dl above fasting sodium and chloride leads to thick inspissated secretion
level with a disaccharide load of 2 g/kg); (iv) breath H2 in the epithelial linings of lungs, sweat glands, pancreas
excretion of more than 11 parts per million following a and intestinal mucosa. These trigger inflammatory process
loading dose of lactose or the offending carbohydrate; and leading to fibrosis. In the lungs, thick mucus plugs obstruct
(v) enzyme assay on mucosal biopsies showing low levels bronchioles leading to collapse, stasis and infection.
of disaccharidases. Parenchymal and bronchial damages together lead to
chronic pulmonary disease. In the newborn period, thick
Treatment
meconium plugs which have not been liquefied by the
As majority of cases in clinical practice have secondary pancreatic juice in the intestinal tract of fetus, may cause
transient lactose intolerance, symptoms usually subside intestinal obstruction or meconium ileus. The patients with
while the child is kept on a low lactose formula. Lactose malabsorption usually have insufficient or low bicar
content of the diet can be gradually increased within days bonate with low pH in the intestines. Increased secretion
(as in post-enteritis syndromes) or weeks in more severe of chlorides in the sweat may be an independent associated
cases. Lactose in the diet may be reduced by (i) preparation
defect.
of milk cereal mixtures, e.g. sooji-porridge, and (ii) for
severe cases, use of a formula based on either soy protein, Clinical Features
comminuted chicken meat or calcium caseinate.
Intestinal obstruction may be an initial manifestation in
Carbohydrates are provided as glucose or sucrose or
the neonatal period (meconium ileus). This may be due to
simple carbohydrate like rice.
the presence of abnormal protein and mucoprotein
Defects of Monosaccharide Transport secreted by the pancreatic enzymes. Later these children
tend to retain the food residue in the ileum, caecum and
These include inborn and acquired forms of glucose and
colon and these may form firm masses. Respiratory system
galactose intolerance. The former are rare. The basic distur
is most commonly affected and they manifest with
bance is a defect in the transport mechanisms. The treat
recurrent and persistent pneumonia. In addition, other
ment of these inborn errors consists of exclusion of glucose
systems like gastrointestinal, reproductive, endocrinal are
and galactose from the diet. The diet is difficult and
also affected significantly.
monotonous and consists of calcium caseinate, vegetable
oils, fructose, salts and vitamins. Secondary forms of mono The gastrointestinal manifestations of cystic fibrosis are
saccharide transport defects occasionally follow enteritis as follows:
and celiac disease. Risk for these defects is particularly high Gastrointestinal: Meconium ileus, chronic diarrhea,
in severely malnourished children. In chronic enteritis, the malabsorption, steatorrhoea, pain abdomen, constipation,
bacterial flora deconjugates the bile acids which interfere distal intestinal obstructive syndrome, Ileo-cecal
with the absorption of glucose and galactose. intussusception, fibrosing colonopathy and rectal
prolapse;
Cystic Fibrosis
Cystic fibrosis (CF) is an inherited disorder with autosomal Hepatobiliary. Fatty liver, jaundice, portal hypertension,
recessive transmission. CF was thought to be extremely multilobular biliary cirrhosis, hepatic failure, and gall
rare in India. However, recent reports suggest that CF is stones;
probably more common than previously believed, but Pancreatic: Recurrent/chronic pancreatitis, exocrine and
precise prevalence is not known. In majority of cases it is
endocrine pancreatic dysfunction.
not diagnosed because of low index of suspicion and lack
of wide availability of confirmatory tests. The patho Nutritional: Vitamin deficiency (primarily fat-soluble),
genesis, diagnosis and therapy of CF are discussed in micronutrient deficiency (zinc, iron and copper), and
Chapter 13. failure to thrive.
Diseases of Gastrointestinal System and Liver 275
Diagnosis viscosity and has been used for CF patients with liver
The diagnosis is suspected from the onset of diarrhea early involvement. Breathing exercises with chest physio
in infancy, usually associated with recurrent respiratory therapy are encouraged.
infections. D-xylose absorption test is normal as this In tropical countries, additional salt (1-2 gm/day)
monosaccharide does not need hydrolysis before should be provided to compensate for excessive loss of
absorption. Trypsin in the duodenal juice and stools is chlorides.
reduced. X-ray film of the chest shows pulmonary
Bleeding Per Rectum
involvement. Analysis of the sweat for chlorides is a
reliable diagnostic test. Level of chlorides above 60 mEq/ Rectal bleeding (hematochezia) refers to passage of bright
L in sweat obtained by pilocarpine iontophoresis is red blood from the anus, often mixed with stool and/or
suggestive of the diagnosis. Specific mutations can now blood clots. Rectal bleeding in infants and children is an
be identified. Genetic detection of mutations (like delta alarming symptom for the parents and requires additional
F508) help in confirming the diagnosis. investigation. Practically, localization of hemorrhage
relative to the Treitz ligamentum directs the initial
Treatment evaluation and resuscitation. The presentation depends
There is no definite treatment. Supportive treatment on severity of bleeding. Moderate or severe rectal
depends on the severity of disease and associated bleeding, associated with passage of clots, can quickly
complications and usually involves a combination of deplete a patient's body of blood, leading to symptoms of
medicines and home treatment. Home treatments include weakness, and hypotension and may shock.
getting rid of mucus, eating healthy foods, and exercising Most rectal bleeding comes from the colon, rectum, or
to help prevent infections and complications. anus. The color of the blood during rectal bleeding often
depends on the location of the bleeding in the gastro
Nutrition: A child with CF should be offered a calorie dense intestinal tract. Thus, bleeding from the anus, rectum, and
diet (130-150% of RDA) with adequate carbohydrate and the sigmoid colon tend to be bright red, whereas bleeding
protein content. Fat should be more from vegetable origin from the transverse colon and the right colon tend to be
and rich in polyunsaturated fatty acids. Medium chain dark red or maroon. In some patients bleeding from the
triglycerides use is quite beneficial in CF children showing right colon can be black, "tarry" (sticky) and foul smelling.
failure to thrive due to malabsorption. Fat-soluble The black, smelly and tarry stool is called melena. Melena
vitamins to be supplemented at two times RDA. occurs when blood stays for longer time in the colon for
Medical treatment: Pancreatic supplement (enteric coated, bacterial degradation and usually indicates bleeding site
acid resistant, microsphere preparation) is given along to be the upper gastrointestinal tract (above Treitz
with feed/meal depending on the patient's clinical ligament). But, melena also may occur with bleeding from
response. The usual dosage of enzyme supplement is; the right colon. Rarely, massive bleeding from the upper
Infants: 2000^000 Units lipase/120 ml formula or with gastrointestinal tract can cause rapid transit of the blood
each nursing or 450-900 units lipase/gram of dietary fat; resulting in bright red rectal bleeding. Sometimes the
Children 1-4 years: 1,000-2,000 Units lipase/kg/meal bleeding may be too slow to cause either rectal bleeding
or 500^,000 Units lipase/gm of dietary fat; and or melena and detectable by testing for occult blood in
Children >4 years: 500-2000 Units lipase/kg/meal or stool.
500-4,000 Units lipase/gm of dietary fat.
Use of antacids, sodium bicarbonate and antihistamine
Causes
along with the enzyme is desirable. If the diarrhea persists Common causes of rectal bleeding in children include anal
in spite of adequate therapy, other causes like secondary fissures, hemorrhoids (associated with portal
disaccharide intolerance can be considered and managed hypertension), polyps of the rectum and colon, ulcerative
accordingly. Taurine and lecithine supplements should colitis, ulcerative proctitis, Crohn's colitis, infectious
be given to provide substrate for increased hepatic colitis, ischemic colitis, diverticulosis, abnormal blood
synthesis of bile acids. In resistant cases, misoprostol, a vessels (angiodysplasia), Meckel's diverticula and rarely
prostaglandin analogue had been used to inhibit gastric cancers. In India and other similar communities, infectious
acid secretion and stimulate bicarbonate secretion in upper colitis is the commonest cause of rectal bleeding.
gut.
Long-term antibiotics are essential for preventing Evaluation
pulmonary complications as discussed in Chapter 13. Accurately diagnosing the location and the cause of rectal
Humidification of the inspired air helps. Aerosol therapy bleeding is important for directing treatment. Diagnosis
with mucolytic agents such as DNase (inhalation), with rectal bleeding relies on the history and physical
acetylcystein (oral) may promote clearing the viscid examination, blood tests, proctoscopy/anoscopy, flexible
secretions. Ursodeoxycholic acid (UDCA) is a hydrophilic sigmoidoscopy, colonoscopy, radionuclide scans and
bile acid which improves bile flow by reducing bile angiograms.
276 Essential Pediatrics
due to immunological abnormalities, which may be adults and children with IBD, affecting 25%-35% of
primary defects or just secondary phenomena. Defect is patients
probably in cell-mediated immunity. It seems that
Crohn's disease: In contrast to UC, the presentation in CD
environmental factor or factors are also necessary to
often is subtle, leading to a delay in diagnosis. Gastro
trigger and maintain the diseases. Environmental factors
intestinal symptoms depend on the location, extent, and
may include bacterial pathogens or their products, dietary
severity of involvement. The disease is most often seen in
components, childhood infections, as well as a host of
teenagers but it has been also reported during infancy.
other possibilities. Cell wall-deficient Mycobacteria have
Crampy abdominal pain (usually postprandial) either in
been isolated from surgical specimens resected from
the periumbilical area or right lower quadrant is the usual
Crohn's disease, but role of Mycobacteria in etiopatho-
early symptom. Patients commonly have fever, anorexia,
genesis is not proven.
pallor and weight loss. Colonic CD may mimic UC.
Pathology Chronic diarrhea is the presenting symptom in nearly one-
third of cases. Delayed growth is more common in CD
Ulcerative colitis is a diffuse mucosal inflammation of the
(60 to 88%) than in UC (6 to 12%), with the greatest
colon; it invariably affects the rectum and extends
frequency found in prepubertal children. Perianal disease
proximally for a variable distance in symmetric, uninter
is common, as are anal tags, deep anal fissures, and
rupted pattern to involve part or the entire large bowel.
fistulae. Examination may localize tenderness to the right
Compared with adult-onset UC, childhood-onset disease
lower quadrant, and an inflammatory mass is occasionally
is far more likely to be extensive, with 60-80% of children
felt. Clubbing is seen most frequently in children with
having a pan-colitis. The microscopic features of UC
extensive small bowel disease. Extraintestinal symptoms
include diffuse inflammation confined to the mucosa or
of arthritis, uveitis, stomatitis and erythema nodosum may
submucosa. Typically, there are acute and chronic
be seen in some cases.
inflammation of the mucosa by polymorphonuclear
leukocytes and mononuclear cells, crypt abscesses, Extraintestinal man ifestation:
distortion of the mucosal glands, and goblet cell depletion. Generalized: Fever, weight loss, malaise, ano
In contrast to UC, Crohn's disease is characterized by rexia, fatigue
patchy, transmural chronic inflammation which may affect Ocular: Uveitis, episcleritis, iritis, conjunc
any part of the gastrointestinal tract from the oral cavity tivitis
to the anus. Lesions are focal and asymmetrical. Similar Oral: Cheilitis, stomatitis, aphthae
to UC, CD in children is more likely to be extensive than Pulmonary: Pulmonary vasculitis, fibrosing
CD in adults, most commonly involving both the ileum alveolitis
and colon. Microscopically, the changes in CD extend into Vascular: Vasculitis, thrombosis
the submucosa/transmurally. The inflammation is focal Hepatobiliary: Primary sclerosing cholangitis,
and patchy, both in location and severity. Findings that hepatitis, cholelithiasis
clearly distinguish CD from UC include the presence of Pancreatic: Pancreatitis
transmural inflammation with fissuring ulcers, fistulas, Renal / U rinary: Nephrolithiasis, obstructive hydro
non-caseating granulomas, and vasculitis. nephrosis, enterovesical fistula,
UTI, amyloidosis
Clinical Features Hematologic: Iron deficiency anemia, thrombo
cytosis, Vit B12 deficiency, auto
The clinical presentation of IBD depends on the site and
immune hemolytic anemia
extent of mucosal inflammation.
Endocrine: Decreased growth velocity, dela
Ulcerative colitis: The most common presenting symptoms yed sexual maturation
in UC include passage of blood and mucus mixed with Skin: Erythema nodosum, pyoderma
stools, diarrhea, pain abdomen, tenesmus (pain while gangrenosum, perianal disease
defecation), fever, anorexia, and weight loss. The onset Musculoskeletal: Osteopenia and osteoporosis, arth
may either be insidious or explosive with high, prostration ritis/arthralgias, ankylosing
and continuous bloody diarrhea. Abdominal distension, spondylitis
guarding, and rebound tenderness to palpation with
decrease in bowel sounds requires close supervision due Diagnosis
to the impending risk of developing toxic megacolon. Non Complete blood count may give important clues to the
specific symptoms of anorexia, fatigue, delayed sexual diagnosis, particularly if a high platelet count, anemia and
maturation, and decreased linear growth may be present neutrophil leucocytosis, are noted. Raised inflammatory
but not immediately noticed and if noticed may not markers such as C reactive protein and erythrocyte
prompt a workup for IBD because of their nonspecific sedimentation rate also support the diagnosis. Liver
nature. Extraintestinal manifestations are common in both function tests and serum proteins (albumin and globulin)
278 Essential Pediatrics
should be done to look for hepatic involvement and hypo- promoting growth and development including pubertal
proteinemia. development, and (iv) prevent long-term side-effects of
Perinuclear anti-neutrophil cytoplasmic auto-anti pharmacological treatments. An individualised treatment
bodies (pANCA) and anti-Saccharomyces cerevisiae anti plan, based on type, severity and location of inflammation,
bodies (ASCA) are shown to be useful in differentiating age and psychological factors, is devised for each child.
CD and UC. ASCA are directed against Saccharomyces
Nutritional support: In addition to growth supportive
cerevisiae wall oligomannosidic epitopes while pANCA
function, nutritional therapy is the first-line treatment used
recognize a nuclear membrane antigen of 50 kDa. These
by the majority of paediatric gastroenterologists to induce
tests may have two different serologic profiles: (i)
remission in active CD. It is effective in both small and
"ASCA+/ pANCA-" correlates with CD and (ii) "ASCA/
large bowel CD disease. It does not induce remission in
pANCA +" is associated to UC.
UC but is essential along with pharmacotherapy. The
Radiological studies for evaluation of suspected IBD
mechanism of action for induction of remission is still not
include barium enema and upper gastrointestinal series.
clear. To ensure adequate growth, provide nutrients 125-
In ulcerative colitis, there is granularity of mucosa with
150% of RDA with liberal amounts of micronutrients.
punctate collection of contrast material lodged in small
During acute exacerbations of IBD, parenteral nutrition
ulcers. As the severity increases, the colonic mucosa
may be necessary but has the associated disadvantages of
develops irregularity with spiculations and deeper ulcers.
being more invasive, risk of infection and more expensive.
The typical radiological features of Crohn's disease are
There patients can also be given enteral feeding: elemental
nodularity, ulceration, narrowing and irregularity of the
or polymeric. The usual course of specific nutritional
lumen (String sign).
therapy during exacerbations lasts for 6 weeks, followed
A computed tomography (CT) scan is helpful in the
by a gradual reintroduction of normal oral diet.
diagnosis and management of patients presenting with
acute onset of symptoms or an exacerbation of their Anti-inflammatory drugs
disease. CT can assess both intestinal abnormality and Steroids: Systemic corticosteroid (prednisone or methyl-
extraluminal abnormalities such as abscess formation. prednisolone) therapy is the mainstay of inducing
Ulcerative colitis is associated with mural thickening <1.5 remission in moderate to severe UC. It is also effective in
cm, no thickening of the small bowel, increased perirectal inducing clinical remission in CD with up to a 90% rate of
and presacral fat, target appearance of the rectum, and improvement. The dose is 1-2 mg/kg per day prednisone
lymphadenopathy. Findings consistent with CD include equivalent (max 40-60 mg/ day) for four to six weeks and
mural thickening >2 cm, involvement of the small bowel, then taper. Although corticosteroids act rapidly to alleviate
mesenteric fat-stranding, perianal disease, abscesses, symptoms, they do not heal mucosal lesions and are of no
fistulas, and adenopathy. benefit for maintenance therapy. In addition to oral and
Endoscopic evaluation is an essential tool in the workup parenteral forms of steroids, steroid enemas have been
of IBD. Colonoscopic examination with multiple mucosal used with success in children with distal bowel
biopsies is most important to establish the diagnosis. In involvement. The steroid enema preparation should have
ulcerative colitis, the mucosa is hyperemic, edematous and low systemic absorption and bioavailability, so as to
friable; ulcerations and granular pattern may be seen. The reduce the risk of systemic complications.
mucosal changes start from rectum and extend into colon Aminosalicylates (sulfasalazine): The 5-aminosalicylic acid
with no normal mucosa in between. In Crohn's disease, agents sulfasalazine (50-100 mg/kg/day) and mesalamine
the mucosal changes are patchy and cobblestones like with (40-60 mg/kg/day) are the most widely used amino
normal tissue in between and can have fissures, strictures salicylate preparations used to treat ulcerative colitis and
and fistula openings. Current opinion suggests that an Crohn's disease. They are effective as monotherapy to
upper intestinal endoscopy should be performed at the induce remission in mild to moderate colitis. In patients
same time as a colonoscopy, as a majority of patients with with moderate to severe disease who are refractory to the
IBD may show endoscopic and histological abnormalities aminosalicylates, corticosteroids may induce remission.
in the upper gastrointestinal tract. These agents are continued in the maintainance phase.
Histopathologic features help to distinguish between the Immunosuppressive drugs: In patients who have achieved
two types of IBD as described in pathology section. In remission with corticosteroids, immunomodulators,
approximately 5% of inflammatory bowel disease cases, including azathioprine (1.5-2.5 mg/kg/day) 6-
a definite diagnosis of ulcerative colitis or Crohn's disease mercaptopurine (1-1.5 mg/kg/day), and methotrexate are
cannot be established, in which case the term "indeter helpful in maintaining remission. Immunosuppressive
minate" colitis is used. drugs are used because of their steroid sparing effect.
Biologic therapy: Tumor necrosis factor (TNF) plays an
Treatment important role in the initiation and perpetuation of the
The goals of treatment of IBD in children are; (i) induce inflammatory process in patients with IBD, more so with
remission of the active disease, (ii) to prevent relapse, (iii) patients with CD. Infliximab (monoclonal anti-TNF
Diseases of Gastrointestinal System and Liver 279
antibody) has been approved for use in children with rib margin if the costal angle is narrow. Liver is pushed
moderate to severe inflammatory CD refractory to down in pneumothorax, bronchiolitis and emphysema.
conventional therapy and with actively draining external Visceroptosis associated with rickets and Riedel's lobe
fistulas. It can be used as an alternative to prednisone to cause pitfalls in the interpretation of the liver size. It is,
induce remission or as a first-line therapy in CD with therefore, important to measure the liver span to determine
severe perianal fistulizing disease or in patients with presence of hepatomegaly.The liver span in different age
intolerance to corticosteroids. It has also been used in groups is: infants—5-6.5 cm; 1-5 years—6-7 cm; 5-10
children with severe and steroid refractory ulcerative years—7-9 cm; and 10-15 years—8-10 cm. Besides the size
colitis with positive response. and shape of the liver, consistency and character of the
surface and palpable margin should be evaluated for the
Surgery: Surgical resection is curative in ulcerative colitis
assessment of hepatomegaly. Liver should be examined
but is reserved for those with severe, acute complications;
for tenderness and also auscultated for any murmurs or
colonic dyplasia, persistent disease unresponsive to
bruit. Abdomen should be palpated for other masses or
medical management and severe growth retardation.
enlargement of the spleen.
Surgery is usually avoided in CD as it is not curative.
However, it is indicated for complications of the disease; Pathogenesis of Liver Enlargement
such as perforation/abscess, obstruction, stricture, fistula,
The liver may be enlarged due to: (a) inflammation, (b)
toxic megacolon, or malignancy. Stricture resection or
fatty infiltration, (c) Kupffer cell hyperplasia, (d)
stricturoplasty is used to treat.
congestion, (e) cellular infiltration, and (f) storage of
Psychological support: Emotional and behavioral issues are metabolite (Table 10.20).
common and stem from the chronic nature of the disease.
Anxiety, depression, and antisocial and dependent Splenomegaly
behavior are all common. Due to illness and disease Spleen is enlarged in a large proportion of patients with
exacerbation, lifestyle changes including school chronic liver diseases particularly when portal hyper
attendance may suffer. These issues need to be addressed tension is present. In extrahepatic portal venous
carefully and parents and older children need to be aware
about the nature and course of disease.
obstruction, while liver size remains within normal range, Clinical Features
massive enlargement of spleen may occur due to
Specific symptoms are often obscured by the consequences
associated portal hypertension. Significant splenomegaly
of nonspecific responses of the liver to injuries that lead
with lesser enlargement of liver is present in the following
to hepatocellular damage, decreased liver function,
conditions.
cholestasis and hepatomegaly. Metabolic liver diseases can
broadly be classified under 4 main headings on the basis
Infections
of their dominant clinical presentation: cholestasis,
Malaria and kala azar, infectious mononucleosis, toxo hepatocellular necrosis (acute/subacute), cirrhosis and
plasmosis, cytomegalovirus disease, tuberculosis and hepatomegaly. Clinical signs and symptoms of most
brucellosis. metabolic liver diseases are similar and indistinguishable
from those seen in acquired hepatic disorders such as
Cellular infiltrations infection, intoxication, and immunologic disease. Most of
Leukemia, lymphoma, thalassemia, sickle cell disease the metabolic diseases affecting liver present with
(spleen may not be palpable; absent due to repeated hepatomegaly documented incidentally with or without
infarcts with fibrosis) and histiocytosis. splenomegaly. Most of them are asymptomatic and
anicteric. It may be associated with failure to thrive,
METABOLIC LIVER DISEASE diarrhea, fever, etc.
by varying degrees of hepatocellular necrosis, Table 10.22: Etiology of chronic liver disease
inflammation and fibrosis. It may be defined as a
continuing inflammatory lesion of the liver with the Chronic viral hepatitis
potential to either progress to more severe disease, to • Chronic hepatitis B
continue unchanged, or to subside, spontaneously or with • Chronic hepatitis C
treatment. This definition covers any inflammatory Autoimmune liver disease
disease of the liver not due to acute self-limiting infection • Autoimmune hepatitis-
or to past drug exposure. The possibility of CLD should • Sclerosing cholangitis-
be considered if clinical and biochemical abnormalities • Primary biliary cirrhosis-
persist beyond the expected period of recovery from the • Overlap syndromes
acute liver disease. Metabolic liver disease
The commonly used basis of using apparent duration • Wilson disease
of the disease (of greater than 6 months) is often • Hemochromatosis
misleading in children. Irreversible liver damage may • Indian childhood cirrhosis
have already taken place before any symptoms of the liver • Cystic fibrosis
• Hereditary fructose intolerance
disease are noticed and in the absence of clinical or
• Galactosemia
laboratory feature of chronic liver disease. Many disorders
• Gaucher disease
like autoimmune hepatitis and metabolic disorders should • Niemann Pick disease
be considered CLD at first contact, since left untreated, • Wolman disease
they have the potential to progress to severe and incurable • Glycogen storage disease
liver disease. However, the 6 month cutoff seems
Hepatic venous outflow tract obstruction
appropriate for chronic viral hepatitis due to B and C • Budd Chiari syndrome
infection. • Veno-occlusive disease
Grading and Staging of Chronic Hepatitis Activity Drug-induced biliary malformations
• Choledochal cyst
Grading may be used to describe the severity of
• Congenital hepatic fibrosis
necroinflammatory activity in chronic hepatitis. Staging, • Caroli's disease
on the other hand, is a measure of fibrosis and architectural
alteration, i.e. structural progression of the disease. The Cryptogenic
rationale of staging and grading is to record those features
which indicate the severity and the progression of chronic distension, failure to thrive, shrunken or enlarged liver,
hepatitis, and which might also be of prognostic presence of splenomegaly, ascites and cutaneous porto
significance. systemic shunts. Laboratory investigations may show
elevated transaminases, and elevated serum bilirubin,
Etiology
with or without the reversal of A: G ratio.
The causes of CLD in childhood include chronic hepatitis
with viral agents (HBV, HCV), autoimmune liver disease, Acute Hepatitis
drug induced liver disease, metabolic etiologies and Occasionally, CLD is diagnosed when a child presents
biliary malformations (Table 10.22). with acute viral hepatitis like features. Some features in
Until the early 1980's, Indian childhood cirrhosis (ICC) history and examination may lead to suspicion of presence
accounted for almost 50% of all cases of CLD. The of an underlying chronic liver disease. Metabolic and
incidence of ICC has declined in recent years and is no genetic disorders like Wilson disease, a, antitrypsin
more a major cause of CLD in Indian children. deficiency and autoimmune hepatitis may present as acute
Viral causes of hepatitis, mainly HBV contribute about viral hepatitis for the first time.
8-15% of patients with CLD. Up to one-fourth of CLD
patients may have metabolic etiologies of which Wilson's Asymptomatic Presentation
disease is the commonest. Autoimmune liver disease has Occasionally, the condition is discovered in patients with
been reported in about 2-4% of children with CLD. In up no current or past history of jaundice. The only presenting
to 30-65% of children with suspected liver disease, no
feature might be hepatosplenomegaly with or without
cause can be identified.
failure to thrive. Elevation of transaminases is detected
Clinical Features incidentally. Almost 40-50% of children with CLD may
have such presentations, particularly those with MLD.
Insidious Onset Patients with any of the following features in the history
The patient may have clinical features of prolonged/ should be suspected of having a CLD: history of
repeated episodes of jaundice, features of portal conjugated hyperbilirubinemia in infancy; family history
hypertension, upper gastrointestinal bleed, abdominal of chronic liver disease; inherited or autoimmune
Diseases of Gastrointestinal System and Liver 283
appearance of Anti-HBeAg antibody) is a key event in disease and decompensated cirrhosis are rare during
the evolution of chronic hepatitis B followed by childhood. The diagnosis is based on the presence of anti-
resolution of biochemical and histologic signs of HCV antibodies in the blood and detection of HCV RNA.
inflammatory activity. But recovery from infection is In addition, liver biopsy is required to look for histological
not same as seroconversion and normally evidenced changes of chronic hepatitis and progressive fibrosis.
by the appearance of anti-HBeAg and anti-HBsAg Adequate investigations should be done to rule out other
antibodies and disappearance of HBV DNA and HBsAg associated comorbidities. There are 6 genotypes of HCV
in the blood. It is estimated that about 2-3% of chronic identified worldwide, of which genotypes 1, 2 and 3 are
hepatitis patients spontaneously clear the infection mostly studied. In India, genotype 3 is the commonest
naturally every year, but it is difficult to predict for an genotype amongst adult patients with chronic HCV.
individual patient. Emerging reports suggest that Given the significant morbidity and mortality with
mutants share significant proportion of chronic HBV long-standing hepatitis C infection, treatment should be
infection in children and pose problems of diagnosis, considered for childhood infection. Combination therapy
treatment failure and drug resistance. with IFN-a and ribavirin is approved for treatment of
children aged 3 to 17 years who have chronic HCV
Management infection. Overall sustained viral response rate is 50-64%,
The aims of treatment are sustained cessation of viral but higher response rates (>80%) have been reported for
replication and remission of liver disease. Currently, only genotypes 2 and 3.
two drugs are approved for use in children beyond 2 years
of age: interferon and lamivudine. The overall response Suggested reading
rate of a combination therapy of interferon and lamivudine 1. Arora NK, Das MK, Mathur P. Mishra R. Hepatitis C virus in
varies between 40-60%. Favorable predictors of response children. Intern Semin Pediatr Gastroenterol 2005; 12: 3-8.
2. Jonas MM. Children with hepatitis C. Hepatology 2002; 36:
at the time of initiating therapy are: higher age, elevated
SI73-8.
ALT levels and high HBV DNA levels.
AUTOIMMUNE HEPATITIS
Prognosis
The factors which influence outcome of chronic hepatitis Autoimmune hepatitis (AIH) is a progressive inflam
B are viral (HBV replication status, virus genotype and matory liver disease with clinical, serological, biochemical
mutants, co-infection like HCV or HIV) and clinical (mode and histological findings suggestive of immunologic
reaction against antigens of the host liver leading to
of transmission, age at diagnosis, gender, stage of liver
irreversible changes. It is characterized by the presence
disease at presentation, recurrent flares of hepatitis and
of interface hepatitis and portal plasma cell infiltration
associated hepatic and non-hepatic co-morbidity).
on histologic examination, hypergammaglobulinemia,
Suggested reading and circulating organ nonspecific autoantibodies. Females
are affected more than men, and all ages and ethnic groups
1. Lok ASF, MacMohan BJ. Chronic hepatitis B AASLD Practice
Guidelines. Hepatology 2001; 1225 are susceptible. It occurs infrequently in childhood and
2. Broderick AL, Jonas MM. Hepatitis B in children. Semin Liver Dis. constitutes up to 4-6% of children with chronic liver
2003; 23:59-68. disease. It is uncommonly diagnosed below 2 years of age
3. Elisofon SA. Jonas MM, Hepatitis B and C in children: Current and peaks at 10 to 30 years of age. Autoimmune hepatitis
treatment and future strategies. Clin Liver Dis 2006; 10:133-48.
can occur along with sclerosing cholangitis (overlap
syndrome). It can also develop de novo in patients who
Chronic Hepatitis C
have undergone liver transplantation.
Hepatitis C is caused by an RNA virus, transmitted mainly
through parenteral route, though in childhood perinatal Manifestations
transmission is also important. Vertical transmission of Clinical presentation of AIH is varied. An acute viral
HCV occurs in 4 to 5% of infants born to viremic mothers hepatitis like onset is seen in almost 40-60%, chronic
but is significantly higher (20%) when mothers are co insidious onset in 30-40% and rapid acute liver failure in
infected with untreated HIV. Chronic hepatitis C is 10-15% of children. Features suggesting the presence of
reported to be in about 175 million people worldwide with AIH include associated autoimmune thyroiditis, arthritis,
wide geographic variability in its prevalence; low in hemolytic anemia, vitiligo, nephrotic syndrome, ulcerative
developed countries (1-2%) and higher in Asian countries colitis and insulin dependent diabetes mellitus. The
(up to 6% in Thailand). Hepatocellular carcinoma is likely condition progresses rapidly into cirrhosis and portal
to develop in about 20-30% of these patients over a period hypertension. Hepatocellular carcinoma occurs rarely.
of 10-20 years, but data on children is not available.
Children with chronic hepatitis C are mostly
Diagnosis
asymptomatic and have normal or mildly elevated or AIH has been classified on the basis of presence of
mildly fluctuating serum transaminases. Severe liver autoantibodies and immunogenetic markers into 3 types.
Diseases of Gastrointestinal System and Liver 285
Type 1: These patients are positive for ANA/SMA encephalopathy. There are a multitude of causative factors,
autoantibodies and this is the commonest type seen in which differ between children and adults. Regardless of
childhood. the antecedent cause, the clinical presentation is similar.
Type 2: LKM1 autoantibodies are present in this group The mortality is between 60-80% despite adequate care.
of patients. Definitions: Based on the natural course and clinical
Type 3: This is characterized by the presence of anti- presentation, several nomenclatures are used in clinical
SLA (soluble liver antigen). practice. They are listed below:
• Acute liver failure: This term is used for multisystem
Management
disorder in which severe impairment of liver function
The disease process appears to be more severe in children (INR >1.5 with encephalopathy or INR > 2 with or
as compared to adults, and about 50% pediatric patients without encephalopathy) occurs in association with
have cirrhosis at the time of diagnosis. The goal of therapy hepatocellular necrosis in a patient with no recognized
is control of the disease. Currently, immunosuppression underlying chronic liver disease, within 8 weeks of the
is achieved by corticosteroids and azathioprine, either initial symptoms.
singly or in combination. Prednisolone at 1-2 mg/kg/day • Fulminant liver failure (FHF): This term is used to des
(maximum 60 mg per day) and azathioprine at 1.5-2 mg/ cribe patients without previous liver disease who
kg/day are administered orally. Remission is achieved develop a rapidly progressive liver failure within four
with prednisolone given every day for 8-12 weeks weeks of onset of symptoms.
followed by gradual tapering over 6-8 weeks till a • Hyperacute liver failure: If the features of acute liver
maintenance dose of 0.1-0.2 mg/kg/day or 5 mg per day. failure are evident within one week of onset of
Azathioprine has steroid sparing effect and is added either symptoms, it is termed as hyperacute liver failure.
at the beginning or while tapering steroids. The drug doses • Sub-acute liver failure (SAHF): When the features of liver
are adjusted so as to minimize drug associated adverse failure are gradual occurring over four weeks to six
effects and maintain remission. Flares in disease activity, months after onset of symptoms and associated with
as assessed by an increase in serum aminotransferase level, persistent icterus, ascites and/or encephalopathy.
are treated with a temporary increase in corticosteroid • Chronic liver failure (CLF): Appearance of signs of liver
dose. failure such as hepatic encephalopathy and/or
Most children demonstrate improvement in liver tests clinically detectable ascites at least six months after
within the first 2 to 4 weeks of treatment and 80% to 90% onset of hepatic illness.
achieve laboratory remission in 6 to 12 months. Histologic The survival appears to be inversely related to the
improvement lags behind clinical and laboratory duration of illness: survival with hyperacute liver failure
improvement by 3 to 6 months, and treatment should be is 36%, and sub-acute liver failure is 14%.
continued for at least this period. Medications can be
stopped if liver tests are normal for 1-2 years, no flare ACUTE LIVER FAILURE
during medication and no inflammation on liver biopsy.
Epidemiology
Prognosis The true incidence of ALF in children is not known.
Despite the severe disease at presentation, the response Approximately 0.2% to 1.0% of all acute hepatitis can
to treatment is generally excellent and normalization of progress to liver failure. Liver failure in children is
liver function tests is noted after 6 to 9 months of therapy different from that in adults; in children, especially in
in 75% to 90%. The 10 years survival rate in treated infancy, not only it is very difficult to identify signs of
pediatric patients is over 90%, and the remission rate on early encephalopathy but also encephalopathy can be a
therapy is approximately 80%. late presentation.
Table 10.23: Etiology of acute liver failure preexisting liver disease of any etiology might enhance
the probability of precipitating acute liver failure. Infection
Viral hepatitis (Isolated/mixed)
with HAV or HEV in a child with underlying occult liver
• Hepatitis A, B, C, D, E, and others
disease, e.g. Wilson's disease increases the risk of liver
• Herpes simplex
• Epstein Barr virus failure.
• Parvovirus B19
Precipitating Factors
• Varicella zoster
• Cytomegalovirus The precipitating factors of acute liver failure in patients
• Adenovirus with acute hepatitis include infections, persistent fever,
• Echovirus persistent vomiting, hypovolemia, use of hepatotoxic
• Coxsackie virus drugs (anti-tubercular, antipyretics and anticonvulsants,
Drug induced etc.) and zinc deficiency.
• Acetaminophen (paracetamol)
• Isoniazid Clinical Presentation
• Halothane Most patients with acute liver failure may have no
• Sodium valproate elicitable history of any major medical problems or blood
• Phenytoin
transfusion. Initially the child has non-specific prodromal
Metabolic causes symptoms such as malaise, nausea, fatigue, loss of
• Wilson disease appetite, followed by dark urine and jaundice.
• Neonatal hemochromatosis Hepatic encephalopathy is one of the most important
• Tyrosinemia type 1 presentations of acute liver failure. However, the clinical
• Mitochondrial disorders
appearance of hepatic encephalopathy is variable,
• Hereditary fructose intolerance
depending on the extent and rapidity of hepatic damage,
• Alpha-1 antitrypsin deficiency
• Niemann-Pick disease the degree of portosystemic shunting, and the contribution
• Indian childhood cirrhosis of precipitating factors. Initial symptoms of
• Glycogen storage disease type IV encephalopathy may be subtle and are likely to be passed
• Urea cycle defect off for the behavioral aberration of the child. Change in
• Galactosemia personality is one of the earliest signs of hepatic
Hypoperfusion encephalopathy. A child with acute onset of combative
• Budd Chiari syndrome behavior, irrelevant talking, euphoria or being irritable
• Venoocclusive disease without reason should always be screened for hepatic
• Right sided congestive heart failure failure. Changes in sleep pattern and motor coordination
• Cardiogenic shock are other early markers of hepatic encephalopathy. In
younger patients, the presence of coagulopathy is accepted
Autoimmune hepatitis
as fulfilling the definition of acute liver failure. Hepatic
Mixed: Viral infection on underlying chronic liver disease encephalopathy is staged into 4 grades, grade I through
Unknown causes IV, as given in Table 10.24.
The patients with acute liver failure are at high risk for
to 70% of them may survive without resorting to metabolic (hypoglycemia) and electrolyte imbalance and
transplantation. Hepatitis E is increasingly being labeled infections. Presence of fever, leukocytosis, unexplained
as the causative agent responsible for acute liver failure. hypotension, azotemia, oliguria, worsening encephalo
Hepatitis B is the most common identifiable viral agent pathy, severe acidosis and DIC indicates sepsis and
responsible for acute liver failure worldwide with warrants aggressive investigations for infections and
fulminant hepatitis occurring in approximately 1% of appropriate management. Most often the infecting
cases. Absence of HBeAg and presence of anti-HBeAg organism is a bacterial agent (staphyloccoci or gram-nega-
seems to increase the risk of acute liver failure in newborns tive organisms) but fungal infections are not uncommon.
and infants who have acquired the infection vertically Cerebral edema is a major cause of mortality in patients
from their mothers. Reactivation of latent HBV infection with acute liver failure. A sustained rise of ICP to 30
may lead to fulminant disease, and this usually occurs in mmHg or more is taken as an indication of raised ICP.
immunocompromised patients. Risk of acute liver failure Paroxysmal or sustained systemic hypertension and
increases by 7-8 times with co-infection or super-infection increase in the tone of the muscles of the arms and/or
of HDV and HBV. Super-infection with HDV also carries legs are probably the earliest signs of raised ICP.
greater risk of fulminant hepatitis than simultaneous
infection. HCV is a rare cause of acute liver failure. Management
Autoimmunne liver disease may also present as acute Acute liver failure is a medical emergency associated with
liver failure. Intake of hepatotoxic drugs in a child with an unpredictable and an often fatal course; survival
Diseases of Gastrointestinal System and Liver 287
depends not only on the etiology, degree of hepatocyte Table 10.25: Monitoring of patients with acute liver failure
damage, capacity of the liver to regenerate, but also on
Clinical examination (4 hourly)
the intensive supportive medical care. The goals in the
Pulse rate, respiratory rate, BP and temperature.
evaluation of any child with ALF are:
Fluid intake/output charting (6 hourly)
• To determine the etiology, since it might impact on
Neurological/coma grading (12 hourly)
treatment and prognosis. Biochemical testing (12 hourly)
• To assess the severity of liver failure and the need for Electrolytes, sugar, urea, pH, bicarbonate
liver transplant.
Parameters to be monitored (once daily)
• To provide hepatic support till child recovers spon
Weight, liver span, ascites, evidence of bleeding or infection;
taneously or has liver transplantation. prothrombin time
• To anticipate and prevent complications.
Parameters to be monitored (twice weekly)
The child must be cared for preferably in an ICU setting.
LFT, creatinine, calcium, phosphate
This provides a calm and quite environment, intensive
monitoring facilities and quick access to life supporting Parameters to be monitored (as required)
Evidence of infection: Chest X-ray, blood counts, blood and
systems.
urine cultures, ESR and CRP
Initial workup of the child should include identification
Urinary electrolytes, creatinine and osmolality
of the stage of hepatic encephalopathy, assessment of
metabolic derangements and also the presence of the
precipitating factors. Work up for etiology can be deferred similar to systemic inflammatory response syndrome
till the patient is stabilized because the immediate outcome (SIRS). Hypoglycemia (symptomatic or asymptomatic)
is determined by the degree of derangements in the along with electrolyte and acid-base imbalance is present
hemodynamic parameters (circulating fluid volume, urine in majority of patients. Appropriate management of fluid
output) and biochemical abnormalities (blood sugar, urea, and metabolic abnormalities is important for improving
creatinine, and electrolytes). Investigations that are outcomes (Table 10.26).
necessary for the immediate management of the patient
include those to assess hepatocyte function (liver function Infections
tests—SGOT, SGPT, alkaline phosphatase, bilirubin, Patients with acute liver failure are at increased risk for
prothrombin time), blood chemistry (electrolytes, urea, infections, attributed to impaired immune system, but may
creatinine, sugar, calcium, phosphate) and evidence of not show fever and leukocytosis. Infections are the cause
infection (cultures, blood counts and X-rays). of death in about one-fifth of these patients. The choice of
After initial stabilization, further investigations are
antibiotics depends on the offending agent if identified
better if done simultaneously because stepwise
but in general, it should cover both gram-negative bacteria
investigation protocol causes unnecessary delays in
and staphylococci. The empiric practice is to use a
arriving at a working diagnosis. Specific therapy is
combination of third generation cephalosporins and
available for Wilson's disease and autoimmune hepatitis
cloxacillin. Aminoglycosides are administered if renal
and helps in retarding the liver cell failure.
functions are normal. If there is no improvement within
Monitoring 72 hr, it is prudent to step up antibiotics to cover
A monitoring protocol for patients with acute liver failure Pseudomonas aeruginosa, anaerobic organisms and/or fungi
depending upon individual patient requirements.
is necessary (Table 10.25).
Table 10.26: Management of fluid and metabolic in the body and reducing ammonia production has been
complications in acute liver failure a treatment modality for controlling hepatic encephalo
Fluid intake: Normal maintenance requirement (10% dextrose pathy. Bowel cleansing helps in decreasing the amount of
in N/5 saline) ammonia in the gut by decreasing the colonic bacterial
Hypotension counts and changing the colonic milieu to acidic. To
• Resuscitate with normal saline, Ringer lactate, plasma or achieve adequate cleansing of the bowel, bowel washes
blood need to be given 6-8 hourly with acidic fluid (1 teaspoon
• If mean arterial pressure (diastolic pressure + 1/3 pulse vinegar in 0.5 liter of plain water). In addition, lactulose
pressure) is <60 mmHg start dobutamine may be administered either orally or with NG tube at a
Metabolic acidosis dose of 0.5-2 ml/kg/dose (maximum 30 ml/dose) 6
• Suspect fluid deficit; evaluate for sepsis hourly adjusted to produce 2-4 loose acidic stools per day.
Hypokalemia Lactulose reaches the colon undigested, and is broken
• Give KC1 infusion/100 ml IV fluid according to serum down by the bacteria into monosaccharide sugars. This
K' level increases the local osmolality and acidity, thus causing
3 mEq (1.5 ml) if serum K+ 3-3.50 mEq/L stools to become loose and acidic. Antibiotics (neomycin)
4 mEq (2.0 ml) if serum K+ 2.5-3 mEq/L solution has also been used in patients with acute liver
5 mEq (2.5 ml) if serum K+ 2-2.5 mEq/L failure. In patients with more than grade II encephalo
6 mEq (3.0 ml) if serum K+ < 2 mEq/L pathy, protein intake should be restricted. Hypothermia
Hyponatremia (Na+ <120 mEq/L) (core body temperature of 32°C), selective head cooling
• Restrict fluids to 66-75% maintenance and hypernatremia (145-155 mEq/L) are other suggested
• Restrict Na+ infusion to less than 2 mEq/Kg/day modalities of management of severe intracranial hyperten
Hypernatremia (Na+ >150 mEq/L) sion. No sedatives should be given as they interfere with
• May be precipitated with lactulose administration: the assessment of the status of consciousness of the child.
reduce/stop lactulose Anticonvulsants like phenytoin or phenobarbitone may
• Replace deficit and maintenance fluids with N/3-N/4 be required if seizures are present. Patient should be
saline ventilated electively if encephalopathy progresses to grade
Hypoglycemia (Blood glucose <40 mg/dl) III or more.
• Infuse 50% dextrose @ 1 ml/kg
Coagulopathy
• Increase dextrose concentration to maintain sugar
between 100-200 mg/dl Coagulation defects require administration of fresh frozen
plasma or blood, preferably fresh. Platelets should be
given in cases with thrombocytopenia. Vitamin K at doses
Monitoring intracranial pressure (ICP) in these patients of 5-10 mg is administered intravenously or subcuta
is important because clinical signs and computed neously daily to increase the concentration of vitamin K
tomography scans are insensitive diagnostic methods for dependent coagulation factors. Gastrointestinal bleeds
determining increase in the ICP. The aim of management may respond to cold saline washes, parenteral H2-blockers
is to maintain ICP below 20-25 mmHg and cerebral and antacids. Plasmapheresis causes a rapid improvement
perfusion pressure (mean arterial blood pressure—ICP) of coagulation abnormalities and may remove anticoagu
at >50 mm Hg. Mannitol is the drug of choice and should lant or fibrinolytic products released during hepatocellular
be used as a rapid bolus of 0.5 g/kg as a 20% solution necrosis.
over a 15-minute period. The dose can be repeated if the
serum osmolality is less than 320 mOsm/kg. In cases of Renal Failure and Hepatorenal Syndrome
mannitol-resistant cerebral edema, sodium thiopental can Acute renal failure is noticed in 10-15% children with
be used at a bolus dose of 2-A mg /kg over 15 minutes acute liver failure and can be of prerenal or renal etiology.
followed by a slow intravenous infusion of between 1-2 The hepatorenal syndrome is indicated by decreasing
mg/kg/hr. Patients are nursed with raised head end (30- urine output and rising blood urea and creatinine. The
45%) and head placed in a neutral position. There should urinary Na+ is <10 mEq/L with urinary creatinine: plasma
be minimal handling of patients. Hyperventilation and creatinine ratio more than 30 and urinary osmolality
maintaining arterial pC02 level of 22-26 mmHg has been higher than plasma. There is no effective therapy, but salt
shown to be effective in reducing the cerebral edema. and fluid restriction along with hemodialysis/peritoneal
dialysis may be required.
Hepatic Encephalopathy
The reduced ability to metabolize ammonia, resulting in Specific Treatment of Acute Liver Failure
hyperammonemia, has been ascribed as a major pathway Encouraging results have been reported with use of N-
for development of encephalopathy and cerebral edema. acetylcysteine (NAC) in children with non-acetaminophen
Colonic bacteria produce a significant amount of ammonia induced liver failure. Bioartificial liver support systems
Diseases of Gastrointestinal System and Liver 289
have been developed which temporarily take over the Table 10.27: Causes of portal hypertension
functions of the liver without resorting to liver
Presinusoidal or prehepatic
transplantation, thus giving the injured liver time to
regenerate. These are of two types, bioartificial and Extrahepatic Portal vein or splenic vein thrombosis,
artificial. Bioartificial devices include the extracorporeal splenic AV fistula, massive splenomegaly
Intrahepatic Sarcoidosis, schistosomiasis, congenital
liver assist device (ELAD) and the bioartificial liver (BAL)
hepatic fibrosis, myeloproliferative
which uses dialysis like cartridge, which house human
disorders, nodular regenerative
hepatoblastoma cell line (ELAD) or porcine hepatocytes hyperplasia, idiopathic portal fibrosis
(BAL). The artificial device mostly used is the molecular
Sinusoidal or intrahepatic
adsorbent recycling system (MARS). Availability of these
devices is limited in the country at present. The treatment Cirrhosis due to any cause
of choice for these patients is liver transplantation. Overall Postsinusoidal or posthepatic
survival rate for liver transplantation in children with
Budd Chiari syndrome, right heart failure, constrictive
acute liver failure is 60-70% as compared to 90% in pericarditis, web in interior vena cava
children with chronic liver disease.
Prognosis
EHPVO indicates obstruction in the portal vein outside
Despite supportive care and nursing in intensive care liver and may be at any part in the course of the portal
units, 40-70% children with acute liver failure die. Poor vein. Portal venous thrombosis can occur in cases with
prognostic markers are grade III or more hepatic infections and inflammation (umbilical infection with or
encephalopathy, prothrombin time more than 40 seconds, without catheterization, acute appendicitis, primary
presence of sepsis or chest infection. Hyperacute and acute peritonitis, pancreatitis, portal pyemia), hypercoagulable
liver failure has significantly less mortality (40-60%) states (acute dehydration, polycythemia and inherited and
compared to subacute hepatic failure (60-80%). acquired deficiencies of anticoagulant proteins like protein
C, protein S and antithrombin III), trauma to portal vein
Suggested reading and invasion or compression by tumor or pancreatic mass.
1. Kelly DA. Managing liver failure. Postgrad Med J 2002; 78: 660- Hepatic venous outflow (Budd Chiari syndrome) may
667. be congenital or acquired and the obstruction can be
2. Arora NK, Mathur P, Ahuja A, Oberoi A. Acute liver failure in
anywhere between the hepatic veins and right atrium.
children. Indian J Pediat 2003; 70: 73-79.
3. Bansal S, Dhawan A. Acute Liver Failure. Indian J Pediatr 2006;
Clinical Presentation
73 : 931-934.
4. Cochran JB and Losek JD Acute liver failure in children. Pediatric PH leads to many clinical complications like portosystemic
Em Care 2007; 23:129-135. vascular shunting and related problems and ascites.
Portosystemic vascular shunting is an attempt of the body
PORTAL HYPERTENSION to decompress the portal hypertension by forming shunts
between collaterals from portal vascular channel and
Portal hypertension (PH) is the commonest cause of systemic caval venous channels. These shunts are formed
gastrointestinal bleeding in children of India. PH is defined at various sites of the body. The most serious consequence
a clinical syndrome in which the pressure in the portal of PH is gastrointestinal bleeding usually from the varices
vein rises above 10-12 mmHg (normal value being 7 around the proximal stomach and distal esophagus
mmHg). (gastroesophageal varices). The mortality after hemate
mesis in variceal bleeding is 30% and after recurrent
Causes variceal bleeding is as high as 70% and depends on the
PH can be caused by obstruction to the portal blood flow degree of hepatic function. The clinical presentation of PH
anywhere along its course. According to the anatomical is similar, but the underlying cause may also have the
site of obstruction, causes of PH can be classified into (i) specific features. Patients with EHPVO usually present
pre-hepatic, (ii) hepatic and (iii) post-hepatic causes about 5-6 years of age with hematemesis with or without
though there are many overlaps (Table 10.27). melena. A febrile or upper respiratory illness or drug
Due to availability of different sensitive and intake may predispose to upper GI bleeding. Spleno
sophisticated diagnostic facilities, the etiology can be megaly is almost universal in patients with EHPVO and
found in 90% of cases. There is a remarkable difference in size of spleen is usually dependent on the duration of the
the etiology of portal hypertension between developing blockage. Liver is usually normal in size. Ascites is usually
and developed nations. Studies reveal that extrahepatic rare in these patients. Children with EHPVO also have
portal venous obstruction (EHPVO) is the predominant variable extent of growth retardation.
cause of PH in children in India compared to hepatic The cases of sinusoidal and postsinusoidal portal
causes in developed countries. hypertension often present with hepatomegaly, ascites
290 Essential Pediatrics
and splenomegaly, along with the stigmata of chronic liver Resuscitation and monitoring: For resuscitation, adequate
disease. Ascites is directly related to the development of venous access should be established and intravenous
sinusoidal or postsinusoidal hypertension. Dilated fluids and/or packed cells infused. Vitamin K, infusion
collaterals on abdominal wall radiating outward from the of fresh frozen plasma, and/or platelets may be required
umbilicus, "caput medusae" may be seen. Some may even to correct the coagulopathy. Nasogastic tube should be
have presence of anorectal varices, masquerading as placed and continuous aspiration is done to clear the
hemorrhoids. Some children, especially those less than stomach and assess ongoing bleeding. A H2-receptor
5 years of age, may be suspected to have PH even in antagonist is administered IV to reduce the risk of bleeding
absence of history of upper GI bleeding if splenomegaly from gastric erosions.
is present. These children should be investigated for
presence of portosystemic collaterals and for possible Managing Variceal Bleeding
etiology.
Various pharmacological, mechanical and surgical modes
of arresting variceal hemorrhage are used.
Diagnosis
Pharmacological therapy: Vasoconstrictive drugs commonly
The clinical features of portal hypertension are easy to
used to stop bleeding include vasopressin, or their longer-
detect but confirmation and identification of the
acting analogues such as glypressin and terlipressin. These
underlying etiology may require more detailed investi
drugs induce generalized arteriolar and venous constric
gations. Additionally, the investigations are to be directed
tion, with resultant decreased portal venous flow and thus
towards assessment of the hematological status, liver
pressure, and at least temporary cessation of bleeding in
function and etiology of the liver disease, status of the
50-80% of cases. However, the generalized vasocons
portal vein and hepatic vein, demonstration and identifi
triction also may result in peripheral vascular ischemia,
cation of the varices and site of bleeding collaterals.
myocardial ischemia or infarction and renal tubular
damage. Concurrent administration of arteriolar vasodila
Investigations
tors (e.g. nitroglycerine) is used to attenuate some of these
1. Complete hemogram for degree of anemia and side effects. The other drugs used for this purpose are
evidence of hypersplenism. somatostatin or their longer-acting analogues such as
2. Liver function tests; prothrombin time; specific tests octreotide. These drugs are considered to be safer with
and liver biopsy to identify the exact etiology. minimal systemic vasoconstriction effect compared to
3. Radiology: For demonstration of hepatic vasculature, vasopressin. Whatever drug is used, it is generally advised
collaterals and shunts various noninvasive and invasive to continue drug therapy till a bleeding free interval of
imaging techniques are used. Noninvasive techniques are 24-48 hours is achieved.
ultrasound with duplex Doppler, CT scan and MRI to
identify the liver and splenic morphology, status of the Mechanical therapy: Mechanical modes of therapy include
splenic and hepatic vein and flow. Invasive techniques inflatable balloons for direct compression of the varices.
include splenoportovenography, arterioportography, The commonly used Sengstaken-Blakemore tube has both
percutaneous transhepatic portography and inferior an esophageal and a small gastric balloon which are
venocavography for detailed delineation of the inflated to compress the varices. The complications of
vasculature. Barium swallow is helpful in demons esophageal balloon therapy for varices include aspiration,
trating varices, but not frequently done. esophageal perforation and ischemic (pressure) necrosis
4. Esophagogastroduodenal endoscopy to demonstrate of the mucosa.
the varices and identify the exact site of bleeding. This Endoscopic therapy: The most common and probably the
also gives opportunity to do therapeutic procedures most effective nonsurgical therapies are endoscopic
(ligation or sclerotherapy) to stop bleeding. variceal sclerotherapy and ligation. Highly irritant
solutions such as ethanolamine, polidocanol or even
Management absolute ethanol are injected through endoscopic direct
Management of PH includes treatment of acute upper GI vision into and around the bleeding varix. The subsequent
bleeding and definite treatment to relieve the portal inflammation leads to eventual thrombosis and fibrosis
hypertension. of the varix lumen. Endoscopic ligation or banding of the
varices using rubber bands is a relatively safer method to
Treatment of the Acute Upper GI Bleeding occlude the varices followed by fibrosis. The combination
of endoscopic therapy and either balloon tamponade or
Upper GI bleeding is an emergency and treatment consists
drug therapy to control actively bleeding varices is
of the general resuscitative measures such as volume and
successful in 80-95% of cases.
blood replacement, and specific measures to stop the
bleeding. Vitals (heart rate, respiratory rate, blood pres Surgical methods: When all the above measures fail,
sure, sensorium) and urine output should be monitored. emergency surgery is indicated. The surgical procedures
Diseases of Gastrointestinal System and Liver 291
include devascularization or transaction of the esophagus adenosine triphosphatase (ATPase). This enzyme is
which blocks the blood flow to the varices. Another type expressed mainly in hepatocytes and functions in the
of "surgery" is the transjugular intrahepatic portal- transmembrane transport of copper within hepatocytes.
systemic shunt (TIPS). In this procedure, a temporary Absent or reduced function of ATP7B protein leads to
shunt is created between branches of the hepatic and decreased hepatocellular excretion of copper into bile.
portal veins via a catheter under fluoroscopy to With the declining incidence of Indian childhood
decompress the portal pressure. cirrhosis (ICC), WD has become one of the important
causes of chronic liver disease in India. This disease is
Prophylaxis of Variceal Bleeding interesting and important for pediatricians as it is treatable,
Administration of a p-blocker (propranolol, 1-2 mg/kg/ presents with variable clinical features and importance of
day) reduces the risk of initial bleeding as well as recurrent diagnosis in asymptomatic siblings.
variceal hemorrage. Heart rate should be monitored.
Clinical Features (Table 10.28)
Associated Problems The condition presents with liver disease more often in
Hypersplenism children and younger adult patients than in older adults,
but symptoms at any age are frequently nonspecific. The
Massive splenomegaly may cause excessive destruction
majority of patients with WD present with either predo
of the pooled blood cell components leading to
minantly hepatic or neuropsychiatric symptoms. Most of
thrombocytopenia, leukopenia and anemia. It may need
the patients with neuropsychiatric manifestation have
splenectomy. either clinically asymptomatic or symptomatic liver
involvement.
Liver Transplantation
If the cause of portal hypertension is cirrhosis and hepatic Hepatic Disease
failure, liver transplantation is the definite management. Children and adolescents usually present with primary
hepatic involvement. In general, the younger the age of the
Suggested reading
patient at symptom onset, the greater the degree of liver
Arora NK, Lodha S, Gulati S, et al. Portal hypertension in North Indian involvement. Liver disease may mimic all forms of com
children. Indian J Pediatr 1998; 65: 585-91.
mon liver conditions, including asymptomatic transamina-
semia, acute or chronic hepatitis, fulminant hepatic failure
WILSON DISEASE
and cirrhosis. The degree of liver involvement is variable,
Wilson's disease (WD) is an inborn error of metabolism ranging from asymptomatic hepatosplenomegaly with
characterized by toxic accumulation of copper in liver, mild elevations of certain liver enzymes, to complete liver
brain, cornea and other tissues. The hallmarks of the failure. Associated symptoms include nonspecific general
disease are the presence of liver disease, neurological symptoms, ascites and jaundice, and symptoms such as
symptoms and Kayser-Fleischer corneal rings. It occurs hematemesis and melena that are caused by portal
worldwide with an estimated prevalence of 1 in 3,0000- hypertension. The patients may have jaundice, hepato
50,000. The abnormal gene in WD, ATP7B, located on megaly with or without splenomegaly and features of
chromosome 13 encodes a metal-transporting P-type portal hypertension.
Trientine is also a copper chelator, acting primarily by associated cholestasis, Alagille syndrome, and progressive
enhancing urinary copper excretion. Trientine is as familial intrahepatic cholestasis—Byler's disease). Table
effective as penicillamine with far fewer side-effects and 10.29 lists the causes of cholestasis in infancy.
is used in cases refractory or allergic to penicillamine. The
usual dose is 25 mg/kg/day in 2-3 divided doses one hour Clinical Features
before meals. Ammonium tetrathiomolybdate acts by The infant shows jaundice (conjugated hyperbilirubi
preventing the absorption of copper from GI tract and pre nemia), the yellow urine and/or hypopigmented (acholic/
venting its availability for cellular uptake. The experience pale/clay colored) stools noticed by the parents or
with this drug in children is limited. Zinc prevents intes primary care physician. Infants with EHBA are often full
tinal absorption of copper and excretion in the feces. The term appropriate for date, and look apparently healthy
usual dose is 25-50 mg of elemental zinc daily, taken 1 hr except for jaundice. Those with neonatal hepatitis are
before meals. small for date or growth retarded, and show have
Patients should avoid copper-rich food such as increased association with infections and genetic
chocolate, nuts, shellfish and liver, and abstain from abnormalities. Cholestatic jaundice is often misdiagnosed
cooking or taking food from copper bowls and plates. as associated with breastfeeding.
Liver transplantation is the treatment of choice in
patients with fulminant WD and in those with decom
pensated cirrhosis. In addition to improving survival, liver
transplantation also corrects the biochemical defect. Liver Table 10.29: Etiologies of neonatal cholestasis
transplantation is also indicated in the absence of liver Infections
failure in patients with neurological WD in whom Viral: HBV, HCV, CMV, rubella virus, reovirus-3,
chelation therapy has proved ineffective. adenovirus, coxsackievirus, human herpes virus-6,
varicella zoster virus, herpes simplex virus, parvovirus, HIV
Prognosis Bacterial: Sepsis, urinary tract infection, syphilis, listeriosis,
tuberculosis
WD has a fatal outcome if not treated timely and
Parasitic: Toxoplasmosis, malaria
appropriately. Symptomatic patients require lifelong
treatment. Early initiation of therapy leads to symptomatic Bile duct anomalies
recovery and normal life expectancy. Residual hepatic and Extrahepatic biliary atresia (EHBA) Choledechal cyst
neurological sequelae depends on the degree of damage Alagille syndrome
Non-syndromic bile duct paucity
at the time of initiation of treatment.
Inspissated bile syndrome
Caroli's disease
Suggested reading Choledocholithiasis
1. P. Ferenci. Diagnosis and current therapy of Wilson's disease. Neonatal sclerosing cholangitis
Aliment Pharmacol Ther 2004; 19: 157-165.
Metabolic disorders
2. Roberts EA, Schilsky ML. Diagnosis and Treatment of Wilson's
Galactosemia, Glycogen storage disease, hereditary
Disease: An Update. Hepatology 2008; 47: 2089-2111.
tyrosinemia, neonatal hemochromatosis, hereditary
fructosemia, bile acid synthesis disorders, progressive
NEONATAL CHOLESTASIS familial intrahepatic cholestasis, cystic fibrosis,
Dubin-Johnson syndrome, Rotor syndrome, Niemann
Cholestatic jaundice in infancy is potentially life-
Pick disease, Gaucher disease, Zellweger's syndrome,
threatening problem that indicates severe hepatobiliary
-antitrypsin deficiency
dysfunction. Any infant who is jaundiced beyond 2 weeks
of age needs to be evaluated extensively and urgently to Endocrinopathie s
rule out neonatal cholestasis. Cholestasis is defined if Hypothyroidism, hypopituitarism
absolute direct bilirubin value is greater than 2.0 mg/dl Chromosomal disorders
with total bilirubin more than 10 mg/dl, or a value of Turner syndrome, trisomy 18, trisomy 21, trisomy 13,
direct bilirubin that represents more than 20% of the total Donahue syndrome
bilirubin if the total bilirubin is less than 10 mg/dl. It is
Neoplasia
often associated with dark urine and pale stool. Cholestatic Neonatal leukemia, histiocytosis-X, neuroblastoma,
jaundice is always pathological. hepatoblastoma, erythrophagocytic lymphohistiocytosis
Broadly there are four pathophysiological patterns of
neonatal cholestasis in neonates and young infants; Miscellaneous
(a) obstructive—extrahepatic biliary atresia (EHBA), Neonatal lupus erythematosus, Indian childhood cirrhosis,
perinatal asphyxia, congestive heart failure, Budd
(b) neonatal/giant cell hepatitis, (c) paucity of bile ducts,
Chiari syndrome
and (d) special categories of cholestasis (metabolic,
Idiopathic neonatal hepatitis
cholestasis in premature infants, total parenteral nurtition
294 Essential Pediatrics
Evaluation of Infant with Cholestasis Table 10.30: Investigations for neonatal cholestasis
Several questions arise in a neonate with hyperbili Liver Function
rubinemia, including (1) Is the jaundice physiological or Serum bilirubin (total/conjugated/unconjugated)
pathological, (2) What is the etiology, (3) Which babies Serum transaminases, alkaline phosphatase
require further investigation, (4) What are the investi Gamma glutamyl transpeptidase
Serum proteins, albumin
gations required, (5) Is the jaundice a threat to the infant,
Prothrombin time
(6) What is the treatment, and (7) What is the prognosis?
The evaluation of the infant with cholestasis is a multi- Infections
step process that should follow a logical sequence, which TORCH screen-IgM antibodies
helps us differentiate the broad categories of neonatal Hepatitis B surface antigen, anti-hepatitis C antibodies
cholestasis without wasting time and at minimal cost. It Evidence of sepsis
is important to recognize disorders for which specific Others
treatment is available. Initial evaluation should focus on Ultrasound of hepatobiliary tree
establishing the patency of the biliary tree. It is important Hepatobiliary scintigraphy (HIDA) scan
to diagnose biliary atresia earlier than 2 months of age Liver biopsy
because the success of surgery and outcome is dependent Per-operative cholangiogram
on the age of surgery. Beyond 2 months, adequate biliary Cholangiopancreatography: MR, endoscopic
drainage is achieved in less than one-third of infants with Hematological
EHBA. Hemoglobin, leukocyte and platelet count
Physical examination shows hepatomegaly or Reticulocyte count
hepatosplenomegaly. Liver span is more important than
Metabolic disorders
the liver palpable below costal margin. Hepatomegaly is Urine for amino acids, reducing substances
present in all these patients and those with severe liver Blood, urine pH; bicarbonate
disease show signs of portal hypertension and end stage Investigations for: tyrosinemia, galactosemia, hereditary
liver disease. Eye examination for chorioretinitis, posterior fructose intolerance, alpha-1 anti-trypsin
embryotoxon, cataract, and cherry red spot is done to Urine aminoacidogram
evaluate for metabolic disorders and intrauterine Endocrine disorders
infections. Laboratory work up is carried out with the aim TSH level
of: (1) establishing cholestasis and hepatocellular
dysfunction; (2) arriving at a specific diagnosis; and
(3) differentiate obstructive lesions from neonatal hepatitis of 5-7 days before imaging increases its specificity for the
as detailed in Table 10.30. diagnosis of EHBA.
The combination of a non-excreting HIDA scan along
with GGTP levels > 50 IU/L are highly suggestive of
Differentiation between Obstructive
EHBA. Liver biopsy is considered as the most accurate
Lesion and Neonatal Hepatitis
(90-95%) diagnostic test for differentiating biliary atresia
Patients with obstructive lesion should be identified before from other causes of neonatal cholestasis. In biliary atresia,
2 months to prevent irreversible damage and for possible ductular proliferation and fibrosis are seen, whereas in
surgical intervention. The key challenges to differentiate neonatal hepatitis, there is alteration in lobular archi
obstructive lesion (EHBA) from neonatal hepatitis are: tecture, focal hepatocellular necrosis, and giant cells with
(1) similarity in clinical presentation and overlapping ballooning of their cytoplasm. These changes are promi
values of routine biochemical investigations; (2) one-third nent after 6 weeks of age.
of each are due to mild neonatal hepatitis, severe neonatal Currently, peroperative cholangiography (exploratory
hepatitis and obstructive causes; (3) investigations like or laparoscopically) remains the gold standard to
HID A scan, ERCP/MRCP indicate obstructive lesions but differentiate between EHBA and neonatal hepatitis.
do not help to differentiate with certainty between severe
neonatal hepatitis and obstructive causes; and (4) a Management
proportion of patients with EHBA show TORCH Medical management is usually directed at the specific
antibodies. cause identified, in addition to the supportive therapy for
Radionuclide hepatobiliary scintigraphy [HIDA] is the cholestasis and treatment of sequelae of cholestasis.
used to assess the continuity of the biliary tract with the Most case of neonatal hepatitis cannot be offered definitive
small intestine. Non-visualization of radioactivity within therapy; therefore, supportive care is the mainstay of
24 hours after injection is considered to be abnormal, therapy.
indicating biliary obstruction or severe hepatocellular Nutritional support is important. The goal should be
dysfunction. Priming of liver with phenobarbitone (5 mg/ caloric intake of 150% of RDA based on ideal body weight
kg/day) and betamethasone (0.5 mg/kg/day) for a period with 25-35% calories derived from fat. Medium chain
Diseases of Gastrointestinal System and Liver 295
triglycerides are more water soluble and do not require disease and fulminant hepatic failure due to known or
bile salts for absorption. Supplementation of fat soluble unknown cause. Biliary atresia is the commonest
vitamins is essential as their absorption is impaired in indication (80%) for transplantation in patients below 2
cholestasis. Adequate protein intake (2-3 g/kg/day) is years of age and overall 50% among all pediatric liver
advised. transplants. Contraindications to liver transplantation are
Drugs: Ursodeoxycholic acid (UDCA) is a hydophilic coma with irreversible brain injury, uncontrolled systemic
bile acid, and at a dosage of 20-30 mg/kg/day in two infection, extrahepatic metastasis in liver tumors, and
divided doses has been shown to be beneficial. It is terminal progressive systemic disease, inadequate cardiac
recommended that high dose (five times of RDA) of fat or pulmonary function, and HIV infection.
soluble vitamins along with vitamin E and two times RDA The process of liver transplant requires a multi
of water soluble vitamins should be supplemented for disciplinary approach, integrating all resources available
these infants. A weekly dose of parenteral vitamin K and with the medical fraternity and society. Children usually
D is helpful in infants with severe cholestasis. are seen at an initial consultation by a pediatric hepato-
Surgery: EHBA and choledochal cyst can be surgically logist, transplant surgeon, and a transplant coordinator.
corrected if the liver disease has not progressed to A social worker meets the family and relevant psycho
cirrhosis. Kasai's portoenterostomy is done for EHBA to social issues are addressed. An extensive baseline
reestablish the biliary flow into gut. Outcomes are good if assessment is necessary before taking up a child for
surgery is done before 2 months of age. transplant and dependent on the underlying cause of liver
Patients developing portal hypertension, ascites, disease.
infection and hepatic encephalopathy should be managed Drugs, such as corticosteroids, azathioprine, cyclo-
accordingly. Cholestatic infants should be treated sporine, tacrolimus, sirolimus, and mycophenolate mofetil
aggressively for infections whenever suspected. are used for maintenance immunosuppression. Pediatric
protocols that are steroid sparing or devoid of steroids
Suggested reading are gaining favor and are being used. Apart from the
1. Arora NK, Kohli R, Bal CS, Gupta AK, Gupta SD. Hepatic drugs, a careful clinical observation is required for
technetium-99m-meberferrin imidioacetate scans and serum detecting the complication and early signs of graft
Y-glutamyl transpeptidase levels interpreted in series to differen
rejection. Aggressive nutritional rehabilitation is
tiate between extrahepatic biliary atresia and neonatal hepatitis.
Acta Pediatr 2001; 90: 975-981.
mandatory in the pretransplant and posttransplant phase.
2. Venigalla S, Gourley GR. Neonatal cholestasis. Semin Perinatol
Long-Term Outcome
2004; 28: 348-355.
3. Guideline for the evaluation of cholestatic jaundice in infants: The long term survival of transplant patients varies from
Recommendations of the North American Society for Pediatric center to center and its experience. Outcome has improved
Gastroenterology, Hepatology and Nutrition. J Pediatr Gastro
over the decades and now reaches up to 90% in the first
enterol Nutr 2004; 39:115-128.
years of transplant. Thereafter, the survival rates vary
between 60-80% till 5 years. The main factors which affect
PEDIATRIC LIVER TRANSPLANTATION
the survival rates are age (those younger than 1 year have
Liver transplantation has become the definitive treatment better survival), nutritional status and severity of the
modality for patients with end-stage liver diseases. This disease in the postoperative period.
can be achieved by a cadaveric transplant (transplanting
Suggested reading
liver from a dead donor), living related donor (taking out
a part of the liver from a living donor) or hepatocyte 1. Ferreira CT, Vieira SMG, da Silveria T. Liver transplantation. J
Pediatr (Rio J) 2000; 76 (Suppl 2): S198-S208.
transplant (injecting hepatocytes-experimental stage).
2. McDiarmid SV. Current status of liver transplantation in children.
The clinical situations where transplantation is often Pediatr Clin N Am 2003; 50: 1335-74
required include progressive primary liver disease, stable 3. Kerkar N. Emre S. Issues unique to pediatric liver transplantation.
liver disease with significant morbidity, metabolic liver Clin Liver Dis 2007; 11: 323-35.
11 Hematological Disorders
APPROACH TO ANEMIA oxygen from hemoglobin and increase of blood flow to
Anemia is a sign, which can present at any age. It is the tissues is insufficient to meet requirements. The
maintenance of blood volume occurs by an increase in the
important to investigate the cause of anemia to exclude a
serious underlying ailment and to define the correct volume of plasma and redistribution of blood flow.
management approach. Cardiac output increases in anemia as a consequence of
increased stroke volume; this high output state increases
Definition oxygen delivery to tissues by increasing the flow of blood.
Diversion of blood flow occurs from tissues with lesser
Anemia is present when the hemoglobin level in the blood
oxygen requirements to those with greater needs. Thus
is two standard deviations below the mean for the
skin blood flow is reduced, while cerebral and muscle
particular age and sex being evaluated (Table 11.1). The
blood flow are increased.
physiologic definition of anemia is a condition in which
tissue hypoxia occurs due to inadequate oxygen carrying Clinical Approach
capacity of blood. According to the National Family
The history can give many important clues for the etiology
Health Survey (NHFS-3) data the incidence of anemia in
of anemia, causes vary with age, and in some cases the
urban children is 71%, rural is 84% and overall is 79%.
etiology may be multifactorial (Table 11.2). A family
Physiological Adaptations history of anemia, requirement for blood transfusions and
demise of children, may lead the diagnosis towards
Anemia leads to decreased oxygen-carrying capacity of
thalassemia major; history of gallstones and recurrent
the blood and compensatory physiological adjustments.
episodes of jaundice are found in many types of hemolytic
Tissue hypoxia develops when the enhanced release of
anemia in particular hereditary spherocytosis; only
affected males can be a clue to an X-linked disorder like
glucose 6 phosphate dehydrogenase (G6PD) deficiency.
Table 11.1: Hemoglobin and hematocrit in infancy
and childhood
Mean and lower limit of normal (-2 SD) Table 11.2: Information for evaluation of anemia
Hemoglobin (g/dL) Hematocrit (%) Infants History of maternal infections, anemia
or collagen vascular diseases. Prema
turity, blood loss, jaundice (ABO or Rh
incompatibility, glucose 6 phosphate
dehydrogenase deficiency, sepsis.
Hemangiomas, cephalhematoma. Intake
of breast milk, formula, cow or goat
milk; intake of vitamins and hematinics.
Young children Diet, timing and nutritional quality of
weaning foods. Blood loss, worms, epis-
taxis, hematuria, etc. Family history of
thalassemia/sickle cell anemia. History
of jaundice-hereditary hemolytic
anemias (e.g. hereditary spherocytosis).
Infections, e.g. malaria, tuberculosis.
Other chronic illness, e.g. juvenile
rheumatoid arthritis, etc. Medications,
e.g. anticonvulsants, etc.
296
Hematological Disorders 297
A dietary history is useful; early initiation of cow's milk Severe anemia is characterized by a high output state
and predominantly milk based diet results in poor iron with an elevated pulse pressure and a 'collapsing'
intake or cow's milk allergy leading to anemia. Nutritional character to the pulse. Electrocardiographic changes may
iron deficiency anemia often occurs between 6 months to be found in approximately 30% patients with hemoglobin
2 years due to inadequate weaning, chronic diarrhea or less than 6 g/dl, including depression of the S-T segments,
cow's milk allergy. Adolescents with growth spurt, and flattening or inversion of T waves.
menstruating and pregnant teens are also at risk for iron
Central nervous system symptoms such as dizziness,
deficiency anemia. A pure vegetarian diet and use of goat's
headache, humming in the ears, fainting, tinnitus, lack of
milk may result in megaloblastic anemia. History of pica,
concentration and drowsiness, and with severe anemia,
drug intake, chronic diarrhea, prior surgery, acute and
clouding of consciousness may occur. Examination should
prolonged infections, liver and renal disease, transfusions
be done to find etiological clues to the cause of anemia
and age of onset of symptoms should be taken. History
such as radial limb abnormalities seen in bone marrow
of iron supplements and a lack of response may suggest
failure syndromes, presence of splenomegaly may be
thalassemia. Thalassemia major usually presents at 2-3
months of age, and 70% of these children will present with found in infants or may indicate hemolytic anemia,
symptoms by 6 months. Diamond-Blackfan (pure red cell) infection and storage diseases, lymphadenopathy and
anemia usually presents at 3 months and shows a hepatosplenomegaly may be seen in malignancies or
consistently low reticulocyte count and absence of infections, e.g. malaria and tuberculosis. Petechiae,
erythroid precursors in the bone marrow. Fanconi anemia purpura, icterus or bossing may help to diagnose the cause
has a more variable and later onset, with children of anemia.
presenting at 3-4 years of age or even in adulthood. Lead
toxicity by exposure to lead based paints and chemicals Laboratory Investigation
can occur in children.
It is important to know the age and detailed history of the
Clinical Features child, this information will provide direction to the
laboratory investigation. The complete hemogram will
The hemoglobin level at which symptoms of anemia
reveal if there is isolated anemia, or if other cell lines are
develop depends on two main factors, i.e. the rate of
affected. The red cell indices will demonstrate the type of
development of the anemia and state of the cardiovascular
anemia, mean corpuscular volume (MCV) denotes the size
system of the patient. In general, symptoms occur at a
of the red cells, the mean corpuscular hemoglobin (MCH)
higher hemoglobin level with rapidly developing anemia,
and mean corpuscular hemoglobin content (MCHC)
e.g. due to acute hemorrhage.
provide information on red cell hemoglobinization (Table
Tiredness, lassitude, easy fatigability and generalized
11.3). Using the MCV, anemias can be classified into
muscular weakness are the most common, and frequently
microcytic, normocytic or macrocytic anemia (Figs 11.1,
the earliest symptoms of anemia. In children, this can
11.2, 11.3). Abnormal red cell indices can exist in subjects
present as poor feeding, irritability and inadequate school
even when the underlying disorder is not sufficiently
performance. Pallor is the most prominent and characteris
tic sign. Pallor of the nail beds, oral mucous membranes and severe to cause anemia. In thalassemia minor or iron
conjunctivae are a more reliable indication of anemia. deficiency, the MCV, MCH and MCHC are low and in
Conjunctival pallor is sought by pulling down the lower megaloblastic anemia, the MCV is elevated. The red cell
eyelid. Observing palmer creases and skin pallor, is insuffi distribution width (RDW) denotes the variation in size of
cient in children as the skin creases do not show pigmenta red blood cells, low RDW means all the red blood cells
tion. Facial pallor varies with skin pigmentation and are uniform in size, while a large RDW shows that the
presence of facial edema. Dyspnea on exertion, tachycardia cells vary in size greatly. Examination of the peripheral
and palpitation are common symptoms. Murmurs become smear will reveal the red cell morphology, presence of
more prominent as the degree of anemia increases. They schistocytes, polychromasia, specific red cell morphology
may be caused entirely by the hemodynamic changes or presence of parasites may help in making the diagnosis.
secondary to the anemia itself (hemic murmurs), by The reticulocyte count helps to determine if anemia is
underlying heart disease or a combination of both factors. caused by red cell destruction or decreased production,
Hemic murmurs are mid-systolic 'flow' murmurs, the corrected or absolute reticulocyte count is more useful
reflecting the increased velocity of blood passing through (Table 11.4). When nutritional anemias are suspected, iron
the valves. They are common in the pulmonary area, but status, vitamin B12 and folic acid levels are determined.
can be heard in areas corresponding to any of the heart The reticulocyte count is decreased in bone marrow failure
valves. Very severe anemia can precipitate cardiac failure syndromes, transient erythroblastopenia of infancy and
even in individuals with a normal cardiovascular system. infections, e.g. parvovirus. In cases of anemia with increas
Systolic bruits and postural hypotension can be ed reticulocyte count, a Coombs test will help to identify
demonstrated in patients with moderate to severe anemia. if this is due to immune or hereditary hemolytic anemia.
298 Essential Pediatrics
Table 11.4: The utility of reticulocyte count for the evaluation of anemia
Suggested reading
1. NHFS-3 (2007) Government of India, WEBSITE http:// IRON DEFICIENCY ANEMIA
www.nfhsindia.org/abt.html
Iron deficiency anemia occurs when there is a decrease in
2. Lokeshwar MR, Shah NK. IAP Speciality Series on Pediatric
Hematology and Oncology (under IAP President Action Plan) total body iron content, severe enough to diminish
(2006), Approach to Anemia, 3-17. erythropoiesis and cause anemia.
Pathophysiology Clinical Evaluation
Diminished dietary iron absorption in the proximal small A careful dietary history is important; enquire about type
intestine or excessive loss of body iron can result in iron of milk, weaning foods and supplements. Pica increases
deficiency. Iron is essential for multiple metabolic the risk of helminthic parasites and lead poisoning. The
processes, including oxygen transport, DNA synthesis, common features of anemia are present in proportion to
and electron transport. In severe iron deficiency, the iron the severity and rate of development. Behavioral
containing enzymes are low and this can affect immune symptoms such as irritability, anorexia usually precede
and tissue function. Iron deficiency anemia can result in weakness, fatigue, leg cramps breathlessness and tachy
diminished growth and learning and have serious cardia. Congestive cardiac failure and splenomegaly may
consequences in children. Numerous dietary constituents occur with severe, persistent, untreated iron deficiency
make non-heme iron unabsorbable, e.g. phytates, anemia. Angular stomatitis, glossitis, koilonychia and
phosphates and tannates. platynychia are also seen in severe iron deficiency.
Healthy newborn infants have a total body iron of 250
mg (approximately 80 parts per million, ppm); this Laboratory Diagnosis
decreases to approximately 60 ppm in the first 6 months The evaluation of the peripheral blood smear (Figs 11.4
of life. Body iron is regulated carefully by absorptive cells and 11.5) shows that red cells are microcytic, hypo
in the proximal small intestine, which alter iron absorption chromic, and show anisocytosis, poikilocytosis and
to match body losses of iron. Breast milk iron content is increased RDW. The MCV and MCHC are reduced. Red
more bioavailable than cow's milk. Besides this fact, cell number is reduced, unlike in thalassemia trait/minor
infants who consume cow's milk have more iron where it is increased.
deficiency because bovine milk has a higher concentration The serum iron is reduced while the total iron binding
of calcium, which competes with iron for absorption and capacity (TIBC) is increased, transferrin saturation is
they may have gastrointestinal blood loss due to cow's reduced to less than 16% (normal range 25-50%). The
milk allergy. Multiple intercurrent infections such as reduction in serum ferritin occurs early, and correlates
hookworm infestation and malaria compound the well with the total body iron stores. However, ferritin is
problem. an acute phase reactant and elevated in inflammatory
Hematological Disorders 301
Parenteral Iron
The indications of parenteral iron therapy are limited to
conditions such as (1) intolerance to oral iron, (2)
malabsorption states and (3) ongoing blood loss at a rate
where the oral replacement cannot match iron loss. If
parenteral iron is indicated, then IV preparations are
preferred over IM; iron sucrose IV preparations are safe
and effective. They have been used in children with end
Fig. 11.4: Peripheral smear from a child with iron deficiency anemia, stage renal disease on dialysis and inflammatory bowel
shows microcytosis (the red blood cells are smaller than the small disease. Iron sucrose is administered at a dose of 1-3 mg/
lymphocyte in the field), hypochromia (central pallor >1/3rd of cell kg diluted in 150 ml normal saline as a slow IV infusion
diameter), thrombocytosis, and a few ovalocytes and tear drop cells
over 30-90 minutes.
(moderate anisopoikilocytosis). Jenner-Giemsa x 1000
Dose for parenteral iron: The total dose of parenteral iron in
conditions hence may be falsely elevated in a sick child. milligrams is calculated as follows:
High free erythroprotoporphyrin (FEP) is seen before Iron required = Wt (kg) x 2.3 x (15 - patient hemoglobin
anemia develops. in g/dl) + (500 to 1000) mg
The total calculated dose is given as divided doses.
Treatment
The cause of anemia should be identified and corrected. Blood Transfusions
Hookworm infestation is the most common cause of occult As iron deficiency anemia is readily corrected with
gastrointestinal blood loss in the rural population of India medication, blood transfusions should be avoided in
at all ages. Dietary counselling and treatment of any other young, stable patients. Red cell transfusions are needed
causative factors are required to prevent recurrence or in emergency situations such as in patients where the rate
failure of therapy. Close follow-up is required to assess of blood loss exceeds the expected rise of hemoglobin, for
for adequate response and correction of anemia, this will urgent surgery, hemorrhage or severe anemia with
help to identify iron therapy failure (Table 11.5). congestive cardiac failure. In very severe anemia with
congestive cardiac failure, transfusions must be given
Oral Medication slowly (2-3 ml/kg) with monitoring and diuretic therapy
Oral iron preparations should be taken on an empty if necessary.
stomach or in between meals for best absorption. About
10-20% patients will develop gastrointestinal side effects Suggested reading
such as nausea, epigastric discomfort, vomiting, consti 1. Sachdeva HPS, Gera T, Nestel P. Effect of iron supplementation on
pation and diarrhea. Enteric-coated preparations have mental and motor development in children: systemic review of
randomized controlled trials. Public Health Nutr 2005; 8: 117-132.
fewer side effects, but are also less efficacious and more
2. Kapil US. Technical consultation on "Strategies for prevention and
control of iron deficiency anemia amongst under three children in
India". Indian Pediatr 2002;39:640-647.
Table 11.5: Causes of refractory iron deficiency anemia 3. Leijn E, Monnens LA, Cornelissen EA. Intravenous iron
supplementation in children on hemodialysis. / Nephrol 2004; 17:
Poor compliance with therapy 423-426.
Poorly absorbed iron preparations, e.g. enteric coated
Use of antacids or H2 blockers causing achlorhydria MEGALOBLASTIC ANEMIA
Interaction with food and medications
Associated vitamin B12 or folic acid deficiency Megaloblastic anemia is characterized by macrocytic red
Underlying hemolytic anemia, inflammation or infections cells and erythroid precursors, which show nuclear
Malabsorption states, e.g. celiac disease, giardiasis, H. pylori dysmaturity. The common causes are deficiency of
infection, autoimmune gastritis vitamin B12, (derived from cobalamin) and folic acid. The
High rate of ongoing blood loss incidence varies with the dietary practices and socio
Sideroblastic anemia.
economic patterns. A study has put the incidence of folate
302 Essential Pediatrics
megaloblastic anemia) and cytopenias. Hypersegmented use of anti-folate medications is best remedied by reducing
neutrophils (nuclei with > 6 lobes) may be seen. The reti or eliminating the implicating drug and addition of
culocyte count is important and should be performed. If supplementation. In celiac disease, treatment requires
available, serum B12 and folate levels are assayed. Investi exclusion of dietary gliadin and adequate supple
gation for contributing cause if indicated should be mentation. Folate is available as a 5 mg tablet and overdose
performed. The Schilling test requires radioactive labelled is not associated with adverse effects; a dose of 1-5 mg/
B12 for identification of pernicious anemia and evaluation day is recommended for 3-4 weeks.
of deficiency states, rarely needed in children. Vitamin B12 is administered parenterally at a dose of
Bone marrow evaluation should be performed in 1 mg (1000 |ig) IM. Follow up will show decrease in MCV,
patients with more than one abnormal hematological cell reticulocy tosis and improvement in platelet and neutrophil
line. It can help to rule out other disorders such as leuke counts within a few days of therapy. In one study, tremors
mia, myelodysplasia and aplastic anemia. In megaloblastic and extrapyramidal toxicity have been reported in young
anemia the bone marrow is cellular (Fig. 11.5) and show children, lower doses (250 ng) can be used in infants. In
red cell precursors with nuclear-cytoplasmic asynchrony; patients with pernicious anemia and malabsorption,
granulocyte precursors may also be abnormal. Serum vitamin B12 (1000 |jg) is given parenterally daily for 2
chemistry shows elevated lactate dehydrogenase and weeks, weekly until the hematocrit value is normal and
bilirubin. then monthly for life. Patients with neurological compli
cations should receive 1000 |ig every day for 2 weeks, then
every 2 weeks for 6 months and monthly for life. Oral
supplements can be administered; however absorption is
variable and maybe insufficient in some patients. In dietary
insufficiency, no standard duration of therapy has been
defined. Dietary counselling may be attempted; however
diet may not be altered due to social and cultural reasons.
Following correction of anemia, vitamin B12 supplements
are recommended lifelong (oral supplements daily or
parenteral dose every 3-12 months).
Suggested reading
1. Chandra J, Jain V, Narayan S, Sharma S. Folate and cobalamin
deficiency in megaloblastic anemia in children. Indian Pediatrics
2002; 39: 453-457.
2. Stabler SP, Allen RH. Vitamin B12 deficiency as a world wide
problem. Annu Rev Nutr 2004;24:299-326.
Fig. 11.5 : Bone marrow aspirate from a patient with vitamin B12
deficiency shows erythroid hyperplasia, megaloblastosis and a giant APPROACH TO HEMOLYTIC ANEMIAS
myeloid form (top left). Jenner-Giemsa x 1000
The term hemolytic anemia is limited to conditions in
Differential Diagnosis which the rate of red cell destruction is accelerated and the
Other causes of macrocytosis should be considered in the ability of the bone marrow to respond to the anemia is
differential diagnosis. These include aplastic anemia and unimpaired. Under maximal stimulation, the normal mar
other marrow failure syndromes (pure red cell aplasia, row is capable of increasing its production rate about six to
Fanconi anemia, transient erythroblastopenia of child eight times its basal level. The reticulocyte count is useful in
hood), congenital dyserythropoietic anemia, chronic liver determining the rate of erythroid regeneration in response
disease, hypothyroidism, cold agglutinin disease, myelo- to red cell destruction. The normal reticulocyte count value
in the newborn is 3.2 + 1.4% and in children 1.2 + 0.7%.
dysplastic syndrome and HIV infection.
Table 11.11: Causes of hemolytic anemias of spectrin and ankyrin, the major skeletal membrane
proteins. The degree of skeletal membrane protein
Acquired
deficiency correlates with the degree of hemolysis.
Mechanical Structural changes due to membrane protein deficiency,
Macroangiopathic: Artificial heart valves, march hemo lead to membrane instability, loss of surface area, abnormal
globinuria. membrane permeability and reduced red cell deformabi-
Microangiopathic: Disseminated intravascular coagulation, lity. These defects are accentuated by metabolic depletion;
hemolytic uremic syndrome, thrombotic thrombocytopenic
this is demonstrated by the increase in osmotic fragility
purpura.
after a 24-hr incubation of blood at 37°C. The spleen is the
Infections: malaria, kala azar, Clostridium welchii, etc.
site of destruction of these non-deformable erythrocytes.
Antibody mediated
Warm/cold type autoimmune hemolytic anemia. Patients with hereditary spherocytosis have a mild to
Transfusion reactions, hemolytic disease of newborn. moderate chronic hemolytic anemia. The MCV is decrea
Drugs, e.g. cefotetan, ceftriaxone. sed and MCHC is increased due to cellular dehydration.
Hypersplenism The red cell distribution width is increased due to the
Cryopathic states: cold agglutinin disease, paroxysmal cold presence of spherocytes and increased reticulocytes. These
hemoglobinuria. patients present with jaundice, the degree and age of onset
Physical and chemical injury: burns, snake bite; lead, arsenic varies. Splenomegaly is found in over 75% patients.
toxicity. Gallstones are frequently found, the risk of pigment calculi
Red cell: Paroxysmal nocturnal hemoglobinuria
increases with age.
Hereditary Patients require life long folic acid supplementation at
Hemoglobinopathies: thalassemia, sickle cell disease a dose of 1-5 mg/day to ensure that they do not become
Red cell enzyme defects: glucose-6-phosphate dehydrogenase folate deficient due to the high turnover rate of erythro
deficiency poiesis. Splenectomy does not cure the hemolytic disorder
Cytoskeletal membrane disorders: hereditary spherocytosis. but may reduce the degree of hemolysis. It is the treatment
Unstable hemoglobinopathies. of choice in patients who have severe hemolysis and high
Lipid membrane defects: abetalipoproteinemia transfusion requirement. In patients with mild hemolysis,
Porphyrias. splenectomy should be delayed or avoided. In certain
patients who have an excessively large spleen, splenec
Hemolytic disorders maybe divided into inherited and tomy may diminish the risk of traumatic splenic rupture.
acquired varieties. This classification has a pathogenetic In general splenectomy is performed after 6 yr of age with
significance because the nature of hereditary lesions differs pre-surgical immunization for Hemophilus influenzae type
from that of acquired. Most intrinsic defects are inherited; B, Streptococcus pneumoniae and Neisseria meningitidis.
extrinsic defects are acquired. Exceptions to this genera Following splenectomy, prophylactic penicillin is adminis
lization include paroxysmal nocturnal hemoglobinuria, an tered to prevent sepsis till early adulthood.
acquired disorder characterized by an intrinsic red cell As with other hemolytic anemias, patients with
defect. hereditary spherocytosis are susceptible to aplastic crisis
secondary to infection with human parvovirus B19. This
Management organism selectively invades erythroid progenitor cells
During an acute attack of hemolysis, it is important to and causes a transient arrest in red cell production.
maintain fluid balance and renal output. Management of Patients usually recover in 4-6 weeks.
shock is by the usual appropriate measures, but blood
transfusions, so useful in acute anemia of other types, must ABNORMALITIES IN RED CELL GLYCOLYSIS
be used with caution in the treatment of patients with Glucose is the primary metabolic substrate for erythro
acquired hemolytic anemias. Even with careful blood cytes. Since the mature red cells do not contain mitochon
matching, destruction of the transfused blood with an dria, glucose is metabolized by two chief anerobic
increase in the burden on the kidneys and sometimes pathways: the Embden Meyerhof pump and the hexose
thromboses may occur. Acute autoimmune hemolytic monophosphate shunt. The former accounts for 90% of
anemia is treated with steroids (prednisone 1-2 mg/kg/ glucose utilization. The inability to maintain enough ATP
day), which should be tapered over several months, once required for cellular functions such as deformability,
the patient has demonstrated resolution of ongoing membrane lipid turnover and permeability results in shor
hemolysis. In chronic hemolysis the etiology should be tened red cell life. The hexose shunt is responsible for the
investigated and treated appropriately. remaining 10% of glucose metabolism, this generates
substrates which protect the red cells against oxidant
HEREDITARY SPHEROCYTOSIS injury. A defective pathway causes accumulation of
Several membrane protein defects have been identified in oxidized hemoglobin (Heinz bodies), lipids and mem
hereditary spherocytosis. Many of these result in instability brane proteins in red cells, resulting in hemolysis. The
306 Essential Pediatrics
reticulocyte count is raised and bone marrow shows Table 11.12: Drugs which can cause oxidant stress and
erythroid hyperplasia. A useful screening test is hemolysis in glucose-6-phosphate dehydrogenase deficient
autohemolysis and diagnosis is by specific enzyme assays. patients
Spectrum of Thalassemia
Thalassemia Trait
Patients have mild anemia, abnormal red blood cell
indices, and abnormal hemoglobin HPLC results with
elevated levels of Hb A2 or Hb F, or increase of both. The
peripheral blood film examination usually reveals marked
hypochromia, microcytosis (without anisocytosis which
is usually found with iron deficiency anemia) and presence
of target cells.
Thalassemia Intermedia
This condition is usually due to a compound heterozygous
state, resulting in anemia of intermediate severity, which
usually does not require regular blood transfusions. This
is primarily a clinical diagnosis and requires monitoring
of the child over time to see the clinical evolution of
disease.
Thalassemia Major
This condition is characterized by transfusion-dependent
anemia, splenomegaly, bone deformities, growth retar
dation and hemolytic facies in untreated or inadequately
treated individuals. Examination of the peripheral blood
smear shows severe hypochromia, microcytosis, marked
anisocytosis, fragmented red blood cells, polychromasia,
nucleated RBCs and occasionally immature leukocytes.
Organomegaly is reduced in well transfused patients, but
is marked in patients receiving irregular or inadequate
transfusion support.
level is 1000 to 1500 |_ig/L. Severe toxicity may develop if Cure of Thalassemia Major
chelation is started prematurely. Eye examination, hearing
Hematopoietic stem cell transplantation is the only known
tests and renal function tests are required to monitor the
curative treatment for thalassemia. Poor outcome after
effects of therapy.
stem cell transplantation correlates with the presence of
Deferiprone is an oral chelating agent, although less
hepatomegaly, portal fibrosis and with inadequate
effective than deferoxamine in preventing organ damage.
chelation prior to transplant. The event-free survival rate
It may cause arthritis and agranulocytosis. It is adminis
for patients who have all three features is 59%, compared
tered at a dose of 75 mg/day. Deferasirox is a new oral
to 90% for those who do not have hepatomegaly, fibrosis
chelating agent, which has now become available in India.
and have received proper chelation.
The molecule is a tridentate ligand that binds iron with a
high affinity, forming a 2:1 complex that is excreted in Management of Other Thassemia States
bile and eliminated primarily via the feces. It has shown
Patients with thalassemia intermedia require monitoring
efficacy similar to parenteral agent deferoxamine in
to assess the need for transfusion, since persistent anemia
maintaining or reducing liver iron. This orally active
may retard growth. Hydroxyurea (15-20 mg/kg/d) is
chelator is highly selective for iron; it chelates intracellular
used in an attempt to increase HbF production and reduce
and extracellular excess iron throughout the body,
the need for transfusions, especially in patients with XLM1
including liver, heart reticuloendothelial system and
mutation. Iron therapy should not be used in patients with
circulation. It can lead to rash, gastrointestinal, renal and
thalassemia trait unless its deficiency is confirmed. Genetic
hepatic toxicity, hence creatinine, liver function tests and
counselling is necessary to create awareness and prevent
proteinuria should be monitored. The recommended
thalassemia major in offspring.
starting dose is 20 mg/kg/day.
The spleen acts as a store for nontoxic iron, protecting Suggested reading
the body from extra iron, thus early removal of the spleen
1. Nadkarni A, Gorakshakar AC, Krishnamoorthy R, Ghosh K, Colah
may be harmful. Splenectomy is justified only in patients R, Mohanty D. Molecular pathogenesis and clinical variability of
with hypersplenism, leading to excessive destruction of beta thalassemia syndromes among Indians. Am J Hematol
erythrocytes and increasing the need for frequent blood 2001;68:75-80.
transfusions, resulting in further iron accumulation. 2. Sarnaik SA. Thalassemia and related hemoglobinopathies. Indian
J Pediatr 2005;72:319-324.
Patients who require more than 200-250 mL/kg of packed
red blood cells annually benefit from this procedure. This
SICKLE CELL ANEMIA
is rarely required in children receiving adequate
transfusion therapy. Sickle cell anemia though rare in India with a gene
frequency of 4.3%, occurs in a wide geographical
Other Complications
distribution from Orissa, Maharashtra, Madhya Pradesh
Bone Problems and Jharkand. These patients can present with serious and
The classic 'hair on end' radiologic appearance of the skull, varied hematological manifestations.
results from widening of the diploic spaces and maxillary
Pathophysiology
overgrowth, resulting in maxillary overbite and pro
minence of the upper incisors. These changes contribute Sickle cell anemia is an autosomal recessive disease that
to the classic hemolytic/chipmunk facies observed in results from the substitution of valine for glutamic acid at
patients with thalassemia major. Osteoporosis and osteo position 6 of the (3-globin gene. The sickle red blood cells
penia may result in fractures; the child may need treatment are less deformable and obstruct the microcirculation,
with calcium, vitamin D and bisphosphonates to improve resulting in tissue hypoxia that further promotes sickling.
bone density. Deoxygenation of the heme moiety of sickle hemoglobin
leads to hydrophobic interactions between adjacent sickle
Extramedullary Hematopoiesis hemoglobin (HbS) molecules that aggregate into larger
These occur in patients with severe anemia not receiving polymers. Sickle-shaped red blood cells are rapidly
transfusion therapy. They may cause neuropathy or hemolyzed and have a lifespan of only 10-20 days
paralysis from compression of the spine or peripheral (compared to normal 120 days). Patients who are homo
nerves. Compression fractures and paravertebral expan zygous for the HbS gene have sickle cell disease. Patients
sion of extramedullary masses, which behave clinically who are heterozygous for the HbS gene have sickle trait.
like tumors, are found during the second decade of life.
Clinical Evaluation
Psychosocial
A complete history should be taken for the site, frequency,
As these children survive into adulthood, problems related duration, character and severity of pain, e.g. pleuritic in
to employment, marriage, having families, and the stress acute chest syndrome, joint/bone pain in arthritis or
of chronic illness need to be addressed. osteomyelitis. History of previous similar episodes should
Hematological Disorders 311
mechanical ventilation may be required in children in birth. Acquired aplasia can occur due to exposure to toxins,
whom cerebrovascular accidents have occurred, or with drugs like chloramphenicol, environmental hazards and
acute chest syndrome. Exchange transfusion consists of viral infections (e.g. hepatitis B, C). Single lineage
replacing the patient's red blood cells by normal donor red cytopenias need to be differentiated from transient
blood cells, decreasing sickle hemoglobin (HbS) to less than erythroblastopenia of childhood.
30%. Exchange blood transfusions are indicated in cases of
cerebrovascular accidents and acute chest syndrome. They Clinical Manifestations
may be performed in patients with acute sequestration Physical examination reveals pallor and/or signs of con
crisis or in priapism that does not resolve after adequate gestive heart failure. Ecchymoses, petechiae, gum bleeding
hydration and analgesia. and nose bleeds are associated with thrombocytopenia.
Fever, pneumonia or sepsis, are due to neutropenia. The
Preventive Care child should be evaluated for the stigmata of congenital
All children require prophylaxis with penicillin/amoxi bone marrow failure syndromes (Table 11.14, Figs 11.10 and
cillin, atleast until 5 years of age. They should receive 11.11). However, Fanconi anemia may be present even
immunizations of pneumococcal, meningococcal and H. without abnormal phenotypic features.
influenzae vaccines. They should receive life long folate
supplementation. Hydroxyurea is a cytotoxic agent, which Laboratory Studies
can increase HbF and reduce episodes of pain crises and Hematological features of bone marrow failure include
acute chest syndrome; this may be tried after 5 years of single cytopenia, as seen in pure red cell aplasia and
age. Parents need to learn how to identify complications, amegakaryocytic thrombocytopenic purpura, while in
be informed for necessity and indications for admission aplastic anemia, pancytopenia or bilineage involvement is
and screened for gallstones and stroke. Genetic counsel present. Peripheral blood smear findings are anemia,
ling and testing should be offered. occasionally with macrocytosis (<110 fl) thrombocytopenia
and agranulocytosis. The corrected reticulocyte count is
Suggested reading less than 1%, indicating reduced red cell production. Bone
1. Sachdeva A, Sharma SC, Yadav SP. Sickle cell disease. In: IAP marrow aspirate and biopsy are essential for proper
Speciality series on Pediatric Hematology and Oncology 2006;
diagnosis and evaluation of bone marrow cellularity (Fig.
77-96.
11.12). In general, the marrow is replaced with fat cells and
2. Steinberg MH. Management of sickle cell disease. N Engl J Med
1999;340: 1021-1030. lymphocytes, with very few hematopoietic cells.
Special Tests
APLASTIC ANEMIA
The Ham's test, or sucrose hemolysis test, may be positive
Aplastic anemia is a group of disorders of the hemato in a patient with underlying paroxysmal nocturnal
poietic stem cells that involve one or more cell line hemoglobinuria (red cells lysed by patient's acidified sera);
(erythroid, myeloid, megakaryocytic). Aplastic anemia can and type II congenital dyserythropoietic anemia (CDA)
be inherited or acquired. It can involve just one or all (red cells lysed by other acidified sera but not patient sera),
hematopoietic cell lines. The prevalence of bone marrow but a recent transfusion with packed red blood cells may
failure (hypoplastic, aplastic anemia) is 2-6 cases/million induce a false-negative test result. A more specific test for
population in western literature. In India, the prevalence paroxysmal nocturnal hemoglobinuria is the assay for two
is higher, although exact data is not available. complement regulatory proteins usually present on red
blood cells, CD55 (decay accelerating factor) and CD59
Etiopathogenesis
(membrane inhibitor of reactive lysis) are required for the
Hematopoietic stem cells are damaged by various mecha diagnosis of paroxysmal nocturnal hemoglobinuria. The
nisms (1) an acquired stem cell injury from viruses, toxins deficiency of CD55/59 markers on red blood cells is the
or chemicals; (2) abnormal cellular control of hemato- specific hallmark of paroxysmal nocturnal hemo
poiesis; (3) an abnormal marrow microenvironment; (4) globinuria. The peripheral blood cells in Fanconi anemia
immunologic suppression of hematopoiesis (i.e. mediated show characteristic hypersensitivity and chromosomal
by antibodies, cytotoxic T cells), and (5) mutations in genes, breakage with crosslinking agents (e.g. mitomycin C and
resulting in inherited bone marrow failure syndromes. diepoxybutane). This test for chromosomal fragility may
be positive even in Fanconi anemia patients who lack the
Differential Diagnosis physical stigmata of the disease.
Family and past medical histories help distinguish
inherited from acquired causes. Inherited bone marrow
Treatment
failure syndromes are usually diagnosed in childhood or Supportive care such as packed red cells for anemia,
young adults. They may have characteristic physical platelets for thrombocytopenia and antibiotics for infection
anomalies, familial incidence or thrombocytopenia at are needed. Hematopoietic stem cell transplant is the only
Hematological Disorders 313
Fanconi anemia AR Absent thumbs, absent radius, High risk of acute myeloid
microcephaly, renal anomalies, leukemia, myelodysplasia,
short stature, cafe au lait spots, oral and liver cancers
skin pigmentation
Dyskeratosis X-linked Nail dystrophies, leukoplakia Cancer (usually squamous cell)
congenita recessive, and myelodysplasia.
AD, AR
Single lineage cytopenias
Fig. 11.10 : Child with Fanconi anemia. The child had hyper Fig. 11.11 : Radial ray defects present in a wide spectrum they include
pigmentation, microcephaly and microphthalmia. She also absent or hypoplastic thumbs. The thenar hypoplasia may be missed
demonstrated radial ray defects and growth retardation unless carefully examined
Allogeneic Hematopoietic Bone Marrow Transplant neutrophils, platelets and erythrocytes. During this pe
riod, intensive support is required.
Donor Requirement
For an allogeneic transplant, a HLA identical sibling is Venous access: The transplant process typically involves
the ideal donor. In spite of HLA identity, there is always the use of a long term, silastic, multi-lumen, flexible
variation in the minor histocompatibility loci. These catheter for chemotherapy administration, infusion of
antigenic differences may lead to graft rejection or graft stem cells and supportive care management including
versus host disease. It is also possible to have a successful frequent blood sampling, IV antibiotics, blood components
transplant using a partially matched sibling as a donor, and parenteral nutrition.
or an unrelated HLA identical donor, but the compli
Early infections: Infection remains an important cause of
cations of graft versus host disease and graft rejection are
morbidity and mortality, with bacterial and fungal
very severe. Most centers in India are not conducting
infections being the predominant cause. Early institution
unrelated transplants. Unlike most other organ
of empirical antibiotics to cover gram-negative and gram-
transplants, in hematopoietic transplantation, ABO blood
positive bacteria, with addition of antifungal drugs like
group compatibility is not essential. After successful
amphotericin if fever persists, is practiced in most centers.
hematopoietic transplantation, the blood group of the
recipient will change to that of the donor group. Blood component support: After conditioning therapy,
patients require multiple red cell and platelet transfusions
Conditioning Procedure during the 2-4 week period of pancytopenia, until
Myeloablative conditioning: The standard preparatory engraftment occurs. Patients are immunosuppressed and
regimens given prior to hematopoietic transplantation are at risk of developing transfusion associated—graft versus
myeloablative (suppression of bone marrow). Patients host disease (TA-GVHD) after receiving cellular blood
receive extremely high doses of chemotherapy. The aim products. To prevent this, all cellular blood products
is threefold: (a) eradication of malignant cells or abnormal should be irradiated prior to transfusion, to inactivate
clone of cells, (b) suppression of the immune system of donor lymphocytes. As BMT can be performed even with
the host so that the allograft is not rejected, and (c) clearing ABO incompatibility, hemolysis may occur during
a "physical space" to allow adequate growth of the donor infusion of ABO-incompatible stem cells, or later as a result
stem cells. of the production by donor lymphocytes of isoagglutinins
directed against recipient ABO-antigens.
Non-myeloablative conditioning: The curative potential of
allogeneic hematopoietic transplantation is mediated in Hematopoietic grozvth factors: Hematopoietic colony
part by an immune mediated graft-versus-tumor effect. stimulating factors, such as granulocyte colony stimulating
This has prompted some workers to focus on the use of factor are often administered to patients after infusion of
donor T cells to eradicate both nonmalignant and malig stem cells in order to reduce the duration of neutropenia.
nant cells of host origin, without the use of myeloablative
conditioning regimens. This non-myeloablative condition Toxicity Related to Conditioning
ing, aims to suppress the immunity of the recipient
The conventional myeloablative therapy, given before
sufficiently to allow allogeneic engraftment, without
infusion of the bone marrow causes complications: (a)
destroying the recipient's marrow, with lower regimen
veno-occlusive disease of the liver characterized by (i)
related toxicity.
jaundice, (ii) hepatomegaly and right upper quadrant pain,
Technical Aspects (iii) ascites or unexplained weight pain; (b) hemorrhagic
cystitis characterized by the presence of hematuria,
The donor's marrow is harvested by repeated aspiration
from the posterior and anterior iliac crests, under general dysuria, and urinary frequency in a patient with sterile
or spinal anesthesia. The marrow is collected in a bag with urine; (c) seizures-usually drug induced (cyclosporine,
anticoagulant. The number of marrow cells or total nuclea busulphan) or due to infections; (d) pulmonary compli
ted cells required for successful engraftment is estimated cations; (e) skin and mucosal changes like alopecia, nail
to be at least 1 to 3 x 108 per kg of recipient's body weight. changes and oral mucositis.
Bone marrow is transfused through the veins and the
Failure of Engraftment
donor cells home into the recipient's marrow space and
start engrafting. Engraftment is considered established Failure to engraft after hematopoietic stem cell transplan
when the peripheral neutrophil count reaches 500/cu mm tation (graft dysfunction) or inability to sustain graft (graft
on three successive days. rejection) is a formidable complication. The causes of this
include inadequate stem cell dose, infections, graft-versus-
Supportive Care host disease and immunological mediated processes.
Protective isolation: After transplantation of the marrow, it Fortunately, this complication is uncommon. The
takes 2-3 weeks before engraftment occurs, the time when incidence is higher in unrelated donor and HLA
the stem cells start producing adequate number of mismatched transplant.
316 Essential Pediatrics
Graff Versus Host Disease transplantation. Engraftment takes place more rapidly
In allogeneic bone marrow transplant patients, a unique when peripheral stem cells are used instead of bone
complication occurs, graft versus host disease (GVHD), marrow cells. The advantage of autologous transplant over
which may be acute or chronic. Acute GVHD occurs allogeneic transplant is that there is no GVHD and once
engraftment occurs, graft rejection is unlikely. Thus, there
within the first 3 months after transplant. It classically
is a significant decrease in the complication rates. However,
affects three tissues, namely the skin, gut and liver and
there is a higher risk of tumor relapse as compared to
may be accompanied by fever. The severity can be graded
allogeneic transplants.
according to the extent of skin involvement, degree of
hyperbilirubinemia and severity of diarrhea. Chronic
Peripheral Blood Stem Cell Transplantation
GVHD develops later than 100 days after transplant and
often follows acute GVHD but may also develop de novo; In the past few years an increasing number of peripheral
it is classified as limited or extensive. Clinically it resem blood stem cell transplantations (PBSCT) are being perfor
bles autoimmune disorders like scleroderma with skin med. The procedure is similar to bone marrow transplant
rash, sicca complex, sclerosing bronchioloitis and hepatic except for differences in the method of collection of the
dysfunction. The mortality varies from 20-40%. Manage stem cells and slight changes in the engraftment potential.
ment is with immunosuppressive agents like cyclosporine, It is known that the peripheral blood contains a small
prednisolone, azathioprine, methotrexate and cyclophos proportion of stem cells, approximately 0.1%. This number
can be increased by administration of colony stimulating
phamide in various combinations. Most patients develop
factors, e.g. G-CSF.
self tolerance and after a year or more these drugs can be
tapered off. GVHD is more common in older patients and PBSCT can be autologous or allogeneic. For allogeneic
those with one or more HLA mismatches or unrelated donors, G-CSF is administered for 4 to 5 days, this results
HLA identical transplants. in high circulating stem cells which can be collected by a
cell separator (apheresis) machine. The procedure requires
Tumor Relapse venous access and takes two to four hours. The donor need
not be admitted, does not require anesthesia and is spared
A successful hematopoietic stem cell transplant does not
the pain of marrow aspiration. For autologous PBSCT, the
always mean that the primary disease is cured. A certain
stem cells are collected in a similar fashion, but chemothe
number of patients will relapse from the original malig
rapy is also usually given prior to the harvest to reduce the
nancy, as the tumor cells survive the chemo/ radiotherapy
tumor contamination and to yield a higher proportion of
and graft versus tumor effect.
stem cells.
Late Infections
Cord Blood Stem Cell Transplantation
Infections remain a major complication in the post
transplant period. Viral infections are important causes Placental blood, which is routinely discarded in clinical
of morbidity and mortality after allogeneic stem cell trans practice, is potentially a rich source for allogeneic hemato
plant, the most important infections being cytomegalo poietic stem cells. Cord blood stem cells have distinctive
virus, herpes simplex virus and varicella zoster infection. proliferative advantages which include: (a) enriched
proportion of immature stem cells, (b) higher clonogenic
Bacterial infections with encapsulated organisms occur
growth advantage, (c) increased cell cycle rate, (d) auto
after 3-6 months.
crine growth factors production and (e) increased telomere
Autologous Stem Cell Transplantation length. The small number and relative immaturity of naive
T cells of cord blood lymphocytes is expected to reduce
Autologous bone marrow or peripheral blood stem cell
the risk and severity of GVHD. The activation pattern of
transplantation is a procedure similar to allogeneic bone
cord blood T cells is less in magnitude than that in adult
marrow transplant, the major difference being that the
counterparts. The main limitation of cord blood trans
patient's own stem cells are used for engraftment. The
plants is the limited number of nucleated cells available
concept of performing autologous stem cell transplant is to
in a unit. Compared to bone marrow transplantation, the
permit administration of very high doses of chemo or radio time for engraftment in cord blood transplantation is much
therapy, which would otherwise be fatal, due to severe longer, taking a month for neutrophilic engraftment and
myelosuppression. First the patient's marrow or stem cells more than fifty days for platelet engraftment. There is also
are collected prior to chemotherapy, they are then used to a higher incidence of non-engraftment. This leads to high
'rescue' the patient from the myelotoxicity after the chemo transplant related mortality. The nucleated cell dose
therapy. The procedure is only indicated for malignancies available in a cord blood unit is critical, being one log less
which are chemo/radiosensitive, e.g. leukemia, lym than in a bone marrow transplant. The main advantage of
phoma, neuroblastoma and other solid tumors. Peripheral cord blood transplant is a lower incidence and severity of
blood stem cell transplantation (see below) have virtually GVHD. This allows a 1-2 HLA antigen mismatch even in
replaced bone marrow for autologous stem cell unrelated cord blood transplant.
Hematological Disorders 317
Extrinsic Pathway
Intrinsic Pathway Tissue factor pathway
Table 11.18: Differences in bleeding patterns in platelet disorders versus coagulation disorders
Platelet disorder Coagulation disorder
Site of bleeding Skin, mucous membranes Deep in soft tissues, joints, muscles
(epistaxis, oral, GI tract)
Petechiae Yes No
Ecchymoses Small, superficial Large, deep
Hemarthrosis/muscle bleeding Extremely rare Common
Bleeding after minor trauma Yes No
Bleeding after surgery Immediate, usually mild Delayed (1-2 days), often severe
Examples von Willebrand disease Hemophilia A
Idiopathic thrombocytopenic purpura Hemophilia B
infections, collagen vascular disorders, Langerhans cell a fresh finger stick, this avoids any artefactual errors due
histiocytosis and Wiskott Aldrich syndrome. The mouth to EDTA anticoagulated blood. Initial coagulation screen
and nose should be carefully examined to rule out local ing tests include the PT and aPTT. Specific factor assays can
causes of bleeding. Hemangiomas and telangiectasias, be done to identify factor deficiencies, the degree of factor
may lead to mucocutaneous bleeding in Kasabach Merritt VIII and IX deficiency will dictate the management. The
syndrome and hereditary telangiectasia. aPTT is used for monitoring heparin therapy; PT and its
international normalized standard (INR) are used to assess
Laboratory investigation
therapeutic warfarin effect. Bleeding time is now rarely
A complete hemogram is done for platelet count; peri used due to the problems of reproducibility and reliability.
pheral smear examination shows platelet and red cell This test is abnormal if the platelet count is below
morphology. The optimal peripheral smear is made from 100,000/cu mm (Table 11.19). In systemic vasculitides (e.g.
Hematological Disorders 319
Suggested reading
Roberts HA, Escobar M, White IIGC. Hemophilia A and hemophilia B.
Williams Hematology, 7th edn. Eds. Lichtman, Beutler, et al. McGraw-
Hill Medical, 2006;1867-1886.
VITAMIN K DEFICIENCY
hence 50% cases may occur with the first pregnancy. A Amplification Role of Thrombin
high index of suspicion is required to correctly identify
Thrombin amplifies inflammation and clotting by activa
this condition, since this is a serious entity, which can tion of platelets, and factors V, VIII and IX leading to more
result in intracranial hemorrhage. As there are few specific thrombin production. Activated factor XIII leads to its
tests for its diagnosis it is primarily a diagnosis of exclu cross-linking with fibrin clots making them insoluble,
sion. Postnatal management requires transfusion of while thrombin activable fibrinolysis inhibitor makes clots
washed, maternal platelets (preferably irradiated if resistant to fibrinolysis.
facilities are available) and close monitoring till the platelet
counts normalize). In subsequent pregnancies, the risk for Propagation of Fibrin Deposition
neonatal thrombocytopenia increases. The fetus will need There is suppression of fibrinolysis secondary to sustained
serial ultrasound examinations to see for intracranial increase in plasma levels of plasminogen-activator
hemorrhage; the mother may be given IV immunoglobulin inhibitor (PAI-1).
(1 g/kg repeated every four weeks) with addition of oral Following injury, infection or other precipitating factors
dexamethasone if there is no response. there is release of cytokines, which change the endothelium
from an anticoagulant to a procoagulant surface and
DISSEMINATED INTRAVASCULAR COAGULOPATHY interfere with fibrinolysis. Many of the effects of DIC like
hypotension or acute lung injury are due to the effects of
Disseminated intravascular coagulopathy or coagulation
these cytokines. As DIC continues, fibrinogen, prothrom
(DIC) is an acquired disorder of dysregulation of
bin, platelets and other clotting factors are consumed
hemostasis. The presentation ranges from only an isolated
beyond the capacity of the body to compensate and
derangement of laboratory parameters to a condition of
bleeding ensues. Activated protein C has an anti-inflamma-
severe bleeding from multiple sites, associated with high tory effect and down regulates the tissue factor and decre
mortality. DIC is triggered by a variety of conditions all ases calcium ion flux. It is consumed in DIC and its supple
of which result in activation of the clotting cascade, this mentation may have an important role in DIC due to sepsis.
leads to deposition of fibrin in the microcirculation
resulting in consumption of platelets and clotting factors. Causes
The diagnosis of DIC is clinical (Fig. 11.17). Laboratory The main groups of illnesses causing DIC are infections,
tests merely provide confirmatory evidence. malignancy, tissue necrosis, ABO incompatible blood
transfusion and snakebites (Table 11.21).
Pathophysiology In acute DIC, the patient is critically sick and bleeding
There are three main pathologic processes involved. predominates. Chronic DIC occurs due to a weak or inter
mittent stimulus. The process of destruction and
Initiation of Fibrin Deposition production of clotting factors and platelets is balanced,
Thrombin generation in DIC is mediated by the extrinsic and coagulopathy is compensated. Chronic DIC occurs
(tissue factor) pathway. The tissue factor accumulates on in patients with giant hemangiomas, vasculitides and
activated platelets by binding to platelet P-selectin which some solid tumors.
results in thrombin generation.
Laboratory Features
Screening tests include (i) peripheral blood film examina
tion and hemogram, which reveal schistocytes and
thrombocytopenia; (ii) prothrombin time (PT), activated
partial thromboplastin time (aPTT) and thrombin time
(TT) are prolonged, and fibrinogen level is low. There is
increase in fibrin degradation products or D-dimers. No
single test is diagnostic of DIC. The presence of thrombocy
topenia and hypofibrinogenemia (50% reduction) are the
most sensitive in making a laboratory diagnosis. A DIC
scoring system has been proposed (Table 11.22). An under
lying disorder known to be associated with DIC is a
prerequisite for the use of this algorithm.
Treatment
The underlying disease must be managed appropriately. In
cases of sepsis, antibiotics are required; anti-snake venom
is administered in patients with snake bite. Tissue
Fig. 11.1 7: III child with disseminated intravascular coagulation. perfusion and respiratory function must be maintained by
Shows ecchymoses, purpura and subconjunctival hemorrhages replacement with IV fluid and provision of oxygen support
Hematological Disorders 323
Table 11.21: Disorders which cause acute or chronic disseminated intravascular coagulopathy
Acute DIC Chronic DIC
Medical Septicemia/infections* Solid tumors
Fulminant hepatic failure Kasabach-Merritt syndrome
Heat stroke, hyperpyrexia Liver cirrhosis
Severe burns
Malignancy-acute promyelocytic
leukemia, acute myeloid leukemia,
neuroblastoma
Reye syndrome
Hereditary protein C deficiency
Snake bite
Hemolytic uremic syndrome
Kawasaki disease
Collagen vascular disorders
Surgical Severe renal graft rejection TVascular tumors
Severe trauma-crush injury, multiple tAortic aneurysm
fractures with fat emboli
Major operations
Brain injury
Coagulation tests (platelet count, prothrombin time, fibrinogen, soluble fibrin monomers /fibrin degradation products)
Calculate score
(a) If score > 5: compatible with overt DIC; repeat scoring daily.
(b) If <5 suggestive (not affirmative) of non-overt DIC; repeat in 1-2 days
* In the prospective validation studies, D-dimer assays were used and a value above the upper limit of normal was considered
moderately elevated, whereas a value above 5 times the upper limit of normal was considered as a strong increase.
to correct hypoxia. Coagulopathy may be compounded aPTT and TT, replacement of deficient component is
by vitamin K deficiency, hence vitamin K should be given. useful. Replacement therapy is not indicated if there is no
In patients who have low levels of platelets, fibrinogen clinical bleeding and if no invasive procedures are
and other clotting factors as revealed by prolonged PT, planned.
324 Essential Pediatrics
Table 11.23: Types of blood component therapy, their constituents and guidelines for use
Component Constituents Indication Dose Precautions
Fresh frozen All coagulation Treatment of 15 ml/kg or 1 bag Infuse soon after thawing,
plasma (FFP) factors as in many coagulation per 10 kg as initial may lead to fluid overload.
normal plasma. factor deficiency treatment (constitutes Need ABO compatible units.
0.7-1.0 U/ml of states (prolonged 25-30% replacement
factors II, V, VII, prothrombin time) therapy for
VIII, IX, X, XI, and thrombotic coagulation factors)
XII, XIII and thrombocytopenic
2.5 mg/ml purpura.
fibrinogen
Cryoprecipitate Fibrinogen (150 Fibrinogen defi 1 bag per 5 kg will
mg/bag), Factor ciency or consum raise fibrinogen levels
VIII (80-120 units/ ption, factor VIII by 70 mg/dl
bag), Factor XIII, deficiency
vWD (contains no (hemophilia A),
factor IX) vWD, Factor XIII
deficiency.
Random donor Platelets, contains Thrombocytopenia One unit raises Infuse rapidly, do NOT
platelets (RDP) at least 5.5 x 1010 platelet counts by refrigerate prior to transfusion.
platelets 5-10,000/cu mm.
Dose 1 unit/10 kg
to raise counts by
30,000 to 50,000/cu
mm
Single donor Platelets, contains Thrombocytopenia One collection is Precautions as for random donor
platelets (SDP) at least 3 x 10n equivalent to appro platelets.
platelets. ximately 6 units of
random platelets.
Fresh blood All components To replace acute, Only to be used in Not a good source for platelets or
of blood massive blood loss severe trauma coagulation factors.
Hematological Disorders 325
are the most common causes of arterial thrombosis in Imaging studies include: (i) color Doppler imaging
children. History of fever, recent surgery, trauma, central signals are absent in thrombosed vessels and the lumen
venous catheter use, nephrotic syndrome, dehydration, cannot be compressed with direct pressure. However, this
varicella and other infections, and family history is taken. may not be sufficiently sensitive to detect thrombosis in
The age at which thrombosis occurred and the type of vessels such as subclavian veins, superior vena cava or
thrombosis (deep vein thrombosis, arterial thrombosis or brachiocephalic veins; (ii) echocardiography is useful for
stroke) should be documented. vena caval and proximal subclavian vein thrombosis; (iii)
Symptoms due to deep vein thrombosis include pain computerized tomography of the head with IV contrast is
and swelling of the limb. Pulmonary embolism may useful for detecting venous sinus thrombosis. Both MRI
present with anxiety, breathlessness, pleuritic chest pain, and MRA are better at detecting early arterial ischemic
fever and cough. Symptoms of central nervous system strokes; (iv) chest radiograph may reveal findings of pul
thrombosis include vomiting, lethargy, seizures or monary embolism, which include small pleural effusions
weakness in an extremity. Strokes may occur in utero; with wedge shaped, pleural opacity of pulmonary
newborns will present with seizures and lethargy. Older infarction; (v) ventilation perfusion (V/Q) scintigraphy
children present with headaches and acute onset of is the procedure of choice in children with suspected
weakness in an extremity or hemiplegia. Precipitating pulmonary embolism.
factors like infection, dehydration and trauma are
common. Patients with renal vein thrombosis may present Management
with flank pain and hematuria. Limb edema, erythema Urgent stabilization is required, if possible screening tests
and tenderness on dorsiflexion of the foot (positive for hypercoagulable state (Table 11.25) should be sent prior
Homan's sign) are present in deep vein thrombosis. Signs to initiating anticoagulation therapy. If respiratory distress
of pulmonary embolism are nonspecific and include or neurological problems exist then management in an
diaphoresis, tachycardia and tachypnea. Signs of arterial intensive care unit is required. Children with lower-extre-
thrombosis include diminished or absent peripheral mity deep vein thrombosis can be provided compression
pulses and cool extremities. stockings. Initial therapy requires heparin (unfractionated
or low molecular weight) followed by oral warfarin
Laboratory Evaluation therapy. Close monitoring is required to prevent over
Many clotting factors are consumed in an acute throm dosage and risk of bleeding, underdosing will hamper
bosis, and a low factor level may be the result of the pre resolution of the thrombus. The international normalized
existing thrombosis. The child should be evaluated to rule ratio, which is patient's PT compared to a standard, is the
out DIC with complete blood count, peripheral blood most useful test for monitoring anticoagulation. The INR
smear, prothrombin time, activated partial thromboplastin therapeutic range is 2-3. The duration of therapy depends
time and fibrinogen level (Table 11.24). on the risk of recurrence, assessed by testing for thrombo-
Table 11.24: Initial workup for thrombosis to evaluate for Table 11.25: Common pre-existing factors which increase risk
hypercoagulable state* of thrombosis in children
Complete blood count Acquired conditions
Prothrombin time, activated partial thromboplastin time Sepsis-viral, bacterial
Radiology as indicated by symptoms Disseminated intravascular coagulation
Activated protein C resistance, factor V Leiden mutation Dehydration
Anti thrombin Central venous catheter
Lupus anticoagulant (which may be screened by using the Surgery, trauma
dilute Russell viper venom test) Congenital heart disease
Anticardiolipin antibodies Antiphospholipid antibody syndrome
Malignancy- acute lymphoblastic therapy (L-asparaginase and
Prothrombin gene 20210A mutation
steroids)
Lipoprotein (a) level
Nephrotic syndrome
Plasma homocysteine values
Protein C (Usually decreased in acute thrombosis) Inherited prothrombotic disorders
Free and total protein S (Usually decreased in acute thrombo Resistance to activated protein C
sis) Factor V Leiden
’Heparin therapy affects antithrombin, protein C, protein S Protein C deficiency
and activated protein C resistance tests. Protein S deficiency
Warfarin affects protein C, protein S and antithrombin. Antithrombin deficiency
Prothrombin gene 20210A mutation
Neither drug affects results of anticardiolipin antibodies, fac
Elevated lipoprotein (a) level
tor V Leiden, the prothrombin mutation or lipoprotein(a) or
Hyper homocysteinemia
homocysteine levels.
326 Essential Pediatrics
philia status 3 months after stopping anticoagulants. Table 11.26: List of common causes of neutrophilia
Unfractionated heparin exhibits antithrombin and anti-
Acute
Xa activity, whereas low molecular weight heparin has
Infection—many acute bacterial infections
primarily anti-Xa function.
Drugs—epinephrine, corticosteroids, granulocyte colony
Suggested reading stimulating factor
Hemorrhage
1. Tormene D, Gavasso S, Rossetto V, Simioni P. Thrombosis and
Hypoxia
thrombophilia in children: a systematic review. Semin Thromb
Hemolysis
Hemost 2006; 32: 724-728.
2. Saxena R, Kannan M, Choudhry VP. Laboratory studies in
Stress—Trauma, burns, exercise, heat stroke
coagulation disorders. Indian J Pediatr 2007;74:649-655. Kidney failure, diabetic ketoacidosis, hepatic failure
Leukemoid reaction
Hodgkin's lymphoma, chronic myeloid leukemia
WHITE BLOOD CELLS
Chronic
Evaluation of quantitative and qualitative changes in the
Chronic myeloid leukemia
lymphocytes and myeloid series will help to diagnose
Rheumatological/inflammatory diseases
many infectious, immunologic, malignant and even Hemolytic anemia—sickle cell anemia
endocrine disorders. A detailed history of onset, duration, Post splenectomy state
fever, rashes, lymphadenopathy, organomegaly must be Chronic blood loss
taken. The complete history, including family history and Endocrine-thyrotoxicosis
examination will contribute to the diagnosis. Genetic causes/syndromes
Quantitative changes are a frequent anomaly on the Down syndrome
hemogram report. The differential count will help pinpoint Asplenia
the expanded population of cells. The percentage increase Chronic idiopathic neutrophilia
Leukocyte adhesion defect
over normal range is important, very high counts are
indicative of leukemoid reaction or leukemias. The abso
lute count is required in certain cases, e.g. absolute
eosinophil count for diagnosis of hypereosinophilic are important for ingestion and killing of many pathogenic
syndromes and neutrophil count for degree of immuno bacteria and parasites like M. tuberculosis and Leishmania
deficiency. The morphology of cells may reveal abnormal (Table 11.27). Monocytes are the first granulocytic cells to
size, immaturity, change in nuclear cytoplasmic ratio, recover in post chemotherapy states when white cell
inclusions and abnormal granules. For example, Howell counts recover. Abnormality of macrophage activation
Jolly bodies are found in cases of absent splenic function
due to asplenia or post splenectomy, toxic granulations Table 11.27: List of common causes of monocytosis
and left shift suggests sepsis, Epstein Barr virus infection
Infections: tuberculosis, typhoid, malaria, bacterial endocardi
results in large monocytoid cells, which can be confused tis, brucella, kala azar
for blasts in the peripheral smear. It is also important to Rheumatological/inflammatory diseases: Systemic lupus ery
know if other hematopoietic cell lineages are affected. thematosus, rheumatoid arthritis, ulcerative colitis
Post splenectomy state, hemolytic anemia
Leukocytosis Malignancy. Lymphomas, chronic myeloid leukemia, juvenile
The onset and duration of illness may provide a clue to myelomonocytic leukemia, myelodysplasia
the diagnosis; a history of medications and prior hospitali Myxedema
zation may be contributory. Evaluate the child for
infections, inflammatory, malignant and metabolic
leads to disorders like familial hemophagocytic syndrome.
disorders.
Basophilia is seen in hypersensitivity reactions, chronic
Neutrophils increase in acute bacterial infections, acute myeloid leukemia, Hodgkin lymphoma, varicella
blood loss, hemolysis and diabetic ketoacidosis (Table infection, nephrotic syndrome, hypothyroidism and
11.26). Leukocyte alkaline phosphatase (LAP) is an following antithyroid medications. Eosinophilia occurs in
enzyme present in mature neutrophils, on staining blue many conditions, including allergic disorders (e.g. atopic
granules become visible. This is increased in infections dermatitis, asthma), systemic inflammatory conditions
and leukemoid reaction (very high white blood cell (e.g. inflammatory bowel disease, rheumatoid arthritis),
response to infection). In chronic myeloid leukemia, the malignancies (e.g. Hodgkin lymphoma). Parasites which
neutrophils are LAP deficient so the score is low. invade tissue are more likely to cause eosinophilia, e.g.
The circulating tissue macrophage precursors are the toxocara which causes visceral larva migrans (Table 11.28).
monocytes. These cells migrate to different tissues and Elevated sustained eosinophil counts are associated with
transform into macrophages, e.g. Kupffer cells. These cells cardiac toxicity. Moderate elevated absolute eosinophil
Hematological Disorders 327
Table 11.28: List of common causes of eosinophilia Table 11.30: List of common causes of neutropenia
Acute Acute
Atopic and allergic disorders: e.g. asthma, urticaria, drug Infections: Many viral, bacterial, protozoan, fungal and
hypersensitivity reactions. rickettsial organisms.
Parasitic infestations: toxocara, ascaris, amoebic, strongy Drags: Sulfonamides, phenytoin, phenobarbital, penicillin,
loidiasis, filarial, toxoplasmosis, trichinosis, malaria scabies. phenothiazines
Fungal infections: Bronchopulmonary aspergillosis, Hypersplenism
coccidiomycosis Bone marrow replacement: Leukemia, lymphoma, neuroblastoma
Malignancy: Hodgkin lymphoma, acute myeloid leukemia, Cancer chemotherapy agents, e.g. busulphan, cyclophospha
myeloproliferative syndrome, brain tumors, hypereosinophilic mide
syndrome
Chronic
Chronic
Inherited disorders
Atopic and allergic disorders: pemphigus, dermatitis herpeti Cyclic neutropenia
formis Familial benign neutropenia
Rheumatologic/inflammatory disorders: Inflammatory bowel Kostmann syndrome
disease, rheumatoid arthritis Shwachman- Diamond syndrome
Malignancy, myeloproliferative syndrome, hypereosinophilic Chediak Higashi syndrome
syndrome Glycogen storage disease type lb
Addison disease Autoimmune and isoimmune neutropenia
Kidney rejection, peritoneal dialysis
Vitamin Bu and folate deficiency
Hyper IgE syndrome, Loeffler syndrome, Wiskott Aldrich
syndrome, Omenn syndrome Immune deficiencies: HIV
Thrombocytopenia with absent radii syndrome Metabolic disease: Tyrosinemia, methylmalonic aciduria
Bone marrow failure: Fanconi anemia
ipt
Jb
At
mw
in the affected ear. The presence of ear pain has been found
DISEASES OF THE EAR
to be the most consistent symptom, while the presence or
absence of fever is of variable utility.
OTITIS MEDIA Otoscopic examination generally reveals a red and
bulging tympanic membrane with reduced tympanic
Otitis media is one of the most common infections of early
membrane mobility as measured by either insufflation
childhood. Anatomic features which make this age group
through the otoscope (pneumatic otoscopy) or tympano
particularly susceptible to ear infections include shorter,
metry. A bulging tympanic membrane is the most reliable
more horizontally placed and compliant eustachian tubes,
physical exam sign of AOM. Bulging and reduced mobility
which permit reflux of nasopharyngeal secretions into the
may help to differentiate AOM from redness of the
middle ear. A high incidence of bacterial carriage in the
tympanic membrane due to other causes, e.g. crying, viral
adenoids may also contribute to the frequency of otitis
myringitis, or trauma from aggressive ear cleaning.
media in children. Other risk factors include exposure to
Suppuration (rupture of the drum with ear discharge) may
cigarette smoke, overcrowding, bottle-feeding, cleft palate,
have already occurred, in which case reddish brown fluid
allergic rhinitis, Down syndrome and disorders of
may be seen filling the ear canal. Cleaning of this fluid
mucociliary transport. The same risk factors are operative
in the pathophysiology of the two common varieties of usually reveals an intact drum, as the rupture is small and
otitis media seen in children: acute otitis media (AOM) closes promptly after spontaneous perforation.
and otitis media with effusion (OME).
Treatment
Acute Otitis Media Antimicrobial therapy is the mainstay of treatment.
Childhood acute otitis media (AOM) tends to occur in a Adjuvant treatment with oral decongestant drugs has not
bimodal age distribution, with children between ages 12 been shown to be efficacious, and the use of this class of
and 24 months and between ages 5 and 6 years at greatest drugs is not recommended. Topical decongestants, though
risk. frequently prescribed, are detrimental due to rebound
congestion and nasal and nasopharyngeal mucosal
Etiology irritation. Another frequently misused class of drugs is
Streptococcus pneumoniae and Hemophilus influenzae are the antihistamines, which contribute little to the resolution of
two most common causative organisms of acute otitis otitis media and may precipitate sinus infections due to
media (AOM), accounting for approximately 65% of all their drying effect on mucosal secretions.
cases. About 15% of the cases are due to Moraxella Amoxicillin or co-trimoxazole form the first-line
catarrhnlis, Streptococcus pyogenes and Staphylococcus aureus therapy for AOM. More expensive agents with p-
infection. Respiratory viruses may play an important role lactamase resistance, e.g. amoxicillin-clavulanic acid,
in initiating otitis media and may be the only pathogens cefaclor, cefuroxime or other newer cephalosporins are
involved in some cases, as up to 20% of middle ear useful second-line agents for unresponsive infections, and
aspirates are sterile. their routine first-line use should be limited to comm
unities or patient populations with a demonstrated
Diagnosis prevalence of p-lactamase producing H. influenzae or B.
AOM is characterized by the rapid onset of local and/or catarrhalis.
systemic signs and symptoms in the presence of a middle In the presence of complicated AOM such as intra
ear effusion. There is often a history of recent upper cranial spread of infection, acute mastoiditis, or neonatal
respiratory tract infection. Other symptoms include ear otitis media, aspiration of the middle ear fluid (tympano-
pain, ear tugging or rubbing, fever, excessive crying or centesis) may be performed with an 18-gauge spinal
poor appetite. Older children may report impaired hearing needle and submitted for microbiology.
330 Essential Pediatrics
Initial antibiotic therapy should last at least 7 days, with diagnosed effusions should be observed for this period in
reexamination indicated after 3-4 days and at 3 weeks. nearly all cases. Most practitioners prescribe antibiotics
Many children present with recurrent episodes of acute otitis during this period, though evidence supporting this
media. If particularly troublesome, this condition may be practice is not incontrovertible. Use of antihistamines and
treated either with prolonged antibiotic prophylaxis (e.g. decongestants is not recommended. The benefit of brief
amoxicillin for 3-6 months) or insertion of tympanostomy steroid administration has also not been proven.
tubes. Randomized trials have proved that both of these If effusion persists beyond 3 months, tympanostomy
options are superior to placebo therapy, and that they tube insertion may be considered for significant hearing
appear to have equivalent efficacy in comparison to each loss (>25 dB) (Fig. 12.2). Other indications of tube
other. If a child requires a second set of tympanostomy placement are ear discomfort or pain, altered behavior,
tubes, adenoidectomy is often simultaneously performed. speech delay, recurrent acute otitis media or impending
This not only removes the bacterial reservoir that may cholesteatoma formation from tympanic membrane
contribute to recurrent otitis media, but also relieves retraction. Improvement in hearing as well as ear
possible obstruction of the eustachian tubes in the discomfort is immediate and quite gratifying, but lasts
nasopharynx. only as long as the tubes are in place. Mean time before
extrusion is usually between 6 and 9 months. The majority
Otitis Media with Effusion (OME) of the ears recover by the time the tubes extrude, but some
children require repeated tube placements. Insertion of
Following an episode of AOM, serous or mucoid middle
long-term tubes (of T-tube design) or adenoidectomy may
ear effusions may be seen in a number of children. Effusion
be considered in cases of persistent symptomatic effusion.
has been found to persist in up to 40% of children 1 month
Although many otolaryngologists permit surface
after their first episode of otitis media and in 10% after 3
swimming (but not diving), it is probably safer for children
months. However, many children with fluid effusion in
to avoid swimming altogether to prevent contamination
the middle ear do not have any history of acute middle
of the middle ear space.
ear infections in the past. Pathogenesis of this condition
has not been clearly established, hut infectious, allergic Chronic Suppurative Otitis Media: The Draining Ear
or immunologic mechanisms may be at play.
Persistent or recurrent ear discharge is generally due to
Mild to moderate hearing loss and sensation of ear
chronic inflammation of the middle ear space or mastoid
blockage or pressure are the chief complaints, although air cells. Such infection invariably presents with perfo
the condition may also be asymptomatic. As opposed to ration of the tympanic membrane, which allows egress of
AOM, ear pain is generally not present in children with the suppurative material. Chronic suppurative otitis
OME. Otoscopy reveals a dull tympanic membrane with media (CSOM) most often results from neglected acute
or without a fluid level (Fig.12.1). Diagnosis is established middle ear infections, and is, therefore, much more com
by demonstrating reduced mobility of the tympanic mon in children with inadequate access to primary health
membrane with either pneumatic otoscopy or a type 13 care. It most often occurs in the first five years of life, as
pattern on tympanometry. Since 50% of serous middle ear eustachian tube dysfunction plays a central role in the
effusions resolve spontaneously within 3 months, newly pathophysiology.
Fig. 12.1 : Otitis media with effusion. Note the retraction and thinning
of the tympanic membrane, the draping of the tympanic membrane Fig. 12.2 : A tympanostomy tube in place. The tube is beginning to
over the long process of incus, distortion of the light reflex, and an get extruded, thus appearing higher than the site of its insertion
impression of fluid being present behind the drum (anteroinferior quadrant)
Diseases of Ear, Nose and Throat 331
The most common complication of CSOM is hearing preferred local antibiotic. Ciprofloxacin or ofloxacin ear
loss, which may affect a young child's language develop drops three time a day for about 2 weeks are often
ment and school performance. The hearing loss is usually effective. Aural toilet is provided by keeping the ear as
a conductive loss, resulting from edema/fluid in the dry as possible by wicking at least three times a day. Roll
middle ear and tympanic membrane perforation. How a clean absorbent cloth or strong tissue paper into a wick,
ever, some recent studies have also suggested senso place it in the child's ear, remove when wet, replace the
rineural hearing loss as a possible sequela of CSOM, wick with a clean one, and repeat these steps until the ear
presumably through direct extension of inflammatory is dry.
mediators into the inner ear. The use of systemic antibiotic therapy should be
reserved for infections showing signs of complications or
Etiology
for the presence of systemic involvement. Instructions to
Pseudomonas aeruginosa is the most commonly isolated parents to avoid water entering the affected ear should
organism in CSOM. Other organisms commonly identified also be given. Of note, secondary fungal otitis externa has
include Stapln/lococcus aureus, gram-negative organisms been reported as a complication of topical antibiotic
such as Proteus species and E. coli, and anaerobes. Fungi
treatment. Otolaryngology referral is mandatory for
are also thought to play a role in CSOM, especially
ruling out cholesteatoma.
Aspergillus and Candida species.
Surgery is usually indicated for most cases of CSOM
Diagnosis that do not respond to conservative treatment. Surgical
therapy involves repair of the tympanic membrane
Chronic ear discharge is the hallmark of CSOM. Otoscopy
perforation (tympanoplasty) with or without a
reveals perforation of the tympanic membrane (Fig. 12.3).
mastoidectomy. If cholesteatoma is suspected, ear
A chronically draining ear may also be seen with
exploration via mastoidectomy and cholesteatoma
cholesteatoma, which is a sac of squamous epithelium
removal is mandatory. The primary goal of surgical
extending from the tympanic membrane into the middle
therapy for cholesteatoma is to create a "safe ear" bv
ear (Fig. 12.4). Most cholesteatoma is acquired, although
removal of all cholesteatoma. Hearing preservation is a
whether it arises from extension of a tympanic membrane
retraction pocket, or from aberrant inward migration of secondary goal of the procedure. In simple tympanic
the normal eardrum epithelium, remains unclear. Rarely, membrane perforations without cholesteatoma, surgical
the cholesteatoma may be congenital, arising de novo in repair is now considered appropriate treatment in children
the middle ear space. Though not malignant, cholestea older than 8 years of age. Tympanic membrane repair
toma may cause serious complications by slow expansion protects the ear from further contamination and infection,
and local destruction. These complications are discussed often improves hearing, and may have a positive effect
further in the next section. on the quality of the child's life. The previously held
dictum that tympanoplasty should be delayed until
Treatment adulthood has been challenged by the results of several
Medical therapy consists primarily of: (i) topical studies demonstrates equivalent success rates of surgical
antibiotics, and (ii) aural toilet. Topical quinolones are the repair in children older than 6 to 8 years.
Fig. 1 2 . 3 : Chronic suppurative otitis media with a dry, central Fig. 12.4: Attic cholesteatoma. The entrance of an attic cholesteatoma
perforation. The long process of incus and the stapedius tendon sac (attic perforation) showing wet debris inside. The pars tensa
attaching to the neck of stapes are seen through the perforation. Also shows retraction and tympanosclerosis (whitish plaque antero-
seen is the round window posteriorly inferiorly)
332 Essential Pediatrics
Complications of Otitis Media of the mastoid air cells. Differential diagnosis must include
Untreated otitis media may occasionally cause compli a severe case of otitis externa, as both processes may
cations that, while occurring rarely, have potentially dire present with swelling and tenderness of the ear canal,
consequences. These complications can be further postauricular region and mastoid process. Untreated, this
classified as either intracranial or extracranial (Table 12.1). may progress to an abscess within the confines of the
AOM and its complications are more common in young mastoid cells, or spread externally, leading to the
children, while complications due to CSOM with or formation of subperiosteal or deep neck abscesses.
without cholesteatoma are more common in older Acute coalescent mastoiditis should initially be treated
children. with parenteral antibiotics directed against the afore
mentioned pathogens related to AOM, adding coverage
Table 12.1: Complications of otitis media for gram-negative and anaerobic organisms only if
mastoiditis is superimposed upon a history of a
Intracranial complications
chronically discharging ear, where colonization with such
Meningitis bacteria is common. The presence of an abscess mandates
Brain abscess surgical intervention. Surgery in the form of a cortical
Epidural abscess
mastoidectomy is also indicated for cases with poor
Dural venous (sigmoid sinus) thrombosis
response to parenteral antibiotic therapy, an intracranial
Otitic hydrocephalus
complication or acute mastoiditis in a chronic ear.
Extracranial complications
Other extracranial complications of otitis media include
Subperiosteal abscess
labyrinthine fistula and facial nerve paralysis. Labyrinthine
Labyrinthine fistula
fistula, in which a cholesteatoma has eroded into the inner
Facial nerve paralysis
Acute coalescent mastoiditis ear, presents with vertigo and possibly a sensorineural
hearing loss. Facial nerve paralysis secondary to otitis
media is usually treated with appropriate antibiotics and
myringotomy. If the paralysis is secondary to cholestea
Meningitis is the most common intracranial complication toma, mastoidectomy is indicated.
of both acute and chronic otitis media. Furthermore, AOM
is the most common cause of secondary meningitis. While OTITIS EXTERNA
this is a serious complication, the mortality rate from otitic
meningitis has decreased significantly. Of pertinent Acute diffuse otitis externa (swimmer's ear) presents with
interest is the fact that meningitis is the most common itching, pain and fullness in the affected ear. Erythema
cause of acquired sensorineural hearing loss in children. and edema of the canal skin and tenderness on moving
the pinnae or tragus are diagnostic features. Otorrhea is
Brain abscess is a potentially lethal complication of otitis common, especially in bacterial infections. Swimming is
media. Unlike meningitis, which is caused more frequently a risk factor, but the infection can also result from impacted
by AOM, brain abscesses result almost exclusively from cerumen, hearing aid use, or self-induced trauma from
chronic otitis media. Imaging plays an important role. foreign objects such as hairpins or cotton swabs. The
Broad-spectrum parenteral antibiotics are begun imme etiologic agents of otitis externa are listed in Table 12.2.
diately, and surgical drainage is paramount. Thrombosis Treatment consists of ear canal cleaning by experienced
of the sigmoid or transverse sinus is another important personnel and topical antibiotic drops. Topical antibiotics
intracranial complication of otitis media. Patients typically are highly effective for acute otitis externa with clinical
present with headache, malaise, and high spiking fevers cure rates up to 80%. If edema is significant, ribbon gauze
in a "picket fence" pattern. Treatment involves parenteral or a premanufactured "wick" may be placed in the
antibiotics and surgical drainage of the mastoid. external auditory canal to allow wick-like delivery of the
antibiotic agent. Oral and parenteral antibiotics are
Acute coalescent mastoiditis occurs due to the spread of
reserved for cases with complications. A chronic form of
infection into the mastoid bone. This entity should be
diffuse otitis externa may also be seen.
differentiated from fluid effusion within mastoid air cells,
which is sometimes mistakenly noted radiologically as Localized otitis externa or furunculosis presents as an
"mastoiditis". Such opacification is commonly seen with exquisitely painful, superficial abscess in the outer portion
both acute and chronic OM, is readily apparent on CT
scans, and is of little clinical significance. Coalescent Table 12.2: Etiology of otitis externa
mastoiditis, on the other hand, presents with postauricular Pseadomonas aeruginosa 40%
erythema, tenderness, and edema, and an auricle that is Staphylococcus species 25%
generally displaced inferiorly and laterally. If acute Gram-negative rods (e.g. Proteus, E. coli) 9%
coalescent mastoiditis is suspected, a CT scan should be Other bacteria 13%
Aspergillus/Candida 2%
performed, which would show clouding or coalescence
Diseases of Ear, Nose and Throat 333
of the ear canal. Such infection is commonly ossicles may cause a conductive hearing loss. The most
staphylococcal in origin. Oral antistaphylococcal common cause of conductive deafness in children is otitis
antibiotics and analgesics bring about prompt relief. media with effusion, and is typically of mild to moderate
Occasionally, incision and drainage of a pointing abscess severity. Several congenital syndromes mav also be
may be necessary. associated with middle ear abnormalities, such as Apert,
Crouzon and Treacher-Collins syndromes.
Eczcmatous or psoriatic otitis externa describes a group of
inflammatory conditions in which there is drainage,
Sensorineural Hearing Loss
pruritis and/or scaling of the ear canal skin. Underlying
causes include contact dermatitis, atopic dermatitis and Sensorineural hearing loss (SNHL) is caused by a lesion
seborrheic dermatitis. To treat this condition effectively, of the cochlea, auditory nerve, or central auditory
the primary dermatologic disorder must be addressed. pathway. SNHL can be acquired or congenital. The majority
of pediatric SNHL falls into the acquired (noncongenital)
Otomycosis or fungal otitis externa is most common in category.
humid weather and presents with pain and pruritus of The most common postnatal cause of acquired
the affected ear. These infections are often considered to sensorineural hearing loss is meningitis, while the most
be opportunistic, as they are frequently seen subsequent common prenatal cause is intrauterine infection (e.g.
to treatment of a bacterial infection. Examination reveals TORCH infections, syphilis, mumps, measles). Other
fungal spores and filaments along with cloudy discharge causes of acquired hearing loss include prematurity,
(Fig. 12.5). Aspergillus and Candida are the most common hyperbilirubinemia, perinatal asphyxia/hypoxia, head
pathogens, though other fungi may be implicated. Aural trauma, acquired immunodeficiency syndrome and
toilet and application of a topical antifungal (e.g. clotri ototoxic medications (aminoglycosides, loop diuretics).
mazole) are curative. Congenital causes of sensorineural hearing loss can be
further divided into syndromic and nonsyndromic types.
Although the majority of congenital hearing loss is non
syndromic, there are over 300 genetic syndromes identi
fied to date that are associated with SNHL. Some of the
most common genetic syndromes associated with deafness
include Pendred syndrome, in which patients have thyroid
enlargement, and Usher syndrome, which is associated
with retinitis pigmentosa and blindness. Alport syndrome
and Waardenburg syndrome are also implicated.
Most cases of congenital hearing loss are nonsyndromic,
and the recent sequencing of the human genome has
rapidly advanced our understanding of these disorders.
To date more than 110 chromosome loci and at least 65
genes have been identified that are associated with genetic
hearing loss. Mutations in a single gene, G/B2, may be
responsible for up to 50% of nonsyndromic congenital
Fig. 12.5: Otomycosis. Fungal debris (hyphae and dark-colored
spores) filling the deeper end of the external auditory meatus
hearing loss. G/B2 encodes the protein connexin 26, which
is widely expressed in cells of the inner ear. Screening tests
for the connexin 26 mutation have recently become
HEARING LOSS
available as a means for detecting congenital hearing loss.
The importance of early detection of pediatric hearing loss
should not be underestimated. Unrecognized early Neonatal Screening
hearing loss can impede development of speech, language, All neonates with risk factors for hearing loss must be
and cognitive skills. Separate differential diagnoses exist screened with an auditory brainstem response (ABR) or
for deficits of both the conductive and sensorineural otoacoustic emissions (OAE) test to exclude hearing
components of the hearing mechanism. Pediatric hearing impairment. It must be recognized, however, that use of
loss can be further classified as either congenital or acquired. clinical indicators to focus hearing screens will miss as
A comprehensive discussion of the various causes of many as 50% of all cases of impairment. As a result,
pediatric hearing loss exceeds the scope of this discussion. universal newborn hearing screen programs are becoming
However, several important clinical points are presented commonplace over the last 10 years in the United States
below. and Europe, though not vet in India. The importance of
neonatal screening cannot be overemphasized. Infants in
Conductive Hearing Loss whom treatment for hearing loss is initiated by 6 months
Any process that interferes with the conductive of age are able to maintain language and social develop
mechanism of the ear canal, tympanic membrane, or ment in line with their physical development. This is in
334 Essential Pediatrics
stark contrast to those whose hearing loss is identified after SNHL, in contrast, is generally more difficult to correct
6 months of age. than conductive hearing loss. Treatment of significant
One limitation of newborn screening is that some forms SNHL may require the use of assistive hearing devices
of early-onset hearing loss are not apparent at birth. To such as hearing aids from as early as 3 months of age. The
address this issue, the Joint Committee on Infant Hearing development of cochlear implants has rapidly reshaped
in the United States has identified 10 risk indicators (Table the management of childhood hearing loss. Cochlear
12.3) that should prompt continued monitoring of hearing implantation may be considered for infants as young as
status even in the face of normal neonatal screens. 12 months of age who have a profound bilateral hearing
Treatment includes avoidance of known allergens, use onset of symptoms. A severe URI with fever and purulent
of topical cromolyn sodium and steroid sprays for rhinorrhea also meets the diagnostic criteria for acute
prevention, and antihistamines for relief of symptoms. The sinusitis. Chronic sinusitis is defined as either symptoms
use of oral decongestants is controversial. Topical of sinusitis lasting longer than 3 months, or a patient with
decongestants should also generally be discouraged as recurrent episodes of acute sinusitis. Nasal obstruction,
they cause rebound congestion (short-term) and chemical halitosis, and headache may all be additional features of
rhinitis or rhinitis medicamentosa (long-term). Immuno chronic rhinosinusitis. Imaging should not be used for the
therapy may be beneficial for refractory cases, but its routine diagnosis of sinusitis and should be reserved for
application is now less frequent owing to the success of cases with complications and those being considered for
steroid sprays. surgery. CT scan has been proven to be far superior to
plain X-rays in the imaging of the paranasal sinuses.
Viral Rhinitis Allergic fungal sinusitis is an increasingly recognized
Viral rhinitis or "the common cold," is the most common condition in atopic, immunocompetent patients. Older
cause of both nasal obstruction and rhinorrhea in children. children and adolescents are typically affected. The cause
Children average between six and eight of these upper is hypersensitivity to fungal antigens. This results in a form
respiratory infections per year. Parents often need of chronic rhinosinusitis that is difficult to manage
reassurance that such frequent colds are not abnormal, medically and usually requires surgical intervention.
provided their child has an otherwise normal growth Complications of rhinosinusitis include orbital or intra
pattern. Malaise, low to moderate grade fever, nasal cranial spread of infection. Orbital complications typically
congestion, and rhinorrhea are the presenting symptoms. result from direct extension from an ethmoid sinusitis.
A number of different viruses may be responsible, includ Early orbital complications manifest as periorbital
ing rhinovirus and adenovirus. Treatment is symptomatic (preseptal) cellulitis, while more severe complications
and requires paracetamol and a judicious use of oral include orbital abscess or cavernous sinus thrombosis.
decongestants. Antihistamines are contraindicated. Otitis Ophthalmoplegia, loss of vision and severe toxemia
media and sinusitis are frequent complications. indicate a potentially life-threatening spread of infection
to the cavernous sinus. Intracranial complications such
as meningitis and abscesses may also occur and are more
SINUSITIS
commonly associated with infections of the frontal and
Sinusitis can be classified as either acute or chronic sphenoid sinuses.
sinusitis. The ethmoid and maxillary sinuses are the
earliest to develop and are the ones most commonly Treatment
involved by sinusitis in infancy and early childhood. The
Although a significant number of acute sinusitis episodes
frontal sinuses may become involved only after 5-6 years
will resolve spontaneously, most authors recommend
of life. Isolated sphenoid disease is rare, but can behave
antibiotics as the cornerstone of treatment. As in acute
as a distinct clinical entity from other types of sinusitis.
otitis media, amoxicillin should be the first-line of medical
The ethmoids are now recognized to be the primary site
therapy for acute sinusitis. The exact duration of therapy
of origin of inflammation in most cases of sinusitis.
is not clear, but most clinicians feel that if symptoms have
Risk factors associated with sinusitis include recurrent
already persisted for 7-10 days, the infection should be
upper respiratory infections (URI), allergic rhinitis, cystic
treated for at least 14 days. Longer courses and second-
fibrosis, immunodeficiency, ciliary dyskinesia, daycare
line antibiotic agents are indicated for refractory infections,
attendance, and exposure to tobacco smoke. The most
and parental antibiotics are the agents of choice for
significant factor is the presence of a URI, as 5-10% of
sinusitis with orbital or intracranial complications. Other
these are complicated by sinusitis. A sinus infection should
be considered in any child whose cold symptoms have adjuvant measures that may have a possible benefit
not resolved by 7-10 days. include oral decongestants, mucolytic agents, and topical
nasal saline. Topical decongestants may be used in sinu
Etiology sitis with complications. Antihistamines are detrimental
due to their drying effect on mucosal secretions and are
The most common isolates in acute sinus infections are
S. pneumoniae, H. influenzae and M. cntarrhnlis. These same best avoided.
bacteria are implicated in chronic sinusitis, as are S. aureus, Antibiotics are also the mainstay of treatment for
anaerobes and occasionally fungi. The adenoid pad plays chronic sinusitis. As most of these patients have already
an important role in the pathophysiology of sinusitis, as failed a course of standard-dose amoxicillin, initial therapy
several studies have demonstrated its role as a bacterial may consist of amoxicillin/clavulanate, high-dose
reservoir for the paranasal sinuses. amoxicillin, or cefuroxime. The duration of treatment is
longer than for acute sinusitis, typically 3 to 6 weeks.
Diagnosis Patients who have a true penicillin allergy may be treated
Acute rhinosinusitis typically presents as a URI with with a macrolide antibiotic, although there is increasing
worsening of nasal discharge and cough 7 to 10 days after resistance of sinus pathogens to these drugs. Topical nasal
336 Essential Pediatrics
steroids may also play a role in the treatment of chronic operation to correct a limited portion of the septum may
sinusitis. be justified in a particularly symptomatic child. Turbinate
Surgical intervention for acute sinusitis is limited to hypertrophy usually responds to treatment of allergy,
those with orbital or intracranial complications. Surgery though in refractory cases electrocautery may be used for
may also be considered for patients with chronic sinusitis reduction of turbinate size.
who have not responded to aggressive medical manage
ment. First-line surgical therapy usually consists of EPISTAXIS
adenoidectomy to remove the adenoid pad as a bacterial
Bleeding from the nose occurs frequently in children, most
reservoir for the sinuses. Significant controversy exists
ofen from the anterior portion of the nasal septum at a
regarding the indications for endoscopic sinus surgery
confluence of arterial vessels known as Little's area (or
(ESS) in pediatric patients. Selected circumstances in
Kiesselbach's plexus). Local trauma, especially nose-
which ESS may be of benefit include patients with
picking, is the most common cause of epistaxis in children.
sinonasal polyposis, cystic fibrosis, or those whose
Reduced ambient humidity, as seen during the winter
symptoms have not responded to adenoidectomy.
months in some climates, also places the patient at risk.
Examination reveals prominent vessels in Little's area that
NASAL OBSTRUCTION
bleed promptly when touched with a cotton-tipped probe.
Causes Digital pressure by pinching the nose invariably stops the
Chronic mouth breathing in children, is generally caused bleeding. Avoidance of nose picking, application of an
by blockage of nasal airflow. The site of nasal blockage is antibiotic ointment for lubrication, and, for refractory
more often in the nasopharyngeal area due to adenoid cases, cauterization with topical silver nitrate or electro
hypertrophy, than in the nose itself. Intranasal causes of cautery are curative. Bleeding disorders must be suspected
obstruction include allergic rhinitis, recurrent sinusitis, in children with a suggestive family history, a history of
nasal septum deviation, turbinate hypertrophy, nasal frequent bleeding from other sites, or any nasal bleeding
polyps, and less commonly, neoplasms. As a rule, bilateral which does not respond in the usual fashion.
nasal polyps do not occur in normal children and their Less frequent causes of recurrent epistaxis include
presence should prompt testing for cystic fibrosis. nasopharyngeal angiofibroma and hereditary hemor
Congenital causes of nasal airway obstruction include rhagic telangiectasia (HHT). Nasopharyngeal angio
choanal atresia, dermoid cysts, teratomas, encephaloceles, fibroma is a tumor occurring exclusively in adolescent
and pyriform aperture (bony opening to the nasal cavity males that can cause profuse, brisk bleeding. HHT, also
in the skull) stenosis. known as Osler-Weber-Rendu syndrome, is a genetic
defect in blood vessel structure resulting in arteriovenous
Diagnosis malformations. Patients may suffer from severe, recurrent
Adenoid enlargement should be suspected in children, epistaxis, as well as gastrointestinal bleeds and pulmonary
usually older than 2 years, who present with nasal hemorrhage.
blockage, mouth breathing, sleep disturbance and chronic
CHOANAL ATRESIA
nasal discharge. Examination must rule out nasal
pathology such as septal deviation or polyposis. Neonates Congenital failure of the nasal cavities to open posteriorly
with pyriform aperture stenosis may present with a single into the nasopharynx (choanae) is called choanal atresia.
midline maxillary incisor. CT scan confirms the diagnosis. It is caused by failure of resorption of the buccopharyngeal
membrane during embryonic development. This process
Treatment
may be unilateral or bilateral. Bilateral choanal atresia
Adenoidectomy is recommended for symptomatic usually presents immediately after birth with respiratory
younger children. In older children, it is useful to distress, which is due to the fact that neonates are obligate
remember that pubertal growth of the midface and nose-breathers. The affected baby cycles between spells
regression of adenoid size tends to result in relief of of cyanosis and crying. Attempts at suckling immediately
adenoid-related nasal obstruction from around the age of precipitate cyanosis.
9 years. Pyriform aperture stenosis is treated with surgical Bilateral choanal atresia requires urgent management.
drilling of the bony pyriform aperture. Treatment for The airway may be established immediately by inserting
sinonasal polyposis includes topical and systemic steroids a finger in the baby's mouth; this can be replaced with a
for limited disease. Larger, obstructing polyps usually plastic oropharyngeal airway or a McGovern nipple.
require surgical intervention. Failure of these measures to secure a satisfactory airway
Generally speaking, surgery on the nasal septum may necessitate endotracheal intubation or tracheostomy.
should be avoided in prepubertal children, as it may lead Flexible nasal endoscopy confirms the diagnosis. When
to retardation in midface growth and saddling of the nasal endoscopy is not available, attempts to pass an 8 French
dorsum. However, on rare occasions, a very conservative catheter can aid in diagnosis. Dye or contrast studies are
Diseases of Ear, Nose and Throat 337
pauses, breathholding, or gasping during sleep, as well Table 12.4: Supraglottic vs. tracheal obstruction
as enuresis. Daytime manifestations include morning
Supraglottic obstruction
headache, halitosis and, most importantly, behavioral and
Inspiratory stridor
neurocognitive disorders. Physical examination often
Weak cry/voice
reveals audible breathing with open mouth posture,
Dyspnea is generally mild
hyponasal speech, drooling, and tonsillar hyperplasia. A Less pronounced cough
strong clinical picture may be enough to establish the
Tracheal obstruction
diagnosis, but polysomnography (sleep study) remains the
gold standard for objective correlation of ventilatory Biphasic or expiratory stridor
abnormalities with obstructive symptoms. Normal cry/voice
May have severe dyspnea
Treatment Deep barking, brassy cough
Adenotonsillectomy is generally considered first-line
therapy in most children with OSA. Improvement
following adenotonsillectomy has been demonstrated in endoscopy is generally needed to confirm the clinician's
children with preoperative enuresis and behavioral issues. diagnostic impressions.
Postoperative improvement can also be seen on poly There are a variety of different processes that can cause
somnography. In neonates in whom congenital nasal airway obstruction in children. These can be roughly
masses may be responsible for their OSA, removal of the divided into infectious, congenital, neoplastic, and
mass is curative. Rarely, in the most severe and refractory miscellaneous causes.
cases of OSA, tracheostomy may be considered.
Infections
Suggested reading Croup (laryngotracheobronchitis) is a viral infection of the
1. Darrow DH. Surgery for pediatric sleep apnea. Otolaryngol Clin upper respiratory tract and often presents in children 1-5
N Am 2007; 40: 855-875. years of age with biphasic stridor, brassy or "barking"
2. Johnson RF, Stewart MG. The contemporary approach to diagnosis cough, and low-grade fever. Onset of symptoms is usually
and management of peritonsillar abscess. Curr Opin Otolaryngol
over several days. Chest X-ray reveals a characteristic
Head Neck Surg 2005; 13: 157-160.
3. Mueller DT, Callanan VP. Congenital malformations of the oral narrowing of the subglottic region known as the "steeple
cavity. Otolaryngol Clin N Am 2007; 40: 141-160. sign" (Fig. 12.6).
4. Tewfik TL, Al Garni M. Tonsillopharyngitis: clinical highlights. Most cases of croup are mild and resolve within 1 to 2
J Otolaryngol 2005; 34 Suppl 1: S45-9. days. Conservative management should include reas
surance and oral hydration. Children with stridor at rest
should be hospitalized for close observation and supple
DISEASES OF THE LARYNX AND TRACHEA mental oxygen. Steroids are helpful in moderate to severe
cases. Antibiotics may be indicated if the child fails to
improve or if purulent secretions are present. Coverage
THE STRIDOROUS CHILD should be directed towards Staphylococcus and H.
influenzae.
The term stridor refers to the physical finding of excessively
noisy breathing and is generally due to upper airway
obstruction. The relationship of stridor to the respiratory
cycle often provides a clue to its etiology: inspiratory stridor
suggests obstruction above the vocal cords (supraglottis),
while expiratory stridor usually originates from the distal
trachea. Biphasic (inspiratory and expiratory) stridor
usually originates from a subglottic or proximal tracheal
lesion. Most stridor in children originates from supra-
glottic lesions. Table 12.4 lists the differences between
stridor due to supraglottic and tracheal obstruction.
Evaluation of the stridorous child should include a
thorough history that is frequently diagnostic. Physical
findings associated with stridor include nasal flaring and
suprasternal or intercostal retractions. Radiographs such
as chest X-rays or lateral neck films may confirm a
diagnosis such as retropharyngeal abscess, epiglottitis, or
croup. Barium esophagram may rule out extrinsic
compression by a vascular anomaly. Flexible and rigid Fig. 12.6: Larynsotracheobronchitis (croup). 'Steeple sisn’
340 Essential Pediatrics
Iatrogenic Causes of Stridor occur months after the initial surgery. Preventive
Acquired subglottic stenosis is the most common cause of management is imperative in the child with tracheostomy
acquired stridor in children. It most often results from and includes adequate tube cleaning, humidification, and
long-term endotracheal intubation and resulting scar thorough instructions to home care providers. Long-term
formation. Treatment varies by the severity of the lesion. tracheostomy in children may also affect speech and
Minor stenoses may be observed, while more severe language development.
stenoses may be treated by a variety of surgical methods
including tracheostomy, widening of the stenosis with HOARSENESS
cartilage grafts, and excision of the stenotic segment.
The differential diagnosis for hoarseness is quite long and
Laryngeal granuloma may also result from prolonged can be divided into congenital, neurogenic, neoplastic,
intubation. Endoscopy reveals a granuloma that is typi inflammatory, and traumatic causes. The more common
cally found on the vocal cord. These are often amenable entities among these categories have been previously
to endoscopic removal. discussed in the context of stridor; however, several
additional disorders bear mention.
Neoplasms
Vocal nodules are the most common cause of hoarseness
Recurrent respiratory papilloma (RRP) is the most common
in children, and are generally caused by vocal abuse. The
benign tumor of the larynx and presents with symptoms
severity of hoarseness fluctuates, worsening with vocal
related to gradual airway obstruction. Endoscopy reveals
abuse and improving with rest. They are seen more
single or multiple irregular, wart-like masses in the larynx
frequently in habitually shouting or screaming children.
or pharynx. RRP is caused by human papillomavirus
Endoscopy reveals small, bilateral, opposing nodules,
(HPV) types 6 and 11, which also cause genital condyloma
usually at the junction of the anterior and middle thirds
in adults. Transmission is believed to be from the passage
of the vocal cord. Speech therapy is usually effective in
of the fetus through an infected birth canal. Treatment is
older children. Surgery is rarely indicated.
with CO, laser ablation or microdebrider excision of the
papillomas. Adjunctive therapies include alpha-interferon Reflux laryngitis may result from gastric secretions spilling
and intralesional cidofovir, a potent antiviral agent. onto the larynx. Reflux has been implicated in numerous
Multiple surgical procedures are usually necessary as the conditions, including laryngitis, subglottic stenosis,
disease has a propensity to recur. Tracheostomy is to be chronic sinusitis and otitis media with effusion. Diagnosis
avoided if possible, as it may potentiate spread of the virus is established with 24 hour pH monitoring. Medical
into the distal airway. The clinical course is highly management is usually effective, though surgical fundo-
unpredictable, and death may occur in some children due plication may be needed in severe cases.
to distal tracheobronchial spread and pulmonary
Hypothyroid myxedema may occasionally cause an increase
involvement. The recent development of vaccines against
in vocal fold edema and present as hoarseness or stridor.
HPV holds promise for prevention of this disease.
Thyroid function tests should be measured in the hoarse
Foreign Body child with a clinical history suggestive of hypothyroidism.
Foreign body aspiration should always be considered as Laryngotracheal cleft (LTC) is a rare congenital defect in
a potential cause of stridor and airway obstruction in the posterior cricoid cartilage of the larynx. In its mildest
children. Foreign bodies aspirated most commonly in form, children experience feeding difficulty, recurrent
children are food and coins. Young age is the greatest risk respiratory tract infection, or hoarseness. In its more severe
factor for injury or death from a foreign body in the forms, the cleft may extend interiorly between the entire
aerodigestive tract. Conforming objects such as balloons trachea and esophagus. Severe clefts usually cause
pose the greatest risk of choking death, followed by round significant aspiration pneumonias, and are often not
nonfood objects such as balls or marbles. After establishing compatible with life. LTC may be associated with
airway security, treatment consists of endoscopic hereditary conditions such as Opitz-Frias or Pallister-Hall
visualization and removal by an experienced surgeon. syndromes. Management of symptomatic clefts is surgical.
5. McMurray JS. Disorders of phonation in children. Pediatr Clin Hemangiomas are benign vascular lesions that represent
North Am 2003; 50(2): 363-80. the most common benign tumor of infancy. They typically
6. Rafei K, Lichenstein R. Airway infectious disease emergencies.
present at birth, rapidly proliferate during the first year
Pediatr Clin North Am 2006; 53(2): 215-42.
7. Stamataki S, et al. Juvenile recurrent respiratory papillomatosis: of life, and then slowly involute over the first decade of
Still a mystery disease with difficult management. Head Neck 2007; the child's life. Since up to 70% of these lesions completely
29: 155-62. resolve by age 7, the usual treatment is observation.
Indications for surgery include functional impairment and
bleeding. Surgery may also be useful when cosmetic
NECK MASSES deformities remain after involution. Stridor in a patient
with a head and neck hemangioma should prompt
Neck masses in pediatric patients are quite common. The consideration of a subglottic hemangioma.
etiology can usually be assigned to one of three categories: Less common congenital neck masses include teratomas,
congenital, inflammatory or neoplastic. Although dermoid cysts and thymic cysts.
malignancy is not as common as in adults presenting with
neck masses, the possibility of a malignancy should always INFLAMMATORY NECK MASSES
remain in the differential diagnosis.
Cervical lymphadenopathy from an infective process is by
far the most common neck mass in children. The etiology
CONGENITAL NECK MASSES
may be either viral or bacterial, and an upper respiratory
Branchial cleft cysts are relatively common and may infection is often the cause. Infected lymph nodes are
comprise up to one-third of all congenital neck masses. characteristically tender on physical exam. Lymph nodes
Branchial cleft cysts are named according to the infected with S. aureus or S. pyogenes may suppurate and
associated branchial cleft or pouch (e.g. first, second or form an abscess. Incision and drainage and antibiotics are
third branchial cleft cysts). Second branchial cleft cysts indicated in these cases. If an abscess is not present,
are the most common, and typically present as a lateral management is observation to ensure resolution of the
neck mass just anterior to the sternocleidomastoid adenopathy.
muscle. Imaging with ultrasound or CT scan reveals the
cystic nature of the mass. Treatment is surgical excision. Cat-Scratch disease is caused by the bacteria Bartonella
If possible, infected cysts should be managed with henslae. Lymphadenopathy is a prerequisite for diagnosis,
antibiotics prior to excision. and the head and neck are involved in about one-fourth
of cases. Patients may have mild fever or malaise, and
Thyroglossal duct cysts present as a midline neck mass in there is usually a history of feline contact with or without
the region of the hyoid bone. Together with branchial cleft scratches. Diagnosis is confirmed by serologic testing for
cysts, they comprise over half of congenital neck masses. antibodies against Bartonella. Treatment is with a macro-
They form as a remnant of the thyroid descent tract from lide or aminoglycoside antibiotic. Surgical treatment is
the tongue base into the lower neck, where some tissue rarely necessary.
may also persist as a pyramidal lobe of the thyroid. Most
thyroglossal duct cysts are in the midline, but they can Mycobacterial cervical adenitis is not infrequently seen in
children. It should be suspected when patients fail stand
occasionally present laterally. The cyst will often move
upon tongue protrusion by the patient, due to its origin ard antibiotic therapy. The etiologic agent is usually an
atypical (non-tuberculous) mycobacterium. On physical
from the tongue base. Occasionally this may represent the
exam, the skin overlying the adenopathy may show
patient's only functioning thyroid tissue, and preoperative
imaging of the thyroid is recommended. Treatment is with discoloration. Skin testing can aid in diagnosis. Treatment
includes either complete surgical excision of the involved
the Sistrunk operation, where the cyst is removed along
with the central portion of the hyoid bone. Removing the nodes, or incision and curettage. Anti-mycobacterial
therapy is necessary in some cases .
cyst alone without the hyoid bone leads to high rates of
cyst recurrence. Less frequent etiologies of inflammatory neck masses
include tularemia, brucellosis, Kawasaki disease and
Lymphangiomas, formerly termed cystic hygromas, are sarcoidosis.
congenital malformations of lymph tissue. They present
as a slow growing, painless, compressible mass that can NEOPLASMS
be transilluminated on physical exam. They may become
quite large causing significant functional deficits, airway Lymphomas are the most common pediatric head and neck
compromise, and cosmetic deformity. CT or MRI should malignancy. They may be divided into two histologic
be obtained to assess the extent of the lesion. Treatment is categories, Hodgkin's and non-Hodgkin's.
with surgical excision, although injection of sclerosing The most common clinical presentation is asympto
agents has been reported with some success. matic, unilateral lymphadenopathy. Fever, weight loss,
Diseases of Ear, Nose and Throat 343
and night sweats are usually not seen until late in the Patients generally present with painful parotid enlarge
course of disease. After diagnosis is established by biopsy, ment and fever. They may also present with an acute
treatment is with chemotherapy or radiation therapy. unilateral hearing loss or vestibular weakness. Systemic
manifestations such as meningoencephalitis, pancreatitis,
Rhabdomyosarcoma is the most common soft-tissue
and orchitis may also be present. The incidence of mumps
sarcoma, and the second most common head and neck
has decreased following use of the vaccine.
malignancy in children. Commonly involved sites include
the orbit, nasopharynx, and temporal bone. Treatment Tuberculosis is the most common granulomatous inflam
involves a combination of surgery, chemotherapy and mation of the parotid. It may be limited to the salivary
radiation. glands without lung involvement. Treatment is with
antituberculous drugs. Sarcoidosis may also present with
Thyroid carcinoma is the third most common neck
unilateral or bilateral parotid swelling. It is usually seen
malignancy in children. Previous exposure to ionizing
in association with systemic symptoms and peripheral
radiation is a critically important risk factor. The most
adenopathy. A variety of laboratory tests and radiological
common histologic type is papillary thyroid carcinoma.
studies including chest radiograph support the diagnosis.
Children with thyroid cancer typically present with more
Steroids are of value in treating sarcoid-associated
advanced disease than do adults. Nonetheless, with
xerostomia.
appropriate management, the prognosis is excellent.
More rare malignancies that should remain in the Human Immunodeficiency Virus (HIV) involvement of the
differential diagnosis of a pediatric neck mass include parotid glands is common. HIV-associated salivary gland
salivary gland malignancies, nasopharyngeal carcinoma, disease usually appears as bilateral intraglandular cysts,
and neuroblastoma. although it may be unilateral clinically. Management
usually consists of observation, as the cysts invariably
Suggested reading recur after aspiration. Occasionally, surgery may be
1. Bauer PW, Lusk RP. Neck masses. In: Bluestone CD and Stool SE. indicated for cosmesis alone, as parotid enlargement may
Pediat Otolaryngology, 4th ed. Philadelphia: Saunders, 2003:1629- be severe enough to cause facial disfigurement.
1647.
2. MacArthur CJ. Head and neck hemangiomas of infancy. Curr Opin
Otolaryngol Head Neck Surg 2006; 14: 397-405. Primary Non-neoplastic Diseases
3. Tracy TF Jr, Muratore CS. Management of common head and neck Sialectasis presents as recurrent episodes of painful
masses. Semin Pediatr Surg 2007; 16: 3-13.
unilateral or bilateral parotid swelling associated with
systemic signs and symptoms of infection. Episodes
typically resolve promptly with antibiotic therapy. Onset
DISEASES OF THE SALIVARY GLANDS may be within the first few years of life, and episodes of
recurrent infection tend to remit spontaneously around
Clinical Anatomy puberty. The exact etiology is unknown.
The major salivary glands consist of three paired Acute unilateral pain and swelling of the parotid or
structures: the parotid glands, the submandibular glands submandibular gland with eating may be due to ductal
and the sublingual glands. In addition, there are numerous stricture or to sialolithiasis (stones in the salivary ducts).
minor salivary glands located submucosally throughout While stricture affects both parotid and submandibular
the oral cavity and pharynx. With the exception of viral glands, salivary gland calculi are found far more often in
parotitis, most salivary gland disease is more common in the submandibular glands. Both stricture and sialolithiasis
adults than children. However, there are certain neo are treated most commonly by surgery. However, salivary
plastic, non-neoplastic, and systemic disorders of the gland lithotripsy has also described recently and may
salivary glands that are relevant to pediatric practice. prove to be of value in the future.
Most cysts of the salivary glands are in the parotid and
Infections may be congenital, post-traumatic, neoplastic or infectious.
Bacterial parotid sialoadenitis is frequent in small children A congenital parotid cyst is most likely to be a first
and presents with painful unilateral parotid swelling. branchial arch derivative; this may present as a recurrent,
Purulent material may be expressed from the parotid duct acutely infected, fluctuant mass that may spontaneously
intraorally with parotid massage. The condition is usually rupture and drain. The etiology of a post-traumatic cyst
caused by dehydration, which leads to staphylococcal is suggested by history. A slow, progressive, unilateral
overgrowth in the duct system. Treatment includes oral cyst should be aspirated for cytology to rule out
antibiotics as well as hydration, sialogogues, massage and malignancy. HIV positive status should be suspected for
warm compresses. polycystic changes in the parotids (see above).
Viral parotitis is caused most often by the mumps virus, Mucous retention cysts are derived from minor salivary
although other viruses may mimic its presentation. glands and are found on the lips or mucous membranes.
344 Essential Pediatrics
They usually appear as bluish masses up to 2 centimeters recommended treatment, though complete excision may
in size and are treated surgically. not always be possible.
from the region of oropharynx. On the other hand wheeze • Tropical eosinophilia: This is more frequent in adults
is a high pitched, less intense sound originating from lower than in children. It is an unusual form of infection with
airway obstruction. Various sounds are described in Table filariasis, e.g. Dirofilaria imitis, W. bancrofti, B. malayi.
13.1. Clinical features simulate chronic recurrent asthma.
X-ray films of the lungs show fine infiltration with
Table 13.1: Respiratory sounds snowflake like appearance. This should be distin
Sound Causes Character guished from miliary tuberculosis. The leucocyte
Snoring Oropharyngeal Inspiratory, count shows eosinophilia. Absolute eosinophil count
obstruction low pitched irregular may be more than 1500/mm3. The patients are treated
with diethylcarbamazine (10 mg/kg) in 3 divided
Grunting By partial closure Expiratory, occurs in
doses orally for 2 to 3 weeks. Two or three spaced
of glottis hyaline membrane
disease courses may be required.
Rattling Secretions in Inspiratory, coarse. • Loeffler's syndrome: The pulmonary phase of
trachea/bronchi This sound can also be migration of ascaris larvae may cause wheezing,
felt by placing hands pulmonary problems and eosinophilia in the blood.
over the chest These features are characteristically transient. Visceral
Stridor Obstruction Inspiratory sound, larva migrans due to larval form of toxocara infection
larynx/trachea may be associated do not usually involve the lungs.
with an expiratory
component • Hypersensitivity pneumonitis.
Wheeze Lower airway Continuous musical
Rare Causes
obstruction sound predominantly
expiratory in nature • Inhaled foreign bodies cause unilateral localized
wheeze which begin suddenly. Wheezing tends to be
Rattling continuous and becomes worse with crying, during
excitement and with cold.
Rattling is due to excessive secretions in the pharynx or
• Pressure from enlarged mediastinal nodes.
tracheobronchial tree during breathing. It is present in
• Pressure from anomalous left pulmonary artery com
asthma, bronchitis and tracheobronchial stenosis. Inhala
pressing the right main bronchus.
tion of gastrointestinal content into the tracheobronchial
• Cystic fibrosis. Recurrent wheezing, productive cough
tree can also result in rattling. Some normal infants may
and malabsorption are the usual features.
have transient rattling but prolonged rattling is always
• Pulmonary hemosiderosis.
pathological.
• Tuberculous lymph glands producing compression of
Wheezing airways.
• Mediastinal cysts and tumors causing narrowing of
Wheezing refers to high pitched whistling sounds audible
airways due to external compression.
without auscultation by the stethoscope. Wheezing causes
considerable anxiety to the parents. Partial obstruction of Stridor
the bronchi and bronchioles leading to narrowing
Stridor indicates upper respiratory obstruction and is
produces wheezing. Sufficient air must flow through the
usually accompanied by hoarseness, brassy cough,
narrowed airway to produce the wheezing sound. This
dyspnea, retraction of the chest during inspiration and
may be due to causes within the lumen or in the walls of
restlessness. Accessory muscles of respiration are usually
the bronchi. Pressure from outside the bronchi may also
working.
be responsible in some cases.
Stridor is frequently seen in infants and is often attri
Common Causes buted to (i) small size of the larynx, (ii) loose submucous
• Wheeze associated lower respiratory tract infection connective tissue around the glottic region, and (iii) rigid
(WALRI) All that wheezes is not asthma. Wheezing cricoid cartilage encircling the subglottic zone.
is most often due to heightened sensitivity of the
respiratory tract. Infections of the lower respiratory Acute Stridor
passages may cause bronchospasm in these patients. Acute upper airway obstruction occurring in the region
Attacks of wheezing are always preceded by a cold or of glottis, which is produced by inflammation and edema,
acute respiratory disease. These are most frequent may be life threatening. The obstruction may either be
between 3 to 8 years of age and become less frequent supraglottic as in case of epiglottitis or may be subglottic,
thereafter. These attacks are relieved by simple e.g. in infectious croup, which can be differentiated (Table
antispasmodic drugs. 13.2).
• Bronchiolitis A detailed discussion on acute and chronic stridor is
• Bronchial asthma given in Chapter 12.
348 Essential Pediatrics
Table 13.2: Distinguishing between stridor due to cell type and infective etiology of lower respiratory tract.
supraglottic and tracheal obstruction Rigid bronchoscopy can be used in place of fiberoptic
bronchoscopy; the procedure requires general anesthesia.
Clinical Supraglottic Tracheal
This is commonly used for removal of foreign bodies from
features obstruction obstruction
airways.
Stridor Inspiratory and Usually expiratory
often less serious and more serious Pulmonary Function Tests
Cry Muffled Normal
Pulmonary function tests are important tools for
Dyspnea Less severe More marked
monitoring of a patient with chronic respiratory illness.
Cough Less marked Deep barking or
Flow rates and lung volumes are measured. The procedure
brassy
requires cooperation of the patient. They can be measured
in children above the age of 5-7 years. Commonly used
Dyspnea parameters include: forced expiratory volume in first
Tachypnea means abnormally rapid respiration. Dyspnea second (FEV1), forced vital capacity (FVC), mid expiratory
means labored or difficult breathing, usually accompanied flow rate (FEF25-75) and ratio of FEV1/FVC. Normal
by pain and air hunger. FEV1/FVC ratio is between 0.8-1.0. In obstructive diseases
(asthma) the ratio is reduced. In restrictive lung diseases
Causes of Dyspnea (interstitial lung disease) the ratio of FEV1/FVC is normal
Respiratory system but FVC is reduced below 80% of predicted.
• Newborn: Respiratory distress syndrome, hypoplastic
Blood Gas Analysis
lung, diaphragmatic hernia and eventration, meconium
aspiration. Estimation of partial pressures of oxygen and carbon
• Infants and childhood: Pneumonia, bronchiolitis, dioxide in blood along with blood pH gives fair idea about
bronchial asthma, aspiration, pneumothorax, pleural the pulmonary functions. Arterial blood gas analysis is
effusion, collapse, obstructive emphysema, smoke used for making a diagnosis of respiratory failure as well
inhalation. as monitoring of a child with acute and chronic respiratory
failure. Partial pressures of oxygen less than 60 and of
Cardiovascular system
carbon dioxide more than 50 mm of Hg suggest acute
Congenital heart disease, myocarditis, pulmonary edema,
pericarditis. respiratory failure.
Miscellaneous Imaging
Guillian Barre syndrome, myasthenia gravis, neuro X-ray film and newer imaging like computerized
muscular disease, obesity, painful breathing (fractured tomography are non invasive diagnostic methods. X-ray
ribs, pleuritis), acidosis (diabetes, uremia, salicylate toxi
films help in diagnosis of soft tissue and bony abnor
city), anemia.
malities. This is most commonly used modality for making
a diagnosis of pulmonary infection. A particular pattern
Suggested reading
of pneumonia may suggest the etiological agent of
1. Kabra SK. History taking and physical examination In; Essential
pneumonia. Lobar consolidation suggest infection due to
Pediatric Pulmonology, Kabra SK, Lodha R (Eds). Nobel Vision,
New Delhi 2006;1-10. Streptococcus pneumoniae while evidence of hilar or
2. Phelan PD, Olinksy A, Robertson CF: Rattling and its clinical mediastinal adenopathy suggest a possibility of tubercular
significance. In. Respiratory Illness in Children. London. Blackwell infection. Computerized tomographic scans are used for
Scientific publications, 1994:109-110. visualization of lymph nodes, tumors, bronchiectasis and
pleural pathologies.
INVESTIGATIONS FOR DIAGNOSIS
OF RESPIRATORY ILLNESSES Sweat Chloride Test
Various investigations required for diagnosis of respi Sweat chloride is estimated by quantitative pilocarpine
ratory illness in children include: imaging, microbiological iontophoresis. Chloride in sweat is increased in children
tests, bronchoscopy, pulmonary function test, arterial suffering from cystic fibrosis. In normal children sweat
blood gas analysis and sweat chloride estimation, etc. chloride values are less than 40 mEq/1. In children with
cystic fibrosis it is more than 60 mEq/1. A value of 40-60
Bronchoscopy mEq/1 is borderline and should be repeated.
Bronchoscopy can be of two types, fiberoptic and rigid. Suggested reading
Fiberoptic bronchoscopy is done under local anesthesia
1. Beydon N, Davis SD, Lombardi E, et al. An official American
and sedation. This is used for diagnosis of structural Thoracic Society/European Respiratory Society statement:
abnormality of airways, foreign body in respiratory tract pulmonary function testing in preschool children. Am J Respir Crit
and obtaining bronchoalveolar lavage samples to identify Care Med 2007;175: 1304-45.
Disorders of Respiratory System 349
2. Copley SJ. Application of computed tomography in childhood Snuffles: Clear mucoid discharge from the nose in the
respiratory infections. British Medical Bulletin 2002; 61:263-279. first few weeks of life is called snuffles. The cause is
3. Kabra SK, Kabra M, Gera S, Lodha R, Sridevi KN, Chacko S,
unknown. There is no evidence for allergy or infections.
Mathew J, Shastri S, Ghosh. M. An indigenously developed method
for sweat collection and estimation of chloride for diagnosis of "Snuffles" of congenital syphilis is severe rhinitis with
cystic fibrosis. Indian Pediatrics 2002; 39:1039-1043. bilateral serosanguineous discharge commonly excoria
4. Kabra SK, Lodha R. Investigations in Pulmonology. In Essential ting the upper lip and leaving fine scars. Nasal septum
Pediatric Pulmonology, New Delhi Nobel Vision, 2006;ll-30. may ulcerate leaving a flat nasal bridge.
5. LeGrys VA, Yankaskas JR, Quittell LM, Marshall BC, Mogayzel PJ
Jr;. Cystic Fibrosis Foundation. Diagnostic sweat testing: the Cystic Treatment
Fibrosis Foundation guidelines. J Pediatr 2007;151:85-9.
6. Midulla F, de Blic J, Barbato A, Bush A, Eber E, Kotecha S, Haxby To relieve nasal congestion: Babies sneeze and blow out
E, Moretti C, Pohunek P, Ratjen F: ERS Task Force. Flexible the nasal discharge, if their anterior nares are tickled by
endoscopy of paediatric airways. Eur Respir J 2003; 22: 698-708. the tip of a handkerchief. Nose drops of saline may give
symptomatic relief. Nasal decongestants (ephedrine,
COMMON COLD OR NASOPHARYNGITIS xylomatozoline) may cause rebound congestion. If conges
tion is severe then these should not be used for more than
Common cold is the most frequent medical problem in a few days. Oral nasal decongestants such as pseudo-
childhood and is usually due to infection of the upper ephedrine hydrochloride may be tried in resistant cases
respiratory tract with adenoviruses, influenza, rhinovirus, however routine use should be discouraged. Antihis-
parainfluenza or respiratory syncytial viruses. These are taminics are increasingly being used for allergic colds.
spread by droplet infection. Predisposing factors include Antihistaminics dry up the thin secretions and relieve
chilling, sudden exposure to cold air, and overcrowding. sneezing. Newer non sedating antiallergic drugs including
Rhinitis could also be due to allergy. loratidine and cetirizine may be useful in allergic rhinitis.
Terfenadine should not be prescribed in children because
Clinical Features of potential cardiac toxicity.
These include fever, thin nasal discharge and irritability. Fever is controlled by antipyretics such as paracetamol
Cervical lymph nodes may enlarge. Nasopharyngeal (acetaminophen).
congestion causes nasal obstruction and respiratory
Do not give cough syrups: If the cough is suppressed in
distress. The latter is more common in young infants.
infants and young children, mucoid secretions may be
Eustachian tube opening may be blocked leading to serous
retained in the bronchi and this may predispose to
otitis media and congestion of tympanic membrane. In
spasmodic cough wheezing, atelectasis and suppuration.
allergic rhinitis there is a clear mucoid discharge with
sneezing. There is no contact with an infected patient and Antibiotics are of little value in viral infections. These are
history of allergy is usually present. There is increasing used if the secretions become purulent, the fever continues
recognition of the role of upper respiratory infections in to rise and if the child develops bronchopneumonia. There
the etiopathogenesis of bronchial asthma. is no conclusive evidence that large doses of vitamin C
are helpful.
Narrowing of the airway and pharyngeal irritation
causes dry hacking cough. Excessive lacrimation is due Nursing: These children are best nursed prone (on their
to the blocked lacrimal ducts in the nose. Purulent belly) so that there is no postnasal drip causing irritation
discharge does not necessarily mean secondary infection of the throat. The children should be protected from
all the time as it can result from shedding of epithelial sudden exposure to chills and kept warm during the
and inflammatory cells resulting from viral infection itself. winter months.
The illness usually lasts for three days but cold may persist
ACUTE TONSILLOPHARYNGITIS
up to two weeks. Rhinitis and stuffy nose could become
chronic and last for several weeks. Sore throat is due to acute inflammation of the pharynx
and tonsils. Most often, it is associated with the viral
Complications infections of the upper respiratory tract such as adeno
Otitis media, laryngitis, sinusitis, bronchiolitis, exacer virus, influenza, para influenza virus, enterovirus and
bation of asthma and bronchopneumonia. Ebstain Barr virus. It may, however, be a prodrome of
measles and rubella or may be caused by Streptococcus
Differential Diagnosis pyogenes especially group A beta-hemolytic streptococci.
Mycoplasma pneumoniae and Candida albicans have also
Foreign body: Unilateral serosanguineous or purulent
been incriminated. Irritant fumes and smoke also cause
discharge from the nose indicates presence of foreign
irritation of the throat.
body.
syndromes due to viral or streptococcal infections. because swallowing is painful. Rest in bed accelerates
Hoarseness, cough and rhinitis are more common in viral recovery.
infection. In these, the onset is gradual and there is less
Specific: Antibiotics are not used for viral infections.
toxemia. In streptococcal infections, cervical lymph nodes
Infections with beta hemolytic streptococci are treated
are enlarged and illness is more acute with high fever,
with penicillin V orally, injections of procaine penicillin,
which typically lasts for 4-5 days.
oral erythromycin or oral amoxicillin in adequate doses
Tonsils become swollen and covered with exudates in
for at least 10 days. Parents are likely to stop medication
both types of infections. Younger children may not
after two to three days as the child begins to improve
complain of sore throat but often refuse to feed normally.
clinically. If compliance is a problem, single dose of
Complication benzathine penicillin by intramuscular route is preferred
treatment. Cotrimoxazole which is being commonly used
Acute glomerulonephritis, rheumatic fever, otitis media,
for sinusitis and otitis media is not an appropriate choice
sinusitis, peritonsillar and retropharyngeal abscesses. The
and should not be used for sore throat.
infection may spread down the tracheobronchial tree and
cause tracheobronchitis and pneumonia. Recurrent Attacks of Sore Throat
Table 13.3: Severity of acute laryngotracheobronchitis Atypical organisms: More and more evidence are avail
able to suggest important role of chlamydia spp and myco
plasma in community acquired pneumonia in adults and
children. Pneumocystis carinii: causes pneumonia in
immunocompromised children.
Clinical Features
The risk factors for pneumonia include low birth weight,
malnutrition, vitamin A deficiency, lack of breast-feeding,
passive smoking, large family size, family history of
bronchitis, advanced birth order, crowding, young age
and air pollution. Recent reviews suggest that indoor air
pollution is one of the major risk factor for acute lower
respiratory tract infection in children in developing
countries. Onset of pneumonia may be insidious starting
with upper respiratory tract infection or may be acute with
high fever, dyspnea and grunting respiration. Respiratory
rate is always increased.
Rarely, pneumonia may present with symptoms of
More recently inhalation of budesonide in doses of 1 mg
acute abdominal emergency. This is attributed to referred
twice a day for two days has shown good results.
pain from the pleura. Apical pneumonia may sometimes
Antibiotics do not have any role.
be associated with meningismus and convulsions. In these
Severe croup may need hospitalization, preferably in
patients the cerebrospinal fluid is always clear.
Pediatric Intensive care, with oxygen inhalation, steroids
On examination, there is flaring of alae nasi, retraction
(similar to moderate severity). Worsening distress may
of the lower chest and intercostal spaces. Signs of consoli
need short term ventilation. Antibiotics do not have any
dation are observed in lobar pneumonia.
role unless some bacterial infection is suspected.
1. Russell K, Wiebe N, Saenz A, Ausejo SM, Johnson D, Hartling L, Respiratory infection due to S. pneumoniae are transmitted
Klassen TP. Glucocorticoids for croup. Cochrane Database Syst Rev. by droplets and are more common in the winter months.
2004;(1):CD001955. Overcrowding and diminished host resistance predis
2. Knutson D, Aring A. Viral croup. Am Fam Physician 2004;69: 535- poses children to infection with pneumococci.
40.
Pathology: Bacteria multiply in the alveoli and an inflam
PNEUMONIA matory exudate is formed. Scattered areas of consolidation
occur, which coalesce around the bronchi and later become
Pneumonia may be classified anatomically as lobar or
lobular or lobar in distribution. There is no tissue necrosis.
lobular pneumonia, bronchopneumonia and interstitial
Pathological process passes from the stage of congestion
pneumonia.
to red and gray hepatization before the final stage of
Pathologically, there is a consolidation of alveoli or
resolution.
infiltration of the interstitial tissue with inflammatory cells
or both. Clinical features: Incubation period is 1 to 3 days. The
onset is abrupt with headache, chills, cough and high
Etiology fever. Cough is initially dry but may be associated with
Viral: Viral pneumonia caused by RSV, influenza, para thick rusty sputum. The latter is uncommon in children.
influenza or adenovirus may be responsible for about 40% Pleural pain is complained of and this may be referred to
of the cases. the shoulder or abdomen. Respiration is rapid. In severe
cases there may be grunting chest indrawing, difficulty
Bacterial: In over two-third of the cases, common bacteria
in feeding and cyanosis. Percussion note is impaired, air
cause pneumonia. In first 2 months the common agents
entry is diminished, crepitations and bronchial breathing
include klebsiella, E coli and staphylococci. Between 3
may be heard over areas of consolidation. Bronchophony
months to 3 years common bacteria include S. pneumoniae,
and whispering pectoriloquy may be observed. Menin
H. influenzae and staphylococci. After 3 years of age com
gismus may be present in apical pneumonia.
mon bacterial pathogens include S. pneumoniae and
staphylococci. Gram negative organisms cause pneumonia Diagnosis: The diagnosis is based on history, physical
in early infancy, severe malnutrition and immunocompro examination, X-ray findings of lobar consolidation (Fig.
mised children. 13.1) and leukocytosis. Bacteriological confirmation is
Disorders of Respiratory System 353
difficult but sputum may be examined by Gram staining Diagnosis: The diagnosis of staphylococcal pneumonia
and culture. Blood culture may be positive in 5-15% of is suspected in a newborn or an infant with respiratory
cases. Demonstration of polysaccharide antigen in urine infection who has evidence of staphylococcal infection
and blood are attractive investigations but do not have elsewhere in the body. The characteristic complications
sufficient sensitivity and specificity for confirming of pyo-pneumothorax and pericarditis in an infant are
pneumococcal pneumonia. highly suggestive of the diagnosis. Pneumatoceles are
present in X-ray films of the lung, characteristically in
Treatment: Penicillin G 50,000 units/kg/day is given pneumonia due to staphylococci and klebsiella. These
intravenously or intramuscular in divided doses for 5-7 pneumatoceles are present in X-ray films of the lung (Fig.
days. Procaine penicillin 600,000 units intramuscular per 13.2) characteristically in pneumonia due to staphylococci
day or Penicillin V may be used orally instead. Oxygen and klebsiella. These pneumatoceles persist as thin walled
should be given if cyanosis and respiratory distress are asymptomatic cysts for several weeks. Often staphylococci
present. Alternative may be amoxycillin or ampicillin In can be grown from the blood.
patients allergic to penicillin, the alternatives are chloram
phenicol or cephalosporins (Ceftrioxone/cefotaxime). The Treatment: The child should be immediately hospitalized
latter should be given with caution as cross sensitivity to and isolated to prevent the spread of resistant
penicillin may occur.
Staphylococcal Pneumonia
Staphylococcal pneumonia occurs in infancy and
childhood. The pulmonary lesion may be primary infec
tion of the parenchyma; or may be secondary to genera
lized staphylococcal septicemia. It may be a complication
of measles, influenza and cystic fibrosis of the lungs or
may follow minor staphylococcal pyoderma. Debilitating
conditions including malnutrition, diabetes mellitus,
macrophage dysfunction predispose the children to
infection with staphylococci.
staphylococci to the other patients. Fever is controlled with The child has moderate fever, dyspnea, grunting
antipyretics and hydration is maintained by intravenous respiration and retraction of the lower inter-costal spaces.
infusion of electrolyte solutions in 5% dextrose. Oxygen Presentation may mimic acute bronchiolitis. The course
is administered to relieve the dyspnea and cyanosis. is subacute and prolonged. Complications of Hemophilus
influenzae pneumonia include bacteremia, pericarditis,
Specific: Empyema is aspirated and the pus is sent for
empyema, meningitis and polyarthritis.
culture and tests for sensitivity to antibiotics. Vigorous
antibiotic therapy is carried out with penicillin G, erythro Treatment: H. influenzae pneumonia is best treated with
mycin, cloxacillin or cephalosporin. The latter are prefer ampicillin in a dose of 100 to 150 mg/kg/day and chloram
red for infections with beta lactamase producing phenicol 50 mg/kg/day in four divided doses. Cefotaxime
staphylococci. If the patient does not respond soon, van (100 mg/kg/day) or ceftrioxone (50-75 mg/kg/day) are
comycin or ticoplanin maybe introduced. Therapy should other alternative in seriously ill patients.
continue till all the evidence of the disease disappears both
clinically and radiologically, which usually takes two to Streptococcal Pneumonia
six weeks or even longer. After initial intravenous
Streptococcal infection of the lungs by group A beta
antibiotics remaining course may be completed with oral
hemolytic streptococci is usually secondary to measles,
antibiotics. Prolonged therapy is desirable as the bacteria
chicken pox, influenza or whooping cough.
persist in the necrotic area.
Clinical features: The onset is abrupt fever, chills,
Complications: Pneumatoceles do not require specific dyspnea, rapid respiration, blood streaked sputum, cough
measures. Intercostal decompression may be done for the and extreme prostration characterize the illness. Signs of
large pneumatoceles causing respiratory distress. bronchopneumonia are generally less pronounced, as the
Empyema and pyopneumothorax are treated by inter pathology is usually interstitial.
costal drainage under water seal or low pressure aspi
Complications: Thin serosanguineous or purulent
ration may be done. Metastatic abscesses require surgical
empyema is a usual complication. Pulmonary suppuration
drainage. Significant pleural thickening that is preventing
is less frequent. Ten percent of the patients have bactere
complete expansion of underlying lung may require
mia. When pneumatoceles are present, the condition
decortication. It can be done by open thoracotomy or by
mimics staphylococcal pneumonia.
thoracoscopic surgery. An early thoracoscopic drainage
of empyema may help in prevention of pleural thickening. Diagnosis: X-ray film shows interstitial pneumonia,
Instillation of streptokinase or urokinase in pleural cavity segmental involvement, diffuse peribronchial densities or
when pleural fluid is thin may also help in prevention of an effusion. (This should be distinguished from primary
pleural thickening. atypical pneumonia due to mycoplasma). Blood counts
show increased neutrophils, and the patient looks more
Hemophilus Pneumonia ill in streptococcal pneumonia.
Infections occur usually between the age of three months Treatment: Penicillin G should be given in doses of 50,000
and three years and are nearly always associated with to 100,000 units / kg of body weight, daily in divided doses
bacteremia. for 7-10 days. The response is gradual but recovery is
Infection with H. influenzae usually begins in the generally complete.
nasopharynx and spreads locally or through the blood Empyema is treated by closed drainage with indwelling
stream. Most nasopharyngeal infections are mild and intercostal tube.
confer immunity from subsequent serious illness after the
early months of life. As the infants have transplacentally Primary Atypical Pneumonia
transferred antibodies during the first 3 to 4 months of The etiological agent of primary atypical pneumonia is
life, infection with H. influenzae is relatively less frequent Mycoplasma pneumoniae. The disease is transmitted by
during this period. droplet infection. It occurs in epidemics chiefly in the
Pathology: Pathology is similar to that of infections with winter months. The children living in overcrowded
pneumococci. There is extensive destruction of bronchial environments are more prone to develop pneumonia. The
epithelium and hemorrhagic edema extending into disease is uncommon in children below the age of four
interstitial area. years, although subclinical and mild infections have been
reported in infants.
Clinical features: The onset of the illness is gradual with
nasopharyngeal infection. Certain viral infections as those Clinical features: Incubation period is 12 to 14 days. Onset
due to influenza virus probably act synergistically with may be insidious or abrupt. Initial symptoms are malaise,
H. influenzae. These alter the respiratory epithelial headache, fever, sore throat, myalgia and cough. Cough
resistance and therefore promote proliferation of the is dry at first but later it is associated with mucoid
bacteria in the damaged respiratory epithelium. expectoration which may be blood streaked. Dyspnea is
Disorders of Respiratory System 355
unusual. There are very few physical signs, except mild Hydrocarbon Pneumonia
pharyngeal congestion, cervical lymphadenopathy and a
Kerosene exerts its toxic effects on the lungs and the central
few crepitations. Extrapulmonary manifestations include:
nervous system. It is poorly absorbed from the gastro
hemolytic anemia. intestinal tract. Milk and alcohol promote its absorption.
X-ray: X-ray findings are more extensive than suggested It has low viscosity and less surface tension and therefore
by the physical findings. Poorly defined hazy or fluffy it diffuses quickly from the pharynx into the lungs.
exudates radiate from the hilar regions. Enlargement of Administration of oil apparently decreases the absorption
the hilar lymph nodes and pleural effusion have been from the gastrointestinal tract but it is not used as a
reported. Infiltrates involve one lobe, usually the lower. therapeutic measure. Clinical features of hydrocarbon
pneumonia include cough, dyspnea, high fever, vomiting,
Diagnosis: It is difficult to distinguish M. pneumonia from
drowsiness and coma. Physical signs in lungs are minimal.
viral or rickettsial pneumonia. The leukocyte count is
X-ray film of the chest shows ill defined homogeneous or
usually normal. Cold agglutinins are elevated. M. pneu
patchy opacities, resembling miliary mottling of the lungs.
moniae may be recovered from the pharynx and sputum.
The diagnosis is made rapidly by demonstration of IgM Treatment: Vomiting is not induced. Gastric lavage is
antibody by ELISA during the acute stage. IgG antibodies usually avoided to prevent inadvertent aspiration. The
are demonstrable by complement fixation after one week patient is kept on oxygen. Routine antibiotics are not
of illness and shows increase in titers over 2-4 weeks. indicated. Corticosteroids have little beneficial effect.
ACUTE RESPIRATORY TRACT INFECTION (ARI) in hospital and treated with IV chloramphenicol along
CONTROL PROGRAMME with supportive care (Table 13.4). Recent reports suggest
that common causative agents of pneumonia are getting
Acute lower respiratory tract infections (LRTI) are a
resistant to cotrimoxazole and chloramphenizol. In future
leading cause of mortality in children below 5 years of
these drugs may be replaced with amoxicillin and
age. It has been shown in various studies from developing
penicillins.
countries that the etiological agents in LRTI is bacterial in
50-60% of children. The common bacteria causing LRTI In children below 2 months of age, the presence of any
in preschool children include H. influenzae, S. pneumoniae of the following indicates severe disease: fever (38°C or
and staphylococci. All these are sensitive to antibacterials more), convulsions, abnormally sleepy or difficult to wake,
like cotrimoxazole. Hence judicious use of cotrimoxazole stridor in calm child, wheezing, not feeding, tachypnea,
in children suffering from LRTI may prevent deaths due chest indrawing, altered sensorium, central cyanosis
to pneumonia. The World Health Organization (WHO) grunting, apneic spells or distended abdomen. Such
has recommended certain clinical criteria for diagnosis of children should be referred to hospital for admission and
pneumonia in children at primary health care level for treated with injection ampicillin and gentamicin and
control of LRTI deaths in countries where the infant supportive care.
mortality is more than 40/1000 live births. The clinical
criteria for diagnosis of pneumonia include rapid
Suggested reading
respiration with or without difficulty in respiration. Rapid
respiration is defined as respiratory rate of more than 60, Technical bases for WHO recommendations on the management of
50 or 40/minutes in children below 2 months of age, 2 pneumonia in children at first level health facilities. WHO/ARI/91.20
Geneva: World Health Organization, 1991.
months to 1 year and 1 to 5 years of age respectively.
Difficulty in respiration is defined as lower chest in
drawing. The WHO recommends that in a primary care BRONCHIOLITIS
setting if a child between 2 months to 5 years of age presents It is one of the common serious acute lower respiratory
with cough he should be examined for rapid respiration
infection in infants. Affected infants are between the ages
and difficulty in breathing along with presence of cyanosis
of 1 and 6 months, but the disease can affect children up
or difficulty in feeding (Table 13.4). If the respiration is
to their second birthday. Disease usually occurs in winter
normal, no chest indrawing and he/she is feeding well,
and spring. Respiratory syncytial virus (RSV) is implicated
child is assessed to be suffering from upper respiratory
in most cases. Other causative organisms include para
tract infection and can be managed at home. If the child has
influenza virus, adenovirus, influenza viruses and
rapid respiration but there is no chest indrawing, he/she
M. pneumoniae.
is suffering from pneumonia and can be managed on
ambulatory basis with oral cotrimoxazole for 5 days. Protection against RSV is mediated by antibodies of
If child has chest indrawing, he/she is assessed to be IgG3 subclass. These antibodies have shorter half life and
suffering from severe pneumonia and needs hospitaliza do not cross the placenta in substantial amount so as to
tion. In hospital, the child is managed with IV/IM offer protection to the infant. High quantities of secretary
penicillin. IgA antibodies to RSV are present in the colostrum and
Presence of severe chest indrawing or cyanosis indica breast feeding reduces the likelihood of an infant being
tes very severe pneumonia. Such children are admitted hospitalized with acute bronchiolitis.
Table 13.4: Children aged 2 months to 5 years with cough or difficult breathing:
Clinical classification to facilitate treatment decisions
Signs and symptoms Classification Therapy Where to treat
investigations Treatment
X-ray chest shows hyperinflation and infiltrates (Fig. 13.3); Treatment of bronchiolitis is essentially symptomatic. The
diaphragm is pushed down. The lung fields appear child should be nursed in a humid atmosphere preferably
abnormally translucent. The leukocyte count is normal or in sitting position at angle of 30° to 40° with head and
slightly elevated. A rapid test using monoclonal antibodies neck elevated.
against respiratory syncytial virus on nasopharyngeal Infants with mild disease can be cared for at home in a
aspirate can identify RSV at bed site. humidified atmosphere. If respiratory distress increases
Bronchiolitis is generally a self-limiting illness. The or feeding problems appear, child should be hospitalized.
symptoms subside in three to seven days. Death may occur In hospital moist oxygen inhalation remains the main
in one percent of the severely ill patients due to respiratory stay of treatment. It is administered continuously even in
failure. The relationship of acute bronchiolitis to bronchial the absence of cyanosis. Fluids and electrolyte balance
358 Essential Pediatrics
should be maintained. Very sick infants may need a Inhalation of an allergen leads to a biphasic response
concentration of 60% oxygen given through a hood. Pulse with early and late reactions ultimately causing broncho-
oximetry should be performed regularly to keep oxygen constriction.
saturation of more than 95%. Early reaction starts within 10 minutes of the exposure
Antibiotics have no role. Ribavirin, an antiviral agent to allergen. It is characterized by release of histamine,
has no role in the treatment of infants who were previously leukotrienes C,D,E, prostaglandins, platelet activating
healthy. Ribavirin, however, shortens the course of illness factor and bradykinin from the mast cells following the
in infants with underlying congenital heart disease, interaction of allergen with specific mast cell bound IgE. All
chronic lung disease and immunodeficiency. Ribavirin is these substances cause bronchoconstriction, mucosal
delivered by a nebulizer 16 hours a day for 3-5 days in edema and mucus secretion which manifests as airway
such cases. obstruction. This phase is inhibited by Beta 2 agonist drugs.
Beta 2 adrenergic drugs and ipratropium are not Late phase occurs in about two-third of patients. It
recommended for infants less than 6 months. A recent develops 3-4 hours later with peak at 8-12 hours. Again
analysis of all the studies on use of bronchodilators in there is a release of mast cell mediators. This phase is not
bronchiolitis suggest that salbutamol with ipratropium prevented by premedication with Beta 2 agonist drugs.
inhalation may provide some benefit and there may be However, it is inhibited by premedication with steroids
some beneficial effect of inhaled epinephrine. suggesting that airway narrowing is mainly due to an
Continous positive airway pressure (CPAP) or assisted inflammatory reaction and mucosal edema. This phase
ventilation may be required to control respiratory failure. presents as clinical asthma.
Extracorporeal membrane oxygenation is effective, when Airway resistance is increased more so during exhala
respiratory failure is not controlled by mechanical tion because airways close prematurely during expiration.
ventilation. As a result lungs are hyperinflated; elasticity and fre
quency-dependent compliance of the lungs are reduced.
Suggested reading Breathing involves more work resulting in dyspnea. Per
1. Blom D, Ermers M, Bont L, van Aalderen WM, van Woensel
fusion of inadequately ventilated lungs causes low Pa02
JB.Inhaled corticosteroids during acute bronchiolitis in the In early stages of illness PaC02 also falls because of
prevention of post-bronchiolitic wheezing. Cochrane Database Syst hyperventilation caused by dyspnea. When obstruction
Rev. 2007;:CD004881 becomes more severe, alveolar hypoventilation super
2. Calogero C, Sly PD. Acute viral bronchiolitis: to treat or not to treat- venes. This leads to retention of C02 with a rise of PaC02.
that is the question. J Pediatr. 2007;151:235-7.
With the exhaustion of buffer mechanisms, pH of blood
3. Chavez-Bueno S, Mejias A, Welliver RC.Respiratory syncytial virus
bronchiolitis : current and future strategies for treatment and falls (respiratory acidemia).
prophylaxis. Treat Respir Med. 2006;5:483-94. Bronchial hyperresponsiveness and asthma: Bronchial
4. Spurling GK, Fonseka K, Doust J, Del Mar C.Antibiotics for hyperresponsiveness is one of the most characteristic
bronchiolitis in children. Cochrane Database Syst Rev. 2007 Jan features of asthma. This is attributed to one or more of
24;(1):CD005189.
the following abnormalities:
i. defect in the airway,
ii. abnormal neural control of the airways, and
BRONCHIAL ASTHMA iii. bronchial inflammation
It is suggested that an imbalance between excitatory
Bronchial asthma is a disease characterized by an increased
(cholinergic, alpha-adrenergic and non-cholinergic) and
responsiveness of the airways to various stimuli. It inhibitory mechanisms (adrenergic and non-adrenergic)
manifests by widespread narrowing of the airways increases bronchial reactivity. Bronchoconstriction results
causing paroxysmal dyspnea, wheezing or cough. The from increased cholinergic activity causing bronchial
diffuse obstruction to the airflow is reversible in a large smooth muscle to contract and bronchodilatation results
majority of cases, either spontaneously or in response to from non-adrenergic system and endogenous catechola
treatment. Bronchial reactivity is a necessary component mines acting on the beta adrenergic receptors and pros
of asthma. Asthma is a result of multifactorial inheritance. taglandin E2. There are both inhibitory and excitatory non-
adrenergic non-cholinergic nerves which secrete certain
PATHOPHYSIOLOGY neuropeptides. Two of these have been well studied.
Vasoactive intestinal peptides (VIP) relax smooth muscles
Airway obstruction in asthma is caused by (i) edema and
of bronchi while substance-P increases smooth muscle
inflammation of mucous membrane lining the airways,
tone, mucus hypersecretion and microvascular leakage.
(ii) excessive secretion of mucus, inflammatory cells and
cellular debris and (iii) spasm of the smooth muscle of
PATHOLOGY
bronchi. Obstruction is diffuse but not uniform.
Asthma has been classified as extrinsic (IgE mediated, Airway inflammation is now considered to be the basic
triggered by allergens) and intrinsic (non IgE mediated, pathology in asthma: This is initiated by degranulation
triggered by infection). of mast cells. Degranulated mast cells release various
Disorders of Respiratory System 359
mediators of inflammation as discussed earlier. These spasmodic coughing more so at night. In early phase of
mediators damage the wall of the airways leading to the attack cough is non-productive. The patient becomes
epithelial shedding and mucus secretion. Inflammatory dyspneic, with prolonged expiration and wheezing. Acces
mediators also influence reactivity via neural mechanisms. sory muscles of respiration are excessively used. The child
sweats profusely, may develop cyanosis and becomes
Triggers of an attack of asthma: Only a few cases of
apprehensive and restless and may appear fatigued.
asthma in children are directly related to the specific
In severe episodes the child may show air hunger. The
allergen exposure. chest is hyper-resonant because of excessive air trapping.
Exposure to allergens in the environment that are As the obstruction becomes severe, the airflow decreases
inhaled, plays a significant role in the pathogenesis of markedly. As a result the breath sounds become feeble.
chronic asthma. A marked increase in the incidence of Wheezing which was earlier audible may disappear. This
asthma occurred in areas in which high levels of aeroaller- is an ominous sign. Absence of wheezing in the presence
gens such as house dust mites (dermatophagoids), molds of cyanosis and respiratory distress should not be
such as alternaria or other industrial allergens were considered as an evidence of clinical improvement. As the
present. Smoke, hydrocarbons, drugs such as aspirin, non- child starts improving clinically, the airflow increases and
steroidal-anti-inflammatory drugs, tartarazine trigger an wheezing may reappear. With the remission of the attack
attack. Prolonged allergen avoidance reduces allergen wheeze again disappears.
specific and mediator induced bronchial reactivity. Severe hypoxemia in asthma results in cyanosis and
Viral infections: Viral infections in the young children cardiac arrhythmias. Pulsus paradoxus indicates severe
and exercise in older child or adult appear to be more illness. Mucus plugs occluding the bronchial tubes cause
frequent triggers of airway narrowing. Exact mechanism collapse of small segments of the lung.
by which viral infections (mainly RSV) induce temporary Persistence of hyperinflation of the chest even after
bronchoconstriction is not clear. Probably viral infections subsidence of asthmatic attack signifies that the apparent
interefere with the integrity of mucosal surface by opening relief from bronchospasm will be short lived. In severe
up the tight intraepithelial cell junctions and thus inducing persistent cases the chest becomes barrel shaped. Clubbing
the shedding of epithelium. It results in mucosal edema of fingers, however, is unusual in uncomplicated cases.
and mucus secretion.
DIAGNOSIS
Role of exercise: Exercise induced asthma occurs in
genetically susceptible individuals with hyper-reactive A prolonged whistling sound heard at the mouth during
airways because of the loss of water and heat from the expiration is called a wheeze. Recurrent attacks of
respiratory tract following exercise. Water loss induces wheezing indicate bronchial asthma. Although inter
mucosal hyperosmolarity which stimulates mediator mittent attacks of coughing may be due to recurrent viral
infections, diagnosis of bronchial asthma must be
release from mast cells.
considered. Cough, which is associated with asthma
Role of weather change: Sudden weather change may generally, worsens after exercise. Sputum is generally
result in (i) loss of heat and water from lower airways clear and mucoid but expectoration of yellowish sputum
and (ii) sudden release of airborne allergens in atmosphere does not exclude the diagnosis of asthma. This may be
thus resulting in exacerbation of asthma. attributed to large number of eosinophils in the sputum.
Emotional factors: Emotional stress operated through Chronic spasmodic cough may suggest occult asthma.
vagus, initiating bronchial smooth muscles to contract.
Role of food: Allergy to food proteins or additives in food Investigations
plays an insignificant role in the pathogenesis of asthma. Pulmonary function test (PFT): The diagnosis of asthma
These should be incriminated only on a very strong is clinical in most cases, hence PFTs may not play
association with the illness. significant role. However PFTs play an important role in
diagnosis of doubtful cases and in monitoring of response
Endocrine factors: Some endocrinal changes may increase
to treatment. The important parameters in spirometry
symptoms of asthma. Children may get increase in
include PEFR, FEV1, FVC and FEV25-75. In asthma FEVj /
symptoms during puberty.
FVC is less than 0.8 (normal 0.8-1) FEV1 is commonly used
parameter for documentation of severity of asthma.
CLINICAL FEATURES
FEV25-75 is effort independent and is probably more
The clinical features of asthma are variable. Symptoms sensitive indicator of airway obstruction. PEFR can be
vary from simple recurrent cough to severe wheezing. measured easily with peak expiratory flow meter, while
Children may present with recurrent cough with or for other parameters spirometer is required. PEER may
without wheezing. The symptoms occur with change in be used as diagnostic tool in doubtful cases as well as
season, aggravated by exercise and more in nights. Acute monitoring of treatment. Abnormality in PEFR suggestive
asthma may usually begin with a cold, or bouts of of asthma include: a diurnal variation of more than 20%,
360 Essential Pediatrics
< 80% of predicted and improvement of > 20% after and nitrofuran, etc. In the acute form of illness, these
bronchodilator therapy. children suffer from fever, chills, dyspnea, malaise, aches
and pain, loud inspiratory rales (crackles) at bases of lung
Absolute eosinophil counts: Significance of eosinophilia
and weight loss. X-ray of the chest shows interstitial
for distinguishing between allergic, vasomotor or infec
pneumonia. Bronchial markings are prominent. The levels
tious nature of the chronic respiratory obstructive disease
of IgE antibodies to the specific antigen are increased. The
is limited. When eosinophilia is present, bronchial obstruc
skin test shows arthus phenomenon with local hemor
tion generally responds well to antispasmodic therapy and
rhage, edema and local pain within 8 hours of the test.
the condition is often reversible. The eosinophil count may
Diagnosis is established by lung biopsy.
be low in cases associated with infection. Steroid
medication in asthma causes eosinopenia. Cystic fibrosis: Children with cystic fibrosis may present
Chest X-ray film: The X-ray film of the chest shows with recurrent wheezing but over a period of time they
bilateral and symmetric air trapping in case of asthma. develop clubbing, there may be history of passing large
Patches of atelectasis of varying sizes due to mucus plugs foul smelling stools suggesting malabsorption. X-ray film
are not unusual. Main pulmonary artery is prominent due may show evidence of hyperinflation, peribronchial
to pulmonary hypertension. Bronchial cuffing may occur cuffing and pneumonia. Diagnosis can be established by
due to the presence of edema fluid in perivascular and doing sweat chloride estimation.
peribronchial interstitial space. Extensive areas of collapse
or consolidation should suggest an alternative diagnosis. MANAGEMENT
Chest X-ray film may be normal. Goals of therapy are (i) Maintenance of near normal pul
Allergy test: Skin test and RAST (radio-allergo-sorbent monary function (ii) Maintenance of near normal physical
allergen specific IgE) have limited usefulness. Few activity (iii) Prevention of night-time cough or wheezing
children need skin tests to identify sensitivity to different with minimal chronic symptoms (iv) Prevention of
antigens since the role of desensitization in therapy is not exacerbation of asthma and (v) Avoiding adverse effects
fully established. of medication.
Effective long-term management of asthma involves
Differential Diagnosis three major areas:
1. Identification and elimination of exacerbating factors.
Bronchiolitis: Bronchiolitis always occurs within the first
2. Pharmacological therapy.
2 years, usually within the first 6 months of life. It is
3. Education of patient and parents about the nature of
commoner in winter or spring months. Generally there is
a single attack. Repeated attacks indicate asthma. disease and the steps required to avoid acute exacer
bation.
Hyperinflation of chest with scattered areas of infiltration
may be seen in chest X-ray. On the other hand, asthma
may start at any age; more than 3 episodes are usual and Identification and Elimination
wheezing is prominent. Infants diagnosed as bronchiolitis of Exacerbating Factors
who present with family history of allergy have eczema Common factors associated with development and preci
or whose IgE levels are elevated, are most likely candidates pitation of asthma include passive smoking, associated
for developing asthma. allergic disorders, inadequate ventilation at home leading
Congenital malformations causing obstruction viz., to dampness, cold air, cold food, smoke, dust and pets in
vascular rings such as aberrant right subclavian artery or the family. Acute respiratory infection due to viruses is
double aortic arch, bronchogenic cysts and tacheomalacia the most common cause of exacerbation of asthma.
should be excluded in differential diagnosis.
Follozving measures may help in decreasing the triggers:
Aspiration of foreign body: Wheeze, if present is
1. The bedroom of the child should be kept clean and
generally localized. The history of foreign body aspiration
as free from dust as possible. Wet mopping of the
may be forgotten. An area with diminished air entry, with
floor should be done because dry dusting increases
or without hyperresonance on percussion especially in
exposure of the child to house dust.
children, may be due to obstructive emphysema because
of a check-valve type of obstruction due to the foreign 2. Heavy tapestry attracts dust and therefore light plain
body. Most children develop frequent infections in the cloth sheets should be used as curtains in the child's
lung around the foreign body. room.
Hypersensitivity pneumonitis: A puzzling acute or 3. Carpets, stuffed furniture, loose clothing, wall
chronic lung disease may be observed following inhalation hangings, calendars and books attract lot of dust and
of organic dust such as molds, wood or cotton dust, bird should be regularly cleaned at periodic intervals.
droppings, fur dust, grain, or following exposure to certain 4. The bed of the child should be made of light material
chemicals or drugs such as epoxy resins, PAS, sulfonamide and should be aired regularly.
Disorders of Respiratory System 361
5. Keeping of animal pets should be discouraged, as The newer inhalation steroid, fluticasone is considered to
the child may be sensitive to their fur. be superior to BDP/BDS.
6. Generally, it is not necessary to restrict the diet of The main concern with the use of inhalation steroids is
the child because bronchial asthma due to food the effect on growth. An approximately 20 percent
allergy is unusual. reduction in the growth velocity during the first year of
7. Adolescent patients should be advised to refrain treatment with inhaled steroids is reported. Subsequently
from smoking. the growth velocity recovers and children ultimately attain
8. Exposure to strong or pungent odors such as wet predicted adult height.
paint, dissinfectants and smoke should be mini
mized.
Mast Cell Stabilizers
9. The child should not go to attics or basements, espe In this group the drugs included are cromolyn sodium,
cially if these were unoccupied and kept closed for nedocromil sodium and ketotifen.
some days. These should be properly cleaned and Cromolyn sodium belongs to chromone group of
aired for some time, before the asthmatic patient goes chemicals. It reduces bronchial reactivity and symptoms
there. induced by irritants, antigens and exercise. Indications for
use of cromolyn includes mild to moderate persistent
Pharmacotherapy asthma and exercise induced asthma. It should be given
The pharmacological therapy of bronchial asthma involves at least for 6-8 weeks before declaring it ineffective. Now
use of drugs that relax smooth muscle and dilate the it is not available in the market.
airways and drugs that decrease inflammation and Nedocromil is another nonsteroidal drug used for con
thereby prevent exacerbations. The medications used for trol of mild to moderate asthma. Ketotifen is another mast
long-term treatment of asthma include bronchodilators, cell stabilizer. It is administered orally. Significant clinical
steroids, mast cell stabilizers, leukotriene modifiers and improvement may be evident after 14 weeks of therapy.
theophylline. They have been described in a tabular form
Leukotriene Modifiers
in Table 13.5.
Leukotriene inhibitors are new pharmacological agents
Bronchodilators for the treatment of mild to moderate persistent asthma
This group of drugs provides symptomatic relief. They and exercise-induced asthma. Leukotriene inhibitors act
may be short acting and long acting. The commonly used either by decreasing the synthesis of leukotrienes
short acting bronchodilators are adrenaline, terbutaline (Zileuton) or by antagonizing the receptors (Montelukast
and salbutamol. All of these have quick onset of action. and Zafirlukast).
Adrenaline stimulates a and both |3 receptors; thus causes Montelukast and zafirlukast have received approval for
cardiac side effects. Terbutaline and salbutamol are use in pediatric asthma patients. Montelukast can be used
specific P-2 agonist and hence, have least cardiac side in children above one year of age while zafirlukast above
6 years of age.
effects. Adrenaline is given subcutaneously. The other two
agents can be administered by oral/inhalation or
Theophylline
parenteral route. Inhalation route is preferred because of
quick onset of action and least side effects. Theophylline has concentration-dependent broncho
Long acting beta agonists include salmeterol and dilator effects. The bronchodilator effect is exerted by
formoterol. Both these drugs are specific beta 2 agonist and inhibition of phosphodiesterase. In addition, theophylline
have a longer duration of action of 12-24 hours. Its efficacy has anti-inflammatory and immunomodulatory effects at
has been demonstrated in children above four years of age. therapeutic serum concentration that appears to be distinct
from its bronchodilator properties. Most recent guidelines
Corticosteroids recommend theophylline as an alternative second inferior
Asthma is a chronic inflammatory disease of airways. drug for mild persistent asthma. It can also be used as
Corticosteroids being potent anti-inflammatory agents, are adjunctive therapy (largely for control of nocturnal
the corner stone of long-term treatment of asthma. symptoms) in moderate or severe persistent asthma.
Systemic glucocorticoids used early in the treatment of
Immunotherapy
acute exacerbation can lessen the need for visits to
emergency department and hospitalization. The advan This consists of giving gradually increasing quantities of
tage of inhaled administration of corticosteroids is an allergen extract to a clinically sensitive subject, so as to
application of the potent medication to the sites where it ameliorate the symptoms associated with subsequent
is specifically needed. This potentially reduces the risk exposure to causative allergen. This is considered only
for systemic adverse effect of these medications. occasionally in highly selected children who are sensitive
The commonly used inhaled steroids include beclome- to a specific allergen such as grass pollen, mites, etc. It is
thasone, budesonide and fluticasone. Beclomethasone done only under specialist supervision and must, usually
(BDP) or budesonide (BDS) has almost the same effect. be given for 3 years.
362 Essential Pediatrics
Salmeterol 25 |ig/puff MDI Tachycardia, tremors, 1-2 puffs 12-24 hourly Long-term prevention of
Dry powder capsules 50 |ig/ headache, hypokalemia, 1 dry powder cap symptoms. Particularly useful
cap (Rotacap) hyperglycemia (minimal inhalation 12-24 hourly for nocturnal symptoms exer
with inhalation route) cise induced bronchospasm
Formoterol 12|rg/puff MDI 1-2 puffs 12-24 hourly Not for treatment of acute
Dry powder capsules 12 |ig/cap 1-2 dry powder cap symptoms. Used with anti
(Rotacap) inhalation 12-24 hourly inflammatory therapy not as
substitute.
Theophylline 100, 150, 200, Toxicity at >20 |ig/ml, 5-15 mg/kg/day Drug interactions (anti-tuber
300 mg tablets nausea, headache, 2 divided dose cular, anticonvulsants, cipro
Oral tachycardia, drowsiness, floxacin). May be used in
step II when inhalation
route not possible
Mast cell stabilizers
Sodium cromoglycate Medicinal taste 5 mg/puff Continuous prophylaxis for
5 mg/puff MDI Reflex coughing control of symptoms. May
Nedocromil sodium Bitter taste, cough 1-2 puffs 3-4 times a day take 4-6 weeks for clinically
inhalation evident effect.
Ketotifen 1 mg tab May cause sedation 1 mg twice a day
and 1 mg/5 ml and weight gain
Corticosteroids
Inhaled corticosteroids Cough, dysphonia, oral 50-800 (ig/day in 2-3 Not recommended as
Beclomethasone thrush (gargling, spacer divided doses relievers. Budesonide and
50,100,200,250 ng/puff use minimizes effects) 50-800 |ig/day in 2 doses fluticasone almost completely
Budesonide 50, 100, 200, inactivated during first pass
|ig/puff MDI At dose of 400-800 |ig/day 25—400 |ig/ day in 2 divided metabolism and thus have
Respules-0.5 and 1 mg/ml negligible side effects doses minimal systemic side effects
Rotacaps 100/200/400 (rg/cap
Fluticasone 25,50,125 (ig/puff MDI High dose for long duration
Dry powder capsules: Use minimum required dose
50, 100, 250 ng/cap preferably alternate day
Respules: 0.5 and 1 mg per ml May cause systemic side
effects
Montelukast 4, 5, 10 mg tabs Generally well tolerated 2-5 years: 4 mg per day Exercise induced asthma
Churg-Strauss syndrome 5-12 years 5 mg per day Alternative to long acting
reported >12 years 10 mg per day (3-agonist
PHARMACOLOGICAL MANAGEMENT and need for medication, hospital visit and hospitalization.
Result of pulmonary function tests (PFTs) by spirometer
Assessment of Severity provides objective evidence of severity. PEFR measure
Successful management of asthma requires grading the ment is an easy alternative to spirometry in day-to-day
severity of the disease according to the frequency and practice. PEFR is easier to perform and can be performed
severity of symptoms and functional impairment. This is in children older than 5-6 years of age.
assessed by asking the frequency of symptoms including Children with asthma can be classified into 4 groups
disturbance of sleep, effect on day-to-day activity of child on the basis of information obtained from parents and
Disorders of Respiratory System 363
PEFR measurement, i.e. intermittent, mild persistent, Mild episodic asthma should be treated with salbuta
moderate persistent and severe persistent asthma. This is mol or terbutaline as and when required. If inhalation
presented in a tabular form in Table 13.6. cannot be used due to any reason oral route can be used.
Mild persistent asthma needs daily treatment with
maintenance medication. They can be cromolyn sodium
Table 13.6: Classification of asthma according to severity
5-10 mg by inhalation route, 6-8 hourly or inhalation
steroids (BPD, BDS) in the dose of 200 |ag/day in two
divided doses or slow release theophylline 5-15 mg/kg/
day in two divided doses. The selection of either prepara
tion is based on feasibility for inhalation, problems of com
pliance and cost of medications. The drug of choice in mild
persistent asthma is a low dose inhaled steroid. If inhala
tion is not feasible due to any reason (cost of medication/
not able to take inhalation) a trial of leucotriene modifiers
or oral theophylline can be given.
Moderate persistent asthma needs to be treated with
inhalation steroid 200-400 )ig/day in 2 divided doses and
long acting (3-agonist (formoterol/salmeterol). Montelu
kast can be used at this step as add on treatment for better
control of asthma symptoms.
Severe persistent asthma needs inhalation steroids in
the dose of 400-800 Lig/day in 2-3 divided doses. For relief
of symptoms long acting (3-agonist and slow release
theophylline needs to be given regularly. Montelukast can
Selection of Medication be used at this step as add on treatment for better control
After the assessment of severity, appropriate anti asthma of asthma symptoms. If there is persistence of symptoms
drugs are selected. The stepwise treatment of asthma low dose prednisolone may have to be used, preferably
alternate day.
according to the severity is given in tabular form in table
13.7. Selection of Appropriate Inhalation Device
Drugs used as maintenance treatment of asthma can be
Table 13.7: Step wise treatment of asthma administered by inhalation or oral route. Drugs used by
the inhalation route are more effective, i.e. have a rapid
Long term prevention
onset of action, and have fewer side effects. Most impor
Step 4 Inhaled short acting (3-agonist as required
tant in the delivery of effective therapy to asthmatic chil
Severe + Inhaled corticosteroids Budesonide/
dren is the optimal use of appropriate inhalation devices.
Persistent Beclomethasone, 400 |ig twice daily may
Commonly available inhalation devices are as follows:
increase up to 1000 |ig/day + Long
acting bronchodilator: long acting inhaled
Metered Dose Inhaler
(32 agonist and/ or sustained release
theophylline + corticosteroids low dose An MDI is a device, which delivers a fixed amount of
alternate day (if no relief with above medication in aerosol form each time it is activated (Fig.
treatment) 13.4). It can be used for exacerbation and maintenance
Step 3 Inhaled short acting (3-agonist as therapy. They are effective but require considerable co
Moderate required + Inhaled corticosteroids ordination, i.e. press and-breath co-ordination. This may
persistent Budesonide/ beclomethasone, 200^00 |ig
not be possible in young children. After actuation the drug
divided twice daily. If needed long acting
comes out at a pressure and a significant amount of the
bronchodilator: long acting inhaled (32
drug gets deposited in the oropharynx. To overcome this
agonist salmeterol 50 |ig once/twice daily
and/or sustained release theophylline problem of co-ordination it is used with spacer. MDIs
continue to work past the labeled number of doses because
Step 2 Inhaled short acting (3-agonist as
Mild persistent required + Inhaled corticosteroids of excess propellant. Therefore, a track of number of
Budesonide/beclomethasone, 100-200 |ig actuations should be kept to ensure that children receive
or cromolyn or sustained release adequate therapy when needed.
theophylline or leukotriene modifiers
Step 1 Inhaled short acting (3-agonist as required Metered Dose Inhaler With Spacer
Intermittent for symptoms relief. If they are needed Use of spacer inhalation device with a MDI should be
more than 3 times a week move to step 2. encouraged as it results in a larger proportion of the
364 Essential Pediatrics
Fig. 13.6 : Metered dose inhaler with spacer and baby mask
medication being deposited in the lung, with less
impaction in the oropharynx (Fig. 13.5). They also
Dry Powder Inhaler (DPI)
overcome the problems of poor technique and
coordination of actuation and inspiration, which occur, These are breath-activated devices like Rotahaler (Fig.
with the use of MDIs alone. Furthermore, use of spacer 13.7), Diskhaler, Spinhaler, Turbohaler and Acuhaler.
allows MDI to be used for the young patient. MDI used They can be used in children above 4-5 years of age. They
with spacer has been found to be comparable to nebulizer have the advantage of being portable and eliminate the
in delivering salbutamol in acute exacerbation of asthma need to co-ordinate actuation with breathing. In addition
in children. Spacers have the limitation of being bulky, they are environmental friendly, as they do not contain
relatively costly and cannot be used in young infants and CFC. Moreover, the effect of powder inhalers is dependent
toddlers. A home-made spacer prepared from mineral upon a certain inspiratory flow rate and therefore there is
water bottle has been shown to be equally effective in a risk of reduced effect during episodes of acute wheeze
delivering salbutamol in acute exacerbation. or in children with low pulmonary function.
Fig. 13,5: Metered dose inhaler with spacer Fig. 13.7: Rotahaler
Disorders of Respiratory System 365
leucotriene modifiers. Short acting beta agonists should should be given to them. Acute exacerbation can be
be taken before going for exercise, as their duration of identified by increase in cough, wheeze and breathless
action is short. Long acting beta agonists can be taken in ness. PEFR, if measured, may be decreased by 15% from
the morning and they continue to prevent exercise- the baseline. For acute exacerbation parents should
induced bronchoconstriction throughout day time, hence administer short acting P2 agonists by MDI + spacer +
preferable in children who find it difficult to take short facemask, one puff at a time, repeated every 30-60 seconds
acting beta agonists before exercise in school. Leucotriene up to a maximum of 10 puffs with monitoring of symp
modifiers are alternative to long acting beta agonists. toms. If symptoms are relieved and PEFR is increased at
the end of inhalation the child can be continued on salbu
Seasonal Asthma tamol/ terbutaline every 4-6 hours and a visit to treating
A small proportion of children get symptoms of asthma physician is planned. If there is no improvement or partial
for a shorter period in a particular season. They remain improvement or there are symptoms of life threatening
asymptomatic for the rest of the year. These children can attack at any time, the child should be immediately trans
be started on maintenance treatment 2 weeks in advance. ferred to a hospital.
Medications are selected according to severity of asthma. Administration of a single dose of prednisolone (1-2
These children should be examined again after discon mg/kg) before going to hospital in a child who has
tinuing the medications after the season is over. symptoms of life threatening asthma or does not show
satisfactory improvement after inhalation therapy at home
EDUCATION OF PARENTS may be useful.
Such patients should be immediately be started on oxy be assessed for long term treatment. In case of no improve
gen inhalation injection of terbutalin or adrenaline is given ment at end of one hour the inhalation of salbutamol is
subcutaneously, inhalation of salbutamol or terbutalin and continued and ipratropium 250 microgram is also added
ipratropium is started, an injection of hydrocortisone 10 every 20 minutes. An injection of hydrocortisone 10 mg/
mg/kg is given and an arrangement is made to transfer the kg is given and reassessed at end of two hours. If there is
patient to ICU preferably with an accompanying physician. good response the patient is treated like the early respon
In ICU if patient shows improvement the salbutamol/ ders. In case of no response; injectable theophylline bolus
terbutalin inhalation is continued every 20-30 minutes, 5 followed by continuous infusion is started. Such patients
mg/kg of hydrocotisone is continued every 6-8 hourly till may respond well to magnesium infusion in doses of 50
patient start accepting orally. If patient does not improve mg/kg dissolved in dextrose over 30 minutes. If no
or deteriorates a loading dose of theophylline is infused. improvement these patients should be prepared for
Another drug that can be used in such a situation is magne possible mechanical ventilation.
sium sulphate in doses of 50 mg/kg as intravenous infusion
over 30 minutes. If there is no improvement with this Monitoring Treatment
management, patient is prepared for mechanical venti Repeat PEF/PFTs measurement 15-30 minutes after
lation. Patient is also screened for causes of poor response starting treatment. Chart PEFR before and after the child
such as acidosis, pneumothorax, electrolyte imbalance and is given nebulized beta-agonist and at least 4 times daily
infection and treated accordingly. throughout the hospital stay. Pulse oximetry to maintain
Sa02 above 92%.
Treatment of Mild Acute Asthma
Patients with mild exacerbation have cough, rapid respi Transfer to Intensive Care Unit
ration and some wheezing but no chest indrawing and is The patient should be accompanied by a doctor prepared
able to speak and drink well. PEFR if can be measured is to intubate if FEV, is deteriorating, hypoxia or hypercap
> 80% of predicted and oxygen saturation is more than nia are worsening or persistent and in cases with exhaus
95% in room air. tion, feeble respiration, confusion, drowsiness, coma or
Such patients should be given beta 2 agonists by respiratory arrest.
nebuliser or MDI + Spacer with or without face mask. If
later is used than one puff of medicine is repeated every When to Discharge from the Hospital
minute up to 10 puffs. In case of significant improvement Patient should have been on discharge medication for 24
the patient can be sent home on inhalation or oral beta hours and had inhaler technique checked and recorded.
agonists every 6-8 hours along with general instructions Treatment should include soluble steroids tablets and
and called back after 1-2 weeks for reassessment and long inhaled steroids in addition to the broncholdilator. The
term treatment. In case of no response or poor response patient should be given a self management plan or
the patient should be treated as moderate exacerbation. instructions should be given to the parents.
aspiration is a choke, gag, cough or localized wheeze. After are administered for 4 to 6 weeks. Physiotherapy is carried
the initial episode, symptoms may improve for some time out for effective drainage of the pus. Surgical resection of
and the whole episode may be forgotten. Subsequently, the involved area of lung is indicated if medical therapy
the course of illness depends on the nature of foreign body, is not effective.
its size, extent and the site of obstruction. Foreign bodies
of organic or vegetable source swell up and cause more BRONCHIECTASIS
symptoms. A partial obstruction may cause ball valve type
Bronchiectasis is a chronic suppurative disease char
effect leading to localized hyperinflation. The overlying
acterized by destruction of the bronchial and peribronchial
chest wall may show hyperresonance, diminished vocal
tissues, dilatation of the bronchi and accumulation of
resonance and poor air entry. In small children, it may be
infected material in the dependent bronchi.
difficult to elicit hyperresonance. Thus a localized area of
poor air entry in a child with chronic respiratory illness Etiopathogenesis
should arouse suspicion of a foreign body. Complete
Most cases follow recurrent episodes of respiratory
obstruction and surrounding inflammation cause distal
infections such as bronchitis, bronchiolitis, post measles
atelectasis and suppuration of the surrounding paren
or post pertussis pulmonary infections, cystic fibrosis and
chyma of the lungs. The elastic recoil of the bronchi is lost
pneumonitis in infancy and early childhood. Infections
and the bronchi show segmental dilatation with eventual
damage the bronchial wall and cause segmental areas of
development of bronchiectasis. In children incidence of
collapse, which exert a negative pressure on the damaged
right and left bronchial location of foreign body is nearly
bronchi, causing them to dilate. The bronchial dilation is
equal. These children are treated by removal of foreign
widespread and patchy. The bronchi may show cylin
body through a rigid bronchoscope. Appropriate antibio
drical, fusiform or saccular dilatation.
tics are given for secondary infection. Bronchoscopy
Aspiration of foreign body, food, or mucus plug in the
should be undertaken if the clinical and radiological pic
bronchus may occlude the bronchial lumen and cause
ture suggests the diagnosis even when the history of
segmental areas of collapse. The bronchi are dilated due
foreign body aspiration is not forthcoming.
to negative pressure by the collapsed segment. If the
Suggested reading occlusion is relieved before the stagnant secretions are
infected and the bronchial wall is damaged, the bron
1. Yadav SP, Singh J, Aggarwal N, Goel A. Airway foreign bodies in
children: experience of 132 cases. Singapore Med J 2007 48: chiectasis is reversible. The bronchial dilatations are gene
850-3. rally segmental or lobar. Extrinsic compression by the
2. Pinzoni F, Boniotti C, Molinaro SM, Baraldi A, Berlucchi M. Inhaled tuberculous lymph nodes often causes collapse of right
foreign bodies in pediatric patients: Review of personal experience. middle lobe.
Int J Pediatr Otorhinolaryngol. 2007;71:1897-1903.
Congenital disorders of bronchi such as broncho-
LUNG ABSCESS malacia, communicating type of bronchial cyst or
sequestrated lung may be the cause of bronchiectasis in
Lung abscess in children is most frequently a complication some cases. Kartagener syndrome is characterized by
of bacterial pneumonia especially those due to S. aureus bronchiectasis, situs inversus and sinusitis and is attri
and pneumoniae. It may also develop in sequestration of buted to disorder to ciliary motility (immotile cilia syn
lung tissue or in association with foreign bodies, bronchial drome). Cystic fibrosis is characterised by recurrent lower
cysts or stenosis. Staphylococcal lungs abscess are often respiratory infections associated with malabsorption.
multiple, while those complicating aspiration are solitary. Immunodeficiency syndromes may be responsible for
The abscess may rupture into the pleural space leading to recurrent pulmonary infections and bronchiectasis.
pyopneumothorax. The main pathological changes are of
necrosis and liquefaction with inflammation in the sur Clinical Manifestations
rounding lung tissue. The onset is generally insidious. The respiratory infections
tend to persist longer and recur frequently with waxing
Clinical Features
and waning. Often the illness can be traced back to an
The patient has fever, anorexia, lethargy, pallor, cough with episode of measles or whooping cough. A history of
foul smelling expectoration. Physical signs may be inhalation of foreign body is usually not forthcoming as it
minimal. Amphoric breath sounds, coarse crepitations and is often forgotten.
whispering pectoriloquy are characteristic but often not The most prominent symptom is cough with copious
elicitable. The diagnosis is confirmed by plain X-ray film mucopurulent expectoration. Cough is more marked in
and CT scan of chest. some postures because of irritation of the infected
secretions draining into fresh areas of lung. Likewise the
Treatment
cough is more marked when the child wakes up in the
Appropriate antibiotics to which the organisms isolated morning due to a change of posture. Younger children
from the sputum or bronchoscopic aspirate are sensitive, may not expectorate out the sputum which they swallow.
Disorders of Respiratory System 369
In the course of illness, the sputum may become blood the United Kingdom. It is less common in African Ameri
streaked or even frank hemoptysis may occur. In chronic cans (1 in 15000) and in Asian Americans (1:31000). It
cases clubbing of fingers is seen. also affects other ethnic groups such as black population
The general health is poor, with recurrent infections. with an incidence of 1 in 17,000 and the native American
The patient complains of loss of appetite, irritability and population with an approximate incidence of 1 in 80,000.
poor weight gain. The incidence in migrant Indian populations in the
UK has been estimated between 1 in 10000 to 12000.
Investigations The precise incidence of CF among Indians is unknown.
X-ray film of the chest shows honeycombing of the
involved area indicating multiple small abscess cavities. Molecular Genetics
Bronchography which was considered as gold standard The basic defect in CF is a mutation in the gene for chloride
for diagnosis of bronchiectasis has been replaced with high conductance channel, i.e. cystic fibrosis transmembrane
resolution computerized scan (HRCT of chest). Broncho conductance regulator (CFTR). The failure of chloride
scopy is undertaken where structural abnormalities of conductance by epithelial cells leads to dehydration of
airway is considered. Sputum should be sent for culture secretions that are too viscid and difficult to clear. The
and sensitivity. Tuberculin reaction is done to exclude defective gene is located at long arm of chromosome 7.
tuberculosis. Pilocarpine iontophoresis is done for esti Till now more than 1400 mutations in the gene have been
mating sweat chloride in cases suspected to be suffering recognized. Commonest mutation is Delta F 508 and
from cystic fibrosis. constitute upto 70% in Caucasian population. The
frequency of mutation in Indian children is 25-30%.
Prevention
Most cases follow acute respiratory infections, which are Clinical Manifestations
inadequately treated. All pulmonary infections should be The clinical features depend on age of diagnosis, suppor
treated promptly and adequately till the chest is clear of tive care received and treatment. The common clinical
all signs, long after the fever has subsided. Even in presentation includes meconium ileus in neonatal period,
ordinary pulmonary infections, airway should be kept recurrent bronchiolitis in infancy and early childhood,
patent by encouraging postural drainage. Measles and recurrent lower respiratory tract infections, chronic lung
whooping cough should be prevented by specific disease, bronchiectasis, steatorrhea and with increasing
immunization. Prompt medical help should be sought if age pancreatitis, and azoospermia. Pancreatic insuffi
there is any suspicion of inhalation of a foreign body. ciency is present in > 85% of CF patients (Table 13.10).
Management Diagnosis
During acute exacerbations, bacterial infections should be The diagnosis of CF should be suspected by the presence
controlled and airway kept clear of secretions. This is of a typical phenotype or family history and confirmed
facilitated by effective cough at regular intervals and by the demonstration of a high sweat chloride (>60 mEq/
postural drainage. Assistance by a specially trained L) on at least two occasions and/or by identifying two CF
pulmonary physiotherapist may be useful. Surgical causing mutations. Nasal potential difference measure
resection of the involved area should be undertaken only ments can be used as an adjunct to sweat test but is not
in children who have marked symptoms despite adequate widely available.
the medical treatment and in whom the disease is
localized. Extrinsic compression of bronchi by mediastinal Management
masses requires surgical intervention. In young children The treatment of cystic fibrosis in children includes
with generalized disease associated with recurrent respiratory management, nutritional care, anticipation and
pulmonary infections, ill advised surgery may make the early diagnosis of liver disease, diabetes and other organ
patient worse. If the child cannot cooperate in post surgery dysfunction.
postural coughing, segmental or lobar collapse may occur
in the postoperative period and new bronchiectatic lesions Respiratory Management
may appear. Children with generalized disease may The principle components of care includes airway
improve significantly clinically with medical treatment clearance techniques, antibiotics and antiinflammatory
alone during adolescence. agents
Table 13.10: Common clinical features of cystic fibrosis(%) shock, tissue injury, aspiration, toxins, microthrombi,
0-2 years %
intravascular coagulation, uremia and increased intra
cranial pressure.
Meconium ileus 10-15
There is increased permeability of alveolar capillary
Obstructive jaundice 5-10
membrane leading to aggregation of leukocytes in pul
Bleeding diathesis 5-10
monary circulation. Mediators such as free oxygen radicals
Heat prostration/hyponatremia 5-10
Failure to thrive 60-70 and platelet activating factors are released and injure
Steatorrhea 85 vascular epithelium. In the acute stage there is edema and
Rectal prolapse 20 hyaline membrane formation. Subsequently fibrosis
Bronchitis/bronchiolitis 10 occurs. Microthrombi formation in vessels contributes to
Staphylococcal pneumonia 40-50 increased pulmonary vascular resistance and right to left
2-12 years shunting.
Malabsorption 85 Clinical Features
Recurrent pneumonia 60
Nasal polyposis 6-36
ARDS can occur at any age. Initially symptoms are less
Intussusception 1-5 and lungs are clear. Later on within 6-8 hours, patient
becomes breathless. After 12 hours of insult, refractory
> 13 years
hypoxia occurs followed by hypercapnia. Radiologically
Chronic pulmonary disease 70 most lung fields are affected with reticular opacities.
Clubbing 60 Mortality is very high, being 50-60% even in good centers.
Abnormal glucose tolerance 20-30
Diabetes mellitus 7 Treatment
Chronic intestinal obstruction 1-20
Focal biliary cirrhosis Patient is to be managed in an intensive care unit with
Portal hypertension 25 cardiorespiratory monitoring and artificial ventilation.
Gallstones 4-14 Ventilation is achieved by high PEEP or inverse ratio
Azoospermia 98 ventilation. Cause of ARDS is to be treated simultaneously.
Suggested reading
Lodha R, Kabra SK, Pandey RM. Acute respiratory distress syndrome:
i. Increasing caloric intake by encouraging parents to experience at a tertiary care hospital. Indian Pediatrics 2001; 38:
feed the child more frequently. If appetite is poor due 1154-59.
to persistent infection, feeding may be given by
nasogastric route or by gastrostomy. DIAGNOSTIC APPROACH TO CHRONIC COUGH
ii. Supplement fat soluble vitamins: Due to pancreatic
Chronic cough can be quite distressing.
insufficiency, there will be deficiency of fat soluble
vitamins. Vitamin A, D and E are supplemented in Type of Cough
twice the recommended doses. These should be given
along with food and enzymes. Staccato paroxysms of cough suggest whooping cough or
iii. Replace pancreatic enzymes: Enteric coated tablets or chlamydia infection. Barking or brassy cough associated
spherules of pancreatic enzymes are given with each with changes in the voice indicate laryngotracheal disease.
feed. Enzymes are started at doses of 1000-2000 IU of In case of postnasal drip, cough appears to be like an
lipase/Kg in divided doses and modified bsaed on attempt to clear the throat and described as a hawking
weight gain, nature of stool (frequency, amount and cough. Cough of psychogenic nature has a honking char
smell) and abdominal symptoms. acter (Table 13.11).
Suggested reading
Sputum
1. Kabra S K, Kabra M, Lodha R, Shastri S. Cystic fibrosis in India.
Pediatric Pulmonology 2007; 42: 1087-1094. Purulent sputum indicates the presence of suppurative
2. Kabra SK, Kabra M, Gera S, Lodha R, Sridevi KN, Chacko S, lung disease. Although sputum is mucoid in cases of
Mathew J, Shastri S, Ghosh M An indigenously developed method asthma, a yellowish sputum may be present in some cases
for sweat collection and estimation of chloride for diagnosis of due to the presence of a large number of eosinophils in it.
cystic fibrosis. Indian Pediatrics 2002; 39:1039-1043.
Hemoptysis indicates the possibility of bronchiectasis,
tuberculosis, mitral stenosis, cystic fibrosis or foreign body
ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
in the bronchus.
It is defined as pulmonary edema not originating from
the heart. The most common cause is severe pneumonia Wheezing
followed by sepsis. Other predisposing factors include Wheezing is indicative of asthma.
Disorders of Respiratory System 371
Table 13.11: Diagnosis of chronic cough with Bronchodilators are useful in the treatment of children
relation to age with cough due to occult asthma because of retained
tracheobronchial secretions. Mucociliary transport of
Age Cases
secretions is helped by the beta-adrenergic agonists and
Onset Laryngeal webs, vascular rings or H the xanthine group of drugs both in the asthmatic as well
from birth type tracheoesophageal fistula as in non-asthmatic children with chronic bronchitis.
Starting Congenital infections (rubella, CMV) Physiotherapy, e.g. chest clapping, vibrations and
in first month leading to interstitial pneumonia postural drainage are useful in facilitating removal of
Early infancy Gastroesophageal reflux leading to bronchial secretions.
vomiting and aspiration
During Bronchitis, asthma, cystic fibrosis, Suggested reading
late infancy whooping cough Marchant JM, Masters IB, Taylor SM, Cox NC, Seymour GJ, Chang AB.
Pre-school age Recurrent bronchitis, allergic Evaluation and outcome of young children with chronic cough. Chest
bronchitis, asthma, foreign body, 2006;129:1132-41.
chronic suppurative lung disease,
pulmonary eosinophilia EMPYEMA THORACIS
At all ages Asthma, whooping cough, viral Empyema thoracis is collection of pus in the pleural cavity.
bronchitis, tuberculosis, foreign body
This is commonly caused as a complication of pneumonia
aspiration.
or rupture of subdiaphragmatic or liver abscess in the
pleura. Commonly it is sequel of staphylococcal pneu
monia. It can occur secondary to pneumonia due to other
Seasonal Cough
organisms including S. pneumoniae, gram-negative bacilli
Chronic cough which is more common in certain seasons and mycoplasma.
during the year should arouse the suspicion of asthma. Clinical features include fever, breathing difficulty,
Chronic cough occurring only in winter months is usually toxic appearance of child. There is decreased movement
indicative of viral etiology. of respiration with decreased air entry and vocal reso
nance. Percussion note is dull. Occasionally it may mani
Nutrition of the Child
fest as a pulsatile swelling over chest and is called
Severe nutritional disturbance in association with chronic empyema necessitans.
cough is found in cases of tuberculosis, bronchiectasis, An X-ray film of chest shows shift in mediastinum with
pertussis, cystic fibrosis, severe chronic asthma or immune obliteration of costophrenic angle and varying degree of
deficiency syndromes. opacification. A pleural tap may show purulent material
full of pus cells with high protein and low sugar. Gram
Investigations stain and culture may show causative agent. Empyema
Chest X-ray film, examination of the sputum, blood counts should be differentiated from other causes of pleural effu
and tuberculin test may be necessary for arriving at a sion including tubercular and neoplastic.
definitive diagnosis. Bronchoscopy may be necessary in Therapy of emyema consists of administration of
some cases. CT scan of chest is a non invasive investi antibiotics active against staphylococcus, i.e. cloxacillin,
gation. vancomycin. The pus is drained by putting continuous
under water seal intercostal drainage tube. One time drain
Non-specific Therapy age of fluid under thoracoscopy is preferred if facility
Cough suppressants are preferably avoided in children. exists. After antibiotics and drainage if lung is not expand
These are indicated only, if the cough is dry and exhaus ing or there is loculations in the pleura a CT scan of chest
ting or, if it disturbs sleep and prevents adequate nutrition, for evidence of thickening of pleura or loculated empyema
e.g. in whooping cough. Dextromethorphan is an effective can be obtained and patient considered for decortication
cough suppressant and is non-habit forming. by thoracotomy or thoracoscopy.
14 Disorders of
Cardiovascular System
CONGESTIVE CARDIAC FAILURE Table 14.1: Heart failure due to diastolic dysfunction
Every cardiac patient has a potential for developing con Mitral or tricuspid valve stenosis*
gestive cardiac failure (CCF). Congestive cardiac failure Constrictive pericarditis
by itself is not a diagnosis. It is a clinical syndrome due to Restrictive cardiomyopathy
an underlying anatomical or pathological cause, which is Acute ventricular volume overload (acute aortic or mitral valve
the primary diagnosis. regurgitation)
CCF is defined as Inability of the heart to maintain an Myocardial ischemia*
output, at rest or during stress, necessary for the metabolic needs Marked ventricular hypertrophy (hypertrophic cardio
of the body (systolic failure) and inability to receive blood into myopathy, storage disorders of myocardium, hypertension,
the ventricular cavities at loiv pressure during diastole (diastolic severe aortic or pulmonary valve stenosis)
failure). Thus, due to systolic failure, it is unable to propel Dilated cardiomyopathy*
blood into the aorta and in diastolic failure, it receives *Mitral or tricuspid stenosis result in elevated atrial pressures
inadequate amount of blood. Diastolic failure is recog with normal ventricular diastolic pressures
nized by clinical features of heart failure with evidence of *Often associated with combined systolic and diastolic
dysfunction
increased filling pressures with preserved systolic function
and, in many instances, cardiac output. An increase in left
sided filling pressures results in dyspnea from pulmonary
congestion. An increase in right-sided filling pressures Table 14.2: Causes of congestive cardiac failure
results in tender hepatomegaly and edema. Besides hyper Infants Children
trophied ventricles, diastolic failure occurs in restrictive
Congenital heart disease Rheumatic fever, rheumatic
heart disease and constrictive pericarditis. While mitral
Myocarditis, primary heart disease
and tricuspid valve stenoses result in elevated atrial
myocardial disease Congenital heart disease
pressure, they are not, in the strictest sense, diastolic heart Rhythm disorders complicated by anemia,
failure. Systolic failure, however, is a much more common (tachy-, bradyarrhythmias) infection or endocarditis
clinical problem. Kawasaki disease with Systemic hypertension
coronary occlusion Myocarditis, primary
Etiopathogenesis Anemia myocardial disease
Miscellaneous Pulmonary hypertension
The causes of diastolic failure are indicated in Table 14.1.
Infections (primary, secondary)
The management of diastolic failure has been covered with
Hypoglycemia
each condition. The causes of systolic failure or mixed Hypocalcemia
systolic and diastolic failure can be classified according Neonatal asphyxia
to age (Table 14.2). Rheumatic fever (RF) and rheumatic Persistent pulmonary
heart disease (RHD) are typically encountered beyond 5 hypertension of
years of age. In regions where it is common (mostly neonate (PPHN)
underserved and rural populations) it is a common cause
of heart failure. Its prevalence is declining in urban
populations. years, unless complicated by anemia, infection or infective
endocarditis. This statement is largely true but for a few
Congenital Heart Disease exceptions. These include congenital heart defects asso
ciated with valve regurgitation and/or severe hypoxia.
Keith pointed out over 50 years ago that if a patient of
congenital heart disease does not develop CCF within the Left to right shunts: Patients with left to right shunts tend
first year of life, he is not likely to do so in the next 10 to develop CCF around 6-8 weeks of life. At birth, the
372
Disorders of Cardiovascular System 373
pulmonary vascular resistance is high, and the pulmonary substantial increase in pulmonary blood flow. The hypoxia
artery pressure more or less equals the systemic pressure. is typically less than transposition with intact ventricular
The left to right shunt is small, whether the communication septum because of better mixing.
is at the atrial, ventricular or pulmonary artery level. The
Total anomalous pulmonary venous return (TAPVR): This
maximum fall in the pulmonary vascular resistance occurs, in
condition refers to anomalous drainage of the pulmonary
the first few zveeks of life and then more slowly for a few
venous blood into the right side (either to the right atrium
months. The size of the shunt gradually increases and
or one of the veins draining into the right atrium). The
reaches its maximum around the age of six weeks. If the
obstructed form of TAPVR is associated with obstruction
baby is going to develop CCF due to a large shunt, he will
to pulmonary venous drainage (often at the level of the
do so at this time. The chances of a later increase in the
vein that finally communicates with the systemic veins).
shunt are minimal. Therefore, if CCF is not apparent by
This presents early in the neonatal period or sometimes
this time it is not likely to occur, unless the left to right
during the first weeks of life with severe pulmonary
shunt is associated with arch obstruction or regurgitation
hypertension, heart failure and severe hypoxia. The
of the atrioventricular valve. Associated anemia or infec
unobstructed form may present in the first few months of
tion may also precipitate CCF at an earlier age. Prematu
life with heart failure and varying degrees of pulmonary
rity results in a relatively early regression of the pul
hypertension. Occasionally, unobstructed TAPVR is
monary vasculature and left to right shunts tend to
undetected in infancy and manifests late in life.
manifest at even 3-4 weeks of age with CCF.
Congenital atrioventricular valve regurgitation: Unlike left to
Right to left shunts: The patients with right to left shunts at right shunts, mitral or tricuspid valve regurgitation can
the ventricular or pulmonary artery level have either result in CCF at an early age. Congenital TR manifests
pulmonic stenosis or pulmonary arterial hypertension. early because the elevated pulmonary artery pressure
Since the right ventricle is decompressed by the right to increases its severity. If the TR is not severe, it may
left shunt, CCF does not occur. Right to left shunt at the improve with time as pulmonary vascular resistance
atrial level can be secondary to obstruction at the right declines.
ventricular outlet or inlet. The former presents with CCF The age of occurrence of CCF suggests the underlying
in first few days of life, if the obstruction is severe or there cause (Table 14.3). The occurrence of CCF at an unexpec
is atresia. With less severe obstruction, CCF develops late. tedly early age for a patient thought to have a simple shunt
The commonest obstruction at the right ventricular inlet lesion should prompt search for an associated condition,
is tricuspid atresia. If patients with tricuspid atresia such as coarctation.
manifest signs of right-sided congestion, they do so
because they have a small communication at the atrial Myocardial Disease
level. It is a form of mechanical obstruction like tricuspid Dilated cardiomyopathy (DCM) refers to a group of
valve stenosis or mitral stenosis. conditions of diverse etiology in which both ventricles are
enlarged with reduced contractility. It is considered the
Obstructive lesions: In congenital obstructive lesions of the
result of a variety of disease processes affecting the heart
heart, CCF is a relatively late phenomenon. Flowever,
muscle. Causes of DCM include infections, metabolic
atresia or critical stenosis of aortic, mitral or pulmonary
derangements, hereditary disorders, nutritional
valve can result in CCF within the first few days of life. If
the lesion is mild, they may go on for years before the
increasing severity makes the child symptomatic.
Coarctation of the aorta can result in CCF within the first Table 14.3: Time of onset of congestive failure
few weeks or months of life. However, if these patients Age Lesion
do not manifest CCF in the first year of life, collaterals Birth-72 hr Pulmonary, mitral and aortic atresias
develop and prevent onset of failure by decompressing 4 days-1 week Hypoplastic left and right heart syndromes,
the obstruction. Therefore, obstructive lesions show CCF transposition and malposition of great arteries
either soon after birth or later when the child is older. 1-4 weeks Transposition and malposition complexes,
endocardial fibroelastosis, coarctation of aorta
Transpositions: Patients with transposition of great arteries 1-2 months Transposition and malposition complexes,
(TGA) typically present early in the first 1-2 weeks of life endocardial cushion defects, ventricular septal
with severe hypoxia resulting from poor mixing of defect, patent ductus arteriosus, total ano
systemic and pulmonary venous blood. CCF may be malous pulmonary venous return, anomalous
associated with intense hypoxia with resultant myocardial left coronary artery from pulmonary artery
dysfunction. More commonly, CCF is the result of a large 2-6 months Transposition and malposition complexes,
VSD or PDA occurring in association with transposition ventricular septal defect, patient ductus
arteriosus, total anomalous pulmonary venous
with markedly increased pulmonary blood flow. These
return, aortic stenosis, coarctation of aorta
infants may present as early as 4 weeks because of the
374 Essential Pediatrics
Slow weight gain is related to two factors. The infant Treatment of Congestive Cardiac Failure
takes small feeds because of easy fatiguability and there CCF means "inadequate cardiac output." The manage
is an excessive loss of calories from increased work of ment of CCF consists in a determined "four-pronged
breathing associated with CCF. Uncommonly, there may attack" for the correction of the inadequate output.
be an unusual gain in weight due to collection of water, i. Reducing cardiac work
manifesting as facial puffiness or rarely as edema on the ii. Augmenting myocardial contractility
feet. The difficulty in feeding may manifest itself as 'poor iii. Improving cardiac performance
feeder', a complaint that the baby does not take more than iv. Correcting the underlying cause
one to two ounces of milk at a time or that he is hungry CCF represents an emergency in newborns; identi
within a few minutes after taking a small feed. Shortness fication of the cause is necessary since initiating specific
of breath or fatigue from feeding results in the baby treatment can be life-saving; examples include duct
accepting only a small amount of milk at a time. A few dependent systemic circulation (critical coarctation, aortic
minutes rest relieves him and since he is still hungry, he stenosis, interrupted aortic arch). These newborns require
starts crying. The result is an irritable infant crying all the prostaglandin infusion for stabilization.
time. Often a mother may state that the baby breathes too
fast while feeding or that the baby is more comfortable Reducing Cardiac Work
and breathes better when held against the shoulder— The work of the heart is reduced by restricting the patient's
which is the equivalent of orthopnea in older children. activities, sedatives, treatment of fever, anemia, obesity, and
Not infrequently, the baby may be brought with the com using vasodilators. Neonates should be nursed in an
plaints of persistent hoarse crying, wheezing, excessive incubator with minimal handling. The baby is kept
perspiration and less commonly, puffiness of face (Table propped up at an incline of about 30°; pooling of edema
14.4). fluid in dependent areas reduces its collection in lungs,
reducing the work of breathing.
Table 14.4: Symptoms of congestive cardiac failure At a temperature of 36 to 37°C, the overall circulatory
and metabolic needs are minimal, thus reducing work of
Poor weight gain
heart. Humidified oxygen to maintain a concentration of
Difficulty in feeding
Breathes too fast; breathes better when held against the 40-50%, improves impaired oxygenation secondary to
shoulder pulmonary congestion, thus reducing the work of heart
Persistent cough and wheezing by reducing requirements of cardiac output. If the patient
Irritability, excessive perspiration and restlessness is restless or dyspneic, sedatives are used. Morphine
Pedal edema sulfate in doses of 0.05 mg/kg SC provides effective
sedation. A benzodiazepine such as midazolam is also
useful for sedation in selected circumstances. Sedatives
Left-sided failure is indicated by tachypnea and tachy
reduce anxiety and lower catecholamine secretion,
cardia. Persistent cough, especially on lying down, hoarse reducing physical activity, the respiratory and heart rates.
cry and wheezing are other evidences of left-sided failure. The requirements of oxygen fall, and this reduces the
The well known and familiar basal rales in the chest are cardiac workload. Use of sedatives may also be useful in
hardly ever audible. Right-sided failure is indicated by restricting physical activity in children.
hepatomegaly and facial puffiness. Examination of the neck Presence of fever, anemia or infection increases the
veins in small babies is not helpful. Firstly, it is difficult to work of the heart. In infants and small children, the
evaluate the short neck with baby fat and secondly, studies presence of superadded infection in congested lungs is
show that the right atrial pressure stays normal in more difficult to recognize. Antibiotics are, therefore, necessary
than one-half of infants with CCF. Edema on the feet occurs in the management of CCF in infants. Anemia imposes
late. Common to both left and right-sided failure is the stress on the heart because of the decreased oxygen
presence of cardiac enlargement, third sound gallop and poor carrying capacity of blood. Anemia results in tachycardia
peripheral pulses with or without cyanosis (Table 14.5). and in a hyperkinetic circulatory state. Correction of
anemia will result in decreased cardiac work. If transfusion
is indicated, packed red cells (10-20 ml/kg) can be given
Table 14.5: Signs of congestive cardiac failure in infants
along with a single IV dose of frusemide (1 mg/kg). Less
Left-sided failure Failure of either side Right-sided failure common conditions, which worsen cardiac function,
Cardiac enlargement Hepatomegaly include pulmonary emboli, thyrotoxicosis and obesity.
Tachypnea
Tachycardia Gallop rhythm (S3) Facial edema Vasodilators: Have been used for the management of CCF
Cough Peripheral cyanosis Jugular venous to counteract compensatory mechanisms at work to
improve the inadequate cardiac output. Arteriolar and
Wheezing Small volume pulse engorgement
venous vasoconstriction is mediated through catechola
Rales in chest Absence of weight gain Edema on feet
mines. Arteriolar constriction maintains blood pressure
376 Essential Pediatrics
Fig.14.1: Low cardiac output (CO) results in vasoconstriction Fig. 14.2: By reducing the systemic vascular resistance and decreasing
increasing systemic vascular resistance (SVR) and venous tone leading the venous tone vasodilators provide better work capacity. LVEDP—
to increase in the work of heart left ventricular end-diastolic pressure
by increasing the systemic vascular resistance, which inhibitors. Since ACE inhibitors might cause first dose
increases cardiac work (Fig.14.1). Venoconstriction results hypotension, the first dose should be one quarter of the
in decreased venous capacitance and increased venous calculated dose. The patient should be recumbent for the
return, thereby increasing the filling pressures of the first 6 hr to prevent unusual fall in blood pressure. Aspirin
ventricles to increase the cardiac output. Since the and non-steroidal antiinflammatory drugs attenuate the
compensatory mechanisms are inappropriately excessive, effects of ACE inhibitors and increase the possibility of
vasodilators, by reducing the arteriolar and venous vaso renal toxicity. In the presence of renal dysfunction, it is
constriction, reduce the work of heart (Fig. 14.2). preferable to use ramipril since it is excreted through
Traditionally, nitrates were used as preferential venodi- kidneys as well as liver.
lators and hydralazine as an arteriolar dilator (Table 14.6). In the acute care setting sodium nitroprusside is often
The use of ACE inhibitors (captopril and enalapril) is now used as a vasodilator. It has effects on both the venous as
well established in infants and children. Besides being well as the arterial systems. Phosphodiesterase inhibitors
vasodilators, ACE inhibitors have other useful effects in such as milrinone have become very popular, especially
CCF. They suppress the renin-angiotensin-aldosterone in postoperative settings. They have powerful vasodila-
system, thus reducing vasoconstriction as well as sodium tory and inotropic effects. The indications for use of
and water retention. They prevent potassium loss, vasodilators include, acute mitral or aortic regurgitation,
reducing the risk of arrhythmias. By suppressing ventricular dysfunction due to myocarditis, anomalous
catecholamines, they prevent arrhythmias as well as the coronary artery from pulmonary artery and in postopera
adverse effects of catecholamines on the myocardium. The tive setting.
major side effect of ACE inhibitor is cough, which can be Although P-adrenergic blockers are known to precipi
quite troublesome. Persistent cough may necessitate the tate CCF, they have been found to improve survival
use of angiotensin receptor blockers (losartan, irbesartan, especially in patients with DCM, who continue to have
valsartan). Initially it is necessary to monitor the renal inappropriate tachycardia. The most useful agents include
function: urinalysis, serum electrolytes, creatinine and metoprolol and carvedilol. The latter is preferred because
urea once a week for 6-8 weeks after starting ACE it combines the properties of |3-blockers with peripheral
vasodilation. Treatment with carvedilol (begun at 0.08- Digitalis is used with caution in the following situations
0.4 mg/kg/day and increased to maximum 1 mg/kg/day) (a) premature neonates; (b) CCF due to myocarditis;
has been shown to improve survival in patients with DCM. (c) intensely cyanotic patients; and (d) CCF associated with
Calcium channel blockers have been shown to have a large heart. The dosage for premature infants is indicated
adverse effects in CCF and should be avoided, unless in Table 14.7. In other situations, it is better to use half the
indicated for control of systemic hypertension. calculated digitalizing as well as the maintenance dose
initially. Myocardial damage, gross cardiomegaly, hypo
Augmenting Myocardial Contractility xia, acidosis, hepatic, renal and pulmonary insufficiency
Augmenting myocardial contractility by inotropic drugs increase the sensitivity of the myocardium to digitalis.
like digitalis improves cardiac output. In infants and Better control for therapy and avoidance of toxicity is
children, only digoxin is used. It has a rapid onset of action possible with digoxin assays.
and is eliminated quickly. It is available for oral and Patients receiving combined treatment with digoxin
parenteral administration. Oral digoxin is available in and frusemide should preferably receive PO potassium
white (Lanoxin-Burroughs Welcome) 0.25 mg tablets and chloride 1-2 mEq/kg/day in divided doses (15 ml of 10%
as Digoxin elixir (1 mL contains 0.05 mg). Guidelines for solution provides 20 mEq).
use of digoxin are given in Table 14.7. Digitalis decreases
heart rate and increases myocardial contractility. The Inotropic Agents
strength and velocity of myocardial contraction is increas Apart from digoxin, these agents belong to two groups:
ed due to action on the myocardium. (i) catecholaminic inotropic agents, e.g. dopamine and
dobutamine; and (ii) non-catechol, non-digitalis glycoside
agents, e.g. amrinone and milrinone. Of these, only the
Table 14.7: Digoxin and frusemide dosage former are useful; amrinone, milrinone, xamoterol and
Digitalizing Maintenance dose flosequinon are not safe and do not prolong life. In a
Digoxin dose mg/kg (fraction digitalizing dose) patient with CCF if the blood pressure is low, dopamine
should be used as an infusion. At a dose less than 5 mg /
Premature, neonates 0.04 1/4
kg /min, it causes peripheral vasodilation and increases
1 month-one year 0.08 1/3 to 1/4
myocardial contractility. The renal blood flow improves,
1-3 years 0.06 1/3 to 1/4
1/3 resulting in natriuresis. In higher doses, it results in peri
Above 3 years 0.04
pheral vasoconstriction. Dobutamine has certain advan
Frusemide tages over dopamine. It does not need to be administered
1-3 mg/kg/day PO via a central line. The dose of dobutamine is 2-15 mg/
1 mg/kg/dose IV kg /min. It should be increased gradually until the desired
response is achieved.
In patients with DCM, dobutamine has been used as a
24 hr infusion once or twice a week. Another inotropic
Except for premature babies, the smaller the child, the agent, used in adults is ibopamine. This is an orally
better he can tolerate digitalis. In a hospitalized patient effective agent, which releases epinine, with inotropic,
full digitalization should be sought to maximize benefit. vasodilator and natriuretic effects.
If one-quarter or one-half of a full digitalizing dose is The use of digitalis for its inotropic effect is
given, the increase in cardiac contractility is 14 or Vi respec controversial. In CCF, the serum level of catecholamines
tively of the full digitalizing dose. Unlike adults, children is high. CCF is associated with myocardial dysfunction.
should be digitalized within a 24 hr period; Vi of the If the myocardium is failing it should be provided rest
calculated digitalizing dose is given initially, another 1/4 using vasodilators rather than inotropic agents. Use of
in 6-8 hr and the remaining 1 /4 in next 6-8 hr. The main inotropic agents is like flogging a tired horse. High
tenance dose varies from 1/4 to 1/3 of the daily catecholamine levels have been shown to be toxic to
digitalizing dose, started 24 hr after the first dose. Before myocardium in animals. Lastly, digitalis has a low
the third dose is given, an EKG should be obtained to rule therapeutic to toxic ratio and can result in serious life-
out digitalis toxicity. The parenteral dose is 7/10 of the threatening arrhythmias. A number of studies have
oral dose. confirmed that the use of digoxin is beneficial for symptom
The patient should be observed for signs of digitalis relief and that digoxin should be used whether the patient
toxicity. In most patients, the toxicity can be controlled has mild, moderately severe or severe CCF, with or
by omitting the next one-two doses. The PR interval of without sinus rhythm. Digoxin is a second-line drug like
the EKG is a useful indicator of toxicity in children. If the ACE inhibitors. Both can be combined for a synergistic
PR interval widens to one and a half times of the initial effect. By increasing cardiac output, digoxin lowers the
PR interval, digitalis toxicity is present. In infants, the systemic impedence indirectly, thus to some extent
upper limit of normal PR interval is 0.14 second. unloading the ventricles.
378 Essential Pediatrics
Improving Cardiac Performance by the most important purpose of clinical evaluation and
Reducing Venous Return (Preload) diagnostic tests in children with suspected DCM is to
Diuretics reduce the blood volume, decrease venous return identify correctable conditions that present with ventri
and ventricular filling. This tends to reduce the heart size. cular dysfunction. The commonest conditions missed are
The larger the heart, the more the wall tension and the atrial tachyarrhythmias, coarctation of the aorta and
poorer is its performance. With reduction in heart size and obstructive aortitis.
volume, the myocardial function and the cardiac output The presence of CCF in a child with rheumatic heart disease
improve. Diuretics reduce the total body sodium, thus does not necessarily mean presence of active carditis. In any
reducing the blood pressure and the peripheral vascular patient of rheumatic heart disease, if active carditis has
resistance. This helps in increasing the cardiac output and been excluded and an adequate trial given to medical
reducing the work of the heart. The increase in blood management, operative treatment should be considered.
volume is a compensatory phenomenon in CCF. If It is important to look for sustained tachyarrhythmia on
reduction of blood volume is vigorous, it may cause the EKG. The heart failure is corrected once the arrhythmia
hypotension and elevation of blood urea nitrogen. is managed. Anomalous origin of the left coronary artery
Diuretics are the first line of management in congestive is treated surgically. Other primary myocardial diseases
failure. The action of orally administered frusemide starts do not have specific treatment. Prolonged bedrest combined
gg| within 20 minutes. Frusemide interferes with the sodium, with anticongestive measures including vasodilators may be
I potassium and chloride transport in the ascending limb helpful. The prognosis depends on the underlying cause.
jjl of Henle. Patients on frusemide should receive potassium When treating these patients caution should be exercised
ii supplements. With the use of potent diuretics like regarding the use of digitalis. There is evidence to suggest
I frusemide, it is necessary to have frequent checks of the that steroids may be hazardous in patients with Coxsackie
W serum electrolytes to prevent serious electrolyte imba myocarditis. Steroids should be avoided in patients of
lance. It is preferable to combine frusemide with a potas myocarditis in the acute stage, unless they have serious
sium sparing diuretic such as spironolactone, triamterene conduction disturbances or peripheral vascular failure.
or amiloride instead of giving potassium supplements. Patients with DCM may benefit from treatment with beta-
Frusemide activates renin-angiotensin-aldosterone blockers. If endocardial biopsy suggests active inflam
system (RAAS), which is responsible for vasoconstriction mation, treatment with steroids and immunosuppressants
(increases work of heart) and sodium and water retention. may be considered in selected cases. However, there is
If indicated, ACE inhibitors should be combined with little published evidence that supports its use to improve
frusemide; the combination further suppresses the RAAS. eventual prognosis. Patients with endocardial fibro
The other method of altering the body fluid volume is elastosis do not respond well to digitalis. Once digitalis
by restricting the sodium intake. Sodium restriction cannot has been started in these patients, it should be continued
be practised in infants, since low sodium milks are not for a number of years. Early discontinuation may result
easily available. In older children it is not justified to in reappearance of CCF resistant to therapy.
restrict the salt intake excessively since children cannot Uncommon causes of CCF in infants and children
be forced to eat what they do not like. Since salt-free diets include upper respiratory infection, hypoglycemia, neo
are unpalatable, child stops eating and loses weight. Low natal asphyxia and hypocalcemia. Appropriate treatment
sodium diets should be used only if CCF cannot be depends on a high index of suspicion. Hypertrophied
controlled with digitalis, diuretics and ACE inhibitors. tonsils and adenoids by causing upper respiratory
CCF increases calorie requirements. Concentrated milk obstruction, resulting in hypoxia and hypercapnia, can
formulae supplemented by soluble protein preparations cause pulmonary hypertension and CCF. Management
provide more calories. consists of relief of the upper airway obstruction.
either nitrates or carvedilol, whichever was not used decline in RF incidence and RHD prevalence. Surveys
earlier. Therapy with once-daily spironolactone has been conducted at Chandigarh, Indore, Cochin and Vellore
shown to improve outcome. Careful monitoring of serum involving more than 100,000 children (2004-2007) indicate
potassium is required; combined therapy of potassium that the prevalence has dropped to below 1/1000 to as
sparing diuretics, oral potassium supplements and ACE low as 0.5 to 0.6/1000.
inhibitors should be avoided. Step 4 is the intermittent The incidence of rheumatic fever following strepto
use of dobutamine or dopamine with dobutamine coccal sore throat in western countries is 0.3% in the
(separate infusion), if the blood pressure is low. Step 5 general population and 1-3% in crowded communities
involves making sure that the patient is getting all advised like army barracks.
medications. Those not adequately controlled need either
Age and sex: The most common age group is 5-15 yr.
medical or surgical correction of the cause of CCF. The
Though rheumatic fever is believed to be less common
only patients who do not respond to the above measures
below the age of 5 yr, it is unlikely to be so in India, since
and do not have a correctable cause would be patients
established juvenile rheumatic mitral stenosis is often seen
with myocarditis or DCM. For them, Step 6 involves a
in children below the age of 12 years. The sexes are nearly
myocardial biopsy and treatment with corticosteroids if
equally affected, mitral valve disease and chorea being
evidence for active myocarditis is present. In the absence
more common in females, whereas aortic valve involve
of active myocarditis, therapy with (3-blockers (e.g.
ment is more often seen in males.
carvedilol) should be increased to maximum tolerable
levels. Step 7 is the use of ventricular assist devices or Predisposing factors: Poor socioeconomic conditions leading
cardiac transplantation. It is necessary to emphasize that to unhygienic living conditions and overcrowded
the last two steps are applicable only to rare patients with, households are predisposing factors since they help spread
e.g. DCM. infections. Undernutrition, by altering the immune res
ponse, may increase susceptibility. However, recent
Prognosis epidemics in United States have occurred in upper middle
The mortality of CCF in infants is very high (40%), despite class families in the absence of overcrowding and with
best medical treatment. This indicates that early recogni good medical facilities.
tion and referral to specialized centers for infant care
providing both medical and surgical help, is essential to Etiopathogenesis
improve outcome. The etiology of rheumatic fever is unknown. A strong
association with (3-hemolytic streptococci is indicated by
ACUTE RHEUMATIC FEVER the following:
Rheumatic fever is an immunological disorder initiated i. A history of preceding sore throat is available in
by group A beta-hemolytic streptococcus. Recent studies approximately 50% patients.
suggest that besides group A streptococci, group E and G ii. Epidemics of streptococcal infection are followed by
may also cause rheumatic fever. Antibodies produced a high incidence of rheumatic fever.
against some streptococcal cell wall proteins and sugars iii. The seasonal variation of rheumatic fever and
react with the connective tissues of the body and heart streptococcal infection are identical.
and result in rheumatic fever. There is no single test for iv. In patients with established rheumatic heart disease,
the confirmation of diagnosis. There is a strong relation streptococcal infection is followed by recurrence of
ship with streptococcal infection and it is possible to acute rheumatic fever.
prevent rheumatic fever by appropriate treatment of v. Penicillin prophylaxis for streptococcal infection
streptococcal infection with the use of penicillin. prevents recurrences of rheumatic fever in those
patients who have had it earlier.
Epidemiology vi. More than 85% patients with acute rheumatic fever
Rheumatic heart disease constitutes 10-50% of the cardiac consistently show elevated levels of anti-streptococcal
patients in Indian hospitals. The prevalence rate for antibody titer.
rheumatic heart disease in the village population near Though these features indicate the association of
Agra was 2/1000 and in the urban population of rheumatic fever with streptococcal infection, streptococci
Chandigarh it was 2.07/1000 for women and 1.23/1000 have never been isolated from lesions in joints, heart or
for men. Similar figures were obtained in Delhi. A survey the blood. Considerable evidence suggests that the
of 11 cities in India showed a prevalence rate of 0.55 to rheumatic fever is an antigen-antibody reaction. Following
0.67/1000. A survey conducted by the Indian Council of streptococcal sore throat, there is a latent period of 10 days
Medical Research (ICMR) involving 133,000 children 6 to to several weeks before the onset of rheumatic fever. This
16 years in age showed the incidence to be 5.3/1000. latent period is similar to the other antigen-antibody
Selected parts of India are now reporting a significant diseases like serum sickness.
380 Essential Pediatrics
It has been suggested that patients of rheumatic fever major, minor and essential criteria (Table 14.8). Two major
produce antibodies against streptococcal cell wall and cell or one major and two minor criteria are required in the presence
membrane proteins. The streptococcal antigen and human of essential criteria to diagnose acute rheumatic fever. It is
myocardium appear to be identical antigenically. These important to emphasize that these guidelines are meant
antibodies might react with human connective tissue to enable the diagnosis of rheumatic fever and do not mean
especially the cardiac muscle, striated muscle and vascular that a physician should not use his clinical judgment in making
smooth muscle. By immunofluorescence, the antibodies a diagnosis in the absence of these criteria.
have been seen attached to sarcolemma of the cardiac
muscle. Streptococcal products against which antibodies Major Criteria
have been demonstrated include streptolysin, hyaluro- Carditis: The rheumatic carditis is a pancarditis involving
nidase, erythrogenic toxin, streptokinase and deoxyribo the pericardium, myocardium and the endocardium.
nuclease. Carditis occurs in 50-60% of patients with acute rheumatic
The hyaluronic acid capsule of streptococci prevents fever. It is an early manifestation of rheumatic fever so
phagocytosis by leukocytes. Below the capsule, hair-like that by the time a patient seeks help, he already has
fimbriae containing lipoteichoic acid as well as the M, T evidence of carditis. Almost 80% of those patients who
and R proteins are present. Lipoteichoic acid provides the develop carditis do so within the first 2 weeks of the onset
mucosal attachment (destroyed by penicillin). The M, T of rheumatic fever.
and R proteins are utilized for typing the streptococci. The
Pericarditis: Pericarditis results in precordial pain, which
M protein is believed to be the virulence factor of the
streptococcus. Each strain has a type specific M protein. may be quite severe; a friction rub is present on
auscultation. Clinical pericarditis is seen in approximately
A component of the streptococcal cell wall carbohydrate,
N-acetyl glucosamine is also present in human connective 15% of those who have carditis. The EKG may show ST
and T wave changes consistent with pericarditis. Rheu
tissue. Compounds containing N-acetyl glucosamine
matic pericarditis is associated with only small effusions
cross-react with antiserum against human connective
tissue. and does not result in tamponade or constrictive peri
Thus, streptococcal cell wall proteins as well as carditis. A patient of rheumatic pericarditis always has
additional mitral or mitral and aortic regurgitation murmurs.
carbohydrates have the capacity to produce antibodies
If after the disappearance of the pericardial friction rub
capable of reacting with human connective tissue,
there are no murmurs, one can safely exclude rheumatic
resulting in rheumatic fever. Rheumatic fever appears to
fever as the cause of pericarditis. The importance of
be the result of the host's unusual response at both the
cellular and humoral level to streptococcus. Antibodies pericarditis lies in identifying the presence of carditis as
well as the presence of acute rheumatic fever.
against the heart muscle (anti-heart antibodies) and
nervous tissue (anti-neuronal antibodies) are found in high Myocarditis: The features of myocarditis are (i) cardiac
titers in patients with carditis and chorea. The antibodies enlargement, (ii) soft first sound, (iii) protodiastolic (S3)
are specific in that they react with rheumatic tissue, but gallop, (iv) CCF and (v) Carey Coombs' murmur.
not other tissue. However, their exact significance is not
clear. These features, however, do not explain why some
people are susceptible while others are not so susceptible Table 14.8: Criteria for diagnosis of rheumatic fever
to rheumatic fever following streptococcal infection. Major criteria Minor criteria
Human leucocyte antigen (HLA) studies suggest an
Carditis A. Clinical
association with HLA-DR3. Serum 883, a B-cell alloantigen
Arthritis i. Fever
is identified in 100% patients with rheumatic fever.
Subcutaneous nodules ii. Arthralgia
Another antibody labeled D 8/17 identified 100% patients Chorea iii. Previous rheumatic fever,
in USA but only 60% in India. The findings favor genetic Erythema rheumatic heart disease
susceptibility to rheumatic fever, perhaps inherited in marginatum
Mendelian recessive pattern. B. Laboratory
i. Acute phase reactants:
Clinical Features leukocytosis, elevated
sedimentation rate and
The clinical features of rheumatic fever consists of
C-reactive protein
streptococcal sore throat with fever followed 10 days to a ii. Prolonged PR interval on EKG
few weeks later by recurrence of fever and various
Essential criteria
manifestations of acute rheumatic fever. History of sore
throat is available in less than 50% patients. Guidelines Evidence for recent streptococcal infection, as indicated by
for the clinical diagnosis of acute rheumatic fever, a. Increased antistreptolysin O titer
b. Positive throat culture
originally suggested by Duckett Jones were revised by the
c. Recent scarlet fever
American Heart Association. The guidelines consist of
Disorders of Cardiovascular System 381
Myocarditis per se plays little, if any role, in the morbidity in tricuspid regurgitation occurs in 10-30% cases. Isolated
of rheumatic fever. tricuspid valvulitis as a manifestation of acute rheumatic
Carey Coombs' murmur is a delayed diastolic mitral endocarditis does not occur. Clinical evidence of pul
murmur heard during the course of acute rheumatic fever. monary valve involvement in acute rheumatic fever is
It tends to disappear after the myocarditis subsides. never seen.
Although believed to indicate myocarditis, it is unlikely The acute hemodynamic overload resulting from acute
that the murmur is due to myocarditis per se. No other mitral regurgitation and/or aortic regurgitation leads to
myocarditis results in a mitral diastolic murmur unless left ventricular failure and is the main reason for the
associated with significant mitral regurgitation. Most morbidity and mortality of rheumatic fever and rheumatic
likely it is due to increased diastolic flow, secondary to heart disease. The severity of the valvar endocarditis
mitral regurgitation, across inflamed cusps. The disappea causing acute and later chronic hemodynamic overload
rance can be explained by the decrease in the left ventri determines the prognosis of individual patients.
cular size following subsidence of myocarditis, and better
function of the mitral valve—papillary muscle complex. Arthritis: Rheumatic arthritis is a polyarthritis involving
large joints like knees, ankles and elbows. Uncommonly
Evidence for absence of myocarditis playing any role
smaller joints may also be involved. It is a migratory
in the morbidity and mortality of rheumatic fever is based
polyarthritis with the affected joints showing redness,
on the following findings:
warmth, swelling, pain and limitation of movement. It is
1. Troponin T, a marker of myocardial damage, has an early manifestation and occurs in 70-75% cases
been found not to increase during acute rheumatic according to western literature. However, the figures from
fever with carditis indicating absence of significant India indicate that arthritis is seen in 30-50% patients. The
myocardial damage. pain and swelling appear rather quickly, last 3-7 days and
2. Radionuclide evaluation using antimyosin antibody subside spontaneously to appear in some other joint. There
indicates insignificant myocardial uptake (hence is no residual damage to the joint. One clinical observation
absence of significant damage) in the absence of regarding arthritis is that the younger the patient with
pericarditis and CCF. acute rheumatic fever, the less the arthritis and the older
3. Myocardial biopsies during acute rheumatic fever the patient, the more the arthritis.
with carditis have failed to provide information Subcutaneous nodules: Subcutaneous nodules appear on
regarding presence of myocarditis because of paucity
bony prominences like elbows, shins, occiput and spine.
of myocardial damage. They vary in size from pinhead to an almond. They are
4. Echocardiographic evaluation of the left ventricular non-tender. Subcutaneous nodules are a late manifestation
function indicates that the myocardial contractility and appear around 6 weeks after the onset of rheumatic
(the capacity of myocardium to contract) remains fever though they have been described as early as 3 weeks
normal even in the presence of CCF. from the onset. They occur in about 3-20% cases of
5. Pathological evaluation of the myocardium indicates rheumatic fever in India. Patients who have subcutaneous
that the amount of myocardial damage is insufficient nodules almost always have carditis. They last from a few
to explain the mortality. days to weeks but have been known to last for almost a
6. Surgical replacement of mitral and/or aortic valve year.
during acute rheumatic fever results in a rapid Chorea: Sydenham's chorea is a late manifestation occur
control of CCF and decrease in heart size, despite ring about 3 months after the onset of acute rheumatic
investigational evidence for ongoing active rheu
fever. Generally, when a patient manifests chorea, the
matic fever. The surgical findings thus indicate that
signs of inflammation in the form of elevated sedimen
it is the acute hemodynamic overload secondary to tation rate have returned to normal. Chorea consists of
valvar regurgitation, which is responsible for CCF purposeless, jerky movements resulting in deranged
and the morbidity and mortality of acute rheumatic speech, muscular incoordination, awkward gait and
fever. weakness. The affected child is emotionally disturbed and
drops things she or he is carrying. It is 3-4 times more
Endocarditis: The endocarditis is represented by a pan-
common in females as compared to males. Untreated, it
systolic murmur of mitral regurgitation with or without
has a self-limiting course of 2-6 zoeeks.
an associated aortic regurgitation murmur. Pathologically
mitral valve is involved in 100% cases of rheumatic fever Erythema marginatum: Although considered more specific
who have carditis. Clinically, however, 5-8% patients may than other varieties of skin manifestations, it is extremely
present as pure aortic regurgitation. Thus, almost 95% rare in Indians. The rash is faintly reddish, not raised above
patients have mitral regurgitation murmur, a quarter of the skin and non-itching. It starts as a red spot with a pale
them also having an aortic regurgitation murmur and only center, increasing in size to coalesce with adjacent spots
5% pure aortic regurgitation. Tricuspid valvulitis resulting to form a serpiginous outline. We believe that the inability
382 Essential Pediatrics
to recognize erythema marginatum is not because it does is the antistreptolysin 'O' titer (ASO). Considerable
not occur but because of the dark complexion of the skin. confusion exists regarding its value as well as the levels,
Anyone who has seen erythema marginatum would which should be considered significant. Elevated levels
recognize the futility of searching it in a dark com- of ASO only indicate previous streptococcal infection and
plexioned person. It is an early manifestation, predo not rheumatic fever. Although generally the higher the
minantly seen over the trunk. level the more likely one can conclude a recent strepto
coccal infection, lower levels considered "normal" do not
Minor Criteria necessarily exclude a recent streptococcal infection. For
Clinical example, if the basal ASO titer of an individual is 50 units
i. Fever: Rheumatic fever is usually associated with fever. and it goes up to 250 units, it is indicative of recent
The temperature rarely goes above 39.5°C. In the initial streptococcal infection. An isolated figure of 250, if the
attack, it is present in almost 90% patients. previous levels are not known, is not helpful in taking a
ii. Arthralgia: Arthralgia is defined as subjective pain decision. Rising titer of ASO is a strong evidence for a
whereas arthritis means subjective symptoms as well recent streptococcal infection.
as objective signs of joint inflammation. Whereas Positive throat culture for streptococci is relatively
arthritis is a major manifestation, arthralgia is a minor uncommon, when a patient presents with acute rheumatic
manifestation. Figures from India indicate that fever. Positive throat culture can also not be equated with
arthritis and arthralgia together occur in about 90% the diagnosis of rheumatic fever. Positive throat culture
patients. means that streptococci are present in the throat. The
iii. Previous rheumatic fever or rheumatic heart disease: This patient may or may not have rheumatic fever. The third
minor criterion is applicable only for a second attack feature suggestive for the diagnosis of recent streptococcal
of rheumatic fever. infection is the presence of residua of scarlet fever. The
desquamation of skin of palms and soles indicates that
Laboratory the patient has had scarlet fever within the previous two
weeks.
i. Acute phase reactants consist of polymorphonuclear
leukocytosis, increased sedimentation rate and
Echocardiography
presence of C-reactive protein. The leukocyte count is
usually 10,000-15,000 per cu mm. The sedimentation It is a very sensitive investigation for the diagnosis of
rate is usually elevated during acute rheumatic fever rheumatic carditis. Features indicative of rheumatic
and remains so for 4-10 weeks in almost 80% patients. carditis consist of annular dilatation, elongation of the
In a small proportion of patients, it may remain chordae to the anterior leaflet of the mitral valve causing
elevated even beyond 12 weeks. Although CCF tends prolapse and lack of coaptation of the two leaflets resulting
to bring the sedimentation rate down toward normal, in mitral regurgitation. The jet of mitral regurgitation is
it is unlikely that a patient of acute rheumatic fever directed toward the posterolateral wall. There is focal
with CCF will have a normal sedimentation rate. C- nodular thickening of the tips of the mitral leaflets, which
reactive protein is a (3-globulin, which is increased do not have an independent chaotic movement seen with
uniformly in all patients of acute rheumatic fever. It infective endocarditis. In addition, there is variable degree
subsides rapidly if a patient is on steroids. Absence of of increase in the left atrial and ventricular size. Involve
C-reactive protein is strongly against the diagnosis of ment of the aortic valve is recognized as aortic regur
acute rheumatic fever. Presence of C-reactive protein, gitation.
however, is not diagnostic since it becomes positive Though the revised Jones criteria do not include
in many other infections. echocardiographic and Doppler findings for the diagnosis
ii. Prolonged PR interval in the EKG: Prolonged PR interval of carditis, these investigations have improved the
is a non-diagnostic criterion since it can get prolonged recognition of carditis, which at times is not possible
in many infections. It is also not diagnostic of carditis. clinically. This has led to the recognition of the entity of
Higher grades of block like second degree atrio subclinical carditis in which although there are no clinical
ventricular block, especially of the Wenckebach type, findings, the echocardiographic findings indicate mitral
may also be seen. Complete atrioventricular block is regurgitation.
rare. Prolongation of QTc (corrected QT interval) is
also suggestive of myocarditis. Treatment
There is no specific treatment. Management is
Essential Criteria symptomatic combined with suppressive therapy. The
The essential criteria include evidences for recent patients need secondary prophylaxis, and long-term
streptococcal infection. The most useful is the presence of follow-up to establish the natural course of the clinically
antibodies against the streptococci. The commonest in use silent disease.
Disorders of Cardiovascular System 383
Bedrest: All patients with acute rheumatic fever should be this, the reduction in dose is by 5 mg/week. The dose of
kept on bedrest and in those with carditis; the bedrest aspirin is 90 to 120 mg/kg/day in four divided doses. If
should be prolonged until evidence of activity subsides. facilities for estimation of blood levels of salicylate are
Such end points are at times difficult to determine. Patients available, these are maintained between 20-25 mg/dL.
who do not have carditis can be ambulatory in 2-3 weeks, Management of congestive cardiac failure is dealt with
whereas if carditis is present, immobilization is continued previously. It is emphasized that surgical replacement of
for one to three months, especially in the presence of CCF. the mitral and/or aortic valve is indicated if the patient is
deteriorating despite aggressive anticongestive measures.
Diet: In the absence of cardiac involvement, there should
Hemodynamic overload due to mitral and/or aortic
be no restriction in salt intake. Even in the presence of
regurgitation is the main cause of mortality.
cardiac involvement, salt restriction is not necessary unless
CCF is present and not responding well to treatment. Management of Chorea
Penicillin: After obtaining throat cultures, the patient Chorea is a late manifestation. By the time a patient
should be treated with penicillin. Initially the patient is presents as chorea the sedimentation rate as well as the
given therapeutic doses of penicillin, 400,000 units of ASO may be normal. The patient as well as the parents
procaine penicillin, intramuscularly, twice daily for 10 should be reassured and told about the self-limiting course
days. This is followed by treatment with benzathine of the disease. The patient should be provided complete
penicillin 1.2 million units every 21 days, or 0.6 million physical and mental rest. Phenobarbitone 30 mg thrice
units every 15 days. The dose is decided by the patients' daily is given. Other drugs, including chlorpromazine,
muscle mass, since the injections are painful. diazepam, diphenhydramine (Benadryl) or promethazine
(Phenergan) can be administered. Although aspirin and
Suppressive Therapy steroids are supposed not to have a place in the
Aspirin or steroids are given as suppressive therapy. Since management of chorea, we have seen dramatic response
untreated rheumatic fever subsides in 12 weeks in 80% in some patients not doing well on a combination of
patients, either of the two suppressive agents is given for chlorpromazine and phenobarbitone. Long-term follow
12 weeks. Steroids are a more potent suppressive agent up studies in patients of chorea have shown appearance
as compared to aspirin. However, there is no proof that of heart disease in 20% patients in twenty years and 30%
the use of steroids results in less cardiac damage as in thirty years. Penicillin prophylaxis is essential to prevent
compared to aspirin. A number of observations indicate recurrence of rheumatic fever.
that steroids act faster and are superior in the initial
phases. Pericardial friction rub tends to disappear within Prevention of Rheumatic Fever
3-5 days after starting the steroids and a new friction rub It would be ideal to provide primary prevention of
does not appear. Despite adequate doses of aspirin, a new rheumatic fever.
friction rub may still make its appearance. Similarly
Primary prevention: It requires identification of strepto
subcutaneous nodules tend to disappear faster with the
coccal sore throat and its treatment with penicillin. It
use of steroids as compared to aspirin. Lastly, patients
depends on the awareness of parents regarding dangers
who have carditis with CCF have higher mortality if aspi
of sore throat. For primary prevention, it is necessary to
rin is used compared to steroids. In selecting the suppres
educate the community regarding the consequences of
sive drug for an individual patient, the following guide
streptococcal sore throat. Logistically it is difficult since it
lines are followed:
requires (i) identification of sore throat, (ii) rapidly
i. If a patient has carditis with CCF, the use of cortico
confirming that the sore throat is streptococcal, and (iii)
steroids is mandatory.
provision of appropriate treatment.
ii. Carditis without CCF: one may use either steroids or
Data from recent epidemics of rheumatic fever in
aspirin; steroids are preferred.
iii. If the patient does not have carditis, it is preferable to United States indicates that 30-80% of sore throats result
ing in rheumatic fever can be asymptomatic. Rheumatic
use aspirin.
fever could not be prevented in patients of streptococcal
The duration of course for the suppressive agent,
pharyngitis treated by adequate doses of oral penicillin for ten
aspirin or steroids, is 12 weeks. With aspirin, the full doses
days. As such intramuscular benzathine penicillin is mandatory
are given for 10 weeks and then tapered off in next two
for prevention of rheumatic fever. Because asymptomatic
weeks. Full doses of steroids are given for three weeks
streptococcal pharyngitis can result in rheumatic fever,
and then tapered very gradually in the next nine weeks.
primary prevention can only be possible by using an anti-
The steroid most commonly used is prednisone. The dose
streptococcal vaccine. Such a vaccine is under develop
is 60 mg/day for patients weighing more than 20 kg and
ment.
40 mg/day for patients weighing less than 20 kg. This is
continued for 3 weeks and then reduced to 50 mg /day Secondary prevention: It consists in giving long-acting
for 1 week and 40 mg/day for another week. Following benzathine penicillin. The dose is 1.2 million units once
384 Essentia! Pediatrics
every 3 weeks or 0.6 million units every 15 days, ventricle, the left ventricular diastolic pressure increases,
depending on patient age and muscle mass. The injection the left atrial and pulmonary venous pressure increase
is painful and some patients get fever for 24-36 hr and pulmonary congestion appears. There is an increase
following the injection. It is preferable to give the injection in pulmonary arterial pressure and features of pulmonary
on a Saturday afternoon to avoid loss of studies for the arterial hypertension appear. Thus presence of features
child. of pulmonary arterial hypertension in a patient having
Ideally, penicillin prophylaxis should continue life long. pure mitral regurgitation suggests (i) severe mitral
Less than the ideal would be to continue it until the age of regurgitation, or (ii) failing left ventricular myocardium,
35 years. The least satisfactory approach is to give for 5 or (iii) acute mitral regurgitation.
years from the last attack of rheumatic fever. The responsi The mitral regurgitation developing during acute
bility of continuing prophylactic penicillin lies on the rheumatic fever is of sudden onset. It results in an acute
parents, however, unless a physician takes time in hemodynamic overload over the left ventricle. The
explaining the seriousness of the problem and the features of left ventricular failure can occur even with
necessity of continuing penicillin on a long-term basis, the relatively moderate leaks during the acute illness. The size
physician has done his job inadequately. of the left atrium also plays a significant role in mitral
regurgitation. With acute mitral regurgitation the left atrial
RHEUMATIC HEART DISEASE size is normal and the increased volume reaching the left
atrium increases the left atrial and the pulmonary venous
In the pediatric age group, the sequelae of rheumatic fever pressure, resulting in pulmonary congestion and features
consist of mitral, aortic and tricuspid valve disease. The of left ventricular failure. With long standing mitral
mitral valve involvement manifests predominantly as regurgitation the left atrium increases in size to accommo
mitral regurgitation and much less commonly as mitral date the regurgitant volume without increasing the left
stenosis. The aortic valve and tricuspid valve involvement atrial pressure and features of left ventricular failure are
presents exclusively as aortic and tricuspid regurgitation absent. Another important adjustment consists of decrease
respectively. Rheumatic aortic stenosis has never been in the systemic vascular resistance to help increase the forward
described below the age of 15 years. flow. The maximum ejection of blood into the aorta takes
place during early systole. The combination of these two
Mitral Regurgitation
factors results in an increased systolic and decreased
Mitral regurgitation is the commonest manifestation of diastolic pressure in the systemic circuit. The pulse
acute as well as previous rheumatic carditis. In our own pressure is, therefore, increased resulting in the small water
study of 850 patients of rheumatic heart disease below hammer pulse of mitral regurgitation.
the age of 12 years, 750 patients had pure or dominant
mitral regurgitation. Clinical Features
On examination the pulse pressure is relatively wide. The
Hemodynamics resting pulse rate is increased to maintain an adequate
Mitral regurgitation results in a systolic leak of blood to cardiac output. In the absence of pulmonary congestion
the left atrium. The regurgitant volume of blood reaches the respiratory rate is normal. Features of left ventricular
the left atrium during ventricular systole at almost failure are absent and appear late unless the mitral
systemic pressure, however, during diastole it can pass regurgitation is acute, severe or left ventricular myocardium
freely across the mitral valve. Thus, although the left atrial is failing. The heart size is dependent on the severity of
pressure increases during systole, it drops during diastole. mitral regurgitation as well as the status of the left
The mean left atrial pressure, therefore, stays normal or is ventricular myocardium. The cardiac apex is displaced
only slightly increased. There is thus no increase in downward and outward with forcible apex and hyper
pulmonary venous pressure and no pulmonary con kinetic precordium. Less than 10% patients have a systolic
gestion. The increased volume of blood handled by the thrill. The reason for this is the direction of the regurgitant
left atrium and left ventricle results in an increase in the stream, which is backwards into the left atrium. Since the
size of both these chambers. Mitral regurgitation provides left atrium cannot be felt anteriorly over the precordium,
two exits for the left ventricular blood—the forward flow the murmur remains impalpable as a thrill. The first sound
through the aortic valve into the systemic circulation and may be soft, normal or occasionally accentuated. Gene
the backward leak into the left atrium. The forward output rally, it is inaudible as it is masked by the systolic murmur.
becomes insufficient during exertion. This decrease in the The second sound is normally split with mild mitral
systemic output results in fatigue, the commonest regurgitation. With moderate or severe mitral regur
symptom of significant mitral regurgitation. Absence of gitation the second sound is widely split but the width of
pulmonary congestion prevents occurrence of dyspnea splitting varies with respiration becoming narrower
unless the mitral regurgitation is severe or the left during expiration and wider with inspiration. The wide
ventricular myocardium is failing. With failing left splitting is due to an early aortic component of the second
Disorders of Cardiovascular System 385
sound. With failing left ventricle the wide splitting roentgenogram shows cardiac enlargement secondary to
disappears. Except with very mild mitral regurgitation, a left ventricular enlargement, the size depending on the
third sound is audible at the apex and indicates increased early severity of mitral regurgitation. Left atrial enlargement
rapid filling of the left ventricle. With severe mitral may be inferred from the elevation of left bronchus but is
regurgitation a delayed diastolic mitral murmur starting more clearly outlined with barium swallow in right
with the third sound is audible. The delayed diastolic anterior oblique position. In the absence of left ventricular
murmur is secondary to a large flow across the mitral valve failure, there is absence of prominence of pulmonary veins
during diastole. Not infrequently this delayed diastolic as well as features of pulmonary congestion. Echo
murmur may be palpable as a short diastolic thrill. In pure cardiogram shows enlarged left atrium and ventricle.
mitral regurgitation, the delayed diastolic murmur always Doppler echo can quantitate mitral regurgitation non-
ends somewhere in mid-diastole and there is no late diastolic invasively.
(presystolic) accentuation. It may appear unusual but a diastolic
thrill in severe mitral regurgitation is more common than a Differential Diagnosis
systolic thrill. The classical diagnostic sign is the pan- Besides rheumatic fever, other causes of mitral regur
systolic murmur, best heard at the apex and widely gitation in the pediatric age group include (i) atrial septal
radiating to the axilla and back as well as to the left sternal defect of the primum variety; (ii) coarctation of the aorta
border (Fig. 14.3). The pansystolic murmur of rheumatic with mitral regurgitation (congenital); (iii) left ventricular
mitral regurgitation is generally not well heard at the fibroelastosis; (iv) congenital corrected transposition of
second left interspace by the side of the sternum. great arteries; (v) papillary muscle dysfunction in
EKG shows sinus tachycardia and a normal axis. Signs dilatation of left ventricle from any cause including
of left ventricular hypertrophy may be present with long myocarditis; (vi) atrial septal defect of the secundum type
standing and severe mitral regurgitation. The thoracic with floppy mitral valve; (vii) Marfan and Hurler
syndrome, and (viii) anomalous origin of left coronary
artery from pulmonary artery.
LV Treatment
Mild to moderate mitral regurgitation is tolerated for long
fX periods. The severity of mitral regurgitation increases with
time. Medical management consists in the use of digitalis,
I ll
diuretics and vasodilators besides prophylactic penicillin
/
/
/°
/
1
Mitral Stenosis
S1 PSm S2
Rheumatic mitral stenosis is less common than mitral
regurgitation in children. In our analysis of 850 patients
Fig. 14.3: The characteristic pansystolic murmur. As the left ventricular of rheumatic heart disease up to the age of 12 years, the
(LV) pressure exceeds the left atrial pressure (LA) the first sound (S,) diagnosis of pure mitral stenosis was made in 96 patients.
occurs. However, the murmur of mitral regurgitation will also start at Pediatric mitral stenosis constitutes 10% of all rheumatic
the same time masking the Sv Since the maximum difference in the mitral stenosis patients.
LV and LA pressure is quickly reached and maintained throughout
systole, the murmur maintains the same intensity throughout systole Hemodynamics
appearing pansystolic. Finally as the LV pressure drops below the
aortic (Ao) pressure the A2 occurs. The LV pressure is higher than LA Mitral stenosis results in obstruction to flow of blood
pressure at this time and the murmur goes beyond the A2 thus masking across the mitral valve during left ventricular diastole. The
both the St and and the A2. (PSm Pansystolic murmur) left atrium compensates for this obstruction by increasing
386 Essential Pediatrics
its pressure. This increase in pressure results in hyper rheumatic mitral stenosis, based on evaluation of
trophy of the left atrial wall. However, the left atrium is a surgically removed left atrial appendage. The patients of
thin walled chamber and the capacity for its hypertrophy mitral stenosis give history of shortness of breath on
is limited. The increase in left atrial pressure prevents exertion or even at rest depending on the severity. Other
decrease in the blood flow across the mitral valve. Since important symptoms consist of cough, hemoptysis,
there are no valves between the left atrium and the paroxysmal nocturnal dyspnea, attacks of acute pul
pulmonary veins, the increased left atrial pressure is monary edema and atypical angina.
transmitted to pulmonary veins as well. The increased On examination the pulse is of small volume. The
pulmonary venous pressure results in pulmonary respiratory rate is increased except in patients with mild
capillary engorgement and pulmonary congestion, which mitral obstruction. Depending on the severity, there may
produces dyspnea, the commonest symptom of mitral or may not be signs of right sided congestion, in the form
stenosis. The pulmonary arterial pressure increases to of engorged neck veins and enlarged tender liver. The liver
maintain forward flow from the pulmonary artery to the may have systolic pulsations if there is associated tricuspid
left side of the heart. Clinically the pulmonary arterial regurgitation, the jugular venous pulse shows prominent
hypertension is recognized by accentuation of the pul 'a' waves. If tricuspid regurgitation is present, the jugular
monary component of the second sound. The right ventri- veins show dominant 'V' waves. With moderate or severe
_ cle hypertrophies and its systolic pressure increases as mitral stenosis signs of pulmonary congestion in the form
| pulmonary arterial hypertension increases, since it is the of rales are present.
n right ventricle that has to maintain the pulmonary Examination of the precordium reveals a normal sized
pressure as well as the flow. heart with a tapping apex beat, parasternal impulse and
In the absence of tricuspid regurgitation the right ventri- an apical diastolic thrill. The second sound may be
|g cular hypertrophy is concentric without an increase in the palpable at the second left interspace. On auscultation the
size of right ventricular chamber. The heart size stays first sound is accentuated, the second sound normally split
normal. With mild or moderate mitral obstruction, the with a loud pulmonary component. An opening snap of
forward flow through the mitral valve remains normal. the mitral valve is best audible just internal to the apex.
With severe mitral obstruction, the forward flow through The delayed diastolic mitral murmur starts immediately
the mitral valve is diminished. If the flow to the left ventri following the opening snap, diminishes somewhat in
cle decreases, the cardiac output diminishes and peri intensity during mid diastole and accentuates again at the
pherally one feels a small volume pulse. The diminished end of diastole (Fig.14.4). The late diastolic accentuation
cardiac output in severe mitral stenosis is recognized on is always present in the presence of mitral stenosis.
the bedside as cold extremities, with or without peripheral Absence of late diastolic accentuation of murmur is against
cyanosis and a small volume pulse. the diagnosis of dominant mitral stenosis.
The two most unfortunate aspects of mitral stenosis are The EKG shows right axis deviation with right ventri
(i) its occurrence distal to a thin walled left atrium with a cular hypertrophy and P mitrale. Thoracic roentgenogram
limited capacity for hypertrophy, and (ii) absence of valves
between the left atrium and the pulmonary veins. The
former is the main reason because of which the cardiac
output cannot be increased significantly with exercise and
if for any reason the systemic pressure falls and the patient
goes into shock it is extremely difficult to resuscitate the
patient. The latter results in pulmonary congestion and
dyspnea with exercise, limiting the capacity of the patient
to work even with mild obstruction. In the presence of
limited capacity to increase the forward flow, exercise can
precipitate pulmonary edema more readily. The right
ventricular hypertension can result in tricuspid regur
gitation, which is seen in 30% patients with moderate to
severe mitral stenosis.
Clinical Features Fig. 14.4: Mitral stenosis. Simultaneous left ventricular (LV) and left
atrial (LA) tracing. The shaded area represents the gradient between
Boys are affected twice as commonly as girls. The youngest
LV and LA. During this period the delayed diastolic murmur of mitral
patient with pure mitral stenosis seen in our clinic was 5 stenosis is heard. The shape of the murmur on auscultation
years-old. In another patient seen by us at the age of 8 corresponds to the shape of the diastolic gradient. Presence of
years, the diagnosis of mitral stenosis was made at the gradient at the end diastole (arrow) indicates significant mitral stenosis.
age of 4 years elsewhere. Of the operated patients, the The murmur starts after opening snap which will occur when the LV
youngest was 6 years with histological evidence of pressure drops below LA pressure (double arrow)
Disorders of Cardiovascular System 387
Arteriolar pulsations may be seen over the nail bed, uvula, ventricular septal defect with aortic regurgitation,
lips, ear lobes and in the eye grounds. There is also ruptured sinus of Valsalva, anemia and thyrotoxicosis, (ii)
exaggeration of the systolic pressure difference between conditions associated with a non-rheumatic regurgitant diastolic
the brachial and femoral arteries (Hill's sign). Normally murmur like pulmonary regurgitation, aortic regurgitation
the difference between the systolic pressure in the brachial with ventricular septal defect, ruptured sinus of Valsalva
artery and the femoral artery is less than 20 mm of and congenital aortic valve disease. Congenital aortic
mercury, the femoral systolic pressure being higher. valve disease is either a leaking bicuspid aortic valve or
Systolic pressure difference between 20 to 40 mm of aortic stenosis. Pure congenital aortic regurgitation is
mercury suggests mild aortic regurgitation. If the extremely rare. Other conditions, which may result in
difference is between 40 to 60 mm of mercury, it suggests aortic regurgitation, include Marfan syndrome, Hurler
moderate aortic regurgitation. A difference of more than syndrome and idiopathic aortoarteritis.
60 mm of mercury indicates severe aortic regurgitation.
If the stethoscope is put over the brachial or the femoral Management
artery without applying any pressure pistol shot sounds Mild to moderate aortic regurgitation is well tolerated for
may be heard in moderate or severe aortic regurgitation. years. Significant aortic regurgitation, if associated with
A systolic murmur may be heard if pressure is applied to either angina like chest pain or signs of left ventricular
_ partially occlude the artery proximal to the chest piece failure, can only be managed surgically. Surgical treatment
I and a diastolic murmur if pressure is applied distally. This consists of aortic valve replacement, by either homograft
n combination of systolic and diastolic murmurs is the or a prosthetic valve. Operative treatment is indicated for
'k I Duroziez sign. patients who have symptoms of either left ventricular
Examination of the precordium shows cardiac enlarge- failure or angina. Better surgical results are claimed in
|P ment with the apex displaced downward and outward. patients whose cardiothoracic ratio is less than 60%.
The size itself depends on the degree of aortic leak. The Cardiothoracic ratio is an unreliable index especially in
apex is forcible or heaving. With large leaks the whole children. If in a good inspiratory film the cardiothoracic
chest wall may show a back and forth movement. Uncom ratio is more than 55%, cardiac enlargement is present.
monly a diastolic thrill may be palpable at the upper left Before recommending valve replacement surgery one
or right sternal border. The first sound is soft and the aortic should consider: (i) has rheumatic activity and thus active
component of the second sound may be audible or may myocarditis subsided, since active myocarditis by itself
be masked by the regurgitant diastolic murmur. The can cause cardiac enlargement; (ii) is there any suggestion
murmur of aortic regurgitation is a high pitched, decre for progressive deterioration; (iii) is the patient's cardiac
scendo diastolic murmur starting with the aortic status bad enough to warrant prosthetic valve replacement
component of the second sound. The intensity and the and thus commitment to life long anticoagulation.
length of the murmur do not correlate with the severity Digitalis can be used if the patient has CCF, however,
of aortic regurgitation. The murmur is best heard along by slowing the heart rate, digitalis increases the regur
the left sternal border and radiates to the apex and even gitant volume of blood. Treatment with vasodilators,
beyond the apex. With large aortic leaks there is also an especially ACE inhibitors, is useful.
ejection systolic murmur at the second right interspace,
conducted to the neck and not infrequently associated with Aortic Stenosis
a systolic thrill. The systolic murmur is the result of a large Since rheumatic aortic stenosis is not seen in children, this
stroke volume, passing across rough valves. It does not is discussed later in this chapter.
indicate aortic stenosis if the pulse pressure is wide and
the carotid upstroke is brisk. Tricuspid Regurgitation
The EKG shows increase in left ventricular voltages with Features indicative of tricuspid regurgitation are seen in
deep 'S' waves in VI and tall 'R' waves in V6. There are also almost 20-50% patients with rheumatic heart disease in
deep 'Q' waves in left chest leads with tall'T' waves. The our country. In an individual patient it is difficult to decide
pattern of deep 'Q' waves and tall'T' waves has been called whether the tricuspid regurgitation is organic or
diastolic overloading of the left ventricle. Chest X-ray functional.
shows left ventricular cardiomegaly and dilated ascending
aorta. Echocardiogram shows enlarged left ventricle, Hemodynamics
dilated aorta and flutter of anterior mitral leaflet. A Doppler Tricuspid regurgitation results in a systolic backflow of
study quantitates the severity of valvar lesion. blood from the right ventricle to the right atrium. The
systolic leak thus results in a systolic murmur and a
Differential Diagnosis volume overload of the right atrium as well as the right
The differential diagnosis of rheumatic aortic regurgitation ventricle. The volume overload results in an increase in
includes: (i) conditions associated with a wide pulse pressure the size of the right atrium as well as the right ventricle,
like patent ductus arteriosus, arteriovenous fistulae, which is displaced dowmuard and outward. Usually all
Disorders of Cardiovascular System 389
patients with tricuspid regurgitation also have pulmonary tricuspid regurgitation, the EKG is helpful in separating
arterial hypertension. The systolic backflow under these cases from mitral regurgitation. Patients of tricuspid
pressure results in a prominent systolic wave, the V wave, regurgitation of this severity almost always show severe
in the jugular venous pulse as well as the liver. During right ventricular hypertrophy on EKG. Contrast echo and
inspiration the increased venous return increases the flow Doppler can document and quantitate the severity of tri
across the tricuspid valve. Thus both the systolic as well cuspid regurgitation as well as findings of left sided
as the diastolic murmurs at the tricuspid valve become disease.
louder during inspiration. In patients of rheumatic heart
disease the tricuspid regurgitation may be associated Management
either with mitral stenosis or with mitral regurgitation. If All patients with findings of tricuspid regurgitation should
the tricuspid regurgitation is associated with mitral be put on anticongestive measures whether the tricuspid
stenosis it may be either organic or functional due to regurgitation is associated with mitral stenosis or with
pulmonary arterial hypertension. If, on the other hand, mitral regurgitation. This will help in reducing the severity
the tricuspid regurgitation is associated with dominant of tricuspid regurgitation. Further management depends
or pure mitral regurgitation it is most likely organic. This on the associated mitral valve lesion. Patients of mitral
is because mitral regurgitation of a severity to result in stenosis may loose all evidences of tricuspid regurgitation
pulmonary arterial hypertension of a degree to cause following mitral valvotomy. Patients of tricuspid regur
functional tricuspid regurgitation is rare. gitation in association with mitral regurgitation generally
have severe mitral regurgitation. They should initially be
Clinical Features treated conservatively. If, however, there is evidence of
There are no specific symptoms of tricuspid regurgitation. deterioration or lack of improvement during follow up,
It is possible that with the onset of tricuspid regurgitation the patient may have to be sent up for mitral valve repair
the dyspnea may be relieved to some extent in patients of or replacement. At the time of operation the tricuspid
mitral stenosis. The patients may give history of pain in valve can be inspected and tricuspid annuloplasty or
the right hypochondrium due to a congested liver and of repair performed.
fatigue due to a decrease in systemic output. Specific
features of tricuspid regurgitation consist of (i) prominent Clinical Problems in Patients with
V waves in the jugular venous pulse, (ii) systolic pulsations Rheumatic Heart Disease
of the liver, and (iii) a systolic murmur at the lower left There are two major problems that one faces in patients
sternal border increasing in intensity with inspiration. of rheumatic heart disease: (i) Does the patient have active
With milder degrees of regurgitation it is not unusual to or inactive rheumatic fever? and (ii) in a febrile patient, is
have no systolic murmur during expiration, whereas a it active rheumatic fever or infective endocarditis?
grade II—III ejection or pansystolic murmur appears during
inspiration. With severe tricuspid regurgitation a loud Active or Inactive Rheumatic Fever?
grade III to IV pansystolic murmur is heard at the lower A lot of 'judgment' or personal bias is generally involved
left sternal border, which varies little with inspiration and in this decision. For the diagnosis of activity one has to
can be associated with a thrill, (iv) a right ventricular third use the Jones criteria. Presence of cardiac involvement
sound or a short tricuspid delayed diastolic murmur cannot be used as a major criterion since the carditis may
increasing in intensity during inspiration, may be audible be the result of a previous attack of rheumatic fever. How
in marked tricuspid regurgitation. ever, presence of a pericardial friction rub is evidence of
In addition to the above features there are signs of pul active carditis. If the patient has well documented cardiac
monary hypertension and mitral valve disease. In asso findings then the appearance of a new murmur or a signifi
ciation with mitral stenosis, severe tricuspid regurgitation cant increase in a pre-existing murmur is very suggestive
may result in marked dilatation of the right ventricle and for active rheumatic fever. History of arthralgia or arthritis
the whole of the anterior surface, including the apex may within a period of less than 12 weeks is suggestive of active
be formed by the right ventricle. In such patients the apex rheumatic fever specially if associated with elevated
beat is not only displaced outward but also downward. sedimentation rate and ASO titer. Despite CCF it is
This should not be mistaken for left ventricular enlarge unusual for the sedimentation rate to be normal in a
ment. In these cases the pansystolic murmur of tricuspid patient of active rheumatic fever. All patients of rheumatic
regurgitation may be heard from the lower left sternal heart disease must have elevated ASO titer before they
border to the apex. Since the left ventricle is displaced can be labeled as active. The difficulty arises in those
backwards, the mitral stenosis murmur may be audible patients who have relatively low levels of the ASO titer.
only in the axilla or may not be made out at all. It is not In such cases unless serial serum samples are available it
uncommon for these patients to be diagnosed as those of is difficult to decide whether there has been a rise in the
mitral regurgitation. Besides the peripheral signs of level of the ASO titer.
390 Essential Pediatrics
While foreign literature has emphasized that the low levels of ASO titer, it is best to give a therapeutic trial.
presence of CCF in children suggests active carditis, this Since infective endocarditis is more serious, the patient
is not true in India. Patients of severe mitral stenosis with should first be treated for this condition.
tricuspid regurgitation and CCF are not infrequent in
India, though unknown in western countries. Patients with Suggested reading
severe mitral regurgitation and CCF without rheumatic 1. Committee of the American Heart Association. Jones criteria (re
activity are also common. Presence of CCF cannot vised) for guidance in the diagnosis of rheumatic fever. Circula
tion 1965; 32: 664.
therefore be equated with rheumatic activity.
2. Guidelines for the diagnosis of rheumatic fever. JAMA 1992; 268:
2069-2073.
In a Febrile Patient is it Active 3. Narula J, et al. Rheumatic fever. Am Registry Path AFIP. Wash
Rheumatic Fever or Infective Endocarditis? ington DC, 1999.
zation, genitourinary procedures or bronchoscopy can presence of an infection; (ii) indicating involvement of the
result in endocarditis, it is rare to identify a predisposing cardiovascular system; and (iii) indicating the presence
event. The most common predisposition for endocarditis of an immunological reaction to infection. The features
in children is poor dental hygiene. indicating the presence of infection consist of fever, chills,
Drug addicts, especially those using the parenteral rigors, night sweats, general malaise, weakness, loss of
route, are prone to right sided endocarditis, involving the appetite, weight loss and amenorrhea in females. Arthra
tricuspid or pulmonary valve; endocarditis can also affect lgia and diffuse myalgia can occur, however, arthritis does
mitral and/or aortic valves. not occur except in acute endocarditis as part of septicemia
when it is likely to be monarticular.
Pathogenesis
Features indicative of the involvement of the cardio
The pathogenesis of endocarditis depends on the invasive vascular system may be absent in the initial stages. The
ness and virulence of the infective organisms. The earlier acute occurrence of left or right heart failure, development
nomenclature of subacute or acute endocarditis was of a new murmur or change in a pre-existing murmur,
dependent on the course of the disease. In the pre and features suggesting embolic events (e.g. hemiparesis
antibiotic era patients with acute endocarditis (septicemia) from stroke, hematuria from renal infarct, left flank pain
died within six weeks whereas the subacute type of from splenic infarct, and gastrointestinal hemorrhage from
endocarditis, almost always lethal, caused death in about mesenteric embolism) is suggestive. Murmurs due to
six months. The infection generally starts at a jet lesion, aortic, mitral or tricuspid regurgitation may appear; the
that is, where the high pressure jet in a ventricular septal regurgitant lesions progress rapidly causing hemodyna
defect or aortic stenosis hits the endocardium or the mic changes, resulting in CCF.
endothelium. The right ventricular mural endocardium Features of immunological response presenting as
or the tricuspid valve in ventricular septal defect, aortic vasculitis due to infection consist of arthralgia, myalgia,
endothelium in aortic stenosis or coarctation of the aorta, petechiae, Osier's nodes, Janeway lesion, clubbing,
ventricular surface of the aortic valve in aortic regur splenomegaly and microscopic hematuria. Splinter hemor
gitation are the usual sites. rhages are hemorrhagic spots under the nails, though
Bacteremia resulting from an infection such as a boil, suggestive, are not specific for endocarditis as they can
furuncle, otitis media or initiated by an intervention such result from minor injuries. Petechiae over the skin or
as cardiac or urinary catheterization or dental extraction mucous membranes and conjunctiva are seen in about 50%
is necessary for the initiation of endocarditis. Bacteremia patients. Petechiae in the retina are called Roth's spots.
may also result from simple day to day events such as Osier's nodes are tender erythematous nodules over the
brushing teeth. Bacteria that are deposited on the endo pulp of finger tips, but are relatively rare. Janeway lesions
cardium are covered by fibrin and platelets forming are non-tender erythematous patches on the palms and
vegetations. Almost any species of bacteria and some spe soles. Clubbing and splenomegaly tend to appear 3-weeks
cies of fungi can cause endocarditis. S. viridians, S. aureus, after the onset of endocarditis.
enterococci, P. aeruginosa and some gram negative bacilli
In the acute form the symptoms progress rapidly with
are responsible for endocarditis. Fungal endocarditis may
high fever, chills and rigors. Perforation of valve cusps
occur in hospitalized patients with indwelling central
results in acute aortic or mitral regurgitation with pro
venous catheters. gressive downhill course and death within 6-weeks from
the onset. In acute endocarditis, metastatic lesions causing
Clinical Features
abscesses in the central nervous system or elsewhere in
The presence of unexplained fever of 7-10 days duration the body (acute arthritis, splenic or mesenteric abscess,
in a patient with known heart disease should raise the brain abscess or osteomyelitis) are common. Metastatic
suspicion of endocarditis. Patients may also show other abscesses are rare in subacute endocarditis.
features of endocarditis. S. viridans results in a subacute Patients with endocarditis of the right side such as the
form of illness while S. aureus and other pyogenic orga tricuspid or the pulmonary valve throw emboli to the
nisms cause a fulminant (acute) and rapidly progressive lungs. The embolic episodes to lungs may present as
illness. It is possible, however, for an organism like repeated episodes of pneumonitis or septic infarcts resul
staphylococci to cause a subacute form of illness. Identi ting in lung abscesses. This is common with intravenous
fication of endocarditis by the organism is preferable, as drug abusers and patients with VSD.
it helps in deciding the choice of antibiotics as well.
Another useful way for identifying endocarditis is by the Postoperative endocarditis is classified as early (within 60
underlying setting, e.g. postoperative endocarditis, days) and late (after 60 days). Early endocarditis is due to
prosthetic valve endocarditis, endocarditis in drug pyogenic organisms (staphylococcus, pseudomonas, gram
addicts, etc. negative bacilli) introduced at the time of operation. The
Infective endocarditis is rare below the age of two years. patients have high fever with chills and rigors and features
The clinical features are divided into (i) indicating the of septicemia. Late endocarditis is like native valve
392 Essential Pediatrics
endocarditis and the commonest organisms are S. viridans teichoic acid antibodies in staphylococcal endo
and gram negative bacilli. The patients tend to follow the carditis. Rheumatoid factor is positive in approxi
subacute course. Cardiac surgery is an important risk mately 50% cases and normalizes after treatment.
factor for gram negative endocarditis. Prosthetic valve
Echocardiography is a sensitive diagnostic tool for
endocarditis may also be early or late; fungal infection of
detecting vegetations, including in patients with culture
prosthetic valves is associated with high mortality.
negative endocarditis. Echocardiography also identifies
The risk of fungal endocarditis has increased especially
complications like ruptured chordae, perforated cusps and
following cardiac surgery and in intensive care settings.
flail cusps resulting from endocarditis. Vegetations more
Candida is the commonest fungus responsible; infection
than 2 mm can be identified by echocardiography. The
with histoplasma, blastomyces, aspergillus, cryptococcus
sensitivity of echocardiographic identification of endocar
and mucor may occur. Predisposing factors for fungal
ditis is dependent on the site of involvement. For aortic
endocarditis include intravenous drug abuse, indwelling
and mitral valves the sensitivity is more than 90%, and
catheters, intensive antibiotic therapy, prolonged steroid
for tricuspid and pulmonary valves it is 70%. The presence
administration, radiation, immunosuppressive therapy
of vegetations correlates well with the diagnosis of
and prosthetic valves. The incidence of embolism is high,
infective endocarditis. If vegetations can be demonstrated,
since fungal vegetations tend to be large.
the probability of having endocarditis is around 94%. If
vegetations are absent, the probability of not having
Diagnosis
endocarditis is 92%. However, echocardiography is an
- % A positive blood culture, in a patient with underlying heart operator dependent investigation and its utility depends
Hj disease, suspected to have endocarditis is confirmatory on how meticulously it is performed. Potential limitations
I for the diagnosis. Three blood cultures, each of 10 mL, of echocardiography in older children can be overcome
W taken with meticulous aseptic precautions every half hour by transesophageal echocardiography (TEE). Occasionally
are recommended. It has been shown that three blood in smaller children too, TEE proves valuable in arriving
cultures shall detect over 95% cases with a positive blood at a diagnosis. TEE is particularly useful in prosthetic valve
culture. Unfortunately in most reports in our country endocarditis and when complications such as a valve ring
almost 50% patients with endocarditis have negative blood abscess are suspected.
cultures, the commonest cause being previous antibiotic
therapy. Arterial sampling does not offer any advantage Complications
over venous sampling. Other causes of culture negative
endocarditis are technical errors in obtaining specimens Damage to valve cusps or perforation, rupture of chordae
and inappropriate culture techniques. Infection with tendinae result in acute regurgitant lesions causing
unusual organisms, anaerobic organisms and fungi sudden hemodynamic deterioration. Migration of vege
require special culture media and incubation for 2-3 tations may result in embolic neurological deficit, renal
weeks. infarcts with hematuria, mesenteric infarct and melena,
Other investigations, which provide supportive loss of fingers or toes due to obstruction of blood supply.
evidence for diagnosis, are: Damage to the vasa vasorum of blood vessels due to
vasculitis may result in the formation of mycotic aneury
a. Normocytic normochromic anemia: Hemoglobin level
sms, which can rupture and result in massive bleeding.
around 10 g/dL.
Sinus of Valsalva aneurysms following endocarditis of the
b. White cell count: In subacute presentation, leukocyte aortic valve are not uncommon.
counts are normal in approximately 50% patients. The kidneys may be affected in many ways. They may
In acute endocarditis, leukocyte counts are usually have embolic infarct with hematuria, or show postinfec-
elevated. tious GN or membranoproliferative GN resulting in
c. Platelet count may be reduced. albuminuria, microscopic hematuria and acute renal
d. Elevated sedimentation rate in almost all patients. In dysfunction. The finding of IgG, IgM and complement
the presence of advanced CCF or renal insufficiency, deposits on the glomerular basement membrane indicate
sedimentation rates can be normal. that it is an immune complex nephritis. Renal insufficiency
e. Microscopic hematuria and albuminuria are present tends to appear beyond three weeks of the onset of
in 90% cases. endocarditis and is progressive until the endocarditis has
f. Immunological investigations: Investigations, which been cured. Hematuria can persist for three to six months
suggest endocarditis, include increased gamma even after the endocarditis has been cured. However, even
globulins, false positive serology for syphilis, advanced renal insufficiency tends to regress and renal
cryoglobulinemia, low complement levels and function tends to return toward normal after the
circulating immune complexes. Specific antibodies endocarditis has been cured. Presence of mild to moderate
against causative organism may be increased, e.g. renal insufficiency should not be viewed as a poor
high ASO titer in streptococcal endocarditis and anti- prognostic sign.
Disorders of Cardiovascular System 393
Table 14.9: Choice of antibiotics and duration of treatment for infective endocarditis
394 Essential Pediatrics
Observations obtained from human fetuses, indicate that the portal vein with the inferior vena cava thus providing
the course of circulation is quite similar to that found in a low resistance bypass for umbilical venous blood to
fetal lambs. The heart assumes its normal four-chambered reach the inferior vena cava; (iv) widely open foramen
shape by the end of six weeks of intrauterine life. From ovale to provide a route to the oxygenated blood coming
then on only minor changes occur and consist mainly in through the umbilical veins to reach the left atrium and
the growth of the heart as a whole with increasing age of ventricle for distribution to the coronaries and the brain;
the fetus. However, significant differences exist between and lastly (v) widely open ductus arteriosus to allow the
the fetal circulation and postnatal circulation. right ventricular blood to reach the descending aorta since
For the exchange of gases, the fetus is dependent on the lungs are non-functioning.
placental circulation, whereas the neonate is dependent
on the lungs. Following birth, with the first inspiration, Distribution, Oxygen Saturation
the lungs expand with air and the gas exchange function and Partial Pressures of Oxygen
is transferred from the placenta to the lungs. This The umbilical venous blood has a saturation of about 80%
necessitates circulatory adjustments following birth to and a p02 of 32-35. The mixing of umbilical venous blood
transform the fetal circulation to the postnatal circulation. with inferior vena cava stream results in a reduction of
The route of blood flow in the fetus is different from that oxygen saturation to about 70%. The inferior vena caval
in the postnatal state. Blood oxygenated in the placenta is blood represents approximately 65-70% of total venous
I returned by way of the umbilical veins, which enter the return to the heart. One-third of the inferior vena caval
R fetus at the umbilicus and course through to join the portal stream enters the left atrium after crossing the foramen
■* I vein. The ductus venosus provides a low resistance bypass ovale. It mixes with the pulmonary venous return com
I between the portal vein and the inferior vena cava. Most prising of about 8% of the total venous return to the heart.
B of the umbilical venous blood shunts through the ductus The blood reaching the left ventricle has a saturation of
venosus to the interior vena cava. Only a small proportion about 65% and a p02 of 26-28. The left ventricular output
mixes with the portal venous blood and passes through is approximately a half of the right ventricular output. The
the liver. The inferior vena cava blood comprising the right ventricle receives most of the superior vena caval
streams of hepatic veins, umbilical veins and that reaching blood, which constitutes about 22-25% of the total venous
the inferior vena cava directly from lower extremities and return to the heart. The superior vena caval blood has a
kidneys enters the right atrium. On reaching the right saturation of about 40% and p02 of 12-14. It mixes with
atrium the bloodstream is divided into two portions by the inferior vena caval stream reaching the right ventricle
the inferior margin of the septum secundum—the crista as well as the coronary sinus flow. The blood reaching
dividens. About one-third of the total inferior vena cava the pulmonary artery has a saturation of about 50-55%
blood enters the left atrium, through the foramen ovale, and a p02 of 16-18. The saturation of blood in the descen
the rest two-thirds mixes with the venous return from the ding aorta is about 55-60% and p02 20-22 mm.
superior vena cava to enter the right ventricle. In postnatal life the blood leaving the right ventricle,
The blood reaching the left atrium from the right atrium after coursing through the lungs, reaches the left ventricle.
mixes with the small amount of blood reaching the left Two ventricles are connected in series and therefore, the
atrium through the pulmonary veins and passes to the outputs of right and left ventricles are approximately
left ventricle. The left ventricle pumps out the blood into identical. In the fetus very little of the right ventricular
the ascending aorta for distribution to the coronaries, head output reaches the left ventricle through the lungs, the
and upper extremities. The superior vena cava stream, rest goes through the ductus arteriosus into the descen
comprising blood returning from the head and arms, ding aorta. The two ventricles are, therefore, in parallel.
passes almost directly to the right ventricle. Only minor The left ventricle supplies the head and upper extremities,
quantities (1-3%) of this stream reaches the left atrium. while the right ventricle supplies the trunk, viscera and
The right ventricle pumps out blood into the pulmonary the lower extremities.
trunk. A small amount of this blood enters the pulmonary
circulation, the rest passes through the ductus arteriosus Intravascular Pressures in the Fetus
into the descending aorta to mix with the small amount The aorta and the pulmonary trunk are connected by a
of blood reaching the descending aorta from the aortic wide ductus arteriosus. This results in identical pressures
arch (derived from the left ventricle). in the two great arteries (aorta and pulmonary trunk),
In summary the main differences between the fetal approximately 70/45 mm Hg. The systolic pressure in the
circulation and postnatal circulation consist of (i) presence right and left ventricles are also identical and approximate
of placental circulation which provides the gas exchange 70 mm Hg. The volume of blood reaching the right atrium
for the fetus; (ii) absence of gas exchange in the collapsed is considerably larger than that reaching the left atrium.
lungs; this results in very little flow of blood to the lungs In fact the latter's main source of blood is through the right
and consequently very little pulmonary venous return to atrium. The right atrial mean pressure (4 mm Hg) is
the left atrium; (iii) presence of ductus venosus, joining slightly higher than the mean pressure of the left atrium
Disorders of Cardiovascular System 395
(3 mm). In the fetal lamb the pulmonary trunk and right oxygen saturation. An increase in the blood oxygen
ventricular pressures are about 5-8 mm of Hg higher than saturation causes the muscle of the ductus arteriosus to
the left ventricular and aortic pressures toward the end of constrict and close. In full term neonates, the ductus
the pregnancy. arteriosus closes within 10-21 days.
The blood flow to various organs in the fetus is This results in the establishment of the postnatal
determined by local vascular resistance. In postnatal life, circulation. The blood reaching the right atrium through
all pressure measurements are in relation to the atmosphe the superior and inferior vena cava is emptied into the
ric pressure. The intravascular pressures of the fetus, indi right ventricle and pumped into the pulmonary trunk.
cated above, are expressed in relation to the intra-amniotic After gas exchange in the lungs, it reaches the left atrium
pressure. The intra-amniotic pressure is 10-12 mm Hg and ventricle. The latter pumps it out for oxygenation of
higher than the atmospheric pressure. The intra-amniotic the tissues. The venous return again comes back to the
pressure varies directly with intra-abdominal pressure right atrium. The two ventricles are connected in series
and with uterine contractions. Intravascular pressures of and have identical outputs. Over the next several weeks,
the fetus are, therefore, affected by changes in the intra- the pulmonary vascular resistance, pulmonary artery and
amniotic pressures. The fetal heart rate decreases and the right ventricular pressures continue to decline. The adult
blood pressure rises, with increasing maturity of the fetus. relationship of pressures and resistances in the pulmonary
and systemic circulations is established by the end of 2-3
Circulatory Adjustments at Birth weeks (Fig. 14.5).
"functional" murmur. If heart disease is present then we Genetic and chromosomal aberrations are also known to
have to separate congenital from non-congenital lesions. predispose to congenital heart disease. The list of specific
Based on the classical features of the individual lesions chromosomal disorders linked to congenital heart defects
one can then make a specific diagnosis. Once the specific is growing. Trisomy 21, 13 and 18 and Turner syndrome
diagnosis is made, the decision as to what is to be done are associated with a high frequency of congenital heart
for the patient depends on the severity of the lesion. Let disease. Marfan syndrome, Ehler-Danlos syndrome and
us not forget that palliation or curative treatment is most Hurler syndromes may be associated with congenital heart
often surgical treatment. Cardiac operations are major disease. Partial deletion of chromosome 22 (CATCH 22
operations. The diagnosis has to be precise and accurate. syndrome, Di-George syndrome) is being increasingly
The decision regarding operation is dependent on the type recognized in association with conotruncal malformations
and severity of the lesion as well as the type of surgical (e.g. tetralogy of Fallot, persistent truncus arteriosus,
help available. ventricular septal defect with interruption of the aortic
arch).
Incidence
The prevalence of congenital cardiac lesions in India is Diagnostic Implications of
not known. The incidence of congenital cardiac lesions at Circulatory Changes at Birth
birth was originally estimated to be 6-8 per 1000 live births In the section on fetal circulation, it was pointed out that
in the Western countries. Recently it has been realized that the lungs are sparingly perfused since the oxygen and
the incidence is higher, especially if all of the newborns nutritional requirements of the fetus are derived from the
are followed up to the age of 1-year, since some of the mother through the placenta. After birth, the lungs expand
conditions may not be manifest in the first few weeks of and provide oxygenation of blood. The increased flow of
life. Recent figures from the Western literature suggest blood to the pulmonary artery passing through the lungs
the incidence to be about 1/100 live births. This figure and reaching the left atrium, increases the left atrial pressure.
does not include congenital bicuspid aortic valve (2/1000) The effect of this is that the septum primum approximates
or congenital mitral valve prolapse syndrome (6/1000). with the septum secundum and the foramen ovale closes
Congenital heart diseases comprise 17% of all cardiac cases functionally. Clamping of the cord increases the systemic
in the outpatient cardiac clinic of the AIIMS hospital. vascular resistance (resistance to flow of blood in the
systemic arteries). Thus the systemic pressure increases,
Etiology
while the pulmonary artery pressure falls due to lowering
The etiology of the majority of congenital heart diseases of the pulmonary vascular resistance. As a result, flow of
is not known and in most situations no specific directions blood through the ductus arteriosus reverses. Instead of
can be given regarding prevention of congenital cardiac blood flowing from the pulmonary artery to the aorta, as
lesions. Both genders are equally affected, though for in the fetus, the blood flows from aorta to the pulmonary
individual lesions there may be some differences. Right artery. The ductus arteriosus constricts and closes off. The
sided lesions are more common in female patients and pulmonary and systemic circulations thus separate from
left sided lesions are more common in male patients. A each other soon after birth.
higher incidence of congenital heart disease in siblings At this time, however, the pulmonary pressure and
suggests heredity as a factor in the etiology. The strongest resistance is equal or only slightly lower than the systemic
familial tendency is seen in atrial septal defect associated pressure. Therefore, even if there is a communication
with bony abnormalities (Holt Oram syndrome), trans between the two sides like atrial or ventricular septal
mitted in an autosomal dominant manner. Additional defect or patent ductus arteriosus, there is very little flow
examples of conditions with a higher than usual risk of from left to the right side. The pulmonary vascular resis
transmission include obstructive lesions in the left heart. tance falls rapidly to reach normal adult levels by 2-3 weeks
In a study of 26 pairs of twins, only one in each pair had in normal babies. In the presence of a ventricular septal defect
heart disease, suggesting that heredity probably does not or patent ductus arteriosus however, the fall in pulmonary
play as important a role as originally suspected. vascular resistance and pressure is slower and reaches adult
Of the environmental factors the most well known is high values by 6-10 weeks. Since there is little flow across the
altitude. There is a higher incidence of patent ductus abnormal communications like atrial or ventricular septal
arteriosus and atrial septal defects in children born at high defect or patent ductus arteriosus, they do not manifest
altitudes. There is a higher incidence of congenital heart in the first few days of life. The ventricular septal defect
disease in children of mothers with diabetes mellitus. The or patent ductus arteriosus murmurs tend to appear by
occurrence of rubella in the first trimester of pregnancy the middle or the end of the first week of life. It gradually
may result in patent ductus arteriosus and/or branch increases in intensity as the pressure and resistance in the
pulmonary artery stenosis. Maternal intake of thalidomide pulmonary circuit fall. Only by 6-10 weeks when the
or alcohol and maternal phenylketonuria are known to resistance may have reached its lowest value, the
result in specific types of congenital heart disease. maximum shunt would become apparent. In atrial septal
Disorders of Cardiovascular System 397
defect, on the other hand, the right ventricular hypertrophy, It is thus obvious that the pressure in a vessel is
present at birth, prevents a large shunt. A thick ventricle dependent on theflozv through the vessel and the resistance,
cannot expand well in diastole to accommodate a large offered by the vessel to the flow of blood. It is possible to
volume of blood. The right ventricular hypertrophy takes increase the pressure in a vessel either by increasing the
six months or more to regress. Thus, the murmur of atrial flow or by increasing the resistance. Increase in flow
septal defect takes even longer i.e. 6 months, before these through the pulmonary artery means a left to right shunt,
patients are identified. as occurs in atrial or ventricular septal defect or patent
On the other hand, obstructive lesions like aortic stenosis or ductus arteriosus. Generally, this increase in flow is not
pulmonic stenosis and valvular leaks like mitral or tricuspid associated with significant increase in pressure as the
regurgitation are operative from birth. As such the murmur of resistance falls or remains the same. At the same time, the
obstructive lesions as well as valvular leaks are audible distensibility characteristics of the pulmonary artery are
immediately after birth. The clinical manifestations of such that it can accommodate almost three times the nor
congenital lesions associated with atrial, ventricular or mal flow without an increase in pressure. Hence, large left
aortopulmonary communication, therefore, show rapid to right shunts can take place without an increase in pressure.
changes in the first few weeks or months of life. Even if the Increase in pulmonary vascular resistance means obstructive
evaluation of an infant at the age of one week has been felt disease in the pulmonary circuit. The pulmonary vessels
to be normal, it does not rule out the presence of congenital develop medial hypertrophy and later intimal changes are
heart disease. It is also not possible to correctly estimate the added, to further obstruct the flow of blood through the
severity of the lesion in the first few weeks of life. pulmonary circulation. After a certain stage, it is an
irreversible process. The increase in resistance to flow in
Diagnostic Implications of Pressures and the pulmonary circuit is associated with reduction in flow.
Resistances in the Cardiac Chambers and The increase in pressure in the pulmonary artery
Great Vessels associated with normal resistance is called hyperkinetic
pulmonary arterial hypertension whereas when the pressure
The pressures and resistances in the pulmonary and
is increased due to increase in pulmonary vascular
systemic circulations are indicated in Table 14.10. The
resistance, it is called obstructive pulmonary arterial
pulmonary and systemic flows are equal if there are no
hypertension. Clinically both situations are seen and can
abnormal communications between the two sides.
be separated from each other on the bed side.
According to Poiseuille's equation, modified for
Table 14.10 indicates that the pressures in the right sided
application to blood flow through vessels:
chambers and the pulmonary artery are lower than the
Pressure = Flow x Resistance pressures on the left side. As such, if there is a
communication between the two sides, the flow will be
The pressure is measured in mm Hg, flow in liters/ from the left to the right side. The difference in pressure
min and resistance in dynes/sec/cm5 or units (each unit between the two atria is small. As such in an atrial septal
being 80 dynes/ sec/cm5). Although this equation is not defect there is absence of a significant transmission of
accurate when applied to flow of blood in pulmonary and pressure from the left atrium to the right atrium. In the
systemic circuits, it helps in understanding the presence of a ventricular septal defect, however, the flow of
hemodynamics. When applied to systemic and pulmonary blood from the left ventricle to the right ventricle is at a
circuits, it can be rewritten as: considerable difference in systolic pressures between the
two ventricles. There will be some increase in right sided
Systemic pressure = Systemic flow x Peripheral pressure and this depends on the size of the ventricular
vascular resistance septal defect. The smaller the defect, the less the trans
Pulmonary arterial pressure = Pulmonary flow x mission of the ventricular pressure to the right ventricle.
Pulmonary vascular resistance With large defects the pressures in the two ventricles may
be identical. The flow of blood from left to right will
depend on the pulmonary vascular resistance. When the
ductus arteriosus is patent, the blood flows
Table 14.10: Pressure and resistance in the pulmonary
and systemic circuits from the aorta to the pulmonary artery
during both systole as well as diastole,
Pressures mm Hg
because there is considerable difference in
Superior vena cava 0-6 Left atrium 6-10
Right atrium 0-6 Left ventricle 80-120/5-10 the pressures between the two great arteries
Right ventricle 25/0-6 Systemic artery 80-120/60-85 in both phases of the cardiac cycle. The size
Pulmonary artery 25/10 of the ductus arteriosus determines how
Resistance dynes/sec/cm5 (units) much of the aortic pressure will be directly
Pulmonary 80-240 (1-3) Systemic 800-1600 (10-20) transmitted to the pulmonary artery. With a
large patent ductus arteriosus, the pressures
398 Essential Pediatrics
in the aorta and pulmonary artery become identical. The The normal second heart sound can be described in
flow into the pulmonary artery then depends on the three parts:
pulmonary vascular resistance. If the pulmonary vascular i. It has two components, the aortic closure sound (A,)
resistance is low, there will be flow of blood from the aorta and the pulmonary closure sound (P ).
to the pulmonary artery. ii. During quiet breathing both the components are
Another aspect of left to right shunts, which has clinical superimposed on each other during expiration. Thus,
significance, is that in atrial septal defect the right ventricle only a single second sound is heard. During inspira
accommodates the extra volume of the shunted blood tion, the aortic component comes slightly early
during diastole. An atrial septal defect, therefore, causes whereas the pulmonary component is delayed,
a diastolic overload of the right ventricle. In ventricular septal resulting in a splitting of the second sound in which
defects the shunt from left ventricle to the right ventricle is the A, precedes the P .
during systole, as such, the shunted blood reaches the right iii. The aortic component is louder than the pulmonary
ventricle ivhile the latter is also actively contracting and component, except in infants below the age of 3-6
becoming smaller. This results in the flow from the left ventricle months. When we say that the second sound is normal,
going to the pulmonary artery more or less directly. The right it means that we have carefully observed the three
ventricle acts simply as a conduit and the shunt is not a parts of the second sound. Abnormalities of the second
volume load for the right ventricle. The shunted blood sound occur in each of the three parts.
passes through the lungs and finally leads to a diastolic
volume overload of the left ventricle. In patent ductus Abnormalities of the Aortic Component (AJ
arteriosus the flow from the aorta to the pulmonary artery, of the Second Sound
is during both systole as well as diastole. Thus, it results The A2 may be accentuated or diminished in intensity. It can
in a systolic as well as a diastolic volume load of the also occur early or late in timing. The A2 is accentuated in
pulmonary artery. For the left ventricle, patent ductus systemic hypertension and in aortic regurgitation. The A2
arteriosus results in a diastolic volume overload. is diminished in intensity or may be absent when the aortic
valve is immobile because of fibrosis or calcification or
Diagnostic Implications of the when the aortic valve is absent as in aortic valve atresia.
Second Heart Sound
The A2 is delayed in timing when the left ventricular ejection
Auscultation of the heart provides important diagnostic is prolonged as in aortic valvar or subvalvar stenosis,
information. Assessment of the second heart sound is patent ductus arteriosus with a large left to right shunt,
important (Fig. 14.6). aortic regurgitation, left bundle branch block and left
ventricular failure. The A2 occurs early in ventricular septal
defect, mitral regurgitation and constrictive pericarditis.
The recognition of delayed or early A2 on the bed side
will be explained below.
sec or more during expiration. During inspiration if the them. Thus, the interpretation of the single second sound
A2-P2 interval increases further, it is called wide variable is not dependent on auscultation alone.
splitting. If the A2-P2 interval is the same in expiration
and inspiration, it is called widely split and fixed, second Assessment for Presence of Heart Disease
sound. Wide and variable splitting of the S2 is seen in pulmo The assessment of a child for the presence of heart disease
nic stenosis, mitral regurgitation and ventricular septal may be done using Nadas' criteria. Presence of one major
defect. In pulmonic stenosis it is due to a delay in P2 or two minor criteria indicate heart disease (Table 14.11).
whereas in mitral regurgitation and ventricular septal
defect it is due to an early A2. Wide and fixed splitting of Table 14.11: Nadas’ criteria
the S2 occurs in atrial septal defect, right bundle branch Major Minor
block and total anomalous pulmonary venous connection
Systolic murmur Systolic murmur less than
and is due to a delay in P2.
grade III or more grade III
The delay in A2 results in closely split, single or
Diastolic murmur Abnormal second sound
paradoxically split S2. This is recognized on the bedside Cyanosis Abnormal ECG
only if one is looking for it. The S2 is split in expiration but Congestive cardiac failure Abnormal X-ray
during inspiration the split becomes narrower or Abnormal blood pressure
disappears (Fig. 14.7). A single second sound means that
it is either A2 or P2 or a combination of both A2 and P2.
The decision whether it is A2 or P2 or a combination of Major Criteria
both A2 and P2 depends not on the location or intensity of Systolic murmur grade III or more in intensity: Systolic
the single second sound but on an analysis of the total murmurs are classified into ejection systolic murmurs and
clinical profile. For example, in tetralogy of Fallot only a pansystolic murmurs. A pansystolic murmur is always
single S2 is heard and it is the A2 since P2 is delayed and abnormal no matter what is its intensity. There are only
so soft that it is inaudible. In ventricular septal defect with three lesions which produce a pansystolic murmur and
pulmonary arterial hypertension and right to left shunt these are (a) ventricular septal defect, (b) mitral regur
(Eisenmenger complex) again a single S2 is heard and gitation and (c) tricuspid regurgitation.
represents a combination of A2 and P2. Based on auscul An ejection systolic murmur may be due to an organic
tation alone one may not be able to differentiate between cause or a "functional" murmur. An ejection systolic
tetralogy of Fallot and Eisenmenger complex. However, murmur with a thrill is an organic murmur. A functional
history and thoracic roentgenogram can easily separate grade III ejection systolic murmur may be heard in anemia
or high fever especially in smaller children. Almost 50% of
children at the age of 5 years may have an ejection systolic
murmur. If accompanied with a normal second sound, then
it is unlikely to be significant. Before discarding a murmur
as of no significance, it is necessary to obtain an EKG and
a thoracic roentgenogram. If they are normal, one can
probably exclude heart disease, though another evaluation
after 6 months is preferable.
of the mouth and tongue. It results in polycythemia and of heart disease. The second reason which leads to
clubbing of fingers and toes. Presence of central cyanosis difficulty in assessing the cardiac size is the presence of
indicates presence of heart disease if lung disease is thymus in children up to the age of 2-years, which may
excluded. fallaciously suggest cardiomegaly. Fluoroscopy is useful
in separating the thymic shadow from the heart.
Congestive cardiac failure: Presence of CCF indicates heart
disease, except in neonates and infants who can get cardiac Abnormal blood pressure: It is difficult to obtain accurate
failure from hypoglycemia and anemia. blood pressure in smaller children. If the cuff is small it
would give a falsely high reading of blood pressure,
Minor Criteria whereas if it is too large it gives low readings. The blood
Si/stolic murmur less than grade III in intensity: The value of pressure cuff should cover at least two-thirds of the length
murmurs has already been discussed above. It is necessary of the arm and most of the circumference.
to emphasize that soft, less than grade III murmurs by Based on the presence of one major or two minor criteria
themselves do not exclude heart disease. a decision can be taken that the child has heart disease.
These guidelines are meant to help in identifying the pre
Abnormal second sound: Abnormalities of the second sound
sence of heart disease. It does not follow that the pediatri
always indicate presence of heart disease. It has been
cian should not use his judgment and common sense for
included as a minor criterion only because auscultation is
identifying the presence or absence of heart disease.
an individual and subjective finding. No one is perfect in
auscultation and anyone can be ivrong. If the auscultatory
Features Indicative of the Presence
abnormality can be substantiated by a phonocardiogram
of Congenital Cardiac Lesions
it becomes objective evidence and indicates presence of
heart disease. If the heart disease was diagnosed at or soon after birth, it
favors the presence of congenital cardiac disease. As indi
Abnormal electrocardiogram: Its main value lies in deter cated above, murmurs of obstructive and regurgitant lesions
mining the mean QRS axis, right or left atrial hypertrophy should be audible immediately after birth whereas murmurs of
and right or left ventricular hypertrophy. Criteria for left to right shunts tend to appear somewhat later. If the pre
ventricular hypertrophy, based only on voltage criteria sence of a heart murmur is known within the first year of
are not diagnostic for the presence of heart disease. The life, it is a strong pointer toward the diagnosis of a congeni
voltage of the QRS complexes can be affected by changes tal lesion. The murmurs produced by congenital lesions
in blood viscosity, electrolyte imbalance, position of the tend to be parasternal. However, apical pansystolic mur
electrode on the chest wall and thickness of the chest wall. mur of mitral regurgitation may be heard in atrial septal
If a patient is asymptomatic, the physical examination and defect of the endocardial cushion type defect. Hence,
chest X-ray are normal but the EKG is abnormal, the though parasternal murmurs favor a congenital lesion,
presence of heart disease is not likely. Such a patient presence of an apical murmur does not exclude congenital
should be carefully reevaluated before diagnosing heart heart disease.
disease.
Presence of cyanosis is diagnostic for the presence of con
Abnormal X-ray: The reasons for considering abnormal X- genital cardiac disease. Presence of extracardiac congenital
ray as a minor criterion are twofold. In small children, the anomalies not only favors the presence of a congenital
heart size varies with expiration and inspiration. If there lesion but may also point toward specific defects (Table
is cardiomegaly on a good inspiratory film, it is suggestive 14.12).
Classification of Congenital Heart Diseases is normal or diminished, the radiograph shows the para
doxical finding of prominent and large hilar pulmonary
For the purpose of diagnosing individual anomalies it is
arteries with clear or ischemic peripheral lung fields.
helpful to classify patients of congenital heart disease into
Within these two subgroups of cyanotic patients some
three groups:
patients can be separated from others because of the
Group I Left to right shunts presence of abnormal mixing of blood resulting in a right
Group II Right to left shunts (cyanotic lesions) to left as well as a left to right shunt. Majority of these
Group III Obstructive lesions patients present in early infancy or neonatal life with a
combination of cyanosis, cardiomegaly, congestive cardiac
Left to right shunts: Patients of left to right shunts are failure, increased sweating, absence of weight gain (failure to
characterized by frequent chest infections. Each attack of cold thrive) and mostly plethoric lung fields. These patients
seems to turn into bronchopneumonia, which lasts longer have transposition of great arteries, total anomalous pulmonary
than usual. It is not uncommon for these patients to have venous connection, persistent truncus arteriosus or malposition
six to eight attacks of pneumonia in the first year of life. of great arteries.
Patients of left to right shunts do not have cyanosis. They
have a tendency for increased sweating, which is related Obstructive lesions: The diagnostic features of the patients
to their tendency for developing CCF. Frequent chest of obstructive lesions consist of absence of frequent chest
infections with tachypnea result in the soft rib cage being infections and cyanosis, absence of precordial bulge, presence
drawn inward at the diaphragmatic attachments of the of a forcible or heaving cardiac impulse due to concentric
ribs. This combined with cardiac enlargement gives them hypertrophy of the ventricles without cardiac enlarge
a precordial bulge. On palpation, the precordium is hyper ment, a systolic thrill associated with an ejection systolic
kinetic. On auscultation, they have either a tricuspid or a murmur, absence of tricuspid and mitral delayed diastolic
mitral delayed diastolic murmur. Evaluation of the thoracic murmurs, and presence of delayed corresponding second
roentgenogram shows hyperemic or plethoric lung fields, sound. The only right sided obstructive lesion is pulmonary
as well as cardiomegaly. stenosis whereas the two left sided obstructive lesions are
aortic stenosis and coarctation of the aorta. The chest X-ray
Right to left shunts: Patients of right to left shunts are shows a normal sized heart and normal pulmonary vasculature.
characterized by the presence of cyanosis, which leads to The EKG not only indicates whether the obstructive lesion
polycythemia and clubbing. Cyanotic patients, however, is right or left sided, but is also helpful in indicating the
belong to two subgroups. Some of these patients are severity of the obstruction.
associated with normal or decreased pulmonary arterial
pressure, while others are associated with elevated LEFT TO RIGHT SHUNTS
pulmonary arterial pressure. The patients who have
diminished pulmonary arterial pressure, also have The three main left to right shunts are atrial septal defect of
diminished pulmonary blood flow, due to the presence the ostium secundum and ostium primum variety
of pulmonary stenosis. Cyanotic patients with increased (endocardial cushion defect), ventricular septal defect and
pulmonary arterial pressure (pulmonary arterial hyper patent ductus arteriosus. They can be separated by physical
tension), may have either increased pulmonary blood flow or examination, EKG and chest X-ray.
diminished pulmonary blood flow due to pulmonary vascular
Atrial Septal Defect
obstructive disease. The latter are particularly unfortunate
since they have most probably reached the stage of Atrial septal defect is an abnormal communication
irreversible pulmonary arterial hypertension. Patients between the two atria. The ostium secundum type of atrial
with increased pulmonary blood flow are mildly cyanotic; septal defect is generally anatomically located at the fossa
those with normal or diminished pulmonary blood flow ovalis. It can also be superior or posterior to the fossa
are moderately to severely cyanotic. ovalis. The ostium primum type of the defect (endocardial
'Thus cyanotic patients have either pulmonic stenosis cushion defect) is situated inferior to the fossa ovalis. It is
or pulmonary arterial hypertension. Cyanotic patients with associated with a cleft in the anterior leaflet of the mitral
pulmonic stenosis are characterized by an ejection systolic valve, with or without a cleft in the septal tricuspid leaflet.
murmur, delayed and diminished P2 and ischemic lung fields Atrial septal defect constitutes 13% of patients with
in thoracic roentgenogram. Cyanotic patients with congenital heart disease. The secundum type is ten times
pulmonary arterial hypertension have accentuated and palpable more common than the endocardial cushion type.
P, an ejection systolic murmur and large, main as well as right
and left branches of the pulmonary artery in the thoracic
Hemodynamics
roentgenogram. The appearance of chest X-ray depends Physiologically atrial septal defect results in leaking of
on the pulmonary blood flow. If the pulmonary blood flow oxygenated blood from the left to the right atrium at a
is increased, the lung fields appear plethoric throughout minor difference in pressure between the two atria. The
and cardiomegaly is present. If the pulmonary blood flow left to right shunt is thus silent on auscultation. The right
402 Essential Pediatrics
Clinical Features ii. The patient may have a floppy mitral valve with a
Patients of atrial septal defect are generally asymptomatic. midsystolic click and a late ejection systolic or even a
Mild effort intolerance and frequent chest infections are pansystolic murmur (mitral valve prolapse syn
the only symptoms. CCF is rare. On physical examination drome).
patients of atrial septal defect have a parasternal impulse. iii. Ostium secundum defect associated with rheumatic
A systolic thrill may be palpable at the second left inter mitral regurgitation; and
space in 10% patients. The cardiac enlargement is only mild iv. Secundum atrial septal defect rarely associated with
to moderate. Marked cardiomegaly suggests additional cleft mitral valve resulting in mitral regurgitation.
lesions like mitral valve obstruction (Lutembacher syn The last three conditions have right axis deviation on
drome) or mitral regurgitation. The first sound is normal the EKG. The EKG of ostium secundum atrial septal defect
or may be loud due to a loud tricuspid component of the is characterized by right axis deviation and right
first sound. The second sound is widely split and fixed ventricular hypertrophy. The characteristic configuration
with the P2 being accentuated and widely transmitted of the precordial lead V, is rsR' seen in almost 90% patients
along the left sternal border and up to apex. There is an (Fig. 14.9). Presence of left axis deviation beyond -30°
ejection systolic murmur (grade 3 or less) at the second suggests the ostium primum type of atrial septal defect
and third left interspaces. It is zvidely transmitted all over (Fig. 14.10).
the chest. There is also a delayed diastolic murmur at the lower The thoracic roentgenogram shows mild to moderate
left sternal border. The tricuspid delayed diastolic murmur cardiomegaly, right atrial and right ventricular enlarge
may be mistaken for an early diastolic murmur or a peri ment, prominent main pulmonary artery segment, a
cardial friction rub at the bedside. The error occurs as the relatively small aortic shadow and plethoric lung fields.
tricuspid delayed diastolic murmur starts earlier in the
diastolic period because the tricuspid valve opens before
the mitral valve and the gap between the delayed P2 and
the start of the diastolic murmur may be missed. Systolic
and diastolic murmurs produced at the tricuspid valve
have, at times, a scratchy superficial character almost like
a pericardial friction rub (Fig. 14.8).
Presence of a pansystolic murmur of mitral regurgitation at
the apex in a patient with atrial septal defect suggests four
possibilities: Fig. 14.9: Electrocardiogram of atrial septal defect of the secundum
i. If the EKG reveals left axis deviation of more than- type. Mean QRS axis is +130°. Lead V, shows rsR' characteristic of the
30°, it suggests ostium primum atrial septal defect. defect
Disorders of Cardiovascular System 403
Hemodynamics
A ventricular septal defect results in shunting of
oxygenated blood from the left to the right ventricle. The
left ventricle starts contracting before the right ventricle.
The flow of blood from the left ventricle to the right
ventricle starts early in systole and a pressure gradient is
maintained between the two ventricles throughout systole.
The murmur resulting from the left to right shunt, starts
early, masking the first sound and continues throughout
Fig. 14.10: Electrocardiogram of atrial septal defect of the primum the systole with almost the same intensity appearing as a
type (endocardial cushion or atrioventricular canal defect). The mean pansystolic murmur on auscultation and palpable as a
QRS axis is -45° thrill. Toward the end of systole, the declining left ventri
cular pressure becomes lower than the aortic pressure.
This results in closure of the aortic valve and occurrence
The left atrium does not enlarge in size in atrial septal of A2. At this time, however, the left ventricular pressure
defect. Enlarged left atrium without associated anomalies is still higher than the right ventricular pressure and the
like mitral regurgitation excludes the diagnosis of atrial left to right shunt continues. The pansystolic murmur,
septal defect. Echocardiogram shows increased size of the therefore, ends beyond A2 completely masking it.
right ventricle with paradoxical ventricular septal motion. The left to right ventricular shunt occurs during systole
2D echo in subcostal four chambered view identifies the at a time when the right ventricle is also contracting and
defect. its volume is decreasing. The left to right shunt, therefore,
streams to the pulmonary artery more or less directly. This
Assessment of the Severity
flow of blood across the normal pulmonary valve results
The size of the left to right shunt is directly proportional in an ejection systolic murmur at the pulmonary valve. On the
to the intensity of the two murmurs and the heart size. bedside, however, the ejection systolic murmur cannot be
The larger the shunt the more the cardiomegaly and the separated from the pansystolic murmur. The effect of the
louder the pulmonary and tricuspid murmurs. ejection systolic murmur is a transmission of the pansystolic
murmur to the upper left sternal border, where its ejection
Complications character is recognized since it does not mask the aortic
Pulmonary arterial hypertension due to pulmonary component of the second sound.
vascular obstructive disease is rare below the age of 20-years. The large volume of blood passing through the lungs
It is recognized by the disappearance of the systolic and is recognized on the X-ray as pulmonary plethora. The
diastolic murmurs, appearance of a constant pulmonary increased volume of blood finally reaches the left atrium
ejection click and loud palpable P2. The second sound and may result in left atrial enlargement. Passing through a
continues to be widely split and fixed. normal mitral valve the large volume of blood results in a
delayed diastolic murmur at the apex. The intensity and
Treatment duration of the delayed diastolic murmur at the apex is
The medical management consists in treating chest directly related to the size of the shunt. The large flow
infections. Infective endocarditis is very rare in patients of across the normal mitral valve also results in accentuated
ostium secundum atrial septal defect, unless floppy mitral first sound, not appreciable on the bedside as it is drowned
valve is present. The risk of operation for closure of atrial by the pansystolic murmur. Since the left ventricle has
septal defect is so low that asymptomatic patients are two outlets, the aortic valve allowing forward flow and
referred for surgery. Most surgeons prefer correction with the ventricular septal defect resulting in a backward leak,
the use of heart lung bypass. The ideal age for operation it empties relatively early. This results in an early A2. Since
is between 2-5 years. With use of hypothermia, patients the ejection into the right ventricle and pulmonary artery is
are being operated below the age of 2-years without extra increased because of the left to right shunt the P, is delayed.
risk. Definitive cure is possible with device closure in Therefore, the second sound is zvidely split but varies with
selected patients (see later). respiration in patients of ventricular septal defect with a
404 Essential Pediatrics
large left to right shunt. There is also an increase in the or medium sized ventricular septal defects, the EKG is
intensity of the P2. normal. In patients of ventricular defects with a large left
to right shunt, without pulmonary arterial hypertension,
Clinical Features the EKG shows left ventricular hypertrophy by the time
The patients of ventricular septal defect can become they are 6 months to one-year-old. There are, however,
symptomatic around 6-10 weeks of age. They can develop no ST and T changes suggestive of left ventricular strain
CCF at this time. Premature babies with a ventricular pattern. Patients of ventricular septal defect who have
septal defect can become symptomatic even earlier. either pulmonic stenosis or pulmonary arterial hyperten
Palpitation, dyspnea on exertion and frequent chest sion may show right as well as left ventricular hypertrophy
infection are the main symptoms in older children. On or pure right ventricular hypertrophy. The mean QRS axis
examination the pulse pressure is relatively wide. The lies between +30 to +90°.
precordium is hyperkinetic with a systolic thrill at the left The cardiac silhouette in the thoracic roentgenogram
sternal border. The heart size is enlarged with a left is left ventricular type with the heart size depending on
ventricular type of apex. The first and the second sounds are the size of the left to right shunt. The bigger the left to
masked by a pansystolic murmur at the left sternal border. right shunt, the larger the heart. The pulmonary
The second sound can, however, be made out at the second vasculature is increased. The aorta appears normal or
left interspace or higher. It is widely split and variable with smaller than normal in size. There may be left atrial
accentuated P2. A third sound may be audible at the apex. enlargement in patients with a large left to right shunt.
A loud pansystolic murmur is present at the left sternal Patients of ventricular septal defect with a small shunt
border. The maximum intensity of the murmur may be in either because the ventricular defect is small or because
the third, fourth or the fifth left interspace. It is well heard of the associated pulmonic stenosis or pulmonary arterial
at the second left interspace but not conducted beyond hypertension have a normal sized heart. The pulmonary
the apex. A delayed diastolic murmur, starting with the vasculature is normal with small defects or if there is
third sound is audible at the apex (Fig. 14.11). associated pulmonic stenosis. The pulmonary vasculature
The EKG in ventricular septal defect is quite variable. is plethoric if there is associated pulmonary arterial
All children are born with right ventricular hypertrophy. hypertension. Echocardiogram shows increased left atrial
As such initially all patients of ventricular septal defect and ventricular size as well as exaggerated mitral valve
have right ventricular hypertrophy. Because of the delay motion. 2D echo can identify the site and size of defect in
in the fall of pulmonary vascular resistance due to the 90% cases as well as pick up the presence or absence of
presence of ventricular septal defect, the regression of pulmonic stenosis or pulmonary hypertension.
pulmonary arterial hypertension is delayed and right
ventricular hypertrophy regresses more slowly. In small Assessment of Severity
If the ventricular septal defect is small, the left to right shunt
murmur continues to be pansystolic but since the shunt is
small, the second sound is normally split and the intensity
of P2 is normal. There is also absence of the delayed diastolic
mitral murmur. If the ventricular septal defect is very small
it acts as a stenotic area resulting in an ejection systolic
murmur. This is the commonest cause of the so-called
functional systolic murmurs in children, which disappear
because of spontaneous closure of small defects.
If the ventricular septal defect is large it results in trans
mission of left ventricular systolic pressure to the right ventricle.
The right ventricular pressure increases and the difference
in the systolic pressure between the two ventricles decrea
ses. The left to right shunt murmur becomes shorter and softer
and on the bedside appears as an ejection systolic murmur.
If there is right ventricular outflow obstruction due to
associated infundibular pulmonic stenosis, the right ventri
cular pressure increases and the ventricular septal defect
murmur becomes an ejection systolic murmur. In the
former situation, the pulmonary artery pressure is
increased and results in an accentuated P2; in the latter,
Fig. 14.11: Summary of auscultatory findings in ventricular septal the pulmonary artery pressure is normal or decreased and
defect. LLSB = lower left sternal border. 2 LIS = second left interspace. the P2 is diminished in intensity and delayed in timing
PSM = pansystolic murmur resulting in a widely split, variable S2 with soft P2.
Disorders of Cardiovascular System 405
Patients of ventricular septal defect may have either to assess the development of pulmonic stenosis, pulonary
hyperkinetic pulmonary arterial hypertension or obstructive arterial hypertension or aortic regurgitation.
pulmonary arterial hypertension. The P2 is accentuated in Surgical treatment is indicated if (i) congestive cardiac
both. In the former there is a large left to right shunt failure occurs in infancy and does not respond to medical
whereas the latter is associated with a small left to right management; (ii) the left to right shunt is large (pulmonary
shunt. In hyperkinetic pulmonary arterial hypertension the car flow more than twice the systemic flow); and (iii) there is
diac impulse is hyperkinetic with a pansystolic murmur and associated pulmonic stenosis, pulmonary arterial hyper
thrill, widely split and variable S2 with accentuated P2 and a tension or aortic regurgitation. Surgical treatment is not
mitral delayed diastolic murmur. The obstructive pulmonary indicated in patients with a small ventricular septal defect
arterial hypertension is associated with a forcible parasternal and in those patients who have developed pulmonary
impulse, the thrill is absent or faint, the systolic murmur is arterial hypertension of a severity that a right to left shunt
ejection type, the S2 is normally but closely split zoith accentua has appeared.
ted Pi and there is no mitral murmur. The operative treatment consists in closure of the ventri
Based on physical findings, it is thus possible to disting cular septal defect with the use of a patch. The operation
uish very small, small, medium sized and large ventricular can be performed through the right atrium, which is the
septal defects. It is also possible to determine if there is preferred approach, or through a right ventriculotomy,
associated pulmonic stenosis or pulmonary arterial hyper which leaves majority of the patients with right bundle
tension of the hyperkinetic or obstructive variety. Doppler branch block. The operation can be done as early as a few
echo can provide the gradient between the left and right months after birth if congestive failure cannot be controlled
ventricles, helping in the assessment of right ventricular with medical management. With evidence of pulmonary
and pulmonary pressures. hypertension, the operation should be performed as early
as possible. Most modern centers are able to close the defect
Course and Complications
surgically in young infants. It is unwise to make the sick
Patients of ventricular septal defects can have a very vari infants wait for a certain weight threshold, since most
able course. They may develop congestive cardiac failure infants with large defects do not gain weight satisfactorily.
in infancy, which is associated with a high mortality. It is Episodes of lower respiratory infections require hospitali
estimated that 70-80% of all ventricular defects become zation and are difficult to manage. For very sick infants
smaller or disappears; the latter is called spontaneous with pneumonia who require mechanical ventilation, early
closure. Most (90%) patients who show spontaneous surgery should be considered.
closure, do so by the age of 3 years, though it may occur The major complications of the ventricular defect
later as well. surgery are: (i) complete heart block, (ii) bifascicular block
Patients born with an uncomplicated ventricular septal and (iii) reopened or residual ventricular septal defect.
defect may develop pulmonic stenosis due to hypertrophy These complications are fortunately rare. The risk of
of the right ventricular infundibulum, develop pulmonary surgery in uncomplicated defects is now less than 1% in
arterial hypertension or rarely aortic regurgitation due to pro most centers in our country.
lapse of the right coronary or the non-coronary cusp of Catheter closure of ventricular septal defects is possible
the aortic valve. Development of pulmonary arterial for muscular defects in relatively older children (>8-10
hypertension is a dreaded complication, since if it is of kg). There is a device designed for perimembranous
the obstructive type the patient becomes inoperable. Pati defects as well. However, the risk of complete heart block
ents of ventricular defects may develop CCF in adult life with the membranous defect occluder is significant.
around the age of 30-40 years. It is also possible for a Device closure of ventricular septal defect requires
patient with a relatively small ventricular septal defect to considerable technical expertise and should be attempted
go through the whole life without any symptoms or at dedicated centers.
difficulty. Lastly, the ventricular septal defect is the com
monest congenital lesion complicated by infective endocarditis. Patent Ductus Arteriosus
The incidence of infective endocarditis has been estimated Patent ductus arteriosus (PDA) is a communication
as 2/100 patients in a follow up of 10-years, that is 1 per between the pulmonary artery and the aorta. The aortic
500 patient year. The incidence of endocarditis is small attachment of the ductus arteriosus is just distal to the left
enough that it cannot be considered as an indication for subclavian artery. The ductus arteriosus is present in the
operation in small defects. fetal life but closes functionally and anatomically soon
after birth. The incidence of PDA in our clinic is 11%.
Treatment
Medical management consists in control of congestive
Hemodynamics
cardiac failure, treatment of repeated chest infections, and PDA results in a left to right shunt from the aorta to the
prevention and treatment of anemia and infective pulmonary artery. The flow occurs both during systole and
endocarditis. The patients should be followed carefully diastole as a pressure gradient is present throughout the cardiac
406 Essential Pediatrics
cycle between the tivo great arteries, if the pulmonary artery since the maximum intensity of the continuous murmur
pressure is normal. The flow of blood results in a murmur, occurs at S2 and tends to mask the S2. Clinically there is
which starts in systole, after the first sound and reaches a no point in evaluating the second sound if the patient has
peak at the second sound. The murmur then diminishes a continuous murmur. The continuous murmur indicates
in intensity and is audible during only a part of the dia presence of both a systolic as well as a diastolic difference
stole. Thus, it is a continuous murmur. in pressure between the aorta and pulmonary artery, thus
The PDA results in a systolic as well as diastolic excluding significant pulmonary arterial hypertension. The
overloading of the pulmonary artery. The increased flow murmur starts after the first sound and reaches the peak at the
after passing through the lungs reaches the left atrium second sound. The murmur then diminishes in intensity and is
that enlarges in size. The increased volume of blood audible only during a part of the diastole. The peak at S2
reaching the left atrium enters the left ventricle in diastole, differentiates the PDA murmur from other causes of a
across a normal mitral valve. The passage of this increased continuous murmur. Additionally the systolic portion of
the murmur is grating and rough. It appears to be broken
flow across the mitral valve results in an accentuated first
into multiple systolic sounds, the multiple clicks. The
sound as well as a mitral delayed diastolic murmur. The inten
murmur is best heard at the second left interspace and
sity of the delayed diastolic murmur is directly related to
also belozu the left clavicle where it maintains its continuous
the size of the left to right shunt. With small shunts, there
character. There is a third sound at the apex, followed by
is no mitral diastolic murmur. With moderate sized
a delayed diastolic murmur in large shunts (Fig. 14.12).
shunts, a left ventricular third sound is audible due to
The EKG shows normal axis with left ventricular
rapid early filling of the left ventricle. With large shunts,
dominance or hypertrophy. Deep Q waves in left chest
there is a mitral delayed diastolic murmur. The left ventri
leads with tall'T' waves are characteristic of the volume
cle, as in ventricular septal defects, receives the increased overloading of left ventricle. The EKG almost never shows
volume of blood during diastole. As such, both these ST and T changes suggestive of left ventricular "strain"
lesions cause diastolic overloading of the left ventricle. in uncomplicated PDA below the age of 15-years. Presence
The large volume of blood in the left ventricle causes a of ST and T changes suggests presence of additional aortic
prolongation of the left ventricular systole and an increase stenosis or fibroelastosis. The chest X-ray exhibits cardiac
in the size of the left ventricle to accommodate the extra enlargement with a left ventricular silhouette. The cardiac
volume. The prolonged left ventricular systole results in size depends on the size of the left to right shunt. The
delayed closure of the aortic valve and a late A2. With large larger the shunt the bigger the cardiac size. There may be
left to right shunts, the S2 may be paradoxically split. The left atrial enlargement. The ascending aorta and the aortic
large left ventricular volume ejected into the aorta results knuckle are prominent. The pulmonary vasculature is
in dilatation of the ascending aorta. A dilated ascending aorta
results in an aortic ejection click, which is audible all over
the precordium and precedes the start of the continuous
murmur. The large volume of blood from the left ventricle
passing through a normal aortic valve results in an aortic
ejection systolic murmur that, however, on the bedside is
drowned by the continuous murmur.
Clinical Features
Patients of PDA may become symptomatic in early life
and develop CCF around 6-10 weeks of age. Older
children give history of effort intolerance, palpitation and
frequent chest infections. The flow from the aorta to the
pulmonary artery is a leak from the systemic flow. This
results in a wide pulse pressure and many of the signs of
wide pulse pressure seen in patients with aortic regurgitation
are present in patients who have a PDA. On the bedside,
presence of prominent carotid pulsations in a patient with
features of a left to right shunt is suggestive of the
diagnosis. The cardiac impulse is hyperkinetic with a left
ventricular type of apex. A systolic or a continuous thrill
may be palpable at the second left interspace. The first
sound is accentuated and the second narrowly or paradoxically
split zvith large left to right shunts. With small shunts, the Fig. 14.12: Summary of auscultatory findings in patent ductus
second sound is normally split. The P2 is louder than arteriosus (PDA) M^mitral component of first sound; ESM ejection
normal. It is difficult to evaluate the S2 in patients of PDA, systolic murmur; DDM delayed diastolic murmur,- CONT continuous
Disorders of Cardiovascular System 407
plethoric. 2D echocardiogram can identify the PDA, which fistula; (ii) ruptured sinus of Valsalva fistulae into the right
is confirmed by Doppler. side, (iii) aortico-pulmonary septal defect; (iv) systemic
arteriovenous fistula over the chest; (v) bronchial collateral
Assessment of Severity murmurs; (vi) pulmonary arteriovenous fistula; (vii)
The evaluation of the size of the left to right shunt depends peripheral pulmonic stenosis; (viii) venous hum including
on a number of features: (i) the larger the heart size the the one which is associated with total anomalous
larger the left to right shunt; (ii) absence of third sound pulmonary venous connection; and (ix) small atrial septal
and delayed diastolic murmur indicates a small left to right defect associated with mitral stenosis.
shunt. Presence of the third sound indicates a moderate The impression of continuous murmur due to a
left to right shunt whereas an audible delayed diastolic combination of a pansystolic murmur and regurgitant
murmur suggests a large left to right shunt; (iii) the wider diastolic murmur occurs most commonly in ventricular
the pulse pressure the larger the shunt. septal defect associated with aortic regurgitation. This
difficulty may also occur in combinations of mitral and/
Course and Complications or tricuspid regurgitation with aortic regurgitation.
Neonates and infants have pulmonary hypertension at Combination of aortic stenosis and aortic regurgitation
birth. The regression of pulmonary hypertension occurs never gives an auscultatory impression of a continuous
slowly in the presence of PDA. The murmur is an ejection murmur since a gap between the two murmurs can always
systolic murmur to start with and assumes the continuous be appreciated.
character some weeks or months later. It thus remains
indistinguishable from a ventricular septal defect murmur Treatment
in early life. Differentiation between PDA and ventricular A large PDA is better tolerated by term newborns when
septal defect from the location of the maximum intensity compared to preterm newborns. Premature newborns
of the murmur is also not possible since the infant chest is with a hemodynamically significant PDA that results in
so small. Palpation in the suprasternal notch may help in heart failure, respiratory distress or necrotizing entero
differentiating PDA from a ventricular septal defect since colitis require prompt management. Indomethacin or
the large aorta in ductus becomes palpable. CCF may occur ibuprofen is often attempted. It is likely to be effective
within the first six weeks of life but can be controlled before the age of 2-weeks in preterm newborns and is
medically in most cases. Patients of PDA tend to develop unlikely to be useful in term babies. The dose is 0.1 mg/
pulmonary arterial hypertension earlier than patients of kg/dose, orally, 12 hourly for three doses. Hepatic or renal
ventricular septal defect. Those patients who develop insufficiency or bleeding tendency are contraindications.
pulmonary arterial hypertension lose the diastolic Newborns not responding to these agents require surgical
difference in the aortic and pulmonary pressures first. ligation. The PDA in term infants may close spontaneously
Thus with increasing pulmonary arterial hypertension the as late as one month after birth and it is worth waiting to
diastolic component becomes shorter and may disappear a month even if the duct is large unless CCF is refractory.
altogether, leaving only an ejection systolic murmur. Large PDA may result in congestive cardiac failure in
PDA may be associated with hyperkinetic or obstruc infancy. Echocardiography allows ready confirmation of
tive pulmonary arterial hypertension as in ventricular the diagnosis and estimation of hemodynamic severity of
septal defects. In both situations the murmur loses its the PDA. Catheter-based treatment (occlusive devices or
diastolic component and the P2 is accentuated. The coils) are now realistic in many patients. They are
hyperkinetic pulmonary hypertension is associated with technically challenging in small infants especially those
a large heart and mitral delayed diastolic murmur, <5 kg and should be performed in centers that are
whereas the obstructive variety is accompanied with a accustomed to doing them. Today, indications for surgery
normal heart size and absence of the mitral diastolic mur for PDA include, small infants with large ducts, preterm
mur. With severe pulmonary arterial hypertension and a infants, and ducts that are very large (larger than the size
right to left shunt through a PDA, the normal splitting of of available devices). In our country, surgery is more
S2 is maintained but the murmur disappears and the affordable in many centers and many patients can only
patients develop differential cyanosis. be offered surgery. Occlusive devices are particularly
expensive and often cost 3-4 times that of surgery.
Differential Diagnosis Patients who have a PDA with pulmonary arterial
The differential diagnosis of PDA includes conditions hypertension are considered inoperable if a right to left
capable of giving a continuous murmur over the shunt has appeared because of pulmonary arterial
precordium. In addition, combination of a pansystolic hypertension. Since the right to left shunt through the PDA
murmur with an early diastolic murmur, which are partly flows down the descending aorta, cyanosis is present in
superimposed on each other, may simulate a continuous toes but not in fingers. This is called differential cyanosis
murmur over the precordium. Differential diagnosis of a and is characteristic of PDA with pulmonary arterial
continuous murmur includes: (i) coronary arteriovenous hypertension and right to left shunt.
408 Essential Pediatrics
RIGHT TO LEFT SHUNTS____ ______ _______ and left ventricular pressures have become identical,
increasing severity of pulmonic stenosis reduces the flow
As indicated earlier, patients who are cyanotic have either
of blood into the pulmonary artery and increases the right
pulmonic stenosis or pulmonary arterial hypertension.
to left shunt. As the systolic pressures between the two
Right to Left Shunts with Pulmonic Stenosis ventricles are identical there is little or no left to right shunt
and the ventricular septal defect is silent. The right to left
Examples of this combination include tetralogy of Fallot,
tricuspid atresia and Ebstein's anomaly. shunt is also silent since it occurs at insignificant difference
in pressure between the right ventricle and the aorta. The
Tetralogy of Fallot flow from the right ventricle into the pulmonary artery
Tetralogy of Fallot (TOF) is the commonest cyanotic occurs across the pulmonic stenosis producing an ejection
congenital heart disease in children above the age of two systolic murmur. The more severe the pulmonic stenosis,
years, constituting 75% of all patients. Its incidence in our the less the flow into the pulmonary artery and the bigger
clinic is 17%. Anatomically TOF consists of ventricular the right to left shunt. Thus the more severe the pulmonic
septal defect associated with obstruction to the right stenosis, the shorter the ejection systolic murmur and the
ventricular outflow in the form of infundibular or infundi more the cyanosis. Thus, the severity of cyanosis is directly
bular plus valvular pulmonic stenosis. The constituents proportional to the severity of pulmonic stenosis, but the
of TOF are (i) ventricular septal defect, (ii) pulmonic intensity of the systolic murmur is inversely related to the
I stenosis, (iii) overriding or dextroposed aorta, and (iv) severity of pulmonic stenosis. The ventricular septal defect
jM right ventricular hypertrophy. of TOF is always large enough to allow free exit to the
right to left shunt. Since the right ventricle is effectively
U Hemodynamics decompressed by the ventricular septal defect, CCF never
Jjf Physiologically the pulmonic stenosis causes concentric occurs in TOF. The exceptions to this rule are (i) anemia;
right ventricular hypertrophy without cardiac enlarge (ii) infective endocarditis; (iii) systemic hypertension; (iv)
ment and increase in right ventricular pressure (Fig. 14.13). unrelated myocarditis complicating TOF; and (v) aortic
When the right ventricular pressure is as high as the left or pulmonary valve regurgitation.
ventricular or the aortic pressure, a right to left shunt The right ventricular outflow obstruction results in a
appears to decompress the right ventricle. Once the right delay in the P2. Since the pulmonary artery pressure is
Ao PA
20/10
'
110/75
Fig. 14.13: Digrammatic portrayal: (A) ventricular septal defect, (B) ventricular septal defect with moderate pulmonic stenosis, and (C) Fallot's
tetralogy. (A) In the absence of pulmonic stenosis the right ventricular (RV) and the pulmonary artery (PA) pressures are normal or slightly
elevated. Since the left ventricular (LV) pressure is higher, there is a systolic flow of blood from the LV into the PA through the RV. (B) If a VSD is
associated with moderate pulmonic stenosis, the RV systolic pressure increases and there is RV hypertrophy. The left to right shunt decreases
and the VSD murmur becomes softer. The pulmonic stenosis murmur, however, is loud. (C). In Fallot's tetralogy the RV and LV pressures are
identical. There is no left to right shunt and as such the VSD is silent. The flow from RV to PA decreases, decreasing the intensity of pulmonic
stenosis murmur. A right to left shunt occurs from RV to Aorta (Ao) at identical pressures. As such the right to left shunt is silent
Disorders of Cardiovascular System 409
Clinical Features
Patients with TOF may become symptomatic any time
after birth. Neonates as well as infants may develop anoxic Fig. 14.14: Summary of auscultatory findings in Fallot’s
spells (paroxysmal attacks of dyspnea). Cyanosis may be tetralogy. X = Systolic click
present from birth or make its appearance some years after
birth. The commonest symptoms are dyspnea on exertion
and exercise intolerance. The patients assume a sitting
posture (squatting) as soon as they get dyspneic. Although
squatting is not specific for TOF, it is the commonest
cardiac lesion in which squatting is noted.
Anoxic spells occur predominantly after waking up or
following exertion. The child starts crying, becomes
dyspneic, bluer than before and may lose consciousness.
Convulsions may occur. The frequency varies from once
in a few days to numerous attacks every day.
Physical examination discloses cyanosis, clubbing,
slightly prominent 'a' waves in the jugular venous pulse, normal
sized heart with a mild parasternal impulse, a systolic thrill in
less than 30% patients, normal first sound, single second sound
and an ejection systolic murmur which ends before the audible
single second sound. The only additional auscultation
findings can be a constant ejection click due to a large aorta
or an inconstant ejection click due to additional valvular
pulmonic stenosis (Fig. 14.14).
EKG shows right axis deviation with right ventricular
Fig. 14.15: Thoracic roentgenogram of Fallot's tetralogy. The cardiac
hypertrophy. The 'T' waves are inverted in right size is normal, main pulmonary artery segment is concave, cardiac
precordial leads. T' pulmonale may be present, but is configuration is right ventricular. The lung fields are ischemic and the
uncommon. Vj may show pure 'R' but transition to R/S aorta is large in size
complex occurs at V2. The X-ray shows a normal sized
heart with upturned apex, suggestive of right ventricular
hypertrophy. The absence of main pulmonary artery tetralogy. Paroxysmal attacks of dyspnea can be present
segment gives the shape described as cor-en sabot. The aorta with mild as well as severe TOF. However, effort
is enlarged and a right aortic arch is present in 30%; the intolerance is directly related to the severity.
latter is recognized by its concave impression on the right
Diagnosis
side of trachea. The pulmonary fields are oligemic (Fig.
14.15). Echocardiogram identifies the large overriding Echocardiography allows confirmation of diagnosis and
aorta, right ventricular hypertrophy and outflow also provides additional information required for surgery.
obstruction; aortic-mitral valve continuity is maintained. Cardiac catheterization is seldom necessary.
limit the patients considerably. Each attack of paroxysmal obstruction. The risk of operation is less than 5%; 85-90%
dyspnea or anoxic spell is potentially fatal. Anemia patients return to normal life after surgery. With suitable
reduces the exercise tolerance, and can result in cardiac anatomy, the operation can be performed at any age if
enlargement and CCF making diagnosis difficult. Patients pulmonary arteries are of adequate size and the anterior
are prone to infective endocarditis. Neurological complications descending coronary artery is from the left coronary
occur frequently. Anoxic infarction in the central nervous artery. Major complications include complete heart block,
system may occur during an anoxic spell and result in right bundle branch block, left anterior hemiblock, residual
hemiplegia. Paradoxical embolism to central nervous system ventricular septal defect and residual pulmonic stenosis.
and venous thrombosis due to sluggish circulation from Since the pulmonary valve is frequently excised, patients
polycythemia can also result in hemiplegia. Brain abscess is show pulmonary regurgitation and right ventricular
not an infrequent complication and should be suspected dilatation. Long term risks following surgery include heart
in any patient presenting with irritability, headache, failure and ventricular tachyarrhythmias.
convulsions, vomiting with or without fever and
neurological deficit. Opthalmoscopy need expert Tricuspid Atresia
evaluation since polycythemia results in congested retina Congenital absence of the tricuspid valve is called tricus
and recognition of papilledema is difficult.
pid atresia (Fig. 14.16). The right ventricle is hypoplastic
and inflow portion absent. Tricuspid atresia constitutes
Treatment
2% of all congenital heart disease in our clinic.
ii The medical management of TOF is limited to manage-
^ J ment of complications including anoxic spells (Table 14.13) Hemodynamics
I and correction of anemia. Operative treatment is of two
Atresia of the tricuspid valve results in the absence of a
W types, palliative and definitive. Palliative treatment consists
communication between the right atrium and the right
of anastomosing a systemic artery with the pulmonary
ventricle. The right ventricle is underdeveloped, the inflow
artery to increase the pulmonary blood flow and thus
portion being absent. The only exit for the systemic venous
increase the amount of oxygenated blood reaching the blood coming to the right atrium through the inferior and
systemic circulation. While these procedures prolong life superior vena cava is by way of the patent foramen ovale
and increase the exercise tolerance, the basic disease
or an atrial septal defect. There is complete mixing of the
remains unaltered.
systemic venous and pulmonary venous blood in the left
atrium from where the blood passes to the left ventricle.
Table 14.13: Management of anoxic spells A ventricular septal defect provides communication
between the left ventricle and the outflow portion of the
Knee chest position
right ventricle. The pulmonary artery is connected to the
Humidified oxygen
right ventricular outflow and the aorta arises from the left
Morphine 0.1 to 0.2 mg/kg, SC
ventricle in 70% cases. In 30% patients, aorta arises from
Obtain venous pH; sodium bicarbonate 1-3 ml/kg (diluted) the right ventricle and the pulmonary artery from the left
IV
ventricle. The latter group of patients is called tricuspid
Propranolol 0.1 mg/kg/IV (during spell); 0.5-1 mg/kg/6 atresia with transposition of great arteries. The left
hourly orally (Alternatives: metoprolol, esmolol)
ventricle, therefore, maintains both the systemic as well
Vasopressors: methoxamine (Vasoxyl) IM or IV drip as the pulmonary circulation. The saturation of blood in
Correct anemia the pulmonary artery and the aorta is identical. The
Consider surgery saturation of blood in the aorta depends on the size of
pulmonary blood flow. The larger the pulmonary blood
flow, the more the oxygenated blood coming back to the
The most common procedure is the modified Blalock- left atrium to mix with the unoxygenated blood coming
Taussig shunt, which consists of subclavian artery to from the right atrium and the higher the final mixed
pulmonary artery anastomosis using a Goretex graft. saturation. The pulmonary blood flow is dependent on
Shunts of historic importance include: the size of the ventricular defect, which in tricuspid atresia
i. Classical Blalock-Taussig shunt: subclavian artery is always a muscular defect. The smaller the ventricular
(side opposite the aortic arch) pulmonary artery septal defect, the less the pulmonary blood flow.
anastomosis.
ii. Pott's shunt: descending aorta anastomosed to the Clinical Features
pulmonary artery. Clinical presentation depends on the state of pulmonary
iii. Waterston's shunt: ascending aorta right pulmonary flow, which may be diminished or increased. Patients with
artery anastomosis. diminished pulmonary blood flow constitute 90% of all
The definitive operation consists of closing the cases. Symptoms and physical signs are identical to TOF.
ventricular septal defect and resecting the infundibular Features suggesting tricuspid atresia are (i) left ventricular
Disorders of Cardiovascular System 411
type of apical impulse; (ii) prominent large a waves in pulmonary arterial band (usually under the age of 3
jugular venous pulse; (iii) enlarged liver with presystolic months) for patients who have increased pulmonary blood
pulsations (a waves); and (iv) EKG showing left axis flow and the modified Blalock-Taussig shunt for those
deviation and left ventricular hypertrophy. The mean QRS who have reduced pulmonary blood flow with cyanosis.
axis is around -45°. The P waves may show both right The second operation is the bidirectional Glenn shunt,
and left atrial hypertrophy. The chest X-ray shows where the superior vena cava is anastomosed to the right
oligemic lung fields, left ventricular configuration of the pulmonary artery. This surgery allows effective palliation
cardiac silhouette and a prominent superior vena cava. until the age of 4-6 years. The Fontan operation is finally
Echocardiogram identifies a large single ventricular cavity. required for elimination of cyanosis. Here all the systemic
In the four-chambered view, atretic tricuspid valve can venous return (from both vena cava) is routed to the
be recognized and great vessel relationship established. pulmonary artery. This is at best a palliative procedure
Patients of tricuspid atresia with increased pulmonary and there are important long-term issues in a substantial
blood flow cannot generally be diagnosed accurately proportion of survivors.
clinically. Ebstein Anomaly
the right ventricle into the right atrium. The atrialized right knuckle small. The pulmonary vasculature is diminished.
ventricle contracts with the rest of the ventricle and does Echocardiogram shows the tricuspid and mitral valves
not allow effective forward flow into the pulmonary simultaneously with delayed closure of the tricuspid valve
circulation. The right atrium progressively dilates, to (more than 65 msec). Four chambered view in 2D echo is
accommodate the extra volume. The foramen ovale may diagnostic, since it outlines the displaced tricuspid valve.
be patent or there is an atrial septal defect allowing right
to left shunt, resulting in cyanosis. The left ventricle is Diagnosis and Treatment
hypertrophied and enlarged.
The diagnosis can be easily confirmed by echocar
Clinical Features diography, which also identifies the severity. Intracardiac
EKG with simultaneous pressure recording is of interest.
Patients present with history of cyanosis, effort intolerance
The pressure recording shows right atrial type of pressure,
and fatigue; there may be history of paroxysmal
while the EKG indicates that the catheter is in the ventricle.
tachycardia. On examination, the cyanosis varies from
Surgery is delayed, until symptoms develop. The surgical
slight to severe. Clubbing is present. The jugular venous
treatment consists in obliterating the atrialized portion of
pulse may show a dominant 'V wave but there is usually
the right ventricle and repairing the tricuspid valve.
no venous engorgement. The precordium is quiet with a
left ventricular apical impulse. A systolic thrill may be
Fallot’s Physiology
palpable at the left sternal border. The first sound is split,
however, the tricuspid component cannot be made out, The concept of Fallot's physiology is useful for the bedside
resulting in a single, normally audible first sound. The identification of a group of conditions clinically presenting
abnormal tricuspid valve may produce a mid systolic click. with similar symptoms and signs. The diagnosis of TOF is
The second sound is widely split, but variable with a soft made in a cyanotic child with a normal sized heart, mild
pulmonic component. A right ventricular third sound parasternal impulse, normal first sound and an ejection systolic
and/or a right atrial fourth sound may be audible. The murmur ending before a single second sound. History of paro
abnormal tricuspid valve may produce a mid systolic click. xysmal attacks of dyspnea and squatting may be present.
Thus, triple or quadruple sounds are usually heard. The Identical symptoms and physical findings are present in
murmur may be a midsystolic ejection or pansystolic (i) complete transposition of great arteries with ventricular
murmur. There is also a short tricuspid delayed diastolic septal defect and pulmonic stenosis, (ii) double outlet right
murmur. The systolic and the diastolic murmurs have a ventricle with pulmonic stenosis and a large subaortic
scratchy character, not unlike a pericardial friction rub. ventricular septal defect, (iii) tricuspid atresia with
The EKG characteristically shows P pulmonale, P diminished pulmonary blood flow, (iv) single ventricle
mitrale and right bundle branch block. The R wave in Vj with pulmonic stenosis, and (v) corrected transposition
does not exceed 7 mm; lead V6 shows relatively tall R and of great arteries with ventricular septal defect and pulmo
broad S waves. Wolff Parkinson White type of conduction nic stenosis. The above described symptoms and physical
abnormality may be seen (Fig. 14.17). Chest X-ray shows findings are related to the presence of a large ventricular
right atrial and ventricular enlargement. The main septal defect associated with pulmonic stenosis. Clinically
pulmonary artery segment is prominent and the aortic with the help of EKG and chest X-ray it is not always
possible to separate TOF from the above conditions, except
tricuspid atresia (which shows left axis deviation and left
ventricular hypertrophy). Fallot's physiology identifies
these six anomalies, which are surgically treatable and
potentially correctable. 2D echocardiography can
distinguish and identify these anomalies fairly accurately.
severe cyanosis, CCF, normal first sound, single second operation (Jatene's repair). The pulmonary artery and
sound and an insignificant grade one to two ejection aorta are transected. The distal aorta is anastomosed to
systolic murmur. EKG shows right axis deviation and right the proximal pulmonary stump (neoaortic root) and the
ventricular hypertrophy. The chest X-ray shows cardio- pulmonary artery to the proximal aortic stump (neopul-
megaly with a narrow base and plethoric lung fields. The monary artery). The coronary arteries are moved along to
cardiac silhouette has an "egg on side" appearance. The the neoaortic root along with a cuff of aortic tissue to allow
right upper lung fields appear more plethoric and thymic suturing without compromising coronary blood flow. The
shadow is absent (Fig. 14.19). other operation available for complete TGA is atrial switch
operation (Mustard or Senning) in which the pulmonary
venous blood is redirected to the right ventricle and the
systemic venous blood to the left ventricle, thus
establishing normal route of blood flow. Jatene's switch
operation is preferable to atrial switch since the latter
results in complications like right ventricular failure and
atrial arrhythmias in later life. Most cardiac centers strive
to achieve excellence with the arterial switch because the
long-term results are satisfying.
If a ventricular septal defect is present it can be closed
at the same time. If facilities for definitive repair are not
available, pulmonary artery banding can be done in
patients with a ventricular septal defect to protect the pul
monary vasculature. Since PDA results in early pulmonary
vascular disease, it should be divided as early as possible.
Since patients with TGA tend to develop pulmonary
vascular obstructive disease (Eisenmenger physiology)
early in life even if they have only an atrial communication,
they should be operated as early as possible, ideally below
the age of three months.
Fig. 14.19: Egg on side appearance in transposition
Corrected TGA
Patients of complete TGA with ventricular septal defect In corrected TGA the aorta lies anterior and to the left of
have a large pulmonary blood flow, good mixing at the the pulmonary artery. The ascending aorta forms the left
ventricular level and as such the cyanosis is relatively mild. upper border of the cardiac silhouette. Since the route of
They develop CCF around 4-10 weeks of age. Physical blood flow is normal, it is the associated anomalies, which
findings consist of cyanosis, cardiomegaly, congestive determine the clinical features. The associated anomalies,
failure, normal first sound, single or normally split second present in more than 98%, include (i) ventricular septal
sound and a grade two to four ejection systolic murmur. defect with or without pulmonic stenosis; (ii) left sided
Apical third sound gallop or a middiastolic rumble may Ebstein's anomaly of the tricuspid valve (clinically
be present. EKG shows right axis deviation with biventri simulates mitral regurgitation); and (iii) atrioventricular
cular, right ventricular or left ventricular hypertrophy; conduction defects including complete atrioventricular
chest X-ray shows cardiomegaly, plethoric lung fields and block. The most useful clue for the diagnosis of corrected
some features of pulmonary venous hypertension. TGA is related to inversion of the ventricles. The precordial
leads V4R, Vj, and V2 may show a Q wave which is absent
Treatment in the left precordial leads. The chest roentgenogram
Medical management has little to offer. Oxygenation can shows a smooth left upper border corresponding to the
hardly be improved by administering oxygen. The best ascending aorta. The diagnosis depends on echocardio-
approach consists in doing balloon atrial septostomy graphic identification of ventricular inversion as well as
following confirmation of the diagnosis. This procedure additional anomalies.
can be accomplished in the cardiac catheterization
Total Anomalous Pulmonary Venous Connection
laboratory or on the patient's bedside. The septostomy is
successful only up to the age of 6-12 weeks. Septostomy Total anomalous pulmonary venous connection (TAPVC)
gives temporary relief by providing better mixing as well is an uncommon condition. The pulmonary veins instead
as reducing the left atrial pressure. If the diagnosis can be of joining the left atrium are connected anomalously to
established below the age of two weeks and facilities for result in the total pulmonary venous blood reaching the
operation at this age are available, the patient can be right atrium. TAPVC is classified into supracardiac,
subjected to definitive repair by the arterial switch cardiac, infracardiac and mixed varieties. In supracardiac
Disorders of Cardiovascular System 415
TAPVC, the pulmonary veins join together to form a monale is common. The chest X-ray shows cardiomegaly
common pulmonary vein that drains into the left with plethoric lung fields in non-obstructive TAPVC. In
innominate vein or the right superior vena cava. In the the first two years of life, characteristic pattern of the
cardiac TAPVC, the veins join the coronary sinus or enter 'snowman' or figure of '8' configuration in the supra
the right atrium directly. In the infracardiac variety, the cardiac TAPVC draining to left innominate vein is not
common pulmonary vein drains into the portal vein. seen. Chest X-ray in obstructive TAPVC consists of a
normal sized heart with severe pulmonary venous
Hemodynamics hypertension resulting in a ground glass appearance of
TAPVC results in the pulmonary venous blood reaching the lungs. Echocardiography allows confirmation of the
the right atrium, which also receives the systemic venous diagnosis, definition of the individual pulmonary veins
blood. This results in almost complete mixing of the two and assessment of the site of obstruction if present.
venous returns. The blood flow to the left atrium is The diagnosis of obstructive TAPVC is considered in a
through a patent foramen ovale or atrial septal defect. The cyanotic neonate with a normal sized heart and ground
oxygen saturation in the pulmonary artery is higher or glass lung fields. The diagnosis of non-obstructive TAPVC
identical to that in the aorta because of mixing of the blood is suspected if auscultatory features of atrial septal defect
in the right atrium. Physiologically TAPVC can be divided are associated with either cyanosis or congestive failure
into (a) patients with pulmonary venous obstruction, and in the first 2-3 months of life.
(b) patients without pulmonary venous obstruction.
Pulmonary venous obstruction results in pulmonary Management
hypertension as well as restriction to pulmonary blood Operation is indicated as early as possible since 80% of
flow. In the absence of pulmonary venous obstruction,
infants die within the first three months of life without
the pulmonary blood flow is large and results in CCF
surgical help. Obstructed TAPVC constitute a surgical
between 4-10 weeks of age. TAPVC of the infracardiac
emergency. The results of surgery for both forms of
type is always obstructive, while cardiac and supracardiac
TAPVC are satisfactory but newborns and infants with
types may or may not have pulmonary venous obstruc
obstructed TAPVC might develop pulmonary hyperten
tion.
sive crisis in the postoperative period and need expert
management.
Clinical Features
TAPVC of the non-obstructive type is commoner than the
Cyanosis with Increased Pulmonary Blood Flow
obstructive type. Patients present with cyanosis and CCF
as the fetal pulmonary vasculature regresses, typically A large number of conditions result in the combination of
around 4-10 weeks of age. With large pulmonary blood cyanosis with increased pulmonary blood flow. Common
flow, the cyanosis may be minimal or clinically not to these conditions is the presence of abnormal mixing of
recognizable. The patients are irritable and have failure pulmonary venous blood with the systemic venous blood
to thrive. They also show hyperkinetic precordium, and absence of obstruction to pulmonary blood flow. The
normal or accentuated first sound, widely split and fixed anomalies included in this group of conditions are
second sound with accentuated pulmonic component, transposition of great vessels, total anomalous pulmonary
grade II-IV pulmonary ejection systolic murmur and a venous connection, single ventricle without obstruction
tricuspid flow murmur. The physical findings are identical to pulmonary blood flow, persistent truncus arteriosus,
to that of an atrial septal defect. Presence of CCF at this tricuspid atresia with absence of obstruction to pulmonary
age suggests TAPVC since CCF in atrial septal defect at blood flow and double outlet right ventricle without pul
this age is very rare. A continuous venous hum may be monic stenosis. Patients present with CCF in the neonatal
audible at the upper left or right sternal border or in the period and are characterized by the presence of cyanosis,
suprasternal notch. cardiomegaly and failure to thrive. Almost 80% die within
Patients with obstructive type of TAPVC present with the first 3 months of life due to CCF or pulmonary infec
marked cyanosis and CCF within the first 1-2 weeks of tion. Those who survive develop pulmonary hypertension
life. Physical findings consist of a normal sized heart with due to pulmonary vascular obstructive disease and
parasternal heave, normal first sound, accentuated become inoperable and thus incurable. Echocardiography
pulmonic component of S2 and insignificant murmurs. or cardiac catheterization with angiography are necessary
Tricuspid regurgitation can occur and results in cardio for the specific diagnosis. Operative treatment is not
megaly. possible without the correct diagnosis. Since mortality of
unoperated patients is high and patients develop
Diagnosis Eisenmenger syndrome early, it is necessary that patients
EKG in TAPVC with or without pulmonary venous presenting with cyanosis and increased pulmonary blood
obstruction shows right axis deviation and right flow be referred to centers where facilities for care for such
ventricular hypertrophy. In obstructive TAPVC, P pul patients is available.
416 Essential Pediatrics
Cyanotic Congenital Heart Disease with in patients who have a ventricular septal defect. Patients
Pulmonary Arterial Hypertension with PDA continue to have a normally split S2. A
This group of patients are also termed Eisenmenger pulmonary ejection click, which unlike patients of valvar
syndrome, implying the presence of severe pulmonary pulmonic stenosis, is well heard during inspiration and
arterial hypertension resulting in a right to left shunt at expiration. A functional pulmonary regurgitation murmur
the atrial, ventricular or pulmonary arterial level. can be present along the left sternal border. Patients with
Eisenmenger complex consists of pulmonary arterial atrial septal defect, in whom Eisenmenger physiology is
hypertension with a ventricular septal defect providing uncommon, can develop tricuspid regurgitation (Fig.
the right to left shunt. 14.20).
Hemodynamics
The pulmonary arterial hypertension is due to pulmonary
vascular obstructive disease. If a communication is present
at the pulmonary arterial level or the ventricular level,
the right ventricular pressure cannot go beyond the
systemic pressure. The right to left shunt decompresses
the right ventricle. The right ventricle has only concentric
hypertrophy without significant increase in the size. In
patients who have PDA or ventricular septal defect, there
is only a mild parasternal impulse without a significant
heave. In patients who do not have a ventricular septal
defect or PDA, the right ventricle, besides hypertrophy,
also dilates. The right to left shunt at the atrial level is an
indication of right ventricular failure to accommodate this
volume and push into the pulmonary artery. Thus,
patients of Eisenmenger syndrome with communication
at the atrial level only, exhibit a parasternal heave and
cardiac enlargement. The right ventricular pressure may
even be higher than the systemic pressure.
Fig. 14.20: Summary of auscultatory findings in Eisenmenger
A right to left shunt at the atrial level or the ventricular syndrome
level reaches the ascending aorta and is thus distributed
to the whole systemic circulation. This results in equal
cyanosis of fingers and toes. A right to left shunt through EKG shows right axis deviation and right ventricular
a PDA is directed into the descending aorta, since the hypertrophy; P pulmonale may be present. The chest
ductus joins the arch of aorta distal to the origin of left X-ray is characteristic with prominent pulmonary arterial
subclavian artery. This results in the right to left shunt segment and large right and left main pulmonary arteries,
reaching only the distribution of descending aorta. The but oligemic lung fields. Thus, the hilar area shows
fingers remain pink while the toes show cyanosis and pulmonary plethora while the peripheral fields suggest
clubbing; differential cyanosis is characteristic of pulmonary oligemia.
arterial hypertension with a PDA.
Treatment
The etiology of pulmonary arterial hypertension is not
known. High pulmonary artery oxygen saturation, high There is no role for surgical treatment. Medical manage
flow through the pulmonary artery and hyperreactive ment consists in treating chest infections, correcting anemia
pulmonary vasculature have been considered as possible and managing CCF. Intermittent use of oxygen may help
explanations. relieve syncope, severe headaches and angina-like chest
pain. Ideally, pulmonary vascular obstructive disease
Clinical Features should be prevented from developing. This means careful
Patients present with history of cyanosis, fatigue, effort evaluation and follow up of patients of ventricular septal
intolerance and dyspnea. There may be history of repeated defect and PDA in the first two years of life, when
chest infections in childhood; examination shows cyanosis pulmonary arterial hypertension is generally reversible.
and clubbing. The features indicative of pulmonary Patients with cyanosis and increased pulmonary blood
arterial hypertension consist of parasternal impulse and flow develop Eisenmenger physiology very early and need
palpable S2. The pulmonary component of S2 is accen to be operated by two to three months of age. Patients who
tuated and louder than the aortic component. The splitting have features of pulmonary arterial hypertension should
of S2 remains wide and fixed in atrial septal defect. Due to be operated early to prevent the development of
superimposition of A2 and P2 the second sound is single irreversible pulmonary arterial hypertension.
Disorders of Cardiovascular System 417
Medications have recently become available for the obstruction results in the aortic ejection systolic murmur,
management of pulmonary hypertension. These include which is typically diamond shaped, starting after the first
agents that reduce pulmonary hypertension. The phos- sound and ending before the aortic component of the
phodiestrase-5 inhibitors (sildenafil, tadalafil) selectively second sound with a mid-systolic peak. The systolic
increase the local availability of cyclic GMP in the murmur is always palpable as a thrill at the second right
pulmonary vascular smooth muscles, promoting interspace, suprasternal notch and the carotid vessels. The
pulmonary vasodilation. Bosentan, sitaxsentan and powerful left ventricle can maintain a normal forward
ambrisentan are endothelin receptor blockers, which cardiac output. The prolonged ejection results in the
inhibit the pulmonary vasoconstrictor effects of endo characteristic pulse, which can be best described as slowly
thelin, promote vasodilation and enable vascular remodel rising to a peak, which is sustained and then has a slow
ing. Prostacyclin analogs promote pulmonary vaso down-slope. The peak is low so that the pulse is of low
dilation. The results of preliminary studies with these amplitude and prolonged duration.
agents in Eisenmenger syndrome are promising. Concentric hypertrophy of the left ventricle results in
decreased distensibility of the left ventricle in diastole-
OBSTRUCTIVE LESIONS reduced compliance. In severe aortic stenosis, therefore,
with marked left ventricular hypertrophy, the left ventri
Aortic Stenosis
cular diastolic pressure also rises. With increase in left
Congenital aortic stenosis constitutes about 8% of all ventricular diastolic pressure, the left atrial pressure must
congenital cardiac lesions in our clinic. Pathologically the increase to be able to fill the left ventricle during diastole.
obstruction is at the valve, above the valve (supravalvar) Hence, with severe aortic stenosis accompanied with
or below the valve (subvalvar). At the valve level, the marked left ventricular hypertrophy, a forceful left atrial
aortic stenosis results from either unicuspid or bicuspid contraction results in a palpable as well as audible fourth
aortic valve. Rarely the aortic valve ring may itself be sound (S4). When the left ventricle starts failing in aortic
small. The unicuspid aortic valve is stenotic from its design stenosis, besides hypertrophy dilatation also appears and
and the patients are symptomatic early in life. The bicuspid causes increase in heart size. With left ventricular failure
aortic valve results in significant obstruction when the a third sound (S3) becomes audible.
valves become thicker and relatively immobile, usually In valvar aortic stenosis there is post stenotic dilatation
at 30-40 years of age. Supravalvar aortic stenosis results of the ascending aorta, visible in the posteroanterior
from obstruction in the root of aorta, above the aortic thoracic roentgenogram. In supravalvar and subvalvar
valve. It is typically associated with Williams' syndrome. aortic stenosis the post stenotic dilatation is absent. A
Subvalvar aortic stenosis is of many varieties: dilated ascending aorta is associated with an ejection click.
i. Discrete membranous subvalvar stenosis: Results from In valvar aortic stenosis, the first sound is followed by an
a membrane, with a central or eccentric hole, at the ejection click, which precedes the starts of the murmur.
left ventricular outflow tract. It may be very close to The aortic ejection click is well heard at the apex, and along
the aortic valve or just below the valve ring. the left sternal border.
ii. Fibromuscular subvalvar aortic stenosis: Fibromuscular
tissue present below the aortic valve narrows down
Clinical Features
the left ventricular outflow. The fibromuscular tissue The patients of mild to moderate aortic stenosis are
extends from the septal wall of the left ventricle to asymptomatic. With severe aortic stenosis the initial
the anterior (aortic) leaflet of the mitral valve. symptom is generally dyspnea on exertion. The patients
iii. Idiopathic hypertrophic subaortic stenosis: It is also called may also give history of angina on effort and syncope.
asymmetrical septal hypertrophy or hypertrophic Presence of any one of these three symptoms suggests
obstructive cardiomyopathy. The ventricular septum, severe aortic stenosis. The blood pressure is normal with
hypertrophied out of proportion to the rest of the mild aortic stenosis. The more the severity of aortic stenosis,
ventricular wall, results in narrowing of the left the narrower the pulse pressure. This gives the characteristic
ventricular outflow tract. low amplitude prolonged duration pulse. The cardiac size
remains normal unless left ventricular failure is present.
Hemodynamics The apical impulse is forcible or heaving. In severe aortic
Obstruction at the aortic valve level is overcome by raising stenosis the fourth sound may be palpable. If left
the systolic pressure of the left ventricle. This is brought ventricular failure is present the third sound may be
about by concentric hypertrophy of the left ventricle. palpable. A systolic thrill is palpable at the second right
Because of a powerful, muscular left ventricle, the interspace, suprasternal notch and the carotid arteries. The
emptying of the left ventricle is complete but the duration first sound is normal and followed by an ejection click in
of the systole is prolonged. The prolongation of left valvar aortic stenosis. The aortic component of the second
ventricular ejection time causes delayed closure of the sound (At) is delayed but not diminished in intensity in aortic
aortic valve resulting in delayed A2. The flow across the stenosis. The delay results in normally but closely split,
418 Essential Pediatrics
Assessment of Severity
Fig. 14.21: Aortic stenosis: Diagrammatic portrayal of the In every patient it is necessary to assess the severity of
hemodynamic basis for aortic stenosis murmur. The first sound (S-,) aortic stenosis. Absence of an indication of severity means
occurs as the left ventricular (LV) pressure increases above left atrial
incomplete diagnosis. The clinical assessment of severity
(LA) pressure. This is followed by the ejection click (X) occurring after
depends on the following
the aortic valve opens. The shape of the gradient between LV and
aorta (Ao) corresponds to the shape of the aortic ejection systolic a. Symptomatic patients have severe aortic stenosis. If the
murmur (ESm). The murmur ends before the aortic components of patient is asymptomatic, it does not exclude severe
the second sound (Aj) aortic stenosis.
Disorders of Cardiovascular System 419
b. Narrower the pulse pressure, the more severe the aortic valvotomy is done if balloon valvotomy is unsuccessful.
stenosis. The operative treatment for aortic valve is unsatisfactory
c. Presence of a systolic thrill at the second right interspace since a patient who has had valvotomy may develop aortic
suggests at least moderately severe aortic stenosis. If regurgitation. Over the next 5-10 years, the valve may
the thrill is felt only in the suprasternal notch and not become immobile resulting in reappearance of aortic
at the second right interspace, it favors mild or critical stenosis and necessitating valve replacement. Patients who
aortic stenosis in failure. get valve replacement also cannot be considered cured,
d. The later the peak of the ejection systolic murmur, the since none of the prosthetic valves or homograft valves
more severe the narrowing. will last indefinitely. The patients have to be kept on
e. The delay in the A2 is reasonably well correlated with anticoagulants if they have a prosthetic valve replacement
severity. With mild aortic stenosis the S2 is normally and need very careful follow up to ensure that they do
split, with moderate aortic stenosis it is closely split, not develop infective endocarditis.
with severe or critical aortic stenosis it is single or
paradoxically split. Coarctation of the Aorta
f. Presence of S4 is indirect evidence for severe aortic Congenital coarctation of the aorta is located at the junction
stenosis. of the arch with the descending aorta. It is a sharp
g. Presence of S3 indicates severe aortic stenosis and indentation involving the anterior, lateral and the posterior
congestive cardiac failure. wall of the aorta. The medial wall is spared in the
h. ST and T changes on the EKG favor severe aortic narrowing. It may be distal or proximal to the ductus or
stenosis. ligamentum arteriosus and also the left subclavian artery.
i. Cardiac enlargement indicates severe aortic stenosis Forty to 80% patients have a bicuspid aortic valve.
with left ventricular failure.
j. Doppler echo can quantitate the gradient across the Hemodynamics
aortic valve very accurately. The previous classification of preductal (infantile) and
Left ventricular myocardial disease may alter the postductal (adult) coarctation is no more used.
findings to favor a more severe lesion. Physiologically the difference between the preductal and
postductal coarctation depends on the absence or presence
Treatment of collateral anastomosing vessels. In the fetal life, the right
Patients with aortic stenosis should be followed closely, ventricular output passes down the descending aorta
noting the blood pressure, second heart sound and pulse through a wide ductus arteriosus. The left ventricular
pressure on each visit. An EKG should be obtained every output empties into the innominate, left carotid and left
6-12 months. Symptoms should be carefully evaluated, if subclavian arteries. Very little of the left ventricular output
necessary by direct questioning. Doppler echo can be used reaches the descending aorta. The portion of the aorta
to quantitate the gradient at each visit. Aortic stenosis is a distal to the left subclavian and before the portion where
progressive lesion becoming more severe with time. It is the ductus arteriosus joins is called the isthmus. At birth,
a bad disease since it is one of the few lesions that can cause normally the isthmus is the most narrow part of the aorta.
sudden death. The patients should be discouraged from If the fetus has a preductal coarctation it does not interfere
outdoor games, athletics, competitive sports and with his normal hemodynamics and collaterals are not
strenuous exercises if the stenosis is significant (gradients formed as they are not necessary. On the other hand if a
of 50 mm Hg or more). If the clinical assessment is in postductal coarctation is present it is operative in the fetal
doubt, the patient must have echo and Doppler studies life as it interferes with the right ventricular output
for proper assessment. If there is evidence for CCF, the reaching the descending aorta. This stimulates formation
patient should be digitalized. of collaterals even in the fetal life. After birth when the
Balloon aortic valvuloplasty is an established technique right ventricular output is directed into the pulmonary
for non-operative relief of aortic obstruction. A balloon arteries and there is no flow from the pulmonary artery
introduced through the femoral artery can be placed at into the aorta, the descending aorta must receive its total
the aortic valve and inflated to tear the valve along the supply from the left ventricle via the ascending aorta. Since
commissure. It is indicated if the gradient is above 75 mm; in preductal coarctation there are no collaterals, the
the procedure may be repeated if restenosis occurs. neonate becomes symptomatic immediately, hypertension
Significant aortic regurgitation is a contraindication for resulting in left ventricular failure. Neonates who have a
balloon valvotomy. Supravalvar and subvalvar aortic postductal coarctation already have some collaterals and
stenosis do not respond to balloon dilation. are spared from developing severe hypertension and
Surgical treatment is indicated if significant aortic congestive cardiac failure.
regurgitation is associated. The exact mechanism for the production of systemic
The two main operations being done at present are hypertension in coarctation is not known. The aortic
aortic valvotomy and aortic valve replacement. Surgical obstruction is certainly partly responsible for it. The
420 Essential Pediatrics
Clinical Features
The only symptoms in uncomplicated coarctation may be
intermittent claudication, pain and weakness of legs and
dyspnea on running. Examination shows delayed and
weak or impalpable femorals compared to strong brachial
Fig. 14.23: Summary of auscultatory findings in coarctatioon of
arteries. It is possible for the femorals to be impalpable
the aorta. S3 third sound
whereas the dorsalis pedis vessels may be well felt since
the distal pulse pressure is wider. As a rule if the femorals
EKG shows left ventricular hypertrophy; presence of
are well felt in an infant the diagnosis can be excluded.
ST and T wave changes suggests additional aortic stenosis
Rarely it is possible for the patients to continue to have
or endocardial fibroelastosis. Chest X-ray shows a normal
pulmonary arterial hypertension. A patent ductus
sized heart with prominent ascending aorta, and the aortic
arteriosus may support the distal segment of the aorta. In
knuckle. In an over penetrated film, the site of coarctation
such a situation good femoral pulsations may be present
can be localized as the proximal segment is dilated and
in spite of coarctation, which would be preductal in
there is post stenotic dilatation of the distal segment.
location and associated with cyanosis in toes. It is
Barium swallow shows the characteristic 'E' sign and
important to remember that the site of coarctation does
confirms the site of coarctation (Fig. 14.24). The
not determine whether the flow through the PDA is from
characteristic notching of the lower borders of ribs appears
left to right or from right to left. Whether the coarctation
is preductal or postductal, the flow is from left to right
since the distal segment of the aorta in coarctation almost
never has a mean pressure below 50 mm of Hg. If the flow
through the PDA is from right to left, it indicates that there
is severe pulmonary arterial hypertension.
The heart size remains normal with a left ventricular
forcible or heaving apex. A systolic thrill may be palpable
in the suprasternal notch. There are prominent arterial
pulsations in the suprasternal notch and the carotid
vessels. The first sound is accentuated and followed by a
loud constant ejection click. The second sound is normally
split with a loud aortic component. A variable intensity
ejection systolic murmur is heard with the point of
maximum intensity over the back in the interscapular area.
The murmur may be well heard over the precordium. The
murmur starts late in systole after a considerable gap from
the first sound and click. It may appear to go through the
second sound suggesting a continuous murmur. This is
because of the delay in the transmission of pulse from the
heart to the site of coarctation. Continuous murmurs may
be audible over the collaterals in the chest wall but are
uncommon. An aortic ejection systolic murmur and/or
an aortic regurgitation murmur may be present because Fig. 14.24: Barium swallow showing 'E1 sign secondary
of the bicuspid aortic valve (Fig. 14.23). to coarctation
Disorders of Cardiovascular System 421
beyond the age of 10 years. Using suprasternal approach, stenosis gives a wrong impression in the sense that like
coarctation can be visualized by echocardiogram and the coarctation it results in the proximal area being
gradient estimated. hypertensive.
the suprasternal notch. The first sound remains normal The EKG shows right axis deviation and right ventri
and the intensity of P2 is also normal. Moderate pulmonic cular hypertrophy. Pulmonic stenosis is a systolic overload
stenosis results in wide variable splitting of the second for the right ventricle. The systolic overloading pattern in
sound. Severe pulmonic stenosis results in a further the electrocardiogram is suggested by a pure 'R' or a 'qR'
widening of the split. In critical pulmonic stenosis the P2 type of complex in V4R and V, leads. This is not very
is also diminished in intensity and may be so widely split specific and rsR type of complex can be present. P pul
in expiration that further widening during inspiration may monale suggests severe pulmonic stenosis. The thoracic
not be appreciated on auscultation suggesting a fixed split roentgenogram shows a normal sized heart with normal
second sound. A pulmonary ejection click varying with pulmonary vasculature in mild, moderate as well as severe
the respiration follows the first sound. Fourth sound is pulmonic stenosis. Pulmonary oligemia occurs only when
audible in severe as well as critical pulmonic stenosis (Fig. the patients develop a right to left shunt at the atrial level
14.25). If the right ventricle fails, a right ventricular third in severe or critical pulmonic stenosis. The main pul
sound may be audible. Rarely with right ventricular monary artery segment exhibits post stenotic dilatation.
failure, tricuspid regurgitation may appear. Since the right Echocardiogram can identify the site and using Doppler
atrium offers less resistance to flow of blood than the assess the severity of pulmonic obstruction.
obstruction at the pulmonary valve, the flow through the Infundibular pulmonic stenosis is separated from
pulmonary valve diminishes reducing the intensity as well valvar pulmonic stenosis by (i) absence of click in infundi
as the duration of the pulmonary ejection systolic murmur. bular type; (ii) absence of post stenotic dilatation in the
These patients present with significant cyanosis as in thoracic roentgenogram; and (iii) a relatively lower point
Fallot's tetralogy. The pulmonary systolic murmur is a of maximum intensity of the systolic murmur in the third
diamond shaped murmur with mild pulmonic stenosis. and fourth left interspace.
With increasing severity of pulmonic stenosis the duration
and intensity of the murmur increase and the peak is Assessment of Severity
delayed. With moderately severe pulmonic stenosis, the The severity of pulmonic stenosis can be assessed by the
murmur ends just short of the aortic component of the following:
second sound. In critical pulmonic stenosis the pulmonary i. Symptomatic patients have severe pulmonic stenosis.
ejection murmur goes through the aortic component of ii. Cyanosis and cardiac enlargement indicate severe
the second sound, partially or completely masking it. pulmonic stenosis.
iii. The closer the pulmonary ejection click to S,, the more
severe the stenosis.
iv. The wider the splitting of S„ the more severe the
stenosis.
v. The longer the murmur the more severe the stenosis.
Murmur ending before, at or beyond the aortic
component of the second sound indicate moderately
severe, severe and critical pulmonic stenosis
respectively.
vi. A pure R in V, of 20 mm and appearance of S wave
in left precordial leads suggests severe stenosis.
vii. Cardiomegaly and decreased pulmonary flow
indicate severe pulmonic stenosis.
viii. Doppler echo can quantitate the gradient accurately.
Treatment
Unlike valvar aortic stenosis, valvar pulmonic stenosis
does not increase in severity with time. Patients with mild
pulmonic stenosis (Doppler gradient less than 50 mm Hg)
do not require intervention. Balloon valvuloplasty is the
treatment of choice for isolated valvar pulmonic stenosis.
Surgical treatment is indicated if balloon valvotomy is
unsuccessful, as in dysplastic valves or if the pulmonary
valve annulus is small. The operation is done under
cardiopulmonary bypass with a low risk. Infundibular
stenosis requires surgical resection either through atrial
or right ventriculotomy.
Disorders of Cardiovascular System 423
ENDOMYOCARDIAL DISEASES early infancy. The onset may be abrupt with cardio
vascular collapse or gradual with left and right heart
Endomyocardial diseases may be defined as those
failure. Arrhythmias and conduction disturbances are
diseases, which primarily affect endocardium or the
common. There is cardiomegaly, tachycardia, muffled
myocardium of a known or unknown etiology. They are
heart sounds and features of CCF. The electrocardiogram
characterized by CCF, cardiomegaly and arrhythmias.
shows low voltage and non-specific ST-T changes. Chest
Generally, there are no murmurs. However, dilatation of
X-ray reveals cardiomegaly and pulmonary venous
the ventricles may result in functional mitral or tricuspid
hypertension.
regurgitation murmurs.
Treatment consists in management of CCF and
antiarrhythmic drugs. Digoxin should be used cautiously,
Endocardial Fibroelastosis
preferably at one-half to three-quarters of the standard
The etiology of endocardial fibroelastosis is not known. dose. Steroids may be of some benefit in the presence of
Hypoxia, interference with lymphatic drainage, maternal conduction disturbances and cardiovascular collapse.
toxins, toxoplasmosis, mumps and coxsackie B infection They should not be used in the acute phase, when viremia
are considered possible etiological factors. Fetal myo may be present. Use of ACE inhibitors is recommended.
carditis might result in a dilated chamber, which develops
fibroelastosis as a secondary phenomenon. Left atrium, Cardiomyopathies
mitral valve and aortic valve may show milky white The term cardiomyopathy is defined as intrinsic disease
thickening of the endocardium. In the common dilated of the myocardium in which there is no structural
type, left ventricle is enlarged. In the uncommon contrac deformity of the heart. It is called primary cardiomyopathy
ted type, the left ventricle is small but is not hypoplastic. or primary myocardial disease when the etiology is
Endocardial fibroelastosis restricts the systolic ejection unknown. If the myocardial disease is secondary to a
as well as the diastolic filling. As a result the ejection systemic disease, it is termed as secondary cardiomyopathy
fraction is reduced resulting in low cardiac output. (Table 14.14). The myocardial diseases are classified
Elevation of end-diastolic pressure causes pulmonary clinically as (i) dilated type, (ii) restrictive type, and (iii)
venous and arterial hypertension. The end-diastolic hypertrophic type. The hypertrophic cardiomyopathy
volume is increased in the common dilated left ventricle may occur (a) without outflow obstruction, or (b) with
type of endocardial fibroelastosis. outflow obstruction. Obstructive cardiomyopathy is also
The symptoms of CCF start in the first week of life. known as idiopathic hypertrophic subaortic stenosis or
Cardiomegaly and S3 gallop are present. Murmur of mitral asymmetrical septal hypertrophy or hypertrophic
regurgitation may be heard. EKG shows findings obstructive cardiomyopathy (HOCM).
suggestive of left ventricular hypertrophy, with deep S Dilated cardiomyopathy is the commonest form of
waves in right precordial leads and qR with tall R waves myocardial disease seen in children. The onset of CCF may
in the left chest leads, ischemic ST segment changes are be acute or subacute; cardiomegaly and S3 gallop are
also present. Chest X-ray shows cardiomegaly with present. Murmur of mitral regurgitation and uncommonly
pulmonary venous hypertension. On fluoroscopy, cardiac
pulsations are poor. 'M' mode echocardiogram shows
Table 14.14: Secondary cardiomyopathies
enlarged left ventricle with a thick poorly contracting
septum and the posterior left ventricular wall. The left Infection
Viral, bacterial, fungal, rickettsial, parasitic.
atrium is also enlarged. The mitral valve shows reduced
Collagen disorders
EF slope due to low cardiac output. 2D echo shows poorly
Systemic lupus erythematosus, dermatomyositis.
contracting dilated left ventricle/with thickened endo
Metabolic, endocrine disorders
cardium. Beri beri, glycogen storage disease type II (Pompe),
Treatment consists of treatment of CCF. The younger amyloidosis.
the patient at the onset of symptoms, the poorer the Mucopolysaccharidoses, uremia, pheochromocytoma,
prognosis. If the patient responds well to digoxin, it should porphyria.
be continued for several years. In the presence of Neurological, muscular disorders
Friedreich ataxia, muscle dystrophies.
significant mitral regurgitation, mitral annuloplasty or
Medications, toxins
replacement may be required.
Adriamycin, phenothiazine, lead, emetine, chloroquine.
Hematological
Myocarditis Sickle cell anemia, thrombotic thrombocytopenic purpura.
Neoplastic
Infection with ECHO, coxsackie B, rubella, herpes and
Rhabdomyoma, myxoma, leukemia, lymphoma.
influenza virus are known to cause myocarditis;
Miscellaneous
diphtheritic myocarditis is not uncommon in India.
Idiopathic aortitis, cystic fibrosis, glomerulonephritis.
Myocarditis generally occurs in the newborn period and
424 Essential Pediatrics
that of tricuspid regurgitation may be present. The patients normal or smaller than normal left ventricle and
are prone to have embolic phenomena. The EKG is endomyocardial fibrosis (EMF) are the two common types.
variable and may show non-specific ST and T changes with Endomyocardial fibrosis is endemic in the state of Kerala
or without left ventricular hypertrophy. Conduction but rare in North India. Pathologically, there is dense
disturbances, arrhythmias or pseudoinfarction pattern fibrosis in the apical and inflow regions of the left and the
may be present. Echocardiogram shows dilated ventricu right ventricles, which restricts diastolic ventricular filling.
lar cavity without hypertrophy of the free wall of the left The papillary muscles and chordae may be tethered by
ventricle or the septum. The left ventricular contractility the connective tissue, resulting in severe mitral or tricuspid
is markedly reduced. regurgitation. Patients with predominant left sided
Treatment consists in prolonged bedrest and anti- involvement have symptoms of dyspnea, nocturnal
congestive therapy including vasodilators, especially ACE dyspnea, hemoptysis and embolic phenomena. On exami
inhibitors. Bed rest and anticongestive therapy, over a long nation, there is cardiomegaly with or without findings of
period, result in gradual improvement in most patients. mitral regurgitation. Cardiac output is low and there are
If the patient does not show improvement in 2-3 weeks,
features of pulmonary venous and arterial hypertension.
hospitalization is essential. A myocardial biopsy may be
With predominant right sided involvement, the patients
necessary in patients with refractory symptoms, to
present with fatigue from low cardiac output, edema on
determine further management. The role of immuno
feet and ascites. There is cardiomegaly with prominent
suppressive agents and immunoglobulin infusions is not
cardiac pulsations in the second to fourth left interspace
clear.
from a dilated right ventricular outflow. S3 gallop and
[3-blockers were contraindicated in the past since they
tricuspid regurgitation murmur may be present. Treat
might precipitate CCF. However, in patients with dilated
ment consists of decongestive therapy. Decortication or
cardiomyopathies where treatment of the cause is not
stripping of the endocardium with mitral valve replace
possible, their use has been shown to be beneficial. Since
ment has been tried with success.
catecholamine levels are high in CCF and there is down
Restrictive cardiomyopathy of other varieties is
regulation of (3-receptors, [3-blockers control the heart rate,
characterized by a combination of features of left and right
reduce vasoconstriction and upgrade b-receptors. They
may also prevent or retard myocardial damage related to sided failure with a normal sized heart. Clinically or even
high catecholamine levels. The most commonly used b- following cardiac catheterization, it may be difficult to
blockers include metoprolol and carvedilol. Treatment distinguish it from constrictive pericarditis. Echo
with intermittent infusions of dopamine or dobutamine cardiogram is useful in excluding constrictive pericarditis.
is promising. Some patients benefit from treatment with
Hypertrophic Cardiomyopathy (HCM)
carnitine (100 mg/kg/day in divided doses for two days,
followed by 50 mg/kg/day). The hypertrophic cardiomyopathy with obstruction
(HCM) is uncommon in children. It has been reported with
Anomalous Left Coronary Artery or without familial involvement even in neonates.
from Pulmonary Artery (ALCAPA) Pathologically there is asymmetrical hypertrophy of the
ALCAPA needs specific mention as a cause of congestive ventricular septum. The free walls of the left and right
cardiomyopathy since the diagnosis is made by EKG and ventricles are hypertrophied to a lesser extent. The
the treatment is specific. If a patient presenting with ventricular septum bulges into the left ventricle, the
congestive cardiomyopathy with or without a mitral regur malaligned anterior mitral valve leaflet causes obstruction
gitation murmur shows anterolateral myocardial infarction in the left ventricular outflow during systole. Uncom
pattern on the EKG, the diagnosis is that of ALCAPA. monly, there may be right ventricular outflow obstruction
Echocardiogram shows a large right coronary artery and as well. The abnormally oriented mitral valve becomes
absence of the origin of left coronary artery from the aorta. regurgitant.
The left coronary artery is seen to arise from the pulmonary The patients usually present with exertional dyspnea,
artery and usually shows flow in the reverse direction in anginal type of chest pain, palpitation and syncope or a
the left anterior descending artery and the left circumflex murmur may have been detected. Sudden death can occur.
artery. This flow reversal results from collateral flow into The pulse has a sharp upstroke with a bisferiens
the left coronary system from the right coronary artery. character. The apex beat is forcible or heaving. The fourth
Angiography is rarely necessary for the diagnosis of sound may be palpable at the apex. Double or triple apical
ALCAPA. The treatment is mobilization and translocating impulse may be present. The second sound may be
the origin from pulmonary artery to aorta. normally split, single or paradoxically split, depending
on the severity of the left ventricular outflow obstruction.
Restrictive Cardiomyopathy (RCM) An ejection systolic murmur of varying intensity is heard
It is relatively uncommon in children. There is restriction at left sternal edge. A pansystolic murmur or mitral
to ventricular filling. Endocardial fibroelastosis with a regurgitation and a fourth sound may be heard at the apex.
Disorders of Cardiovascular System 425
The ejection systolic murmur increases in intensity by Table 14.15: Etiology of pericardial diseases
maneuvers, which increase the myocardial contractility or
Acute Chronic
decrease the volume of the left ventricle. The murmur
decreases in intensity by procedures, which increase left Bacterial (septicemia) Constrictive pericarditis
ventricular volume or decrease the myocardial contrac Viral Tuberculous
tility. Thus, sudden squatting decreases the intensity of the Tuberculous Non-specific (idiopathic)
murmur, while standing upright from sitting position (by Rheumatic Post-pyogenic
decreasing venous return and left ventricular size) Collagen disorders Post-traumatic
increases the intensity of the systolic murmur. EKG shows Idiopathic Pericardial defects
left ventricular hypertrophy, with or without ischemic Uremic Pericardial cyst
changes; WPW type changes may be present. Echocardio
Postoperative
gram shows disproportionate hypertrophy of the
ventricular septum, systolic anterior motion of the anterior
leaflet of the mitral valve and midsystolic closure of the Acute Pericarditis
aortic valve. Cardiac catheterization and angiography are
Acute pericardial inflammation causes precordial pain,
rarely required. It may be necessary to increase the left
which may be dull, sharp or stabbing in character.
ventricular contractility with isoprenaline to increase the
Occasionally, the pain may be felt over the neck and
magnitude of obstruction during catheterization, or during
shoulder and may worsen on lying down. Child becomes
echocardiographic evaluation.
dyspneic and has cough. The pattern of fever and toxemia
The younger the age of the onset, the poorer the
depends on the etiology. The bedside diagnostic physical
prognosis. The disease may be progressive and sudden
sign is the presence of pericardial friction rub, which is a
death may occur in spite of medical and/or surgical
rough scratchy sound, made up of three components, a
treatment. P-blocking drugs and more recently verapamil
systolic, a diastolic and a presystolic scratch. It can be
have been used to decrease the myocardial contractility
heard anywhere over the precordium, is unrelated to the
and thus the obstruction. For the control of arrhythmias,
respiratory cycle and increases on pressing the chest piece
disopyramide or amiodarone are the drugs of choice, the
of stethoscope over the precordium. The EKG shows
former reduces myocardial contractility as well.
generalized ST elevation in the initial stages. Later the ST
Hypertrophic cardiomyopathy has an autosomal
segment becomes iso-electric and the T waves become
dominant pattern of inheritance with a variable but high
inverted. Still later, the ST segment may be depressed.
degree of penetrance. It is believed to be linked to muta
If effusion develops, the cardiac silhouette increases in
tions in (3-myosin, troponin T and alpha-tropomyosin
size. The heart sounds become muffled and evidence of
genes. Some other genetic factors play a role in
peripheral congestion in the form of raised jugular venous
hypertrophy in hypertrophic cardiomyopathy. Angio
pressure, hepatomegaly and edema may develop. The
tensin converting enzyme (ACE) gene have three alleles,
pericardial friction rub may persist or disappear. If the
DD, ID and II. Patients of HCM with ACE genotype DD
fluid accumulates rapidly, there is marked interference
have more left ventricular hypertrophy than if the
with cardiac filling and features of cardiac tamponade as
genotype is II. ACE inhibitors are known to reduce the
evidenced by (i) rising jugular venous pressure;
muscle mass, which is desirable in patients with hyper (ii) paradoxical inspiratory filling of the neck veins;
trophied left ventricle. However, ACE inhibitors reduce (iii) increasing heart rate; (iv) falling pulse pressure with;
the systemic pressure and may adversely affect the and (v) pulsus paradoxus appear. The EKG shows non
outflow obstruction in patients with HCM. In the absence specific generalized ST and T changes with low voltage
of outflow obstruction, a carefully monitored use of ACE tracings. The chest X-ray shows cardiomegaly with smooth
inhibitors is justified. outline and blunting of the cardio-hepatic angle. The
It is essential that patients with HCM should have a echocardiogram shows an echo-free space behind the
24-hr Holter to document for arrhythmias. In children who posterior left ventricular wall. Pericardiocentesis should
can do exercise, the effect of exercise on the rhythm is be done to determine the etiology as well as to relieve
ascertained. Patients of HCM should be restrained from cardiac tamponade if present. Treatment will depend on
strenuous games and exercise. Digitalis and other the etiology. Surgical drainage is rarely indicated unless
inotropic drugs as well as diuretics and nitrates are the fluid is thick and fibrinous.
contraindicated in patients with hypertrophic obstructive
cardiomyopathy. Chronic Constrictive Pericarditis
around the heart, which restricts the filling of both the of these are post-tuberculous pericarditis. Full course of
ventricles equally. Calcification rarely occurs during antitubercular treatment follows pericardiectomy.
childhood. The myocardium is not involved in the early
stages but in longstanding cases the fibrous process Suggested reading
infiltrates the myocardium as well. This results in Marian AJ, Roberts R. Recent advances in the molecular genetics of
myocardial dysfunction in addition to cardiac restriction. hypertrophic cardiomyopathy. Circulation 1995; 92: 1336-1347.
Fibrosis makes the surgical correction difficult. It also
prevents complete normalization after the operation. CARDIAC RHYTHM DISORDERS
Dyspnea, fatigue and progressive enlargement of the
Cardiac arrhythmias are not infrequent and may be
abdomen are the commonest symptoms. Some patients
potentially life threatening. The reported incidence of
complain of paroxysmal nocturnal dyspnea. Jugular
supraventricular tachycardia (SVT) in children ranges
venous pressure is always elevated with equally promi
from 1 in 250 to 1 in 1000. Recognition of arrhythmias is
nent 'a' and 'v' waves and a prominent 'y' descent.
not always easy and requires a high index of suspicion. It
Inspiratory filling of the neck veins (Kussmaul sign) is seen
in about a half of the cases. Liver is pulsatile, both 'a' and is important to arrive at a precise diagnosis and initiate
V waves being felt. Spleen may be enlarged and ascites specific treatment.
is common. Unilateral or bilateral pleural effusion is a
Recognizing Arrhythmia
common finding. Pulse is fast and of low volume. Pulsus
paradoxus may be present. The clinical features suggestive of an underlying
Normal EKG is against the diagnosis of constrictive arrhythmia are listed in Table 14.16.
pericarditis; all cases show non-specific ST-T changes and
75% cases have low voltage. Occasionally, there is right
Table 14.16: Clinical features in arrhythmias
axis deviation or right ventricular hypertrophy pattern.
Left atrial overload pattern is uncommon in our patients. Irregular heart beat.
Heart rate that is inappropriate for the clinical condition.
The chest X-ray reveals normal sized heart with ragged
Unexplained heart failure.
or shaggy borders, prominent superior vena cava shadow
Underlying cardiac anomaly known to be associated with
merging with the right atrial margin. The lungs may show
rhythm disorders.
pleural effusion and plate atelectasis. Hemodynamic Syncope, palpitations, chest discomfort.
studies reveal elevation of right atrial mean pressure, right Family history of sudden cardiac events.
ventricular end-diastolic pressure, pulmonary artery
diastolic pressure and the pulmonary artery wedge pres
sures. The right ventricular end-diastolic pressure is more
than one-third of the systolic pressure (Fig. 14.26). The Irregular heart rate: The most common cause of an irregular
cardiac index may be normal or reduced, but the stroke heart rate is physiological sinus arrhythmia. This can be
volume is low. easily recognized by an increase in heart rate with inspira
tion and a decrease with expiration. Sinus arrhythmia is
usual following a febrile illness and by drugs that increase
vigil tone (e.g. digoxin), and abolished by exercise.
Irregularities of sinus rhythm are common in premature
infants especially bradycardia associated with apnea
spells. Other common causes of heart rate irregularity in
children include atrial and ventricular premature beats
and conduction disturbances. Less common but poten
tially serious causes are listed in Table 14.17.
Digoxin,
beta blockade
amiodarone
Fig. 14.27: Management algorithm for stable narrow QRS tachycardia. AVNRT : atrioventricular nodal re-entrant
tachycardia; AVRT : atrioventricular re-entrant tachycardia
re-entry, increased automaticity and triggered activity. In This is a useful classification and serves as an excellent
children, the first two mechanisms account in most cases. guide to initial treatment. Age specific normal values for
Clinical and EKG features together with response to QRS duration are given in Table 14.21.
medications and maneuvers distinguish re-entrant tachy
arrhythmias from those due to increased automaticity. Re
Table 14.21: Normal QRS duration at various age groups
entrant arrhythmias have a relatively sudden onset and
Age group QRS duration in seconds
termination. Successful termination with DC cardiover
sion or overdrive pacing (pacing at rates faster than 0-6 months 0.03-0.07 (0.05)
arrhythmia rate) suggests re-entrant mechanism. Auto 1-5 years 0.04-0.08 (0.06)
matic arrhythmias have a relatively slow onset, gradual 10-15 years 0.04-0.09 (0.07)
>15 years 0.06-0.09 (0.08)
acceleration (warm-up to peak rates at onset) and
Values represent range (mean)
deceleration (cool down at termination).
Narroiv QRS tachycardia : Most narrow QRS tachycardias Adenosine administration is diagnostic and therapeutic
(Table 14.22) are well tolerated and allow initial diagnostic (Table 14.23). It acts by producing a marked slowing of
work-up. If a patient is seen during an arrhythmia, all AV node conduction; its effect lasts for a few seconds. Side
attempts should be made to obtain data before terminating effects are short-lived and include flushing, chest pain and
the arrhythmia. Information that should be sought during dyspnea. It is imperative to obtain an EKG record or a
a narrow QRS tachycardia include the P wave morphology rhythm strip during adenosine administration. The medi
and P-QRS relationship. P waves that appear normal cation is administered rapidly at a dose of 50-300 meg/
during the arrhythmia suggest sinus tachycardia. Ectopic kg, followed by a rapid push of normal saline as a bolus.
atrial tachycardia is suggested by abnormal P wave Most re-entrant tachycardias, where AV node is a part of
morphology. Inverted P waves may be seen when atria the circuit (AV node re-entrant tachycardia, AV re-entrant
are activated in a retrograde fashion, e.g. re-entrant tachycardia) are terminated by adenosine, while atrial
tachyarrhythmias involving accessory pathways (AV re flutter is seldom terminated. The transient AV block that
entrant tachycardia). Often P waves are not clearly seen results from adenosine administration can unmask flutter
on the baseline EKG but are unmasked by adenosine. waves on the surface EKG, confirming the diagnosis.
Evidence of 2:1 AV conduction, as suggested by a 2:1 P to Similarly, transient slowing of AV conduction can unmask
QRS ratio during a narrow QRS tachycardia, indicates ectopic atrial tachycardia. If adenosine is not available,
atrial flutter. Evidence of complete AV dissociation (no vagal maneuvers can be attempted. For infants and young
consistent P-QRS relationship) indicates junctional ectopic children, an ice filled plastic bag placed on the face is
tachycardia. effective. Older children can be encouraged to perform
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Age (yr)
Fig. 14.31: Blood pressure levels for boys at 50th percentile for height. Chart depicting 90th (closed diamonds), 95th (open squares)
and 99th + 5 mm (closed triangles) percentile values for (A) systolic and (B) diastolic blood pressures, representing cut off values for the
diagnosis of pre-hypertension, stage I and stage II hypertension respectively in boys (based on the Fourth US Task Force Report on Hypertension).
(Reproduced with permission)
Tables 14.25 and 14.26 show common causes of persistent the upper limbs. In pheochromocytoma, there are episodes
and transient hypertension. of palpitation, sweating and flushing. Weight loss is an
important finding in pheochromocytoma. Patients with
Clinical Features Cushing disease have plethoric facies with buffalo hump
Hypertension per se is asymptomatic. Presence of symp type obesity, hirsutism and abdominal striae.
toms indicates end organ disease. Symptoms attributed With severe hypertension, patients may present in
to hypertension include headache, nausea, vomiting, hypertensive crisis with loss of vision, convulsions, nerve
dizziness, irritability and epistaxis. The clinical features palsies and other neurologic deficits (hypertensive
relate to the underlying disease, renal or endocrine. encephalopathy). Prolonged hypertension results in
Patients with chronic renal damage may show polyuria, hypertensive retinopathy. Congestive cardiac failure as a
polydipsia, weakness, fatigue, pallor, weight loss and manifestation of systemic hypertension is extremely rare
edema. In coarctation of the aorta, femoral pulsations are in children. If present, it should suggest acute glomerulo
weak and the blood pressure in lower limbs is less than in nephritis or idiopathic aortoarteritis.
434 Essential Pediatrics
Table 14.25: Causes of persistent hypertension and postural hypotension indicate the possibility of
pheochromocytoma. Obesity, hirsutism, abdominal striae
Intrinsic renal diseases
and buffalo hump signify Cushing's syndrome. Polyuria,
Chronic glomerulonephritis cramps or tetanic attacks, generalized weakness, absence
Reflux nephropathy
of edema with attacks of severe weakness suggest primary
Obstructive uropathy
hyperaldosteronism. Abdominal mass and history of
Congenital lesions (dysplastic, hypoplastic, polycystic
hematuria suggest renal tumor or renal mass of hydronep
kidneys)
hrosis from obstructive uropathy, or polycystic kidney.
Renovascular
Neurological deficit, whether acute or subacute signify the
Idiopathic (Takayasu) aortoarteritis
possibility of poliomyelitis, Guillain-Barre syndrome or
Renal artery stenosis
intracranial space occupying lesion.
Essential hypertension
Figs 14.33A and B: Atrial septostomy. (A) Balloon catheter in left atrium (B) balloon pulled throush the atrial septum in the right atrium
Disorders of Cardiovascular System 437
Aortic stenosis responds well to balloon valvuloplasty Arterial obstruction: Coarctation of the aorta with a pressure
and has been utilized even in neonates with critical gradient of 20 mm Hg in the presence of systemic hyper
stenosis. The non-elastic inflatable balloon catheter is tension or congestive failure requires relief of obstruction.
introduced percutaneously through the femoral artery and Balloon dilatation of unoperated (referred to as native)
inflated in the aortic valve to relieve the obstruction (Fig. coarctation of the aorta is now an acceptable therapeutic
14.35). The indication for balloon valvotomy is the same modality (Figs 14.36A and B). Balloon dilatation causes a
as for surgical valvotomy. Both procedures allow the child circumferential tear of the intima and media. In the
to grow to an age when valve replacement can be perfor majority of patients, adverse clinical events are absent.
med. The complication of aortic regurgitation is probably Balloon dilatation of native coarctation is currently the
slightly higher than that following surgical valvotomy. treatment of choice for children older than three months.
Balloon aortic valvuloplasty is specially useful in neonates Below the age of three months controversy regarding
and infants where the surgical mortality is high. One major preference for balloon dilatation versus surgical correction
concern in this age group, however, is a high incidence of is still present. For patients who develop recoarctation of
loss of femoral artery pulses (30%) and possible impair the aorta following surgical correction, balloon dilatation
ment of limb growth. This can be avoided by dilating the is the procedure of choice. Metal mesh formed into a tube,
438 Essential Pediatries
Figs 14.36A and B: (A) Coarctation of the aorta (B) balloon dilatation of the coarctation
called stents, are now being utilized to prevent reappea However many venous channels are not surgically
rance of the narrowing. Newer stents, which are self correctable and balloon dilatation is the only approach
expandable or can be expanded or dilated to increase the available even with a high risk.
size of the lumen are now available and being increasingly
deployed. The disadvantage of using stents in infants and Closing Abnormal Openings or Vessels
children is the need for redilation in a growing child. Closure of septal defects: Non-operative closure of secundum
Obstructive aortoarteritis is an important cause of severe atrial septal defect (ASD) located at fossa ovalis area is
hypertension and congestive failure in children in India. possible. Device closure of atrial septal defects has become
Balloon dilatation of the aorta, branches of the aorta as increasingly realistic after the introduction of the
well as renal arteries has been utilized with excellent Amplatzer double disc device. The device (Fig. 14.37) is
results. The need for anticongestive and antihypertensive relatively easy to deploy and in many centers it is offered
treatment may disappear or the requirement of drug as the first line for treatment for ASD.
management considerably reduce following balloon
dilatation with or without a stent.
Branch pulmonary artery stenosis referred to as peripheral
pulmonic stenosis does not respond well to balloon
dilation alone. Use of self expandable or balloon
expandable stents have allowed dilation of branch (or
distal) pulmonary artery stenosis not treatable surgically.
Peripheral pulmonic stenosis could be an isolated lesion
but is more commonly found in association with lesions
constituting Fallot's physiology. It results in persistent
pulmonary arterial hypertension following definitive
repair of these lesions. Following balloon dilatation and
placement of stent the pulmonary artery pressure
decreases and the forward flow increases. Restenosis is
uncommon but if the stents are placed at a young age,
growth of the child may require redilatation.
Most (90%) ventricular defects (VSD) are sub-aortic unwanted abnormal channels. The biggest advantage is
perimembranous in location and not amenable to device avoiding a surgical procedure and shortened hospital stay.
closure. Muscular VSD can be closed with occluding
devices. While the technique is cumbersome, it avoids a Arrhythmia Management
ventriculotomy scar on the myocardium. VSD closure is Identification of accessory pathways using electro
done under echocardiographic control in the laboratory, physiological studies in pre-excitation syndromes and
thus reducing radiation exposure. using radiofrequency ablation results in a permanent cure
of paroxysmal supraventricular tachycardias. Radio
Closure of arterial channels : Non-surgical closure of patent
frequency ablation is avoided in infancy because many
ductus arteriosus (PDA) is done using a number of techni
patients show spontaneous recovery from the condition.
ques, e.g. foam plug and coil embolization. A relatively
Patients with supraventricular tachycardias starting after
small PDA, up to 3 mm can be very effectively closed using
the age of one year, especially those occurring beyond the
coil embolization. The coils are made of stainless steel wire,
age of 6 years are best treated using radiofrequency
which when pushed out of the delivery catheter form a
ablation rather than medical therapy, which may be
coiled spring. They are coated with Dacron fiber to enhance
lifelong. Radiofrequency ablation of ectopic atrial or
clotting of blood around the coil. It is the clotting of blood
junctional tachycardias is rewarding since they respond
and formation of thrombus that results in the closure of the
poorly to drug therapy. Permanent form of junctional
PDA. Closure of larger PDA using Amplatzer device is
reciprocating tachycardia, atrial flutter in postoperative
rapidly gaining acceptance because of its ability to close
patients of Mustard or Senning surgery can also be
larger ducts (up to 10 mm) with almost 100% success.
managed by this procedure. Some forms of ventricular
A number of congenital arterial anomalies can
tachycardia can be managed by radiofrequency ablation
potentially be successfully closed using coils or detachable
rather than medications.
balloons. These include (a) aortopulmonary collaterals in
patients of Fallot's physiology, (b) surgically created Suggested reading
shunts in patients with Fallot's physiology, (c) coronary
Bahl VK, et al. Non-coronary cardiac interventions. The first report of
arteriovenous fistulae, (d) systemic arteriovenous fistulae the non-coronary cardiac intervention. Registry of India. Indian Heart
and (e) pulmonary arteriovenous fistulae or any other I 1997; 49: 97-101.
Disorders of Kidney
15 and Urinary Tract
RENAL ANATOMY AND PHYSIOLOGY activity. The JGA is composed of the afferent and efferent
arterioles, the macula densa and lads cells located between
Kidneys excrete the end products of metabolism and help
these structures. The JGA is involved in systemic blood
to keep the composition and volume of body fluids within
pressure regulation, electrolyte homeostasis and tubulo-
normal range. They are also involved in the regulation of
glomerular feedback.
blood pressure and erythropoiesis, synthesis of ammonia,
and metabolism of vitamin D, hormones and cytokines.
Each kidney is composed of approximately a million Renal Physiology
nephrons, each consisting of a glomerulus and renal Glomerular filtration depends upon the higher pressure
tubule. The glomerulus is made of a tuft of capillaries and in afferent arterioles. The filtration barrier is constituted
a central region of mesangium. The capillaries arise from by the endothelium with slit pores, basement membrane
the afferent arteriole and join to form the efferent arteriole, and podocytes of visceral epithelial cells. Filtration of
the entry and exit being at the hilum of the kidney. The solutes depends upon their molecular size, shape and
capillary wall consists of a fenestrated endothelium, electrical charge.
glomerular basement membrane and foot processes The filtrate from the glomerular capillaries passes from
(podocytes) of visceral epithelial cells. The basement the Bowman's capsule into the proximal convoluted
membrane is made of type IV collagen, laminin and tubule, loop of Henle, distal tubule and collecting ducts.
heparan sulfate proteoglycan. The Bowman's space leads The filtrate contains all the diffusible and ultrafiltrable
into the proximal tubule that has an initial convoluted substances present in plasma. Small quantities of protein
portion and a straight segment. The latter leads to the are usually present, but are reabsorbed in proximal tubule.
descending and ascending limbs of the loop of Henle and Bulk of the glomerular filtrate is reabsorbed into the
the distal tubule. Six to eight distal tubules join to form peritubular capillaries and only 0.5% is excreted as urine.
the collecting ducts that finally enter the renal pelvis. The
renal cortex consists of glomeruli, proximal and distal Tubular Reabsorption
tubules. Renal medulla contains the descending and
The proximal tubules reabsorb about 80% of the glomeru
ascending limbs of the loop of Henle and the collecting
lar filtrate. Normally about 65% of sodium is reabsorbed
ducts.
in the proximal tubule, through several active transport
Renal Vasculature systems. Sodium transport is dependent on the parallel
transport of bicarbonate, chloride, amino acids and glu
The renal artery divides into segmental arteries that branch
cose. Tubular reabsorption of sodium and other permeable
to form interlobar and arcuate arteries. The latter give rise solutes is promoted by the phenomenon of solvent drag
to the intralobar arteries, which provide the afferent
during transport of water across the tubular epithelium.
arterioles for the glomeruli. The efferent arterioles from
The glomerular filtration rate is regulated by tubulo-
the glomeruli form a meshwork of peritubular venous
glomerular feedback that depends upon the functional
capillaries that empty into intralobar veins.
integrity of the JGA. Increased delivery of chloride to the
macula densa results in local activation of renin-
Juxtaglomerular Apparatus (JGA)
angiotensin mechanism. The differential constrictive
The early part of the distal tubule on its ascent from the action of angiotensin on the afferent and efferent arterioles
medulla to the cortex lies near the glomerulus of the same causes a reduction in glomerular filtration. The renin-
nephron. The cells of the tubule that come in contact with angiotensin-aldosterone system, prostaglandins, cate
the afferent arteriole of the glomerulus are denser than cholamines, kinins and natriuretic peptides are involved
the rest, and are called macula densa. The smooth muscle in sodium handling. Potassium is completely reabsorbed
cells of the afferent arteriole, in this region, contain in the proximal tubule; the amount seen in urine depends
prominent cytoplasmic granules that are the site of renin upon its secretion in the distal tubule. Amino acids are
Disorders of Kidney and Urinary Tract 441
also totally reabsorbed in the proximal tubules by different on the first two days of life and 25-120 mL/kg/day during
pathways. the next 4 weeks. The GFR is low at birth (15-20 mL/min/
Distal tubules and collecting ducts are responsible for 1.73 m2 in the first 3 days in term, 10-15 mL/min/1.73 m2
urinary acidification, urinary concentration and regulation in preterm infants). These values increase rapidly to 35-
of sodium balance. Exchange of potassium or hydrogen 45 mL/min/1.73 m2 at 2 weeks and 75-80 mL/min/1.73
ions for sodium takes place in the distal tubules under m2 by 2 months of life.
the regulation of aldosterone. Antidiuretic hormone
mediates absorption of water through insertion of 'water, Tubular Function
channels (aquaporins) on the luminal surface of cells in During the first weeks of life, tubular function follows a
the collecting tubules. Low levels of the hormone, as in pattern similar to GFR but at a lower level. Compared to
central diabetes insipidus, result in large amounts of dilute adults, there is reduced sodium and bicarbonate reabsorp
urine. The converse occurs during dehydration. tion and limited hydrogen ion excretion. The pH of urine
The kidney helps in regulation of acid-base balance by in newborns is inappropriately high for the degree of
maintaining plasma bicarbonate concentration at 24-26 acidemia.
mEq/L. Filtered bicarbonate is almost completely reabsor
bed, 85 to 90% in the proximal tubules and the rest in distal Plasma Osmolality
tubules and collecting ducts. Bicarbonate, consumed in The capacity of the kidneys to concentrate or dilute urine
the buffering of nonvolatile acids, is regenerated by the is limited in neonates. An infant can concentrate his urine
renal excretion of titratable acid and ammonia. Chronic to a maximum of 700-800 mOsm/kg whereas the older
acidosis augments the production of ammonia and thus child can achieve 1200-1400 mOsm/kg. Growing babies
elimination of acid. utilize most of the protein available for growth rather than
catabolize it to urea. Decreased production and excretion
Suggested reading
of urea result in a relatively hyposmolar interstitium
Srivastava RN, Bagga A. Renal anatomy and physiology. In: Pediatric resulting in reduced urinary concentration compared to
Nephrology, 4th edn. Jaypee, New Delhi, 2005;1-19.
older children. The newborn can dilute his urine to a
minimum of 50 mOsm/kg, like an older child. However,
DEVELOPMENT OF STRUCTURE AND FUNCTION
the time taken to excrete a water load is much longer in
Differentiation of the primitive kidney is stimulated by the neonate. Thus, delayed feeding, and overdiluted or
penetration of the metanephros, during the fifth week of concentrated feeds are potentially harmful.
gestation, by the ureteric bud; the latter is an outgrowth
Maturation of Renal Function
of the mesonephric duct. Division of the ureteric bud
within the metanephros induces the development of Renal function continues to improve during the first two
nephrons. The ureteric bud gives rise to the intrarenal years of life, at the end of which, various parameters of
collecting system, renal calyces, pelvis and ureter. The renal function approach adult values, if corrected to
most active period of nephrogenesis is from 20-36 weeks. standard surface area. Structural growth parallels the
The full number of nephrons is present around 36 weeks. functional maturation.
Dysgenesis at various stages of development accounts for
the large variety of congenital anomalies of the kidney Suggested reading
and urinary tract. Postnatal growth of kidneys parallels 1. Srivastava RN, Bagga A. Diseases of the newborn. In: Pediatric
somatic growth and is due to increase in the size of Nephrology, 4th edn. Jaypee, New Delhi, 2005;413—42.
2. Hughson MD. Low birth weight and kidney function: is there a
individual nephrons. However, the latent capacity of the
relationship and is it determined by the intrauterine environment?
kidneys to hypertrophy continues well into adulthood. Am J Kidney Dis 2007; 50(4):531-534.
Thus, unilateral nephrectomy is usually followed by
hypertrophy of the other kidney. DIAGNOSTIC EVALUATION
Glomerular Filtration Common manifestations of renal disorders include edema,
Glomerular filtration begins between 9-12 weeks of hematuria, oligoanuria, dysuria and abnormalities of
gestation, initiating urine formation. Fetal urine is a major micturition, flank pain and ureteric colic. Serious renal
component of the amniotic fluid after 15-16 weeks. The disease may be present with subtle or no symptoms.
fetal kidney receives about 2-4% of cardiac output, Awareness of differences in the pattern of renal disease at
whereas in the neonate renal blood flow amounts to 15- various ages helps in their evaluation.
18% of cardiac output. The serum creatinine level is high
at birth reflecting the maternal value but falls rapidly to
Neonatal Period
about 0.4 mg/dL by the end of the first week. 92% neonates Congenital anomalies of kidney and urinary tract manifest
pass urine within the first 48 hr. Depending on solute commonly in neonatal period. These may be detected
intake, a healthy infant excretes 15-30 mL/kg/day of urine antenatally on maternal ultrasonographic examination.
442 Essential Pediatrics
6 to 14 Years
Enuresis
Most children with nocturnal enuresis have no evidence
Acute post-streptococcal glomerulonephritis (GN) is
of renal disease. Urinalysis and culture are recommended
common; nephrotic syndrome beginning beyond 8-10
in children who show enuresis after having achieved
years of age may be of the non-minimal type. Acute-on-
continence.
chronic renal failure, previously undetected chronic renal
failure, symptomatic hypertension and collagen vascular
Hypertension
diseases are common.
Assessment of blood pressure is necessary in all patients
Clinical Features of Renal Disease with disorders of the kidneys or urinary tract. Sympto
Abnormalities of Micturition matic hypertension in children is chiefly due to a renal
parenchymal or renovascular cause; endocrine conditions
A poor urinary stream in boys, especially in presence of a
are uncommon.
full bladder, suggests obstruction, most commonly due
to posterior urethral valves. Persistent dribbling indicates
Growth Retardation
abnormal ureteric insertion distal to bladder neck. All
infants with meningomyelocele should be evaluated for Physical retardation is an important feature of chronic
bladder dysfunction. renal insufficiency and renal tubular disorders.
Edema Anemia
Acute GN presents with facial puffiness and gross Normocytic normochromic anemia is striking in patients
hematuria; the edema is turgid and does not pit readily with chronic renal failure. Patients with unexplained
on pressure. If fluid intake is not restricted, the edema anemia should be evaluated for a renal disease.
may increase and involve hands, feet and legs. In nephrotic
syndrome, edema develops insidiously, starting with Abdominal Mass
eyelid puffiness most noticeable in the morning. Over a Multicystic renal dysplasia, polycystic kidneys, renal vein
period of several days, there is swelling over the feet and thrombosis, hydronephrosis (secondary to pelviureteric
legs. Edema is soft and easily pits on pressure. Facial junction or urethral obstruction) and Wilms' tumor may
swelling is often mistaken for allergy or insect bite. cause palpable renal masses.
Disorders of Kidney and Urinary Tract 443
The value of the constant K is 0.55, except in infants (K filled with contrast medium; films are taken during and
0.45) and pubertal boys (K 0.7). end-micturition. MCU provides precise details of the
anatomy of the bladder and urethra, presence of
Radionuclide Clearance vesicoureteric reflux and obstruction in the lower urinary
Disappearance curves of the radionuclides, 125I-iothala- tract (e.g. posterior urethral valves, urethral stenosis).
mate, "mTc-DTPA or 51Cr-EDTA following a single IV
injection can be used to accurately compute GFR. Radionuclide Imaging
Urinary Concentration Test Imaging of the kidney and urinary tract has been simpli
fied by radionuclide methods, which have replaced
Following a few hours of fluid deprivation, under careful
conventional radiocontrast studies such as the IVP, MCU
observation, desamino-8-D-arginine vasopressin
and angiography. Radionuclide procedures are non-
(DDAVP) is administered nasally (5-10 |ig in neonates and
invasive, highly sensitive and expose patients to less
infants, 20 (j.g in children) or by IM injection (0.4-1.0 ug in
radiation compared to radiocontrast studies.
infants and young children, 2 |ag in older children). Urine
The compounds, labeled with radioactive ""'techne
is collected every hr for the next 2-3 hr. Following
tium, commonly used include dimercaptosuccinic acid
administration of DDAVP, patients with nephrogenic
(DMSA), diethylenetriamine pentacetic acid (DTPA) and
diabetes insipidus fail to show a rise of urine osmolality
mercaptotriacylglycine (MAG-3). Following IV injection,
that remains below 300 mOsm/kg water (normal >800
mOsm/kg water). Those with deficiency of the anti DMSA attains high concentration in the renal cortex and
diuretic hormone concentrate urine appropriately. provides very high quality images of renal morphology.
This is particularly useful in detection and follow-up of
Imaging of the Urinary Tract renal parenchymal defects associated with urinary tract
Plain X-Ray infections (Fig. 15.1A). DTPA is freely filtered at the glome
rulus with no tubular reabsorption or excretion. A DTPA
The child is given a liquid diet and laxative on the previous renogram is useful for evaluating perfusion and function
night. A plain film of the abdomen provides information
of each kidney. Obstruction to the urine flow can be diag
on renal size, shape and outline and radiopaque calculi.
nosed by studying the effect of IV frusemide on the
The length of normal kidney approximates the height of
renogram. Normally there is a prompt washout of the
first four lumbar vertebrae. A small kidney may indicate
radionuclide, but this clearing may not occur in subjects
hypoplasia or chronic damage. The opposite kidney,
with upper urinary tract obstruction (Fig. 15.IB). Renal
unless diseased, shows compensatory hypertrophy. The
arterial narrowing results in reduced renal blood flow and
utility of information provided by plain films has reduced
an abnormal pattern on the DTPA renogram. This effect
following availability of ultrasonography.
is accentuated by administration of angiotensin converting
Ultrasonography enzyme inhibitors, thus increasing its sensitivity in
diagnosis of renal artery stenosis. MAG-3 provides highly
Ultrasonography is the initial modality for imaging of the
satisfactory information on renal structure and function.
kidney and urinary tract in most renal diseases. This
investigation is readily available, non-invasive and can A 99mTc-labeled radionuclide scan can be used instead
be performed even in uncooperative patients, small infants of the radiocontrast MCU. Radionuclide cystography is
and those with renal failure. The procedure is operator sensitive for detecting vesicoureteric reflux with minimal
dependent and should be done by an experienced radiation exposure. However, this procedure does not
radiologist. Anatomic details of the kidneys, ureters and provide sufficient anatomic details of the bladder and
bladder are examined; Doppler sonography is useful in urethra to recommend its use for initial evaluation of
studying renal blood flow. patients with suspected urinary tract obstruction, nor for
grading of vesicoureteric reflux.
Intravenous Pyelogram (IVP)
A carefully done IVP gives valuable information about Suggested reading
renal anatomy and function. The patient is prepared as 1. Guignard JP; Santos F. Laboratory investigations: In: Pediatric
for a plain X-ray. The contrast medium is injected IV and Nephrology, 5th ed. Avner ED, Harmon WE, Niaudet P. Lippincott
films are taken at 2, 5, 10 and 30 minutes. IVP provides Williams and Wilkins, Philadelphia 2004;399-424.
satisfactory details on renal size, shape, cortical outlines 2. Avni FE, Hall M, Diagnostic imaging. In Pediatric Nephrology,
5th ed.Avner ED, Harmon WE, Niaudet P. Lippincott Williams
and calyceal pattern. The use of IVP has declined following
and Wilkins, Philadelphia 2004;449-473.
the availability of radionuclide imaging. 3. Gupta AK. Imaging of the urinary tract. In: Pediatric Nephrology,
4th ed. Eds. Srivastava RN, Bagga A. Jaypee, New Delhi, 2005,
Micturating Cystourethrogram (MCU) 30-44.
4. Zaffanello M, Franchini M, Fanos V. Is serum cystatin-C a suitable
MCU is necessary for studying the lower urinary tract. A marker of renal function in children? Ann Clin Lab Sci 2007; 37(3):
sterile catheter is introduced into the bladder, which is 233-40.
Disorders of Kidney and Urinary Tract 445
Diagnostic Evaluation
A history of pain in the flank or suprapubic region, dysuria
and edema should be obtained. Physical examination
should include assessment of growth and features of acute
or chronic kidney disease such as edema, hypertension,
unexplained pallor, bony abnormalities and abdominal
mass. An audiogram and a detailed eye examination may
be needed.
A fresh specimen of urine is examined for red cells, red
9 10 11 12 13 14 15 16 17 18 19 20 21 cell casts and protein. Absence of large number of red cells
Minutes in a grossly bloody urine suggests hemoglobinuria (seen
in acute intravascular hemolysis) or myoglobinuria. In
Fig. 15.1 B: Diethylenetriamine pentacetic acid (DTPA) renal scan
showing normal uptake and excretion of radiolabeled dye in right glomerular disease, urine shows dysmorphic red cells, of
kidney. Left kidney shows adequate concentration but non-excretion different shapes, whereas in bleeding from renal pelvis
of the dye, suggesting obstruction at the pelviureteric junction or the lower urinary tract, the red cells maintain normal
morphology (Fig. 15.2). Presence of significant proteinuria
(2+ or more) and/or red cell casts also suggests glomerular
disease. Hypercalciuria should be excluded by the
HEMATURIA
The presence of blood in urine imparts it a color, which
includes various shades of deep red, smoky brown, cola-
color and faint pink. Parents may mistake very concen
trated urine for that containing blood. Microscopic
examination of urine will show red blood cells. Reagent I
coated dipsticks detect free hemoglobin and myoglobin.
Alternatively benzedine or guaic test may be performed.
Red urine may be present in porphyria and following
sugarbeet ingestion. Urine appears orange-colored after
administration of rifampicin or pyridium. Uric acid
crystals may also impart a pink tinge to the nappy.
In childhood, the commonest cause of gross hematuria
is post-infectious GN. Urinary tract stones are not infre
quent. Gross hematuria is rare in acute pyelonephritis.
Important causes of hematuria are listed in Table 15.1.
Conditions that cause persistent microscopic hematuria
include idiopathic hypercalciuria, benign familial
hematuria, Alport syndrome, IgA nephropathy and
membranoproliferative GN. Fig. 15.2 : Hematuria. Note normal morphology of red cell
446 Essential Pediatrics
determination of urinary calcium to creatinine ratio on confirmed by an accurate measurement of 24-hr urinary
one or more random urine samples. calcium; values greater than 4 mg/kg/day are abnormal.
A plain X-ray film of the abdomen and abdominal Blood levels of calcium and magnesium are normal. Idiopathic
ultrasound is done to exclude major renal and urinary tract hypercalciuria should be distinguished from hypercalci
anomalies and calculi. Blood levels of urea and creatinine uria secondary to persistent hypercalcemia (e.g. hyper
are measured; other specialized blood tests depend on the parathyroidism, vitamin D toxicity) or associated with
clinical suspicion of the likely etiology. Surgical conditions renal tubular acidosis. A high fluid intake and diet low in
that cause hematuria can be diagnosed by appropriate animal protein and salt is advised. Therapy with thiazide
imaging methods. Invasive procedures such as cystoscopy diuretics, which reduces urinary calcium excretion, may
are rarely indicated. occasionally be required.
In a significant proportion of cases, mild microscopic
hematuria spontaneously disappears over a period of Suggested reading
several years. Other family members may have a similar 1. Pan CG. Evaluation of gross hematuria. Pediatr Clin North Am
urinary abnormality. If there is no family history of renal 2006; 53:401-412
disease, a renal biopsy is not urgently indicated and the 2. Indian Pediatric Nephrology Group. Consensus statement on
patient kept under long-term observation. evaluation of hematuria. Indian Pediatr 2006; 43: 965-973
3. Halachmi S, Kakiashvili D, Meretyk S. A review on hematuria in
Renal Biopsy children. Scientific World Journal 2006; 6: 311-317
of patients progress to chronic renal failure. and >1 heavy proteinuria. The latter usually corresponds
to 3+ or 4+ reaction on boiling or dipstick test.
Idiopathic Hypercalciuria
Fever, dehydration and heavy exercise may cause
This is a common cause of microscopic and gross hema transient and mild proteinuria. Mild proteinuria may also
turia, and urolithiasis. A family history of hematuria or occur in UTI, hydronephrosis and renal tuberculosis. In
urolithiasis may be present. Urinary calcium to creatinine proximal tubular defects (e.g. Fanconi syndrome) mild
ratio in the early morning 'spot' urine serves as a screening proteinuria may occur, being chiefly composed of low
test. The upper limit of normal is 0.2 (mg/mg); higher molecular weight globulins. Heavy proteinuria (predo
values suggest hypercalciuria. The diagnosis may be minantly albumin) usually indicates glomerular disease.
Disorders of Kidney and Urinary Tract 447
Important causes of asymptomatic proteinuria include Epidemiological studies have shown that asymptomatic
orthostatic proteinuria, chronic glomerular diseases, reflux cases are frequent. The streptococcal infection is usually
nephropathy, renal hypoplasia and rarely renal tubular of the throat or skin, and precedes the onset of nephritis
disorders. In orthostatic (postural) proteinuria, protein is by 1 to 4 weeks. Only a few strains of streptococci are
absent in urine specimen collected after overnight nephritogenic, e.g. types 4 and 12 causing pharyngitis and
recumbence. The pathogenesis of this condition is not clear type 49 causing pyoderma. Post-streptococcal GN is a
but the long-term outcome is good. Continued follow-up typical example of an immune complex disease. The
is necessary until proteinuria disappears. Chronic renal streptococcal antigen-antibody complexes are trapped in
damage from vesicoureteric reflux and UTI may manifest the glomerular capillaries where they activate complement
with proteinuria. Several forms of glomerular diseases, and initiate inflammatory changes.
especially focal segmental glomerulosclerosis, may cause
persistent, asymptomatic proteinuria; microscopic Pathology
hematuria is often associated. A renal biopsy is indicated On light microscopy, the glomeruli are enlarged and ische
in the presence of persistent or heavy proteinuria. Long mic, and the capillary loops narrowed. There is prolifera
term observation is necessary to monitor clinical course tion of mesangial cells and infiltration with neutrophils.
and renal function. Prolonged treatment with angiotensin Immunofluorescence shows granular deposits of IgG and
converting enzyme inhibitors or angiotensin receptor complement (C3) along the capillary walls. Electron-
blockers is effective in reducing persistent proteinuria. microscopy shows deposits on the subepithelial side of
the glomerular basement membrane.
Suggested reading
Srivastava RN. Isolated asymptomatic proteinuria. Indian J Pediatr 2002, Clinical Features
69: 1055-1058.
The onset is rapid, with puffiness around the eyes and
pedal edema. Edema may be more pronounced if fluids
ACUTE GLOMERULONEPHRITIS
have been given in the presence of oliguria. Urine is chara
Acute glomerulonephritis (GN) is characterized by cteristically cola-colored. The degree of oliguria usually
relatively abrupt onset of hematuria, oliguria, edema and correlates with the severity of the disease. Hypertension
hypertension. The clinical and histological severity varies is common. Atypical presentations include (i) convulsions
considerably and is not always correlated. A child with due to hypertensive encephalopathy; (ii) left ventricular
mild disease may go undetected, while in a severe case failure and pulmonary edema, due to malignant hyperten
anuria, hypertensive encephalopathy and heart failure sion and hypervolemia; and (iii) acute renal failure.
may be present. Acute GN following streptococcal
infection is the commonest type in children. A similar Laboratory Findings
presentation may, however, be present in the conditions Urine shows 1+ to 2+ protein with red cells, and red cell
enumerated in Table 15.2. and granular casts. White cells, indicative of glomerular
Appropriate laboratory investigations are carried out inflammation, are also present and should not be regarded
to reach a diagnosis. A renal biopsy may be required if as evidence of UTI. Hemodilution may result in normo-
GN does not appear to be resolving within two weeks. cytic anemia; ESR is often raised. Blood levels of urea and
creatinine are elevated reflecting renal impairment;
POST-STREPTOCOCCAL GLOMERULONEPHRITIS hyponatremia and hyperkalemia occur with continuing
oliguria. The chest X-ray may show prominent vascular
Acute GN following infection by group A beta-hemolytic
markings suggesting hypervolemia. Throat swab culture
streptococci is a common disorder in hospital practice. It
may rarely show (3-hemolytic streptococci. Serologic
mainly involves school-age children and is uncommon evidence for streptococcal infection is present in most
below the age of 3 years; boys are more frequently affected. patients with pharyngitis, though antibiotic therapy may
blunt this response. The ASO titer is increased in more
Table 15.2: Conditions presenting as acute glomerulonephritis than 80% patients. Anti-DNase B is elevated in cases of
streptococcal skin infection. These titers decrease to low
Post-infectious: Streptococci, staphylococci, hepatitis B and
levels within 4 to 6 weeks. The level of serum C3 is low in
C, bacterial endocarditis, infected ventriculoatrial shunts and
90% patients but normalizes by 5-6 weeks. Persistent low
prosthesis
C3 levels indicate other forms of GN.
Systemic vasculitis: Henoch-Schonlein purpura, systemic
lupus erythematosus, polyarteritis nodosa, Wegener's
Management
granulomatosis
Membranoproliferative glomerulonephritis Patients with mild oliguria and normal blood pressure can
be managed at home. Others are best treated in a hospital
IgA nephropathy
since close attention to blood pressure and dietary intake
Familial nephropathy: Alport syndrome
is essential. Strict bedrest is not necessary. Once acute GN
448 Essential Pediatrics
has occurred, treatment with penicillin has no effect on these cases with periodic urinalyses and measurements
the course of the disease, but may be given if active of blood pressure is needed.
pharyngitis or pyoderma is present.
Renal biopsy: A biopsy is rarely indicated in those suspected
The principles of management of patients with severe
to have post-streptococcal GN except when renal function
oliguria and azotemia are discussed later in the chapter.
is severely impaired beyond 7-10 days or serum C3
Diet: The intake of protein, sodium and potassium should remains depressed beyond 6-8 weeks. Patients with
be restricted until blood levels of urea reduce and urine unresolving acute GN (persistent oliguria or azotemia past
output increases. Carbohydrates and fats are allowed. 7-10 days, hypertension or gross hematuria past 2-3
Overhydration is a dangerous complication as it may weeks) or those with features of a systemic illness (e.g.
increase hypertension and precipitate left ventricular systemic lupus) require a kidney biopsy.
failure. Urine output should be accurately measured. Fluid
intake should be restricted to an amount equal to
CRESCENTIC GLOMERULONEPHRITIS
insensible losses and 24-hr urine output.
Weight: The child should be weighed daily. In the presence Rapidly progressive GN (RPGN) is defined as an acute
of severe oliguria, he should lose about 0.5% body weight nephritic illness accompanied by rapid loss of renal
per day because of endogenous catabolism. A gain in function over days to weeks. The histopathological cor
weight necessitates reduction in fluid intake. relate is the presence of crescents (crescentic GN) involving
50% or more glomeruli (Fig. 15.3). The presence of cres
Diuretics: Patients showing modest edema are treated with
cents is a histologic marker of severe glomerular injury,
oral frusemide at a dose of 1-3 mg/kg; the edema which may occur in a number of conditions including
disappears with the return of renal function. Therapy with
postinfectious GN, systemic vasculitides and Goodpasture
IV frusemide (2-4 mg /kg) is necessary in subjects with
syndrome. The severity of clinical and histological features
pulmonary edema.
often correlates. Patients with circumferential crescents
Hypertension: Mild hypertension may be controlled by involving more than 80% glomeruli show advanced renal
restriction of salt and water intake. Effective anti failure; those with noncircumferential crescents in fewer
hypertensive agents include amlodepine, nifedipine, glomeruli have an indolent course. Renal biopsy should,
atenolol or diuretics. Patients with hypertensive emer therefore, be done in patients with severe nephritic fea
gencies need prompt treatment with IV nitroprusside or tures, which do not resolve within 1-2 weeks.
labetalol. The outcome is related to prompt institution of therapy
Left ventricular failure: Hypertension should be controlled and histological severity. Without appropriate treatment,
and IV frusemide given to induce diuresis, leading to patients are at risk for chronic renal failure. Satisfactory
improvement in heart failure. If immediate diuresis is not results have been obtained with administration of IV
seen, steps are taken to initiate urgent dialysis. Venesection methylprednisolone, followed by oral prednisolone and
with removal of 100-200 mL blood or tying rotating cyclophosphamide. Plasmapheresis is beneficial in
tourniquets, to reduce venous return to the heart, is seldom
used. Respiratory support with positive end-expiratory
pressure may be needed.
patients with systemic vasculitides and Goodpasture mofetil and azathioprine) and cyclosporin A, and
syndrome. appropriate treatment of infections has significantly
improved the outcome.
NEPHRITIS IN HENOCH-SCHONLEINPURPURA (HSP)
Suggested reading
HSP is one of the most common vasculitis in children (Fig.
1. Coppo R, Amore A. New perspectives in treatment of glomerulo
15.4). Mild renal involvement indicated by microscopic nephritis. Pediatr Nephrol 2004;19:256-265.
hematuria and mild proteinuria is common. Serum IgA 2. Coppo R. Pediatric IgA nephropathy: clinical and therapeutic
levels may be elevated. Renal biopsy shows mesangial perspectives. Semin Nephrol 2008;28(l):18-26.
proliferation with mesangial deposition of IgA. Most 3. Hogg RJ. IgA nephropathy: What's new? Pediatr Nephrol 2007;
22:1809-1814.
patients recover without any specific treatment. However,
4. Fervenza FC. Henoch-Schonlein purpura nephritis. Int J Dermatol
long-term observation is necessary to detect insidious 2003; 42: 170-177.
renal damage. Rarely a patient may present with nephritic 5. Perfumo F, Martini A. Lupus nephritis in children. Lupus 2005;
or nephrotic syndrome, hypertension, azotemia and 14:83-88.
6. Hejaili FF, Moist LM, Clark WF. Treatment of lupus nephritis.
crescentic GN. Therapy with a combination of steroids,
Drugs 2003;63:257-274.
cyclophosphamide and azathioprine is recommended; the
long-term outcome may not be satisfactory.
HEMOLYTIC UREMIC SYNDROME
D+ HUS
The diarrheal illness that precedes HUS is caused by
verotoxin-producing E. coli (usually E. coli 0157: H7) in
North America and Europe; in the Indian subcontinent
Shigella dysenteriae 1 is the chief pathogen. Cytotoxin-
Fig. 1 5 . 4 : Henoch-Schonlein purpura, extensive rash over mediated injury to the endothelium in the renal micro
lower extremities and gluteal region vasculature leads to localized coagulation and fibrin
deposition. As red cells and platelets traverse these dama
ged vessels, they are injured and sequestered. Though the
RENAL INVOLVEMENT IN SYSTEMIC brunt of the microvascular injury is on the kidney, other
LUPUS ERYTHEMATOSUS organs especially the brain may be affected.
A variety of clinical and renal histological patterns are
Clinical Features
observed. Asymptomatic proteinuria and/or hematuria,
acute nephritic syndrome and nephrotic syndrome are Children less than 2-3 years are usually affected. Follow
most common. Rarely renal involvement may be ing a prodrome of acute diarrhea or dysentery, patients
manifested as rapidly progressive GN. Renal biopsy may show sudden onset of pallor and oliguria. Blood pressure
show almost normal glomeruli, focal or diffuse prolifera may be high. Focal or generalized seizures and alteration
tive GN or membranous nephropathy. Immunofluore of consciousness are common.
scence studies show mesangial and capillary wall deposits
of IgG and C3, and usually Clq and IgA. Antinuclear and Investigations
double-stranded DNA autoantibodies are present in the The blood film shows broken and distorted red cells,
blood of most cases with lupus nephritis; C3 levels are increased reticulocyte count and high blood levels of LDH;
reduced. Coombs' test is negative. Thrombocytopenia and
Remissions and relapses, and progressive renal damage neutrophilic leukocytosis are usually present. Urine shows
characterize the course of the disease. Infections and end microscopic hematuria and mild proteinuria. Blood levels
stage renal disease is the chief cause of mortality. of urea and creatinine are elevated reflecting the severity
Management with judicious use of corticosteroids, of the renal failure. On renal biopsy, the endothelial cells
cytotoxic drugs (cyclophosphamide, mycophenolate are swollen and separated from the basement membrane
450 Essential Pediatrics
Mortality during the acute episode of D+ HUS is low. On (i) Minimal change nephrotic syndrome (MCNS) (ii)
follow up, 20-30% patients show varying degree of Nephrotic syndrome with significant lesions (Table 15.3).
residual renal damage. Factors suggestive of poor outcome Steroid sensitive nephrotic syndrome (which is usually
include oligoanuria for more than 2 weeks, severe MCNS) has a satisfactory long-term outcome. In contrast,
neurological involvement and presence of renal cortical steroid resistant nephrotic syndrome (usually associated
necrosis. The acute and long-term outcome in patients with with significant glomerular lesions) has a less satisfactory
D- HUS is often unsatisfactory; recurrent episodes of the course and a significant proportion progress to chronic
illness may occur. renal failure.
MCNS accounts for 80% cases of nephrotic syndrome in The onset is insidious with edema first noticed around
children. Renal biopsy does not show significant abnor the eyes and subsequently on legs. It is soft and pits easily
malities on light microscopy (Fig. 15.5A). Electron micro on pressure. Gradually edema becomes generalized, with
scopy shows non-specific obliteration of epithelial foot ascites, hydrothorax and hydrocele (Fig. 15.6). With incre
processes. Immunofluorescence studies do not demons asing edema, urine output may fall. The blood pressure is
trate deposition of immune reactants except occasional usually normal; sustained elevation suggests the
mesangial IgM. On ther other hand, patients with focal possibility of significant glomerular lesions. The bloated
segmental glomerulosclerosis (FSGS) show evidence of appearance and relative well being of the child is mis
sclerosis involving a segment of the glomerular tuft (Fig. leading and after the loss of edema, severe muscle wasting
15.5B). The pathogenesis of MCNS is obscure. There is is revealed. Infections may be present at the onset and
evidence to suggest perturbation of the cell-mediated during relapses.
immunity, which through yet undefined mechanisms
alters the permselectivity of the glomerular filter, resulting
in massive proteinuria. A primary abnormality of the
epithelial foot processes (podocytes) is also postulated.
Laboratory Findings
Urine examination shows heavy (3+ to 4+) proteinuria.
Gross hematuria or persistent microscopic hematuria
suggests the likelihood of significant glomerular lesions.
Hyaline and granular casts may be present. Serum albu
min is low and values less than 1 g/dL are often obtained.
Hypercholesterolemia may impart a milky appearance to
the plasma. Blood urea and creatinine values are usually
within the normal range, except when there is hypovo
lemia and fall in renal perfusion.
Blood levels of IgG are low and those of IgM elevated;
C3 level is normal. The severity of glomerular damage is
reflected in the passage of proteins of large molecular
weight, chiefly globulin. Protein selectivity is the ratio of
the clearance of high molecular weight (e.g. IgG) to low
Fig. 15.5B: Histological features in a 6-year-old girl with steroid resis molecular weight proteins (e.g. transferrin, albumin). A
tant nephrotic syndrome secondary to focal segmental glomerulo low ratio indicates highly selective proteinuria, as in
sclerosis. Note the hilar sclerosis involving large areas of the glomeru MCNS. However, this information does not offer
lus and adhesions to the Bowman's capsule diagnostic help.
452 Essential Pediatrics
A renal biopsy is not required to confirm the diagnosis is reduced or within 2 weeks of its discontinuation (steroid
of MCNS prior to starting treatment. A biopsy is dependent). About 20-5% patients either do not respond
recommended in children with atypical features at the to the initial treatment with prednisolone, or do so
onset (age below 12 months, gross or persistent micro transiently and later cease to respond (steroid resistant).
scopic hematuria, low blood C3, hypertension or impaired
renal function). Patients who continue to show nephrotic Management of Relapse
range proteinuria despite appropriate steroid therapy An upper respiratory infection or a febrile episode often
require a biopsy to determine the underlying disorder.
precipitates a relapse; occasionally there is no obvious
cause. Mild proteinuria (1+ to 2+) may sometime occur
Management
during such infections and spontaneously disappear. It is
Initial Episode prudent to wait for a few days before starting treatment.
The child should receive a high protein diet. Salt is However, if urine shows 3+ or 4+ protein (for more than
restricted to the amount in usual cooking with no extra 3-4 days) or if edema appears, prednisolone should be
salt given. Any associated infection is treated. The pre promptly administered (2 mg/kg daily) for 10-14 days,
sence of tuberculosis should be looked for. Diuretics are which induces remission, followed by alternate day
administered only if edema is significant. Frusemide (1-4 treatment (1.5 mg/kg) for the next 4 weeks.
mg/kg/d in 2 divided doses) alone or with an aldosterone The first 2-3 relapses are treated in the manner
antagonist, spironolactone (2-3 mg/kg/d in 2 divided described above. Once the pattern of relapses is known,
doses) is adequate. Diuretics should be used cautiously therapy is individualized. Figure 15.7 outlines the manage
and overzealous fluid loss avoided. ment of patients with steroid sensitive nephrotic
For the past three decades, a modified version of the syndrome.
corticosteroid regimen suggested by the International
Study Group on Kidney Disease in Children has been Treatment of Patients with Frequent Relapses
used. The latter consists of prednisolone 60 mg/m2/day
Long-term alternate day prednisolone: Following completion
given in three divided doses for 4 weeks, followed by 40
of treatment for a relapse, alternate day prednisolone is
mg/m2 on alternate days for the next 4 weeks, after which
slowly tapered to a minimum maintenance dose (usually
treatment is discontinued. A number of studies indicate
0.3-0.7 mg/kg) that keeps the patient in remission without
that intensive prednisolone therapy for the initial episode
causing steroid toxicity. This dose is maintained for
has beneficial effect on the long-term course of nephrotic
9-12 months. Relapses, while on this therapy, are treated
syndrome. The current recommendation is to administer
with daily prednisolone until urine is protein-free for
prednisolone at a dose of 2 mg/kg/day in divided doses
3 days, after which alternate-day therapy is resumed.
for 6 weeks, followed by 1.5 mg/kg on alternate days (as
Treatment for repeated breakthrough relapses may cause
a single morning dose) for another 6 weeks; therapy is
steroid toxicity. Such children should not be exposed to
then stopped. Other regimens are being explored.
further large doses of prednisolone and given one of the
About 90-95% children with MCNS will respond to
second-line drugs discussed below.
prednisolone with diuresis, loss of edema and abolition
of proteinuria, usually by 10-14 days. Steroid therapy Levamisole: This immunomodulator is effective in reducing
results in cushingoid features and hypertension that might relapse rates in a proportion of patients with frequent
need treatment. relapsing or steroid dependent nephrotic syndrome. After
inducing remission, levamisole is administered at a dose
Parent Education of 2-2.5 mg/kg on alternate days. Alternate day predni
The parents should be explained about the disease and solone is given in decreasing doses, until a dose of 0.3-0.5
the usual outcome, and their cooperation ensured. They mg/kg is reached, for 3-6 months; it is occasionally
are taught how to examine urine for protein, which should possible to further reduce the dose of prednisolone or
be done periodically to detect a relapse early. During the discontinue it altogether. Treatment with levamisole is
periods of remission, no dietary or physical restrictions given for 1-2 years or longer. The chief side effect is
are imposed. leukopenia, which should be monitored every 2 months.
Encephalopathy with seizures and skin rash are reported
Subsequent Course rarely.
A small proportion of patients have only a single episode Cyclophosphamide: Treatment with alkylating agents is
of the illness, while the majority shows relapses. Some effective in many patients with frequent relapsing or
patients have three or less relapses in a year (infrequent steroid dependent nephrotic syndrome. A 12-week course
relapsers), while others have four or more relapses of treatment with cyclophosphamide or chlorambucil may
(frequent relapsers). About 15% remain in remission while induce long-lasting remission in 50% cases. The former is
on prednisolone therapy and relapse whenever the dose preferred in view of comparative safety and wider
Disorders of Kidney and Urinary Tract 453
Prednisolone 2 mg/kg daily for 6 weeks, followed by 1.5 mg/kg on alternate days for 6 weeks
1 r ▼
Infrequent relapses Frequent relapses Steroid resistance
L ^ Steroid dependence
Chronic GN is not a single disease entity, but comprises This is a focal or diffuse inflammatory reaction of the renal
advanced stages of several forms of GN. In most cases, interstitium with secondary involvement of the tubules,
the glomerular disease is primary and not part of a and rarely, glomeruli. Acute interstitial nephritis is usually
systemic disorder. However, chronic GN may occur in due to infections or drugs (e.g. ampicillin, cephalosporins).
systemic lupus erythematosus, microscopic polyarteritis, The common causes of chronic interstitial nephritis include
familial nephropathies and nephropathies due to drugs urinary tract obstruction and vesicoureteric reflux.
and toxins. Variable glomerular deposition of immuno Interstitial nephritis may also be a feature of a systemic
globulin, complement and fibrin is found on immuno disorder (e.g. systemic lupus, vasculitis, associated with
fluorescence studies. Renal biopsy examination in early uveitis); autoantibodies to the tubular basement mem
stages shows one of several patterns. brane are found in some cases. In many instances, no cause
i. Proliferative GN (mesangial proliferative GN, crescen is determined.
tic GN, MPGN) The clinical features are non-specific and include
ii. Focal segmental glomerulosclerosis abdominal pain, anorexia, pallor, headache and edema.
Hypertension is generally absent. The presence of
iii. Membranous nephropathy
progressive renal insufficiency associated with satisfactory
In late stages, renal histologic changes are nonspecific. urine output, and urinary abnormalities such as hypo
Most glomeruli are sclerosed with corresponding tubular, sthenuria and mild proteinuria suggest the diagnosis.
interstitial and vascular changes. It is usually very difficult Leukocytes are frequently seen in the urine and Wright's
to determine the type of GN that led to such changes. Post stain of the urine sediment may reveal eosinophils,
streptococcal acute GN seldom leads to chronic GN. especially in drug-associated disease. The blood eosino
phil count may be increased.
Clinical Features A renal biopsy establishes the diagnosis and helps
The patient may be asymptomatic and the disease detected assess severity. Drug-related interstitial nephritis is treated
on routine urine examination. Others may show failure with stoppage of the offending drug; treatment with
to thrive, persistent anemia, moderate to severe hyper corticosteroids is beneficial. Systemic illness, if any, should
tension, edema, nocturia, microscopic or gross hematuria, be appropriately managed. The treatment of chronic
bone pains and deformities. interstitial nephritis is symptomatic.
an important cause of morbidity and might result in renal urine stream and palpable bladder suggest urinary ob
damage, often in association with vesicoureteric reflux struction.
(VUR). During infancy, UTI are as common in boys and
girls, since (i) the route of infection is often hematogenous, Diagnosis
and (ii) boys have a higher incidence of urinary tract
The diagnosis of UTI is confirmed by urine culture. Urine
anomalies, particularly posterior urethral valves. Beyond
is obtained by suprapubic bladder aspiration or urethral
infancy, the incidence of UTI and asymptomatic bacteri- catheterization in children below 2 yr, and a careful 'clean-
uria is higher in girls. catch' procedure in older children. The specimen is stored
at 4° C until transported to the laboratory. An uncen
Microbiology trifuged urine specimen may be examined in a counting
UTI, in most cases, are caused by E. coli that forms the chamber. The presence of more than 10 white cells/cu mm
predominant periurethral flora. Klebsiella, Enterobacter, is abnormal. The presence of bacteriuria on oil immersion
Proteus, Pseudomonas, enterococcus and Candida are microscopy of a fresh uncentrifuged urine specimen
encountered in presence of obstruction, instrumentation suggests significant bacteriuria. Dipstick examination
and poor immune state. (combining detection of leukocyte esterase and nitrite) is
The adhesion of bacteria to epithelial cells may have a as sensitive as microscopic urinalysis in screening for UTI.
central role in UTI. Bacterial adhesion is mediated by The definitive diagnosis of UTI depends on the urine
fimbriae, which are proteinaceous, hair-like extensions culture showing 105 or more bacteria per mL. However,
from the bacterial cell surface. The fimbriae recognize infants with symptomatic UTI may show colony counts
specific receptors on the epithelial cell membrane. P-blood of 104 to 105/mL. Any colony growth in urine obtained by
group antigens are the receptors for E. coli having fimbriae suprapubic aspiration is significant. Tests to differentiate
on their surface. Such organisms are an important cause upper from lower UTI are of little practical value.
of acute pyelonephritis in the absence of VUR. Some E.
coli strains possess invasive toxins and hemolysins, and Treatment
are more pathogenic. Once UTI is suspected, a urine specimen is sent for culture
and treatment started. The choice of initial treatment depends
Predisposing Factors on the age and clinical condition of the patient, and presence of
VUR, obstructive uropathy and neurogenic bladder complications or structural abnormalities. Antibiotic therapy
predispose to UTI in almost 30-40% children. Obstructive is modified, if required, once culture result is available.
uropathy is more common in boys. Neurogenic bladder Follozving treatment of the first episode of UTI, plans are made
may be associated with meningomyelocele, or follow for evaluation of the urinary tract. Treatment with prophy
neoplasm or trauma to the lumbosacral region. Children lactic antibiotics is given until results of imaging are
with malnutrition, renal parenchymal disease or those available.
receiving immunosuppressive therapy are also susceptible General measures: The child is encouraged to take large
to UTI. There is evidence that circumcision may protect amount of fluids and empty the bladder frequently to
against UTI, especially in infancy. prevent stasis of urine.
\
dose, which is one-fifth of the usual therapeutic dose (see
below). In view of nausea and abdominal discomfort
associated with nitrofurantoin, therapy with cotrimoxa
zole is preferred. Trimethoprim alone is as effective as
cotrimoxazole but is not available in India. Treatment with
cephalexin is preferred in infants less than 4-months-old
and children with G6PD deficiency. Drugs that tend to
I
select resistant bacteria in the bowel including amoxicillin,
i nalidixic acid and other quinolones are not suitable for
prophylaxis. Breakthrough infections during prophylaxis
are treated with appropriate antibiotics.
The indications for surgical correction of primary VUR
are limited and include poor compliance or intolerance to
medical treatment. Surgery might also be indicated in
patients showing recurrent breakthrough UTI despite
prophylaxis, appearance of new scars or persistence of
grade IV-V reflux beyond 2-yr of age. Surgical procedures
of ureteric reimplantation have cure rates of 95-97%. The
precise indications for endoscopic submucosal injection
(e.g. of Teflon or other biocompatible products) at the
ureteric orifice are not defined.
Follow up evaluation should be performed annually
with urinalysis and measurement of height, weight and
blood pressure. Urine cultures should be obtained in
presence of symptoms suggestive of a UTI. Follow up renal
ultrasonography and cystography should be performed
every 12-18 months.
Reflux Nephropathy
This is characterized by renal cortical scarring, predo
minantly at the poles. The underlying calyces lose their
normal concave shape and show clubbing. Such scarring
occurs early in life when the kidneys are still growing;
Fig. 15.8B: Micturating cystourethrogram showing bilateral formation of fresh scars after 5-6 yr of age is uncommon.
grade IV primary vesicoureteric reflux Reflux nephropathy is an important cause of hypertension
and end stage renal disease in children.
Management
Long-Term Prophylaxis in Children with UTI
The primary goal of treatment is prevention of pyelo
nephritis and complications of reflux nephropathy. Medi The indications for antibiotic prophylaxis are as follows:
cal therapy is based on the principle that VUR resolves 1. Children below 3 yr of age who have received treatment
with time, and antibiotics maintain urine sterility and for the first UTI and are being investigated for an
prevent infections while awaiting spontaneous resolution. underlying etiology.
The basis for surgical therapy is that, in select situations, 2. Children with normal urinary tract and no VUR, but
ongoing VUR has the potential to cause significant renal with three or more UTI in one year. Prophylaxis is
injury and elimination of reflux will minimize this continued until the child is free of UTI for 6 months.
likelihood. Long-term controlled studies have shown that 3. UTI with VUR. Prophylaxis until the child is free from
outcomes such as recurrence of UTI, and renal scarring, reflux.
growth and functions are similar when patients are treated Medications used for prophylaxis are listed in Table
with antibiotic prophylaxis or surgery. 15.5.
Disorders of Kidney and Urinary Tract 459
Suggested reading in serum creatinine of more than or equal to 1.5 fold from
1. Greenbaum LA, Mesrobian HG. Vesicoureteral reflux. Pediatr Clin baseline, or (ii) reduction in urine output (oliguria of less
North Am 2006; 53(3): 413-427. than 0.5 ml/kg per hour for >6-hr).
2. Hodson EM, Wheeler DM, Vimalchandra D, Smith GH, Craig JC.
Interventions for primary vesicoureteric reflux. Cochrane Database Incidence and Etiology
Syst Rev 2007; (3): CD001532.
3. Williams GJ, Wei L, Lee A, Craig JC. Long-term antibiotics for ARF (not including functional oliguria that rapidly
preventing recurrent urinary tract infection in children. Cochrane responds to fluid volume repletion) accounts for 2-5%
Database Syst Rev 2006; 3: CD001534. admissions to general pediatric wards across the world.
4. Callewaert PR. What is new in surgical treatment of vesicoureteric In developing countries, common causes for ARF in
reflux? Eur J Pediatr 2007; 166: 763-768.
children include gastroenteritis with dehydration, serious
infections, D+ hemolytic uremic syndrome (HUS), post-
ACUTE RENAL FAILURE
infectious and crescentic glomerulonephritis (GN) and
Acute renal failure (ARF) denotes an acute impairment of intravascular hemolysis (in patients with G6PD defi
renal function resulting in retention of nitrogenous wastes ciency). In developed countries, ARF follows major sur
and other biochemical derangement. Oliguria or anuria gical procedures, D+ HUS and severe systemic infections.
is a prominent feature, though rarely urine output may A list of common causes is shown in Table 15.6.
be normal. ARF is a common, life-threatening situation in The causes of ARF are broadly divided into pre-renal,
childhood, where proper assessment and adequate intrinsic renal and post-renal. Pre-renal failure is renal insuf
treatment are crucial. ficiency due to systemic hypovolemia or renal hypo
In the absence of a standard definition of ARF and perfusion. In the early stages, this is rapidly reversible by
recognizing that the occurrence of azotemia represents the infusion of fluids but, if prolonged or severe, may lead to
end-result of a variety of conditions, the term acute kidney acute tubular necrosis. Post-renal failure occurs conse
injury (AKI) is proposed to reflect the entire spectrum of quent to mechanical obstruction in the collecting system.
the disorder. Patients are considered to have AKI if there
is abrupt (within 48-hr) reduction in kidney function, Acute-on-Chronic Renal Failure
defined as either (i) an absolute increase in serum Occasionally a patient with undetected chronic renal
creatinine of more than or equal to 0.3 mg/dl or increase disease may present for the first time with acute onset of
Infections, drugs
Autoimmune Renal vein thrombosis
Idiopathic
POST-RENAL
Calculus, posterior urethral valves
460 Essential Pediatrics
Abnormalities directly related to the derangement intake should be achieved as early as possible. A diet
caused by loss of renal function include acidotic breathing, containing 0.8-1.0 g/kg of protein in infants and 0.6-0.8
alteration of sensorium and irregularities of cardiac rate g/kg in older children and a minimum of 50-60 Cal/kg is
and rhythm. In acute tubular necrosis, clinical examination recommended. The latter requirement can be met by
may reveal no abnormality except for dehydration. The adding liberal amounts of carbohydrates and fats to the
oliguric phase lasts about 3-10 days, during which period diet. Vitamin and micronutrient supplements are
the biochemical and clinical abnormalities gradually provided. In patients with oligoanuria and fluid overload,
worsen; more rapidly if infection, trauma and bleeding daily caloric requirement cannot be met due to fluid
are associated. Subsequently urine output increases restriction. These patients require early initiation of
steadily. A diuretic phase maybe observed, usually lasting dialysis to allow adequate caloric intake.
for a week, during which large amounts of water and
electrolytes, particularly potassium may be lost. The Treatment of Complications
patient may get dehydrated if these losses are not
In a child with ARF, immediate attention is directed
adequately replaced.
towards detection and management of life-threatening
Laboratory Evaluation complications.
These include complete blood counts, and estimation of Fluid overload: Children with pulmonary edema and
blood levels of urea, creatinine, electrolytes, pH and congestive cardiac failure are treated using standard
bicarbonate, and urinalysis. An EKG is done to examine guidelines. If the condition does not improve, patients
for evidence of hyperkalemia and chest X-ray for pul require endotracheal intubation and assisted ventilation.
monary plethora and cardiac enlargement. Ultrasono
graphy is a useful imaging tool because of its non-depen- Hyperkalemia: Hyperkalemia is an emergency as the
dence on renal function. It allows visualization of the resultant cardiac toxicity may cause sudden death. Urgent
pelvicalyceal system, and assessment of renal size, treatment is instituted depending on blood potassium
structural anomalies and calculi. Additional tests are done, levels and EKG changes. Concomitant metabolic acidosis
where appropriate, to determine the cause of ARF. should be corrected. Calcium antagonizes the cardio-
toxicity of hyperkalemia; for immediate effect, the dose is
Management 0.5-1 mL/kg of 10% calcium gluconate given IV over 5-
Prompt clinical and laboratory evaluation is necessary. 10 minutes. Administration of sodium bicarbonate also
Complications such as dehydration or fluid overload, lowers serum potassium by favoring its uptake by cells;
hypertension, heart failure, severe anemia, hyperkalemia 1-2 mL/kg of a 7.5% solution is infused over 10-20
and acidosis may already be present and require urgent minutes. Nebulized administration of salbutamol (5-10
treatment. mg) may be beneficial through a similar mechanism, the
effect is seen within 20-30 minutes. Cellular uptake of
Fluid and Electrolytes potassium is also achieved by administration of glucose
Fluid and electrolyte intake must be meticulously 0.5 g/kg along with soluble insulin 0.1 U/kg IV over 90
regulated. The daily fluid requirement amounts to minutes. Exchange resins (calcium resonium 1 g/kg/day)
insensible water losses (300-400 mL/m2), urinary output may be given orally or by enema to eliminate potassium
and extrarenal fluid losses. Insensible fluid losses should from the gut. The onset of action of resins is slow and
be replaced with 5% glucose solution with little or no their role in treatment of life-threatening hyperkalemia
potassium. The composition of urinary and extrarenal limited.
losses should be analyzed and replaced accordingly. It is The benefit following administration of calcium gluco
usually possible to administer the required amounts of nate, salbutamol, sodium bicarbonate and glucose-insulin
fluid by mouth. is transient, and most patients with hyperkalemia
Fluid therapy is guided by intake and output analysis, secondary to ARF require dialysis.
weight, physical examination and serum sodium. If fluid
Metabolic acidosis: Severe acidosis is treated by adminis
in an appropriate volume and composition is given, the
tration of sodium bicarbonate, 1-2 mEq/kg, aiming to
patient should lose 0.5-1% of his weight every day because
raise the serum bicarbonate level to 15-17 mEq/L. Patients
of tissue breakdown. The serum sodium concentration
should be monitored for fluid retention and hypertension;
should stay within the normal range. A rapid weight loss
and rising serum sodium suggest inadequate fluid correction of acidosis may precipitate hypocalcemic
replacement, while an absence of weight loss and low seizures. Persistence of acidosis requires dialysis
serum sodium indicate fluid excess. treatment.
related to the rapidity of rise rather than the absolute value Both hemodialysis and peritoneal dialysis are effective
of the blood pressure. in the management of ARF. Peritoneal dialysis does not
require vascular access and sophisticated equipment, and
Symptomatic hypertension needs to be lowered gradually: Too
is easy to perform even in neonates. This makes it the
rapid reduction may result in ischemia and infarction of
preferred dialysis procedure in children (Table 5.8).
regions in the brain, spinal cord and retina. Blood pressure
is reduced by one-third of the total desired reduction
during the first 6-8 hr, a further third over the next 12-24
Table 15.8: Indications for dialysis in acute renal failure
hr and the final third over the following 2-3 days. Infusion
of nitroprusside (0.5-8 |ig/kg per minute) causes a Severe hyperkalemia (serum potassium >6.5 mEq/L)
predictable reduction in blood pressure; the rate of Dysnatremia (serum sodium <130 or >150 mEq/L)
infusion can then be titrated depending on the response.
Severe acidosis (pH <7.2, TCOz<12 mEq/L)
Since the half-life of this drug is in minutes, it may be
Uremic encephalopathy
stopped if there is a precipitous fall in blood pressure.
Frusemide (1-2 mg/kg IV) is given if there are features of Pulmonary edema; congestive heart failure
fluid excess. IV infusion of labetalol is as effective as
sodium nitroprusside.
Once the patient is asymptomatic, maintenance oral Peritoneal dialysis: The abdominal skin is prepared as for a
therapy is instituted using a calcium channel blocker surgical procedure. After ensuring that the bladder is
(nifedipine, amlodepine), beta-adrenergic blocker (ateno empty, lignocaine is infiltrated in the midline at a point
lol), or vasodilator (prazosin) alone or in combination. midway between the umbilicus and pubic symphysis.
Hyponatremia: Hyponatremia (serum sodium <130 mEq/ Dialysis fluid 20 mL/kg is infused to distend the peritoneal
L) usually is the result of excessive fluid administration cavity. A small incision is made in the skin and linea alba
rather than salt loss. Plasma sodium concentration >125 and the peritoneal catheter introduced and advanced into
mEq/L is rarely symptomatic. Sodium concentration the paracolic gutter. It is fixed to the skin with purse-string
between 120-125 mEq/L may be associated with sutures. The dialysis fluid is infused 30-50 mL/kg, left in
encephalopathy, lethargy and seizures. Fluid restriction the peritoneal cavity for 30 to 45 minutes and then allowed
is the primary mode of therapy. Treatment with hyperto to flow, using a siphon effect, into the draining bottle. The
nic saline is reserved for those with symptomatic entire system is kept as an air-free, closed system. Thirty-
hyponatremia or level <115-120 mEq/L. A dose of 6 mL/ 40 cycles are carried out. Potassium is not added in the
kg of 3% saline (given over 30-60 minutes) raises serum first 5-10 cycles, to enable correction of hyperkalemia.
sodium by 5 mEq/L. Hypertonic saline must be used Later, 3-4 mEq/L potassium chloride is added to the
cautiously because of potential complications of fluid dialysis fluid. Overhydration and pulmonary edema can
overload and hypertension. be relieved using concentrated dialysis fluid.
The results of peritoneal dialysis are gratifying. In acute
General Supportive Care tubular necrosis, often a single dialysis is adequate. The
Patients with ARF should be managed under intensive procedure can, however, be repeated if necessary. If the
care conditions. Accurate records of intake and output and need for prolonged dialysis is anticipated, a silastic
daily weight should be maintained. Urine should be Tenckhoff catheter should be surgically placed. The most
collected by condom drainage; bladder should preferably important complication is peritonitis. Meticulous aseptic
not be catheterized. The risk of infection is high and precautions will minimize its incidence. The dialysate
appropriate preventive measures are necessary. Prophy should be examined for white cells and bacteria and
lactic antibiotics are not recommended but infections cultured.
should be promptly detected and treated. The dosage of Continuous hemofiltration: Continuous hemofiltration
antibiotics often needs to be modified. employs a filtration cartridge that permits efficient
removal of excess fluid as protein-free plasma. An
Dialysis
appropriate vascular access allows adequate blood inflow
The purpose of dialysis is to remove endogenous and and outflow. The patient's cardiac output provides the
exogenous toxins and maintain fluid, electrolyte and acid- driving force for the hemofilter. The procedure is
base balance until renal function recovers. The indications particularly useful for the management of patients with
for dialysis are listed in Table 15.8. It is important to assess severe fluid overload, and renal failure secondary to
the clinical situation and anticipate the course of ARF in cardiovascular and abdominal surgery, burns, heart
each case, depending on the type and severity of renal failure and septic shock. Continuous hemofiltration
injury. Dialysis should be started early to prevent occurrence provides smoother control of ultrafiltered volume and
of complications, especially in In/percatabolic states (e.g. gradual correction of metabolic abnormalities in unstable
extensive trauma and infections). patients with multi-organ failure.
Disorders of Kidney and Urinary Tract 463
Table 15.10: Common causes of chronic kidney disease obstruction, UTI, severe hypertension, drug toxicity and
dehydration). Appropriate imaging studies are done.
Glomerulonephritis: Idiopathic (e.g. focal segmental glome
rulosclerosis); secondary (to systemic lupus erythematosus, Blood counts and levels of urea, creatinine, electrolytes,
IgA nephropathy, microscopic polyarteritis, Henoch Schonlein pH, bicarbonate, calcium, phosphate, alkaline phos
purpura). phatase, parathormone, protein and albumin are obtained.
Reflux nephropathy Blood levels of ferritin and transferrin saturation are
obtained in patients with anemia. GFR can be estimated
Obstructive uropathy: Posterior urethral valves, pelviureteric
based on serum creatinine and height; its accurate
junction obstruction, renal stones.
assessment by creatinine clearance or radionuclide
Developmental anomalies: Bilateral renal hypoplasia,
methods is rarely necessary.
dysplasia.
Familial nephropathy: Nephronophthisis, Alport syndrome, Management
polycystic kidneys.
Optimal management of chronic renal failure involves a
Others: Hemolytic uremic syndrome, amyloidosis, renal vein team approach involving pediatric nephrologist, trained
thrombosis, renal cortical necrosis.
nurse, dietitian, social worker and orthopedic surgeon.
Every attempt is made to keep the child ambulatory and
there is a critical loss of nephron mass, the renal failure is active. Constant encouragement and emotional support
progressive, and the symptom complex similar in most are necessary. At the initial stages, management aims at
cases. Most children with CKD stage I-III (GFR more than maintaining nutrition and retarding progression of the
30 ml/min/1.73 m2) are asymptomatic; reduction of GFR renal failure. Later, treatment of complications and renal
below this level is associated with symptoms. End stage replacement therapy in the form of dialysis or trans
renal disease (ESRD) is characterized by decline of renal plantation is required.
function to a degree when life cannot be sustained without
Retarding Progression of Renal Failure
chronic dialyses or transplantation. This usually corres
ponds to GFR of 5-10 mL/min/1.73 m2. Children should consume the recommended dietary
intake of protein, avoiding excessive intake. Hypertension
Pathophysiology and Clinical Features should be adequately controlled. Long term therapy with
Loss of urinary concentrating ability results in frequent angiotensin converting enzyme inhibitors has been shown
passage of urine, nocturia and increased thirst. Anemia to reduce proteinuria and may retard progression of renal
that is usually normocytic and normochromic is chiefly failure.
due to reduced renal erythropoietin production. Mild
Diet
hemolysis and blood loss from gastrointestinal tract may
also contribute. Careful attention to diet is essential Recommended daily
Resistance to the action of growth hormone, the levels amounts of calories should be ensured. A diet high in
of which are increased, is considered to be responsible polyunsaturated fats, such as corn oil and medium chain
for growth failure. Anorexia, malnutrition and skeletal triglycerides and complex carbohydrates is preferred.
deformities contribute to growth retardation. Abnor Water restriction is usually not necessary, except in ESRD
malities in metabolism of calcium and phosphate and bone or presence of fluid overload. Excessive use of diuretics,
disease results from hyperphosphatemia, lack of renal overzealous restriction of salt and gastroenteritis may lead
formation of 1,25 dihydroxyvitamin D3, deficiency of to dehydration that should be corrected.
calcium, chronic acidosis and secondary hyperpara i. Proteins: The protein intake should be 1-2 g/kg/day;
thyroidism. Systemic acidosis is secondary to loss of proteins consumed should be of high biologic value.
nephrons with decreased ammonia formation and ii. Sodium: Since renal regulation of sodium reabsorption
consequent failure to buffer hydrogen ions. is impaired, its dietary intake needs to be individua
The blood pressure may be increased and optic fundi lized. Some infants are polyuric and lose large
show hypertensive retinopathy. Severe proximal muscle amounts of sodium requiring salt supplementation.
weakness, peripheral neuropathy, itching, purpura and Children with chronic glomerulonephritis retain
pericarditis are late features. Infections are common and sodium and water, which contributes to hypertension.
may acutely worsen renal function. Failure to thrive, growth These patients require salt and water restriction and
retardation, anemia, hypertension and bony deformities may may benefit from diuretics.
often be the presenting features of chronic renal failure, without iii. Potassium: Renal regulation of potassium balance is
a previous history of renal disease. maintained until very late, but the capacity to rapidly
excrete a potassium load is reduced. Dietary items
Investigations
with large potassium content should be avoided.
The patient should be investigated to find the cause of iv. Calcium and phosphorus: Calcium supplements are
renal failure and detect reversible factors (e.g. urinary tract given as calcium carbonate or acetate. Excessive
Disorders of Kidney and Urinary Tract 465
Hypertension
Hypertension in patients with proteinuria and glomerular
filtration rate >30 ml/min/1.73 m2 should preferably be
treated with angiotensin converting enzyme inhibitors
(e.g. enalapril). Beta-adrenergic blockers (atenolol) and
calcium channel antagonists (nifedipine, amlodipine) are
also effective agents; the latter are the preferred initial
choice in CKD stage IV-V. Additional treatment with loop
diuretics is beneficial in those with fluid overload. Patients
with severe hypertension, uncontrolled with the above
medications, may require additional treatment with
clonidine or prazosin.
Anemia
Subcutaneous administration of recombinant human
erythropoietin allows satisfactory increase in levels of
hemoglobin. Patients should receive iron and folic acid
supplements. Patients on hemodialysis should receive
intravenous iron supplementation. The dose of erythro
poietin should be adjusted to achieve target hemoglobin
of 11-12 g/dL. Inadequate response to erythropoietin may
occur due to iron deficiency, chronic infection, aluminum
Fig. 15.9 : Mineral bone disease in a 10-year-oid boy with stage 5
toxicity and severe hyperparathyroidism. Patients with
chronic kidney disease secondary to neurogenic bladder. Note the
hemoglobin level below 6 g/dL who are unable to afford
short stature (height 108 cm), frontal bossing, chest wall and lower
erythropoietin, should receive leukocyte-poor, packed red
limb deformities
cell transfusions to raise levels. Blood should be transfused
slowly, since it may aggravate hypertension and heart hyperparathyroidism in CRF. With reduction of renal
failure. function, phosphate balance is initially maintained by its
increased excretion from the normal nephrons. However,
Infections
when the GFR falls below 25%, blood phosphate levels
Urinary tract and other infections should be promptly rise.
treated with effective and least toxic drugs. The dosage of The symptoms are vague and nonspecific. Bone pain,
most drugs requires modification (reduction of dosage muscle weakness, growth retardation and skeletal
and/or increase in dosing interval), depending on the deformities are prominent. Blood examination shows
severity of renal failure. hypocalcemia, hyperphosphatemia and raised levels of
alkaline phosphatase and parathyroid hormone. X-rays
Growth
reveal metaphyseal changes suggestive of rickets.
Optimization of caloric and protein intake and treatment Radiologic features of secondary hyperparathyroidism are
of mineral bone disease is important. Administration of initially seen in the phalanges and clavicles.
recombinant human growth hormone improves growth Treatment is based on dietary restriction of phosphate,
velocity in children with chronic renal failure. The high and administration of phosphate binders and vitamin D.
cost of this treatment, however, limits its use. When GFR is reduced below 50%, phosphate containing
dietary articles (e.g. dairy products) are restricted. Blood
Mineral Bone Disease phosphate levels should be maintained in the normal
Mineral bone disease is a serious problem in children as it range. Calcium carbonate or acetate, 0.5-1 g/day with
occurs during the period of active growth. (Fig. 15.9). Its meals, reduces intestinal absorption of phosphate. The
prevention and adequate treatment is crucial. The renal excretion of aluminum, in children with renal failure,
proximal nephron is the chief site of synthesis of 1, 25 is poor; its accumulation may increase the risk of bone
dihydroxyvitamin D3 (calcitriol), the most potent disease and aluminum-related encephalopathy. Prolonged
metabolite of vitamin D. Its decreased production is an administration of aluminum hydroxide as a phosphate
important factor in the pathogenesis of secondary binder is therefore avoided.
466 Essential Pediatrics
Vitamin D analogs with short half-life are preferred. Chronic Hemodialysis (HD)
Medications that maybe used include calcitriol (20-50 ng/
Chronic HD is mostly carried out in the hospital setting.
kg/day) or la-hydroxy D3 (25-50 ng/kg/day). Excessive
These children require vascular access either an
vitamin D intake may cause hypercalcemia and hyper
arteriovenous fistula or graft, or a double lumen
calciuria, which should be monitored. Osteotomy may be
indwelling catheter in a central vein (e.g. internal jugular,
required to correct bony deformities.
femoral or subclavian vein). Dialysis is done for 3-4
hours/session, with a frequency of 3 sessions/week.
Long-Term Care
The rate of progression of chronic renal injury is very
variable. In some disorders (e.g. hemolytic uremic
syndrome, crescentic GN), stage V CKD is present within
few weeks or months. In others (e.g. reflux nephropathy
and some forms of chronic GN), the rate of deterioration
of renal function may be slow. Patients showing a rapid
deterioration of renal function should be evaluated for
potentially reversible complications (infection, urinary
outflow obstruction, fluid loss, hypertension and use of
nephrotoxic drugs).
Suggested reading
1. Chan JC, Williams DM, Roth KS. Kidney failure in infants and
children. Pediatr Rev 2002; 23: 47-60.
2. Hari P, Singla IK, Mantan M, Bagga A. Chronic renal failure in
children. Indian Pediatr 2003; 40: 1035-1042.
3. Hogg RJ, et al. National Kidney Foundation's Kidney Disease Fig. 15.10: Hemodialysis in a patient with end stage renal disease.
Outcomes Quality Initiative. Clinical practice guidelines for chronic Note the vascular access through a catheter in the internal jugular vein,
kidney disease in children and adolescents. Pediatrics 2003; 111: hemodialysis machine and the dialyzer (solid arrow)
1416-1421.
4. Haycock GB. Management of acute and chronic renal failure in
the newborn. Semin Neonatol 2003; 8: 325-334. During a hemodialysis session, blood is circulated through
an extracorporeal circuit that includes a hollow fiber
RENAL REPLACEMENT THERAPY dialyzer (artificial kidney) (Fig. 15.10). Anticoagulation of
Preparation of a child for end stage care should be the circuit is achieved by systemic heparinization. The
discussed in advance with the family members. The procedure requires high degree of technical expertise and
financial resources and the family support available need for continuous monitoring.
should be addressed. The different forms of renal
Renal Transplantation
replacement therapy available are chronic peritoneal
dialysis, hemodialysis and renal transplantation. In The feasibility and efficacy of renal transplantation as
children with stage V CKD (ESRD), transplantation is the standard therapy for ESRD in children is well established.
desired form of therapy. Social and economic reasons have Advances in surgical skills, availability of better immuno
precluded the availability of renal replacement therapy suppressive medications and ability to prevent and treat
for children in developing countries. infections, has improved the short and long term outcome.
The usual immunosuppressive therapy is a combination
Chronic Peritoneal Dialysis (PD) of a calcineurin inhibitor (cyclosporin, tacrolimus), purine
Chronic PD is done through a Tenckhoff catheter tunneled synthesis inhibitor (azathioprine, mycophenolate mofetil)
through the abdominal wall into the peritoneum. Chronic and prednisolone. Long-term allograft survival is better
PD can be done manually (ambulatory PD) or with the with live compared to deceased donors. Following
help of an automatic cycler (cyclic PD). The duration of successful renal transplantation the child can lead a
dialysis is usually 10-12 hr a day during which 4-6 cycles normal life and resume physical activity and schooling.
are performed. Chronic PD is preferred to chronic The allograft survival varies between 10-17 years.
hemodialysis since it is done at home, without the need
Suggested reading
for hospital visits. Patients on chronic PD have less
1. Hari P, Kanitkar M, Mantan M, Bagga A. Hemodialysis in children.
restriction on fluid and caloric intake; control of
Indian Pediatr 2002 39: 375-80.
hypertension is better and hematocrit is maintained. The 2. White CT, Gowrishankar M, Feber J. Peritoneal Dialysis Working
success of chronic PD, however, relies upon the motivation Group. Clinical practice guidelines for pediatric peritoneal dialysis.
of families to carry out the procedure. Pediatr Nephrol 2006; 21: 1059-1066.
Disorders of Kidney and Urinary Tract 467
3. Fischbach M, Edefonti A, Schroder C, Watson A; The European metabolic acidosis and inappropriately high urine pH. The
Pediatric Dialysis Working Group. Hemodialysis in children: plasma anion gap [Na+ -(Cl- + HC03 )] is in the normal
general practical guidelines. Pediatr Nephrol 2005; 20: 1054-1066.
range of 10-14 mEq/L. The renal function is normal or
4. White CT, Trnka P, Matsell DG. Selected primary care issues and
comorbidities in children who are on maintenance dialysis: a only mildly impaired. Two main forms are recognized:
review for the pediatric nephrologist. Clin J Am Soc Nephrol 2007; distal RTA (type I) and proximal RTA (type II). A third
2: 847-857. variety (type IV) distinguished by the presence of
hypoaldosteronism and hyperkalemia is not common in
DISORDERS OF RENAL TUBULAR TRANSPORT children. Incomplete and mixed forms often occur.
In comparison to glomerular diseases, tubular disorders Rena] acidification: Depending on dietary protein intake,
are less common. Early and correct diagnosis is essential children produce about 1-3 mEq/kg/day of non-volatile
since specific management is possible in many cases. The acids. The reabsorption of filtered bicarbonate as well as
diagnosis of a primary tubular disorder implies that there excretion of acid is mediated by tubular secretion of
is no significant impairment of glomerular function or hydrogen ions (H+). In the proximal tubule, filtered HC03
tubulointerstitial inflammation. A tubular disorder may combines with H+ to form H2C03 that rapidly dissociates
be congenital or acquired and involve a single function of to H20 and C02 (catalyzed by carbonic anhydrase at the
a tubule (renal glucosuria, nephrogenic diabetes insipidus) brush border of the tubular basement membrane). COz
or multiple functions (Fanconi syndrome). diffuses along its concentration gradient into the tubular
cell, combining with H20 to generate HC03~ that is
Initial Evaluation absorbed by the peritubular capillaries. The proximal
Children with primary defects in tubular function usually tubule reabsorbs 80-90% of the filtered HCOf; the
present during infancy. Table 15.11 shows important remainder is reabsorbed distally. In the distal tubule, the
clinical features of patients with such disorders. Most renal secreted H+ ions combine with the major urinary buffers,
tubular disorders can be diagnosed following careful sodium hydrogen phosphate (Na2HP04) and ammonia
interpretation of urine and plasma biochemistry. Urine (NH3) to form NaH2P04 and Nl 14' (measured in urine as
dipstick analysis may reveal glucosuria and proteinuria. titratable acidity and ammonium ion respectively). The
Detection of low molecular weight proteinuria (e.g. retinol distal nephron generates and maintains a steep pH
gradient between the blood and urine, but its capacity to
binding protein, (3-2 microglobulin) suggests proximal
secrete H+ ions is small. Thus, even a slight increase in
tubular dysfunction. The osmolality of early morning
distal HC03~ delivery results in increase in urine pH.
urine sample (first urine passed on awakening) is a useful
Extracellular fluid volume and potassium balance also
test of renal concentrating ability; a value of >700-800
regulate H+ secretion and HC03 reabsorption.
mOsm/kg is normal. Levels of electrolytes, calcium, creati
nine and amino acids may be measured on a random urine
Distal RTA
sample. These values are usually expressed as the solute/
creatinine ratio to allow for differences in urine concen Distal (type I) RTA is due to defective secretion of H+ in
tration. Blood levels of sodium, potassium, chloride, the distal tubule. Children present with failure to thrive,
calcium, magnesium and phosphate are determined; polyuria and polydipsia, hypokalemic muscle weakness
tubular reabsorption of phosphate and other solutes can and rickets. Ultrasonography may show nephrocalcinosis.
The condition is often sporadic, but may be inherited
be calculated. If metabolic acidosis is detected, estimation
(dominant, recessive or X-linked). There is an association
of plasma and urine anion gap and urine pH is
with systemic diseases (systemic lupus erythematosus,
recommended.
Wilson disease) and with drug toxicity (lithium, analge
sics, amphotericin B).
Table 15.11: Features suggesting renal tubular disorder
Growth retardation, failure to thrive Diagnosis: The biochemical abnormalities include hyper
Delayed motor milestones chloremic metabolic acidosis, hypokalemia, increased
Polyuria, polydipsia urinary excretion of calcium and decreased urinary citrate.
Recurrent episodes of unexplained fever, vomiting, Urinary net acid excretion (titratable acid and ammonium)
dehydration; episodic weakness is markedly reduced. Despite moderate to severe acidosis,
Rickets, bone pains patients cannot lower urine pH below 6. Proximal
Constipation bicarbonate absorption is usually normal though younger
Craving for salt and savory foods children may occasionally show some bicarbonate
Renal, ureteric calculi wasting. Measurement of the difference between urinary
and blood C02, during the passage of alkaline urine, is a
reliable indicator of distal tubular acidification. Normally
RENAL TUBULAR ACIDOSIS (RTA)
the difference is more than 20 mm Hg, provided the urine
RTA encompasses conditions characterized by a defect of pH is >7.5. In children with distal RTA, the urine to blood
renal acidification, which result in hyperchloremic C02 gradient is reduced below 10 mm Hg.
468 Essential Pediatrics
renal tubular transport mechanisms are normal. The Endemic Vesical Calculi
disorder is asymptomatic and benign. Vesical calculi are common in young boys (below 5-yr-
old) in some parts of the country, e.g. Rajasthan, Andhra
CYSTINURIA___ ____ Pradesh and north-eastern states, having become less
prevalent in most regions of the country. They are common
This autosomal recessive disorder is characterized by
in neighboring countries including Pakistan and
impaired proximal tubular reabsorption of cystine and
Afghanistan.
dibasic amino acids (ornithine, lysine and arginine).
Supersaturation of urine with cystine crystals may lead These stones are usually single, and composed of
to formation of recurrent radiopaque calculi. A high fluid ammonium acid urate and calcium oxalate. Consumption
intake and urinary alkalization should be ensured. of a predominantly cereal (wheat or jowar) based, low
Administration of penicillamine may prevent formation calcium and phosphate, and high oxalate diet is related to
of calculi. its etiology. Recurrent diarrheal episodes may contribute
by causing dehydration, and an acidic, concentrated urine.
BARTTER SYNDROME __________ A high intake of dairy products and animal proteins has
led to reduction in the prevalence of these stones. Treat
Bartter syndrome results from excessive chloride, ment is surgical with suprapubic cystolithotomy. The risk
potassium and sodium wasting in the thick ascending limb of recurrence is very low.
of the loop of Henle. Clinical features include failure to
thrive, polyuria, polydipsia and recurrent episodes of Renal Calculi
dehydration. The neonatal form of the disease is parti
These are uncommon in children. Detailed investigations
cularly severe with maternal polyhydramnios, postnatal
should be done to determine the underlying etiology. The
polyuria, dehydration, hypercalciuria and nephrocalci-
commonest metabolic cause is idiopathic hypercalciuria.
nosis. Patients show marked hypokalemia with high
Other causes include hyperoxaluria, distal RTA, hyper
urinary potassium, hypochloremic metabolic alkalosis and
parathyroidism and cystinuria. Magnesium ammonium
increased levels of plasma renin and aldosterone.
phosphate (struvite) calculi may occur due to recurrent
Hyperplasia of the juxtaglomerular apparatus is seen.
UTI, often with underlying urinary obstruction. No under
Bartter syndrome should be differentiated from other
lying cause is found in a significant proportion of cases.
conditions with persistent hypokalemic metabolic
alkalosis by the presence of normal blood pressure, and Stones less than 5-7 mm in size may pass spon
high urinary chloride and calcium excretion. Treatment taneously. Extracorporeal shock wave lithotripsy (ESWL)
with potassium chloride supplements is necessary. Use may suffice for small stones. Percutaneous nephro
of prostaglandin synthase inhibitors (indomethacin lithotomy may be appropriate in patients with relative
contraindication for ESWL or with stones too large for
2-3 mg/kg/day or ibuprofen 20-30 mg/kg/day) is
lithotripsy. Ureteroscopy is useful for distal and mid
beneficial.
ureteric calculi. Open surgery is necessary for stones more
than 3 cm in size or those with associated pelviureteric
Suggested reading
junction obstruction. UTI should be treated and a large
1. Bagga A, Dillon M. Inherited disorders of sodium and water
fluid intake ensured. Patients with idiopathic hypercalci
handling. In: Comprehensive Clinical Nephrology. Eds. Johnson
RJ, Feehally J. Mosby, London, 2000;52.1-52.12. uria may benefit from a low salt intake; dietary calcium
2. Bagga A, Bajpai A, Menon S. Approach to renal tubular disorders. restriction is not necessary. Persistent hypercalciuria is
Indian J Pediatr 2005;72(9): 771-6. treated with oral potassium citrate, an inhibitor of
3. Bagga A, Sinha A. Evaluation of renal tubular acidosis. Indian J crystallization. Thiazide diuretics reduce urine calcium
Pediatr 2007; 74(7): 679-86. excretion, reducing the risk of stone formation; their long
4. Majzoub JA, Srivatsa A. Diabetes insipidus. Pediatr Endocrinol Rev term use is, however, restricted due to side effects.
2006; 4 Suppl 1: 60-65. Prolonged alkali supplementation is necessary in patients
with distal RTA.
UROLITHIASIS
Calculus disease of the urinary tract may affect the urinary Suggested reading
bladder or kidneys. Symptoms include dysuria, hypo 1. Nicoletta JA, Lande MB. Medical evaluation and treatment of
gastric pain, hematuria and occasionally urinary infec urolithiasis. Pediatr Clin North Am 2006; 53: 479-491.
tions. Children with a metabolic abnormality are likely to 2. Durkee CT, Balcom A. Surgical management of urolithiasis. Pediatr
form recurrent and multiple stones. Ultrasonography Clin North Am 2006; 53: 465-477.
3. Mantan M, Bagga A, Virdi VS, Menon S, Hari P. Etiology of
detects most radiopaque and radiolucent calculi and
nephrocalcinosis in northern Indian children. Pediatr Nephrol 2007;
nephrocalcinosis. High resolution computerized tomo 22: 829-833.
graphy detects even minute calculi; intravenous pyelo 4. Mohamed J, Riadh M, Abdellatif N. Urolithiasis in infants. Pediatr
graphy is useful if ureteric calculus is suspected. Surg Int 2007; 23: 295-299.
470 Essential Pediatrics
asymptomatic at birth. These children need to be evaluated years, the gene loci, for many of these conditions have
with a renal ultrasound at 4-7 days of life. Neonates been identified. While improving understanding of the
showing hydronephrosis should undergo a MCU and/or pathogenesis, genetic tools have enabled rapid and precise
DTPA renal scan to detect vesicoureteric reflux and/or diagnosis of these conditions.
urinary tract obstruction, and evaluate differential renal
function. Neonates with posterior urethral valve, solitary Polycystic Kidneys
kidney or bilateral hydronephrosis and impaired renal The infantile form of polycystic kidney disease is inherited
function require prompt management. In a majority, in an autosomal recessive manner. The kidneys are large
hydronephrosis is non-obstructive and spontaneous and palpable and filled with masses of cysts. Prenatal
resolution occurs by 2-5 years of age. Most patients, ultrasound is a reliable screening procedure and may be
therefore, require a period of waiting and close clinical performed in 'at-risk' families. The onset of hypertension
and radiological follow up. Surgery is indicated in pre and renal insufficiency is in early childhood but the
sence of symptoms (e.g. abdominal mass, recurrent UTI, prognosis is variable. Congenital hepatic fibrosis may be
hypertension) or deterioration of differential renal associated and cause portal hypertension.
function. The adult form of polycystic kidneys (inheritance
Suggested reading autosomal dominant) usually manifests with episodic
hematuria, hypertension and palpable kidneys during the
third decade of life, but may present in childhood. Renal
1. Indian Pediatric Nephrology Group, Indian Academy of Pediatrics.
Consensus statement on management of antenatally detected
hydronephrosis. Indian Pediatr 2001, 38: 1244-1251. insufficiency develops gradually. Cysts may occur in the
2. Carr MC. Prenatal management of urogenital disorders. Urol Clin liver, spleen and pancreas; cardiac valvular anomalies and
North Am 2004; 31(3): 389-97. berry aneurysms of the cerebral arteries are associated.
3. Nakai H, Asanuma H, Shishido S, Kitahara S, Yasuda K. Changing
Cystic kidneys may occasionally be found on screening a
parent or grandparent.
concepts in urological management of the congenital anomalies of
kidney and urinary tract, CAKUT. Pediatr Int 2003; 45: 634-641.
4. Becker A, Baum M. Obstructive uropathy. Early Hum Dev 2006;
82: 15-22. Suggested reading
1. Griinfeld JP. Congenital/inherited kidney diseases: how to identify
HEREDITARY NEPHROPATHIES them early and how to manage them. Clin Exp Nephrol 2005; 9:
The principal hormones produced by the anterior Table 16.3: Etiology of growth hormone deficiency
pituitary are thyroid stimulating hormone (TSH), adreno Congenital
corticotropic hormone (ACTH), follicle-stimulating
hormone (FSH), luteinizing hormone (LH), growth Genetic defects:
hormone (GH) and prolactin (PRL). These hormones Isolated GH deficiency
regulate actions of adrenals (ACTH), thyroid (TSH) and Type I : Autosomal recessive
gonads (LH and FSH). The secretion of anterior pituitary Type II: Autosomal dominant
TRH) and hormones produced by the target glands. The Idiopathic GHRH deficiency
hypothalamic tropic hormones are transported to the Developmental defects: Pituitary aplasia, hypoplasia,
anterior pituitary by the hypothalamic-pituitary-hypo anencephaly, holoprosencephaly, midfacial anomalies,
physeal portal system. GH has specific growth promoting septooptic dysplasia
action on protein synthesis, skeletal growth and inter Acquired
mediary metabolism. These effects are mediated through Tumors: Hypothalamic, pituitary, other intracranial tumors
synthesis of insulin-like growth factor 1 (IGF-1). IGF-1 in Irradiation
turn circulates bound to binding proteins called IGFBP; Infections: Encephalitis, meningitis, tuberculosis, toxoplasmosis
the major one being IGFBP3. The levels of IGF-1 and Infiltration: Histiocytosis, hemochromatosis, sarcoidosis
IGFBP3 are thus surrogate markers of GH action. Injury: Perinatal insult (breech), head injury, surgery
Posterior pituitary hormones (arginine vasopressin— Vascular: Aneurysm, infarction
AVP and oxytocin) are secreted by neurons located in the GH growth hormone, GHRH growth hormone releasing
hypothalamic nuclei. AVP (also known as the antidiuretic hormone
Evaluation
The need for evaluation of a short child is based on height
and growth velocity. No work-up is required if height is
more than -2 SDS (third percentile) or growth velocity is
above 25th percentile. On the other hand, immediate
evaluation is warranted if height SDS is less than -3 (first
percentile). Children with height SDS between -2 to -3
should be followed-up. Work-up is required if growth
velocity is below 25th percentile.
History: Perinatal history, birth weight and length should
be recorded. History of birth asphyxia, breech presen
tation, neonatal hypoglycemia, and prolonged jaundice
may be the early indicators of GHD. Features of chronic
infections, cardiopulmonary disorders, malabsorption and
raised intracranial tension should be looked for. Presence
of polyuria and polydipsia suggests diabetes insipidus,
diabetes mellitus and/or renal tubular acidosis. Consti
pation, delayed milestones, lethargy and cold intolerance
are indicative of hypothyroidism. Accurate estimation of
dietary recall forms an integral part of evaluation of short
stature. Family history of short stature or delayed puberty Fig. 16.4: Achondroplasia: Note the abnormal body proportions and
may suggest the diagnosis of familial short stature (FSS) facies
or constitutional delay of puberty and growth.
Examination: The first step in evaluation is detailed anthro Table 16.4: Pointers to the etiology of short stature
pometric assessment (weight, weight for height and head Pointer Etiology
circumference). Weight loss is suggestive of nutritional Midline defects, Growth hormone deficiency
etiology (malnutrition, systemic illness, and malabsorp micropenis
tion) while weight is preserved in most endocrine dis Rickets Renal failure, malabsorption, renal
orders. Body proportions are helpful in identifying skeletal tubular acidosis
dysplasia. Lower segment (LS) is measured from the pubic Pallor Renal failure, malabsorption,
symphysis to the feet. Upper segment (US) is obtained by nutritional anemia
subtracting it from height. The US:LS ratio is 1.7:1 at birth Malnutrition Protein energy malnutrition,
and decreases by 0.07-0.1 each year to reach 1:1 by 7-10 malabsorption, celiac disease,
years of age. Increased US:LS ratio suggests hypothyroi cystic fibrosis
dism, achondroplasia (Fig. 16.4) and Turner syndrome Obesity Hypothyroidism, Cushing
4 r ......
Normal
Abnormal Hemogram, LFT, RFT, Bone age, chest X-ray,
Genetic syndrome Malabsorption studies, Blood gas
Skeletal dysplasia
v............. ............J
Normal
Thyroid profile,
Celiac serology, Karyotype in girls
Normal
IGF-1, IGFBP3
GH provocation tests
Fig. 16.5: Approach to a child with short stature. SDS standard deviation score,- LFT liver function tests; RFT renal function tests;
IGF-1 insulin-like growth factor-1, IGFBP3 IGF binding protein-3; GH growth hormone
till epiphyseal closure. The treatment is very expensive antimongoloid slant of the palpebral fissure. Mental re
and should be started only if it could be given for at least tardation is present in about 85% cases, affecting
2 years. Growth hormone has also been recommended for expressive language, motor development and attention
Turner syndrome, chronic renal failure, small for deficits. GH secretion and activity are normal. Hereditary
gestational age infants, Prader Willi syndrome and tall stature, obesity, precocious puberty, Marfan syndrome an
idiopathic short stature. lipodystrophy should be ruled out by appropriate tests.
Medical management involves the use of long acting
Suggested reading somatostatin analog like octreotide. GH receptor
1. Lifshitz F, Botero D. Worrisome growth. In: Pediatric antagonist (Pegviosomant) is also proposed for treatment.
Endocrinology, 4th edn. Eds: Lifshitz F, Marcel Dekker, New York, Partial or complete resection of pituitary adenoma is
2.
2003;l-47.
Rosenfeld GR, Cohen P. Disorders of growth hormone /insulin like
indicated if there is evidence of raised intracranial tension.
growth factor and action. In: Pediatric Endocrinology, 2nd Edn. Suggested reading
Eds: Sperling MA. Saunders, Philadelphia. 2002, 211-288.
3. Patel L, Clayton PE. Normal and disordered growth. In: Clinical Patel L, Clayton PE. Normal and disordered growth. In: Clinical
Pediatric endocrinology, 5th edn. Eds: Brook CGD, Clayton PE, Pediatric Endocrinology, 5th edition. Eds: Brook CGD, Clayton PE,
Brown RS. Blackwell Publishers, London. 2005;90-112. Brown RS, Blackwell Publishers, London. 2005;90-112.
4. Reiter EO, Rosenfeld RG. Normal and aberrant growth. In Williams
Textbook of Endocrinology, 10th edn. Eds: PR Larsen, HM DIABETES INSIPIDUS AND POLYURIA
Kronenberg, S Melmed, KS Polonsky, Philadelphia: WB Saunders.,
2003;1003-1114. Polyuria (urine output more than 5 ml/kg/hour or 2 L/
5. Bajpai A, Sharma J, Menon PSN (eds). Short Stature. In: Practical m2/day) is a common pediatric problem. Careful
Pediatric Endocrinology. Jaypee Brothers Medical Publishers Pvt evaluation of polyuria is essential, as it may be the only
Ltd, New Delhi. 2003;3-8.
manifestation of serious disease (diabetes mellitus, brain
6. Bajpai A, Menon PSN. Insulin like growth factors axis and growth
disorders. Indian J Pediatr 2006;73:67-71 tumor, renal tubular acidosis).
7. Bajpai A, Menon PS. Growth hormone therapy. Indian J Pediatr
2005;72:139-144. Physiology
Maintenance of water balance involves regulation of urine
GROWTH HORMONE EXCESS _______________ output and thirst. Thirst is controlled by the hypothalamus
Pituitary gigantism is rare in children but may be the only under the effect of osmoreceptors. Urine output is
clue to underlying pituitary adenoma, which may be determined by solute load, hydration status and urine
isolated or associated with multiple endocrine involve concentration capacity. Increased solute load as in diabetes
ments in the setting of multiple endocrine neoplasia or mellitus results in polyuria. Fluid homeostasis involves
McCune Albright syndrome. close interaction of AVP, renin-angiotensin-aldosterone
GH excess results in somatic overgrowth or gigantism. system and atrial natriuretic peptide (ANP) .AVP secreted
Its increased secretion after the fusion of skeletal epiphyses by the hypothalamus, acts on the V2 receptors in collecting
causes features of acromegaly. Features are coarse with duct to increase free water resorption. This involves
prominent jaw, broad nose, enlarged tongue, bushy eye migration of aquaporin water channels. AVP secretion is
brows, thick skin and dorsal kyphosis. Muscle weakness, regulated by plasma osmolality with minor effect of blood
bony and cartilaginous overgrowth, cardiomyopathy and volume. The renin-angiotensin-aldosterone system is central
pigmentation of skin may be present. Destruction of the to the regulation of sodium, fluid and blood pressure. The
anterior pituitary by adenoma may result in hypothy system is activated by the production of renin by the
roidism and hypogonadism. Headache, visual field defects juxtaglomerular cells in response to volume depletion and
such as bitemporal hemianopsia and enlargement of the low blood pressure. Renin acts on angiotensinogen to form
blind spot are common. angiotensin I. Angiotensin I is then converted by the
The diagnosis is based on clinical examination, serial angiotensin convertase enzyme to angiotensin II. Angio
photographs of the child, growth assessment and tensin II acts on adrenal cortex to increase aldosterone
investigations. Skull X-ray films show enlarged sella production and blood vessels to cause vasoconstriction.
turcica with erosion of the margins. Tufting of the Aldosterone acts on the distal convoluted tubule and
phalanges and increased heel pad thickness may be collecting duct to increase sodium and fluid resorption
present. CT or MRI scan determines the extent of the and potassium excretion.
tumor. GH levels are elevated to as high as 400 ng/mL; Etiology
these are not suppressed by a glucose tolerance test. Polyuria may result from increased solute load or impaired
GH excess should be differentiated from Sotos syndrome renal concentrating capacity (Table 16.5).
(cerebral gigantism) characterized by large size at birth,
excessive growth in early childhood, advanced height, Diabetes mellitus: Diabetes mellitus is an important cause
weight and bone age. The skull is large with prominent of polyuria. The condition presents with polydipsia,
forehead and jaw, high arched palate, hypertelorism and polyphagia, recurrent infections and weight loss.
478 Essential Pediatrics
Table 16.5: Causes of polyuria including tuberculosis have also been linked with the
Increased fluid intake development of central Dl.
Iatrogenic Nephrogenic Dl results from inherited or acquired
Compulsive water drinking (psychogenic polydipsia) resistance to AVP. Hypokalemia and hypercalcemia are
Increased urinary solute excretion important causes of nephrogenic Dl. The genetic defects
Osmotic diuresis—Diabetes mellitus, mannitol treatment associated with nephrogenic Dl include X-linked AVP
Salt loss—Adrenal insufficiency, diuretics, cerebral salt receptor mutation and rare autosomal recessive aquaporin
wasting, aldosterone resistance mutations. Acquired causes include obstructive uropathy,
Impaired urinary concentration nephrocalcinosis and exposure to drugs (lithium and
Inefficient AVP action (Diabetes insipidus, Dl) demeclocycline).
Central Dl (Neurogenic Dl) Inefficient aldosterone action: These conditions include
Genetic defects—Autosomal recessive, autosomal adrenal insufficiency, isolated aldosterone deficiency or
dominant, DIDMOAD syndrome
aldosterone resistance. They present with hyponatremia,
Malformations—Septo-optic dysplasia, holoprosencephaly,
hyperkalemia and dehydration. The condition may be
anencephaly
Neurological insults—Head trauma, neurosurgery,
lethal if undiagnosed. Failure to thrive is common.
infection, brain death Pigmentation is characteristic of adrenal insufficiency.
Infiltrative disorders—Sarcoidosis, histiocytosis Polyuria and salt wasting in the neonatal period should
CNS tumors—Craniopharyngioma, germinoma, prompt evaluation for congenital adrenal hyperplasia.
pinealoma Genital ambiguity in girls may be the only clue to
Nephrogenic Dl diagnosis.
Excessive water drinking: The condition is extremely rare
Genetic—X linked (V2 receptor), AR, AD (aquaporin defect)
Acquired—Hypokalemia, hypercalcemia, obstructive
uropathy, nephrocalcinosis
and is a diagnosis of exclusion. Low urine osmolality
Renal disorders
makes it difficult to differentiate from diabetes insipidus.
Renal tubular acidosis Evaluation
Bartter syndrome
Gitelman syndrome Subjective estimates of urine output and nocturia may
suggest polyuria; they however cannot substitute
measurement of 24-hour urine output (or fluid intake).
Renal disorders: While most renal parenchymal diseases
Urine output in excess of 2 L/m2/day or 5 ml/kg/hour is
present with decreased urine output; polyuria is common suggestive of polyuria. Once confirmed, the child needs
in obstructive uropathy. Polyuria is often the presenting work up for the etiology.
feature of tubular disorders like renal tubular acidosis
(RTA), Bartter syndrome and Gitelman syndrome. These Clinical: Diabetes mellitus is suggested by features like
conditions are associated with severe failure to thrive and polyphagia, recurrent infections and failure to thrive.
bony deformity. Renal tubular acidosis is suggested by acidotic breathing,
bony deformities or muscle weakness. History of head
Diabetes Insipidus trauma, neurosurgery, exposure to radiation and features
Inefficient AVP action (diabetes insipidus, Dl) is an of focal deficits and raised intracranial tension should be
important cause of polyuria. The condition presents with evaluated. Neurological and fundus examination should
low urine osmolality in the wake of high plasma osmo be performed. Careful search for features of histiocytosis
lality. Dl is due to decreased AVP production (central Dl) like ear discharge, proptosis, rash, organomegaly, lymph
or action (nephrogenic Dl). Dehydration is unusual in the adenopathy, bony defects and seborrheic dermatitis is
absence of abnormality in thirst mechanism. Infants are essential (Table 16.6).
at a high risk of developing hypernatremic dehydration. Investigations: Initial investigations should include urine
Central Dl is commonly related to intracranial pathology sugar and early morning specific gravity or osmolality.
(brain tumor, malformation, neurosurgery, trauma and Blood gas, urea, electrolytes, calcium and creatinine
infection). Craniopharyngioma presents with diabetes should be estimated. High plasma osmolality (more than
insipidus, growth retardation and skull calcification. A 300 mOsm/kg or serum sodium more than 145 mmol/L)
strategically located tumor in the pituitary stalk like and low urine osmolality (less than 300 mOsm/kg, urine
germinoma, on the other hand, may be missed on neuro specific gravity less than 1.005) is suggestive of Dl, which
imaging emphasizing the need of periodic neuroimaging. should be classified further on the basis of response to
CNS malformations such as septo-optic dysplasia and AVP. Patients with normal plasma osmolality and low
holoprosencephaly, display central Dl and anterior urine osmolality (less than 700 mOsm/kg) should undergo
pituitary defects. Histiocytosis is the commonest infiltrative water deprivation test. Urinary osmolality more than 700
disorder associated with central Dl. CNS infections mOsm/kg (specific gravity more than 1.010) excludes Dl.
Endocrine and Metabolic Disorders 479
Management
Table 16.6: Pointers to diagnosis of polyuria
Feature Diagnosis Management of polyuria is guided by the underlying
cause. Treatment of diabetes mellitus (insulin), adrenal
Mid line defects Central diabetes insipidus (DI) insufficiency (hydrocortisone) and renal tubular acidosis
Rickets Renal tubular acidosis (RTA), renal
(bicarbonate) is effective in reducing urine output.
failure
Behavioral therapy is recommended for psychological
Failure to thrive Nephrogenic DI, RTA, congenital
adrenal hyperplasia , Bartter
polydipsia.
syndrome Central DI: Central DI is managed with vasopressin
Rash, seborrhea, Histiocytosis analogs. Desmopressin, a vasopressin analog has
bone defects increased potency and prolonged duration of action. It is
Hyperpigmentation Adrenal insufficiency
given intranasal (2.5-10 mg 12 hourly) or orally (50-200
jag 12 hourly). Patients should be allowed to have at least
Muscle weakness, Hypokalemia (RTA, Bartter
one urine output before giving the next dose of the drug
neck flop syndrome)
to avoid fluid overload. Patients with idiopathic DI should
Genital ambiguity Congenital adrenal hyperplasia be followed for evolving brain tumors.
Mental retardation CNS malformations, nephrogenic DI
Nephrogenic DI: Hydrochlorothiazide-amiloride combi
nation (1-2 mg/kg/day) reduces urine output by 40%.
This paradoxical effect results from decreased delivery of
MRI of the hypothalamic-pituitary region and anterior free water to collecting ducts and distal tubule (site of AVP
pituitary evaluation should he done in central DI. action) due to increased sodium absorption in the proximal
Evaluation of nephrogenic DI includes renal imaging and tubule. Addition of indomethacin to this regimen reduces
serum electrolytes. urine output to 50-70%. This should be combined with
Water deprivation test: The test is indicated in children with salt restriction and reduction in solute load.
polyuria, low urinary osmolality and normal plasma Suggested reading
osmolality. The aim is to increase plasma osmolality above
300 mOsm/kg (or serum sodium above 145 mmol/L) to 1. Bajpai A, Sharma J, Menon PSN (eds). Diabetes insipidus. In:
allow opportunity for maximal renal concentration. Renal Practical Pediatric Endocrinology. Jaypee Brothers Medical
Publishers, New Delhi. 2003;!7-23.
failure and renal tubular acidosis should be excluded 2. Ghirardello S, Malattia C, Scagnelli P, Maghnie M. Current
before the test. Water deprivation test is not required in Perspectives on the pathogenesis of central diabetes insipidus. J
the presence of hypernatremia. The test should be done Pediatr Endocrinol Metab. 2005;18:631-45.
in an inpatient basis due to risk of dehydration. Water 3. Muglia LJ. Majzoub JA. Disorders of the posterior pituitary. In:
deprivation is started early in the morning. The child Pediatric Endocrinology, Eds: Sperling MA. WB Saunders 2002,
Philadelphia, 289-322. ’
should be weighed and target weight loss calculated (5%
of total body weight). Samples for blood sodium, potas
sium, sugar, osmolality and urine osmolality should be DISORDERS OF THYROID
obtained. Body weight, urine output and urine and blood
osmolality should be monitored hourly. The test should Thyroid hormones play an important role in the regulation
be stopped when urine osmolality increases above 700 of growth, development and homeostasis. Disorders of
mOsm/kg (or specific gravity more than 1.010; excludes thyroid glands are one of the most common pediatric
DI), plasma osmolality increases above 300 mOsm/kg (or endocrine diseases.
serum sodium above 145 mmol/L; target achieved) or
weight loss is more than 5% (risk of dehydration). Urine Physiology
osmolality below 300 mOsm/kg in the presence of plasma The thyroid gland is formed by an invagination of endo-
osmolality above 300 mOsm/kg is diagnostic of DI and derm of the foregut with a pouch in the floor of the
should be further evaluated with response to vasopressin.
Children with urine osmolality between 300-700 mOsm/ pharynx migrating to the thyroid cartilage. The gland
kg with plasma osmolality above 300 mOsm/kg may have to its position foramen
migrates from
in the
cecum located at the base of tongue
neck. Thyroid hormone biosynthesis
partial central or nephrogenic DI. involves interaction of iodine, tyrosine, thyroglobulin and
Vasopressin response test: This test is performed for thyroid peroxidase enzyme. The first step is transport of
differentiation of complete central DI from nephrogenic iodine using sodium-iodine co-transporter. Iodine is then
DI. Urine osmolality is measured one and four hours after organified to monoiodotyrosine (MIT) and diiodotyrosine
vasopressin injection. An increase in urine osmolality by (DIT). This is followed by production of T4 (by coupling
more than 50% of baseline levels is diagnostic of central of 2 DIT molecules) and T3 (by coupling of one DIT and
DI while lower increase is suggestive of nephrogenic DI. one MIT molecule). Thyroid peroxidase, the enzyme
480 Essential Pediatrics
regulating this process, is the rate-limiting enzyme in Table 16.7: Etiology of hypothyroidism
thyroid hormone synthesis. This is followed by proteolysis
and release of thyroid hormones in to the circulation. This Central
their maximum by 24 hours. Their levels fall to normal in synthesis, disordered development or destruction of
the next few weeks. TSH levels should be estimated either thyroid gland are the causes of primary hypothyroidism.
at birth or at day 3 for neonatal screening. Iodine deficiency is the commonest cause of hypo
thyroidism in certain parts of India. In certain endemic
iodine deficient areas, the incidence of congenital
Assessment of Thyroid Function
hypothyroidism is significantly higher compared to
Thyroid functions are assessed by estimation of TSH free nonendemic regions. Thyroid dysgenesis is the most com
and total T3 and T4. TSH is the most sensitive indicator of mon cause of congenital hypothyroidism in nonendemic
primary hypothyroidism but has no value in the diagnosis areas (75% of all cases). The disorder encompasses a
of central hypothyroidism. T4 levels are better indicator spectrum ranging from complete agenesis, partial agenesis
of thyroid status than T3 due to increased conversion of and ectopic thyroid. As most of these disorders are
T4 to T3 during thyroid deplete state. Considering the sporadic, no genetic association has been observed.
wide variability in the levels of circulating thyroid binding Increased incidence of thyroid dysgenesis is noted in
globulin (TBG), estimation of free thyroid hormone is Down syndrome. Biosynthetic defects include disorders
superior to total levels in the diagnosis of hypothyroidism. affecting iodine transport, peroxidation, thyroglobulin
Low FT4 and TSH levels are suggestive of central hypo synthesis and deiodination. Pendred syndrome, a disorder
thyroidism while high TSH levels indicate primary hypo of the pendrin gene, is associated with decreased
thyroidism. Repeated elevation in TSH in the presence of intracellular transport of iodine and deafness. Thyroid
normal FT4 is suggestive of compensated primary enlargement is common and takes the form of smooth
hypothyroidism. rounded colloid goiter. Transient congenital hypothyroi
dism may occur following transplacental passage of TSH
HYPOTHYROIDISM receptor blocking antibodies, iodine exposure and
treatment with drugs like amiodarone.
Decreased production of thyroid hormones has significant
impact on growth and development. Thus while untreated Autoimmune thyroiditis is the most common cause of
congenital hypothyroidism has devastating intellectual acquired hypothyroidism. The disorder is more common
and developmental consequences, acquired hypothy in girls and presents with subtle clinical features. Short
stature may be the only manifestation. Goiter is often
roidism adversely affects growth and school performance. nodular and firm in contradistinction to the soft and uni
form goiter in patients with dyshormonogenesis. Thyroid
Etiology
peroxidase and thyroglobulin antibodies are usually
Hypothyroidism could be caused by defects in the present. Autoimmune thyroiditis may be associated with
hypothalamus, pituitary, thyroid gland or in the other autoimmune endocrinopathies like adrenal insuffi
peripheral sensitivity to thyroxin (Table 16.7). ciency, type 1 diabetes mellitus and hypoparathyroidism.
Endocrine and Metabolic Disorders 481
Table 16.13: Estimation of thyroid size by palpation of iodine deficiency disorders and working to ensure that
Stage 0 No goiter only iodized salt will be used in India. The recommended
Stage 1A Goiter detectable only by palpation and not
daily intake of iodine is 40-120 |ig for children up to the age
visible even when the neck is fully extended. of 10; 150 |j.g for older children and ad ults and an additional
Stage IB Goiter palpable but visible only when the neck 25 and 50 |ag during pregnancy and lactation respectively.
is fully extended (this stage also includes Based on an assumption of a mean intake of salt of 5 gm/
nodular glands even if not goitrous). day, the recommended level of iodination is one part of
Stage 2 Goiter visible when the neck is in normal iodine in 25,000 to 50,000 parts of salt.
position; palpation not needed for diagnosis.
Stage 3 Very large goiter, which can be recognized at a HYPERTHYROIDISM
considerable distance.
Hyperthyroidism is uncommon in children. It is most com
monly seen in young girls, caused by Graves disease (Ta
Table 16.14: Classification of severity of iodine deficiency ble 16.15).
Grade I Mean daily urinary excretion of more than 50
(ig but less than 100 ng iodine per 24 hr, per
Table 16.15: Etiology of hyperthyroidism
gm of creatinine or per liter of urine. At this
Infancy
level goiter will be rare.
Transplacental passage of thyroid antibodies
Grade II Mean daily excretion between 25-50 ng per 24
TSH receptor activating mutation
hrs, per gm of creatinine or per liter of urine.
At this level goiter is frequent with nodular After infancy
goiter and hypothyroidism of varying degrees. Graves disease (TSH receptor stimulating antibody)
Grade III Mean daily excretion below 25 fig per 24 hrs, Release of preformed thyroid hormone - Subacute thyroiditis
per gm of creatinine or per liter of urine. Goiter Toxic thyroid nodule, toxic multinodular goiter
will be frequent and cretinism is very common Iatrogenic
at this level Pituitary resistance to T3
Endemic cretinism is a disorder associated with endemic The condition should be suspected in children with
goiter and severe iodine deficiency with characteristic weight loss with increased appetite, tremors, diarrhea,
clinical features, which include deafmutism, squint, warm extremities, increased sweating and anxiety. Inabi
mental retardation and characteristic spastic or rigid lity to concentrate, personality changes, mood instability
neuromotor disorder. Two types of endemic cretinism and poor school performance are common. The diagnosis
are described. The neurological cretinism is characterized is confirmed by the demonstration of elevated serum free
by deaf-mutism, squint, proximal spasticity and rigidity T4 and T3 levels. Frequently serum T4 levels may remain
more in the lower extremities, disorders of stance and gait normal with elevated serum T3 (T3 toxicosis). Clinical
with preservation of vegetative functions, occasional signs examination reveals firm homogeneous goiter. Eye signs
of cerebellar or oculomotor disturbance and severe mental are common and are related to sympathetic overactivity
deficiency. Myxedematous cretinism is characterized by (lid lag, ophthalmoplegia, absence of wrinkling) or auto
retarded psychomotor development, severe short stature, immune infiltration (chemosis, proptosis). Tachycardia,
coarse facial features and myxedema without deafmutism. cardiac arrhythmia and high output cardiac failure may
The pathogenesis of endemic cretinism is poorly occur.
understood. Iodine deficiency is also associated with poor The presence of goiter, infiltrative eye signs and hyper
school performance in children and recurrent pregnancy thyroidism is suggestive of Graves disease. Absence of
loss in women. goiter should raise the possibility of transient hyper
thyroidism as part of autoimmune thyroiditis. TSH levels
Prevention and Control are usually undetectable in Graves disease. Ultrasono
Iodine deficiency disorders are best prevented as treatment graphy, nuclear scan and RAIU are helpful in diagnosing
is usually ineffective. Iodinated salt or iodized oil are highly toxic nodule or diffuse goiter.
efficacious in preventing iodine deficiency. Goiters while Antithyroid drugs are ineffective in the acute phase due
on treatment may shrink with appearance of nodules. to significant lag period in their onset of action. Treatment
Treatment of endemic cretinism may eliminate signs of with propylthiouracil (5 mg/kg/day) is preferred to
hypothyroidism but neuromotor and intellectual defi methimazole (0.5 mg/kg/day) in the acute stage. Beta
ciency are irreversible. Surgical removal of large goiters is blockers (propranolol 2 mg/kg/day in two divided dose)
useful in airway obstruction and for cosmetic reasons. are effective in amelioration of sympathetic symptoms.
The National Goiter Control Program of the Ministry of Iodinated contrast (idopate 0.001 |ag/kg/day) and Lugol's
Health in India began in 1962 with the establishment of salt iodine (5% iodine and 10% potassium iodide; 126 mg/ml
iodination plants. The program is directed towards control iodine, 1 drop 8 hourly) are effective in reversal of features
486 Essential Pediatrics
of hyperthyroidism. Prednisolone (1-2 mg/kg/day) in calcium levels, lowers serum calcium levels by decreasing
hibits peripheral conversion of T4 to T3 and is useful in bone resorption and increasing urinary calcium excretion.
treatment of hyperthyroid storm. Cardiac failure
refractory to these measures requires treatment with HYPOCALCEMIA
digitalis. Hypocalcemia (total calcium lower than 8 mg/dL) is an
Surgery and radioiodine ablation should be considered important metabolic condition. Estimation of ionic calcium
in patients showing failure of medical management. is important for confirmation of hypocalcemia (ionic
Patients with large or toxic nodular goiter require partial calcium less than 1.1 mmol/L). Empirical formula for
or total thyroidectomy. Radioiodine (I131) is now calculation of ionic calcium may be used if ionic levels
increasingly used in the management. are not available.
Congenital hyperthyroidism: One percent of babies born to
mothers with Graves disease show fetal thyrotoxicosis and Ionized Ca = Total Ca -0.8 x (albumin g/dL -4)
cardiac failure. Management includes maternal anti Clinical Features
thyroid drugs and digitalis. Presentation usually occurs
within the first week of life but may be delayed if mother In the neonatal period, subtle clinical features like lethargy,
is on antithyroid medications or has concomitant TSH jitteriness and poor feeding are characteristic of hypo
receptor blocking antibody. Treatment should include calcemia. Seizures are common and hypocalcemia is the
antithyroid drugs, propranolol and corticosteroids. The commonest biochemical abnormality associated with
condition is self-limiting and resolves over 3-6 months. neonatal seizures. In the postneonatal period, the
commonest presentation is with tetany (simultaneous
contraction of groups of muscles). This is most commonly
DISORDERS OF CALCIUM METABOLISM
observed in hands (adduction of thumbs along with
extension of the proximal interphalangeal joints and
Calcium plays an important role in the regulation of neuro flexion of distal interphalangeal joints) and feet (flexion
transmission, muscular contractility, cardiac function and and internal rotation of lower limbs) resulting in
hormone signaling. Disorders of calcium homeostasis carpopedal spasm. In milder cases, latent tetany can be
present as acute emergency as well as a chronic disorder. detected by tests of neuromuscular excitability. Tapping
of facial nerve at the angle of jaw results in contraction of
facial muscles (Chvostek sign). Inflating blood pressure
Physiology cuff above the systolic blood pressure for more than 5
Calcium homeostasis involves interaction of gastro minutes triggers spasm of the hand muscles (Trousseau
intestinal absorption, bone resorption and renal excretion. sign). Severe hypocalcemia presents with laryngeal spasm
Most body calcium (99%) is stored in the bone and is in and cardiac failure. Hypocalcemia should be considered
constant equilibrium with serum calcium. Regulation of in children with seizures, dilated cardiomyopathy and
bone resorption is responsible for acute calcium homeos unexplained stridor. The diagnosis is confirmed by the
tasis while renal excretion and gastrointestinal absorption demonstration of prolonged QT interval on ECG (Q„TC
regulates chronic calcium status. Parathyroid hormone more than 0.2 seconds).
(PTH), vitamin D and calcitonin are the key regulators of Q„TC = Q„TV ,RR
calcium metabolism. Calcium sensing receptor present in (Q„T = Interval from beginning of Q wave to beginning of T wave;
the parathyroid gland and kidneys senses serum calcium RR = RR interval)
levels. Reduced action of the receptor in the presence of
low serum calcium levels results in increased PTH Etiology
secretion and inhibition of renal calcium excretion. PTH Hypocalcemia may be caused by chelation of calcium or
increases serum calcium by stimulating bone resorption inefficient PTH or vitamin D (Table 16.16) action.
(osteoblast), calcitriol production (proximal tubule) and PTH related: Inefficient PTH action caused by decreased
renal calcium resorption (distal tubule). PTH also increases production (hypoparathyroidism) or action (pseudohypo
phosphate excretion resulting in hypophosphatemia. parathyroidism) is an important cause of hypocalcemia.
Calcitriol is the only hormone that regulates calcium
absorption. Calcitriol is formed by activation of vitamin These disorders are characterized by high phosphate levels
D in the liver (25-hydroxylation) and kidney (1-hydroxy- due to impaired phosphaturic action of PTH. Hypopara
lation). Sunlight is the major source of vitamin D with thyroidism may occur as part of congenital malformation
minor contribution from dietary sources, la-hydroxylase (isolated or genetic syndromes) or acquired destruction
enzyme in the kidneys is the rate limiting step of calcitriol of the parathyroid glands (autoimmune, infiltration or
synthesis. The activity of the enzyme is affected by serum surgery).
calcium, PTH and vitamin D levels. Calcitonin, secreted Autoimmune hypoparathyroidism is the most common form
by the parafollicular cells of thyroid in response to elevated in older children and frequently associated with
Endocrine and Metabolic Disorders 487
Table 16.16: Etiology of hypocalcemia periods of rapid bone growth (4-8 weeks of life). VDDR
PTH deficiency (Hypoparathyroidism)
presents with early onset severe hypocalcemia and rickets.
Aplasia: DiGeorge syndrome Increased chelation: Increased calcium binding results in
Autoimmune destruction: Polyglandular autoimmune disorders reduction of ionic calcium and features of hypocalcemia.
I and II This is most commonly related to high phosphate levels
Infiltration: Wilson disease, hemochromatosis, thalassemia
(renal failure or release of intracellular phosphate due to
Transient: Hypomagnesemia, maternal hyperparathyroidism,
post-surgery
hemolysis, tumor lysis or rhabdomyolyis). Increased
phosphate levels in cow's milk and commercial formula
PTH resistance (Pseudohypoparathyroidism) is an important cause of neonatal hypocalcemia. Metabolic
Vitamin D deficiency or respiratory alkalosis increases albumin binding of calcium
Nutritional: Poor intake, malabsorption resulting in hypocalcemia.
la-hydroxylase deficiency: Renal failure, VDDR I
II
Calcitriol resistance: VDDR Evaluation
Increased inactivation: Phenytoin, phenobarbitone
Evaluation is directed towards identification of etiology
Chelation and assessment of the severity of illness.
Phosphate load
Tumor lyses Clinical: Adequacy of airway, breathing and circulation
Rhabdomyolyis should be assessed. Detailed history of the age of onset,
Top feeds presenting features, frequency of episodes of hypocalcemia
VDDR: Vitamin D dependent rickets and family history should be obtained. Neonates should be
screened for prematurity, birth asphyxia, maternal
hyperparathyroidism and initiation of top feeds. History
autoimmune polyendocrinopathy type 1. DiGeorge suggestive of renal failure, liver disease, malnutrition,
syndrome characterized by abnormal development of decreased exposure to sunlight indicates vitamin D related
third and fourth pharyngeal pouches, is caused by deletion causes. Congestive cardiac failure, recurrent infections and
of part of chromosome 22q. This results in maldevelop- abnormal facies are suggestive of DiGeorge syndrome.
ment of thymus (resulting in T cell immunodeficiency),
parathyroid (resulting in hypoparathyroidism), heart Investigations: Initial evaluation should include serum
(resulting in conotruncal defects) and face (abnormal phosphate levels, renal and liver function tests and serum
facies). alkaline phosphatase (Table 16.17, Fig. 16.9). Phosphate
regulation is dependent on PTH and inefficient PTH action
Hypomagnesemia is an important cause of transient results in hyperphosphatemia. Hypocalcemia due to
hypoparathyroidism and should be excluded in children decreased vitamin D action is associated with secondary
with refractory hypocalcemia. hyperparathyroidism and low phosphate levels. Thus
PTH resistance (pseudohypoparathyroidism, PHP), is caused hypocalcemia with hyperphosphatemia in the absence of
phosphate load
by inactivating mutation in the gene encoding for stimu renal function suggests (exogenous or tissue lysis) and normal
latory subunit of G protein (Gsa). This presents with magnesemia should be considered parathyroid insufficiency. Hypo
clinical features of hypoparathyroidism in the wake of tory hypocalcemia and normal orin low patients with refrac
elevated PTH levels. PHP may be associated with the 25-hydroxyvitamin D levels should bephosphate levels.
measured in
phenotype of Albright's hereditary osteodystrophy (AHO) children with rickets to identify vitamin D deficiency.
such as round facies, brachydactyly, short stature, obesity,
short fourth and fifth metacarpals (brachymetacarpia), Therapeutic
are not
trial to vitamin D may be used if these levels
available. No response to vitamin D should prompt
subcutaneous calcifications and various bony deformities. evaluation for renal failure, renal tubular acidosis, liver
Vitamin D related: Vitamin D deficiency (nutritional, disease and malabsorption. Normal work-up for these
malabsorption), decreased la-hydroxylase action (renal conditions is suggestive of vitamin D dependent rickets.
failure, vitamin D dependent rickets - VDDR I), increased
inactivation of vitamin D (antiepileptic drugs) and Management
calcitriol resistance (VDDR II) are associated with When the clinical picture is suggestive of hypocalcemia
hypocalcemia. Phosphate levels are low due to secondary and tests are not available, parenteral calcium should be
hyperparathyroidism. Vitamin D deficiency is the most administered (2 mL/kg intravenously over 5-10 minutes)
common cause of hypocalcemia in children. The condition after obtaining blood sample for calcium. Calcium
usually presents in infancy or adolescence. Rickets may gluconate (5% 9 mg calcium per mL) is the preparation of
be absent. Maternal vitamin D deficiency is common in choice. Care should be taken to administer the drug slowly
India and results in reduced calcium and vitamin D stores (to avoid cardiac effects) and avoid extravasation (to
in children. These infants develop hypocalcemia during prevent skin necrosis). Parenteral calcium should be
488 Essential Pediatrics
Serum phosphate
High
Renal failure
Rickets Phosphate load
Hypoparathyroidism
Pseudohypoparathyroidism
Vitamin D deficiency
Vitamin D dependent
rickets
Fig. 16.9 : Evaluation of a child with hypocalcemia. Investigation include estimates of blood levels of phosphate, creatinine, magnesium and
parathormone. Levels of vitamin D metabolites may also require to be determined
started at a dose of 80 mg/kg/day and should be e.g. William syndrome (supravalvular aortic stenosis, ab
gradually tapered over two days. Oral calcium carbonate normal facies) or hypophosphatasia (inactivating muta
should be started from day 2. Short course activated tion of alkaline phosphatase). Vitamin D related
vitamin D (calcitriol or la-vitamin D, 20-^10 ng/kg/day hypercalcemia most commonly occurs in patients with
in three divided doses for 2 days) should be given to overdose of vitamin D. Increased la-hydroxylase activity
children with vitamin D deficiency and acute hypo may occur in patients with granulomatous diseases
calcemia. This should be combined with high dose vitamin (tuberculosis, sarcoidosis) or fat necrosis.
D (300,000- 600,000 IU) to replenish body stores of the Clinical features are often nonspecific, including
vitamin. Long term management for PTH defective states muscular weakness, anorexia, nausea, vomiting, consti
includes activated vitamin D (30-60 ng/kg/day) and pation, polydipsia and polyuria. Ectopic calcification in
calcium (50 mg/kg/day) in the form of calcium carbonate. the kidney, basal ganglia and skin are common. Bony
VDDR is managed with activated vitamin D and calcium deformities and pathological fractures may be present.
phosphate. Higher doses of vitamin D may be required in Infants present with failure to thrive, poor feeding,
patients with VDDR II. hypotonia and seizures. Serum total and ionized calcium
levels are elevated with low levels of phosphate.
HYPERCALCEMIA Hyperparathyroidism is associated with elevated levels
Hypercalcemia (serum calcium more than 11 mg/dL) is of parathormone (PTH).
rare in children. Its causes include increased bone intake followed byacute
Treatment of hypercalcemia involves high fluid
resorption (hyperparathyroidism, malignancy and and antiresorptive agents are(1indicated
frusemide mg/kg). Bisphosphonates
if there is no
immobilization) or excessive vitamin D action (iatrogenic response to these measures. Hemodialysis may be
excess; increased lcx-hydroxylase activity). required in refractory cases. Surgical exploration is
Hyperparathyroidism is the commonest cause of chronic indicated in all cases of hyperparathyroidism. The glands
hypercalcemia in children. Homozygous inactivating should be carefully inspected and adenoma, if present,
mutations of the calcium sensing receptor present with should be removed. Short course of glucocorticoids
severe neonatal hyperparathyroidism. Parathyroid (prednisolone 2 mg/kg/day for 3 weeks) is indicated in
adenoma is rare before the age of 10 years. Rarely, children with iatrogenic vitamin D excess or increased la-
hypercalcemia may be associated with other conditions, alpha hydroxylase action (fat necrosis or sarcoidosis).
Endocrine and Metabolic Disorders 489
Cushing Syndrome
DISORDERS OF ADRENAL GLANDS
Classic features of Cushing syndrome such as central
The adrenal cortex produces important hormones obesity, striae, moon facies and buffalo hump are rare in
involved in the regulation of fluid and electrolyte children (Fig. 16.10). Growth failure and obesity are
homeostasis, glucose regulation and response to stress. common; other features include hypertension, hirsutism,
delayed puberty, behavioral problems, bone pain and
Physiology muscle weakness.
Adrenal cortex produces three important groups of
hormones—the glucocorticoids, mineralocorticoids and
androgens. The outermost zona glomerulosa synthesizes
aldosterone, while the zona reticularis and fasciculata
synthesize glucocorticoids (cortisol) and androgens
(dehydroepiandrosterone—DHEA, and androstene-
dione). The process of steroidogenesis involves conversion
of cholesterol to steroid hormones through a series of
enzymatic processes. Cholesterol is transferred into the
mitochondria in a process mediated by the steroidogenic
acute regulatory protein (StAR), an ACTH-dependent
protein. The most clinically relevant step in steroido
genesis is 21-hydroxylation of progesterone and 17-hydro-
xyprogesterone (170HP) to deoxicorticosterone (DOC) Fig. 16.10: Cushing disease secondary to pituitary adenoma: Note
and 11-deoxicorticosterone (11DOC) respectively. This is the moon face and hypertrichosis over forehead and upper lip
mediated by the enzyme 21-hydroxylase (P450c21) and is
crucial for the production of cortisol and aldosterone.
Cortisol, the major glucocorticoid hormone has an
Cushing syndrome may be caused by increased
important role in intermediary metabolism causing endogenous production or exogenous administration
increased blood glucose levels and enhanced catabolism (Table 16.18). Prolonged steroid treatment is the
of proteins and lipids. Aldosterone acts on distal renal commonest cause of childhood Cushing syndrome.
tubules and collecting ducts of kidneys to promote sodium Increased adrenal glucocorticoid production may be
and fluid reabsorption. Aldosterone deficiency causes related to increased ACTH levels or represent autonomous
urinary salt wasting resulting in salt wasting crisis. adrenal hyperfunction. Adrenal pathology is more likely
Hyponatremia, hyperkalemia and metabolic acidosis are in young children, while pituitary causes are common
characteristic. Adrenal androgens are necessary for the after puberty. Ectopic ACTH production is rare.
development of pubic and axillary hair.
Adrenocorticotropic hormone (ACTH), a polypeptide Table 16.18: Etiology of Cushing syndrome
secreted by the anterior pituitary, is the principle regulator ACTH dependent causes
of glucocorticoid and androgen synthesis. Intravascular
volume, serum potassium levels and renin-angiotensin Hypothalamic lesions: Increased CRH production
system are the chief regulators of aldosterone synthesis. Pituitary lesions: Microadenoma, macroadenoma
Ectopic lesions: Neuroblastoma, carcinoid tumor, Wilms tumor
ACTH has only a minor role in aldosterone regulation.
ACTH deficiency is therefore not associated with salt ACTH independent causes
wasting crisis. ACTH secretion is stimulated by hypo Adrenal tumor: Carcinoma, adenoma
thalamic CRH and suppressed by cortisol as part of Pigmented nodular hyperplasia
feedback loop. McCune Albright syndrome
Exogenous administration
ADRENOCORTICAL HYPERFUNCTION Glucocorticoids: Oral, parenteral, topical, inhaled ACTH
AND CUSHING SYNDROME
carcinomas tend to secrete excess cortisol, mineralo- measurement of serum cortisol after eight doses of oral
corticoids and androgens. The likelihood of adrenal car dexamethasone (5 (ig/kg per dose, every six hours for two
cinoma is higher in children with early age at onset, rapid days or 1.25 mg/m2/day divided into four doses given
progression, concomitant hyperandrogenism and a large over two days). Serum cortisol levels >5 |ig/dL is diagnos
abdominal mass. tic of Cushing syndrome.
The most important part of evaluation of a child with
ACTH-dependent causes: Increased pituitary ACTH produc
Cushing syndrome is to differentiate ACTH-dependent
tion is the chief cause of endogenous Cushing syndrome.
causes from autonomous adrenal steroid production
Pigmentation due to increased melanocyte stimulating
(Table 16.20). ACTH levels differentiate ACTH-indepen-
hormone is observed. Severe hypertension and hyper
dent (ACTH levels <5 pg/mL) from ACTH-dependent
androgenism is uncommon. Pituitary microadenoma
conditions (ACTH levels >15 pg/mL). Ectopic ACTH
accounts for most cases of childhood ACTH-dependent
production should be suspected in children with
Cushing syndrome. Ectopic ACTH production is rare.
extremely high ACTH levels (>100 pg/mL). High dose
Exogenous causes: Prolonged intake of ACTH, hydro dexamethasone suppression test is based on the principle
cortisone or analogs results in similar features. that high doses of this agent suppress ACTH production
Investigations are directed towards confirming the in individuals with pituitary lesions but not in those with
diagnosis of Cushing syndrome and finding the etiology. ectopic ACTH production. The test involves estimation
The commonly used screening tests include assessment of cortisol levels after eight doses of dexamethasone (20
of diurnal cortisol rhythm, overnight dexamethasone |ig/kg/dose every 6 hours for 2 days or 3.75 mg/m2/day
suppression test and urine free cortisol (Table 16.19). Loss divided into four doses given over two days).
of diurnal rhythm is the earliest marker of hypercorti- Adrenal tumors in children are usually large and
solism. Estimation of morning and evening cortisol has identifiable on ultrasound. Size greater than 10 cm,
been used for screening of Cushing syndrome. Individual vascular invasion, loss of capsule and elevated metabolites
variation in cortisol levels limits the diagnostic value of (dehydroepiandrosterone sulphate, androstenedione and
this test. The estimation of midnight cortisol, the time of 17-OHP) are suggestive of carcinoma. Magnetic resonance
physiological nadir of cortisol, is a useful screening test imaging of the hypothalamic-pituitary region should be
for Cushing syndrome. Overnight dexamethasone sup performed in children with ACTH-dependent Cushing
pression test involves estimation of cortisol levels after a syndrome. Inferior petrosal sinus sampling is the test for
^ single midnight dose of dexamethasone (0.3 mg/m2; identifying the source of ACTH production and should
I maximum dose 1 mg). Lack of suppression of cortisol be performed in children with ACTH-dependent Cushing
levels to less than 5 |ig/dL favors the diagnosis of Cushing syndrome with normal neuroimaging.
II syndrome. 24-hr urine free cortisol is a useful screening Resection of adrenal lesion is recommended for adrenal
I test; levels >75 |ag/m2/day are highly suggestive. Low adenoma and carcinoma. Prolonged cortisol excess causes
W dose dexamethasone suppression test is commonly used suppression of the normal contralateral adrenal gland.
for confirmation of the diagnosis. This involves This mandates close monitoring for adrenal insufficiency
* Diagnostic of Cushing syndrome if levels greater than 3 to 4 times the normal range
UFC - 24-hour urine free cortisol, HDDST- High dose dexamethasone suppression test, ACTH- Adrenocorticotropic hormone,
CRH- Corticotrophin releasing hormone
Endocrine and Metabolic Disorders 491
in the perioperative period. Adrenal carcinoma is highly dexamethasone suppression suggests GRA; no effect is
malignant and has a high rate of recurrence. Pigmented seen in primary hyperaldosteronism. Diagnosis of primary
nodular hyperplasia should be treated with bilateral hyperaldosteronism should be confirmed by adrenal
adrenalectomy. Trans-sphenoidal resection of pituitary imaging.
adenoma is recommended for Cushing disease. Hyperaldosteronism should be managed with salt
Medical management of Cushing syndrome with inhi restriction and anti-aldosterone agents, spironolactone or
bitors of steroidogenesis (ketoconazole, aminogluthemide, eplerenone. Physiological hydrocortisone replacement
cyproheptadine, metyrapone, mitotane) has been tried suppresses ACTH secretion in GRA resulting in resolution
with variable results. of hyperaldosteronism and hypertension. Surgery is the
treatment of choice for adrenal adenoma.
ALDOSTERONE EXCESS
Primary hyperaldosteronism due to increased adrenal al PHEOCHROMOCYTOMA
dosterone production is extremely rare. Secondary Pheochromocytoma is a catecholamine-secreting tumor,
hyperaldosteronism results from factors that activate arising from the chromaffin cells of adrenal medulla. It
renin-angiotensin system. can also arise from the abdominal sympathetic chain,
Primary hyperaldosteronism may be caused by diffuse periadrenal area, or in the thoracic cavity. The condition
hyperplasia or adenoma. Glucocorticoid-remediable aldois extremely rare in children and co-exits with other
steronism (GRA), a genetic disorder involving switch of syndromes such as neurofibromatosis, von Hippel Lindau
Cypll and CypllAS gene, is characterized by regulation disease and multiple endocrine neoplasia type II.
of aldosterone secretion by ACTH resulting in hyper Excessive secretion of catecholamines results in hyper
aldosteronism. Primary hyperaldosteronism should be tension, which is usually sustained and occasionally paro
differentiated from secondary hyperaldosteronism (renal xysmal. The clinical symptoms include headache, palpita
failure, congestive cardiac failure, liver disease and neph tion, pallor, sweating, nausea, vomiting, visual distur
rotic syndrome) and apparent mineralocorticoid excess bances and occasionally convulsions. The diagnosis
(Liddle syndrome, deficiencies of ll|3-hydroxysteroid should be considered only after other common causes of
dehydrogenase, and congenital adrenal hyperplasia due childhood hypertension like renal parenchymal disorders,
to deficiency of 11 (3-hydroxylase and 17a-hydroxylase) renal artery stenosis and coarctation of aorta have been
(Table 16.21). excluded. Diagnosis is established by demonstration of
increased urinary excretion of catecholamines and their
derivatives. Ultrasound, CT scan, MRI scan, and 123IMIBG
Table 16.21: Etiology of hyperaldosteronism (metaiodiobenzylguanidine) scintigraphy are used for
Primary hyperaldosteronism localization. Often the tumors are multiple.
Adenoma, hyperplasia
Surgery is the treatment of choice. Transabdominal
Glucocorticoid remediable hyperaldosteronism exploration of all the sites with removal of tumors is advo
cated. Preoperative alpha blockade is needed and earlier
Secondary hyperaldosteronism
phenoxybenzamine and prazosin were used. Recently
Renal artery stenosis, renin secreting tumor calcium channel blocking agents have been used success
Cardiac failure, nephrotic syndrome, liver disease fully.
Apparent mineralocorticoid excess
ADRENAL INSUFFICIENCY
Liddle syndrome
Congenital adrenal hyperplasia, ll|3-hydroxysteroid Adrenal insufficiency may be related to adrenal loss (pri
dehydrogenase mary adrenal insufficiency; autoimmune destruction, in
fection, hemorrhage), decreased ACTH production (secon
dary adrenal insufficiency) or ACTH resistance.
Hyperaldosteronism is associated with fluid and Autoimmune adrenal dysfunction is the commonest cause
sodium retention along with increased urinary loss of of primary adrenal failure (Addison disease). Autoimmune
potassium. The most common clinical features of primary adrenal failure is often associated with autoimmune
hyperaldosteronism are hypertension and hypokalemic polyendocrinopathies type 1 and 2. Infections like tuber
alkalosis. culosis and HIV are associated with primary adrenal
Hypokalemic alkalosis in a child with low renin hyper failure. Adrenal hemorrhage in the setting of meningoco
tension should prompt evaluation for true or apparent ccal and other bacterial infections (Waterhouse-
aldosterone excess. High aldosterone level in this setting Friderichsen syndrome) is an important cause of insuffi
is suggestive of primary hyperaldosteronism or GRA. The ciency. Congenital adrenal hypoplasia and steroidogenic
conditions may be differentiated by dexamethasone defects (StAR, 21-hydroxylase and 3(3-hydroxysteroid
suppression test. Decrease in aldosterone levels and dehydrogenase deficiencies) present with adrenal insuffi
resolution of clinical and laboratory features after ciency in the neonatal period. Secondary adrenal
492 Essential Pediatrics
insufficiency is caused by congenital malformations should continue throughout the period of stress. Patients
(holoprosencephaly, midline defects) genetic defects or with secondary adrenal insufficiency require lower dose
acquired insult (neurosurgery, tumor, radiation). This is of glucocorticoids (6-10 mg/m2/day); mineralocorticoid
usually associated with other anterior pituitary hormone replacement is not necessary.
deficiency as well. Mineralocorticoid function is preserved
and salt wasting is not observed. Prolonged steroid CONGENITAL ADRENAL HYPERPLASIA
treatment is associated with suppression of the hypo
thalamic-pituitary axis resulting in adrenal insufficiency Congenital adrenal hyperplasia (CAH), a group of
after discontinuation of medications. autosomal recessive defects in steroid synthesis, is
Defects in steroid synthesis and congenital adrenal characterized by deficiency of adrenocortical hormones
hypoplasia manifest in the early neonatal period with on one hand and excess of steroid precursors on the other
polyuria, failure to thrive, recurrent vomiting and shock. (Fig 16.11). CAH is the commonest adrenal disorder in
Acquired adrenal insufficiency presents with slowly childhood.
progressive lethargy, vomiting, salt craving, fatigue,
postural hypotension, fasting hypoglycemia and episodes 21-hydroxylase Deficiency
of shock during severe illness. Adrenal insufficiency is 21-hydroxylase deficiency is the commonest form of CAH
manifest only after 90% of adrenal is damaged. The clinico- accounting for over 90% of all cases. This disorder is
biochemical picture of shock, hyponatremia, hyperkale associated with diminished synthesis of the cortisol and
mia, and hemoconcentration is characteristic of acute aldosterone. Low cortisol levels stimulate ACTH
adrenal insufficiency and warrants immediate steroid synthesis. Elevated ACTH level causes accumulation of
replacement. Primary adrenal insufficiency is characteri steroid precursors (DHEA, androstenedione and 170HP).
zed by hyperpigmentation due to elevated levels of MSH. There is wide variation in presentation of 21-hydroxylase
Hyperpigmentation is present in sun-exposed areas as deficiency ranging from acute life threatening salt wasting
elbows and palmar creases and areas that are normally crises to virilization and premature adrenarche. The
hyperpigmented such as areola and genitalia. disease forms a spectrum of presentation ranging from
All patients suspected to have adrenal insufficiency severe form presenting in the neonatal period with salt
should have urgent serum electrolytes and blood sugar wasting crisis to milder form presenting with virilization
test. Basal levels of cortisol are low but can be in the normal alone to mild hyperandrogenism in late childhood.
range. Elevated plasma renin activity (PRA) indicates Salt wasting (SW)form: These patients are the most severely
mineralocorticoid deficiency. ACTH stimulation test affected and present in the neonatal period with
(cortisol estimation 60 minutes after 0.25 mg of ACTH virilization and salt wasting. Diagnosis is often missed in
injection IM) is the best test for adrenocortical reserve. boys as they lack specific clinical features. They present
Serum cortisol levels lower than 18 |ig/dl are suggestive after second week of life with failure to thrive, polyuria,
of adrenal insufficiency. The next step in evaluation of hyperpigmentation, and shock. Early diagnosis is man
adrenal insufficiency is estimation of ACTH levels. datory to prevent mortality. 21-hydroxylase deficiency
Elevated ACTH levels suggest primary adrenal pathology should be suspected in neonates with ambiguous genitalia,
while low levels points towards pituitary defect. Further polyuria, shock, recurrent vomiting and features of sepsis
evaluation of primary adrenal insufficiency includes with negative septic screen. The diagnosis should be
abdominal CT scan, estimation of anti-adrenal antibodies confirmed immediately by hormonal assay. If these are
and workup for tuberculosis. not available, the child should be managed empirically in
The initial management of salt wasting crisis includes the lines of adrenal insufficiency.
correction of shock by fluid boluses. Hydrocortisone is
given immediately at a dose of 50 mg/m2 followed by 100 Simple virilizing (SV) form: A subset of patients with 21-
mg/m2/day. Frequent monitoring of hemodynamic para hydroxylase deficiency (25%) synthesize enough aldo
meters, urine output and serum electrolytes are required. sterone to prevent adrenal crises. These patients have
Once the child is hemodynamically stable, hydrocortisone features of androgen excess in the form of virilization in
can be tapered to the physiological dose (10 mg/m2/day). girls and peripheral precocious puberty in boys (Fig. 16.12).
Fludrocortisone acetate (0.1 mg/day) should be added Non-classic (NC) form: This disorder is associated with
once the hydrocortisone dose is less than 50 mg/m2/day. partial 21-hydroxylase deficiency. Cortisol and aldo
Long-term management of adrenal insufficiency requires sterone levels are normal. Clinical manifestations are
lifelong replacement of glucocorticoids and mineralo related to mild hyperandrogenism which presents with
corticoids. Parents should be educated about the need of hirsutism, acne and menstrual irregularity.
increasing dose during periods of stress. The dose of
glucocorticoid should be increased 2-3 times in conditions Diagnosis
of minor stress (fever and mild infection) and 4-5 times in Diagnosis of salt washing form is established by
severe stress (severe infection or surgery). These doses demonstration of extreme elevation of 170HP levels
Endocrine and Metabolic Disorders 493
Cholesterol
t.....
3 3
'
Deoxycorticosterone 11 Deoxycortisol Testosterone
t________ ______________ -J
4 4 10
Aldosterone
Management
These patients require lifelong treatment. Patients with
salt washing and virilizing forms should be treated with
hydrocortisone (10-15 mg/m2/day) and fludrocortisone
(0.1 mg/day). Doses should be increased under stressful
conditions as for adrenal insufficiency. After completion
of growth, synthetic glucocorticoid preparations (dexa
methasone, prednisolone) can be used (Table 16.22).
Other Variants
Enzyme deficiencies other than 21-hydroxylase deficiency
account for less than 10% of cases of CAH. Patients with
11 (3-hydroxylase deficiency and 17a-hydroxylase defi
Fig. 16.12: Congenital adrenal hyperplasia secondary to 21- ciency present with hypertension and should be managed
hydroxylase deficiency: Note the clitoral hypertrophy, hyper with hydrocortisone alone. Deficiencies of StAR and 30-
pigmentation and increased rugosity of the labial folds almost giving hydroxysteroid dehydrogenase manifest as salt wasting
a male appearance to the female genitalia. crisis and require addition of mineralocorticoid.
Suggested reading
(10000-20000 ng/dL, normal <90 ng/dL) in the presence 1. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and classification
of clinical and laboratory features of adrenal insufficiency. of Cushing syndrome: a consensus statement. J Clin Endocrinol
170HP levels are elevated to a lesser extent in those with Metab 2003,88:5593-5602.
simple virilizing and non classic forms. The best method 2. Findling JW, H Raff. Screening and diagnosis of Cushing's
of diagnosing these patients is the estimation of 170HP syndrome. Endocrinol Metab Clin North Am 2005;34:385-402.
3. Hopkins RL, Leinung MC. Exogenous Cushing syndrome and
levels before and 60 minutes after an intramuscular glucocorticoid withdrawal. Endocrinol Metab Clin North Am
injection of ACTH (0.25 mg). 2005;34:371-84.
494 Essential Pediatrics
Clinical: Family history of obesity and its complications Fig. 16.14: Laurence Moon Biedl Bardet syndrome: Note the
should be recorded. Detailed history of physical activity, polydactyly
dietary recall and periods of inactivity should be assessed.
Increased appetite in a child with recent onset obesity may
indicate the possibility of a hypothalamic lesion. Delayed Table 16.25: Pointers to diagnosis to obesity
development points towards genetic syndromes associated Feature Etiology
with obesity. Features of raised intracranial tension along Hypogonadism
with history of CNS infection, head trauma or neuro Laurence Moon Biedl Bardet,
Prader Willi syndrome
surgery should point towards the diagnosis of CNS cause Retinitis pigmentosa Alstrom syndrome, Laurence
of obesity. Intake of drugs linked with development of Moon Biedl Bardet syndrome
obesity like steroids and antiepileptics should be inquired. Ear lobe creases, Beckwith Weidemann syndrome
Features of daytime somnolence or sleep apnea are organomegaly
suggestive of obesity severe enough to produce respiratory Short hand and feet, Prader Willi syndrome
embarrassment. Examination for features of endocrino- almond shaped eyes
pathies, dysmorphic syndromes and complications such as Polydactyly Laurence Moon Biedl Bardet
hypertension and acanthosis nigricans should be perfor syndrome, Alstrom syndrome
med. Special emphasis should be given to sexual maturity Buffalo hump, striae Cushing syndrome
and ocular examination. Hypogonadism is an important Metacarpal shortening
Mental retardation
Pseudohypoparathyroidism
feature of obese children with Laurence Moon Biedl Prader Willi syndrome, hypothy
roidism, pseudohypoparathyroi
syndrome and Prader Willi syndromes (Figs 16.13 and dism
16.14, Tables 16.25 and 16.26).
496 Essential Pediatrics
hypothalamic peptide, has been shown to be the key Table 16.29: Comparison of pattern of pubertal
regulator of puberty. Acting as the "on-off switch" of development in boys and girls
puberty, kisspeptin initiates GnRH pulses. Feature Girls Boys
The hypothalamic-pituitary-gonadal axis is under
feedback control. Thus secretion of LH is inhibited by sex Onset
First sign
10-12 years
Breast
12-14 year
Testicular enlargement
hormones (testosterone and estrogen) produced by the development
Leydig cells and theca cells. Inhibin produced by the Growth spurt Early Late (Tanner III
Sertoli and granulosa cells inhibits production of FSH. (Tanner I and II) and IV)
Sexual maturity Menarche Spermarche 15 years
Patterns of Pubertal Development 14 years
The pattern of pubertal development is different in girls
and boys. Puberty starts at around the age of 10 years in
girls (range 8-12 year) and is completed in 5 years. Breast PRECOCIOUS PUBERTY
enlargement (thelarche) is the first event followed by the Pubertal onset before the age of 8 years in girls and 9.5
development of pubic hair (pubarche) and onset of years in boys is suggestive of precocious puberty.
menstrual cycles (menarche). Breast development may be Precocious puberty may be related to stimulation of the
asymmetrical in the initial phase. Menarche usually occurs hypothalamic-pituitary axis (gonadotropin-dependent
2.5 years after thelarche. Discordant pubertal development precocious puberty) or autonomous sex hormone
(menarche within one year of thelarche) suggests production (gonadotropin-independent). Pubertal
hyperestrogenic states with withdrawal bleeding. In boys, development may involve all aspects of pubertal
puberty starts with testicular enlargement at 11.5 years development or restricted to one component (premature
(range 9 years to 14 years). This is followed by penile thelarche, adrenarche or menarche).
enlargement and pubarche. Spermarche occurs by the age
of 14 years. Precocious Puberty in Girls
The stage of pubertal assessment is assessed using
Tanner staging system (Table 16.28). Breast development Precocious puberty is common in girls and may represent
beyond Tanner II in girls and testicular volume greater normal variation in the age at onset of puberty. In most
than 4 ml indicates onset of puberty. Maximum growth cases, puberty is slowly progressive with no long-term
spurt occurs during early puberty in girls (Tanner II—III) adverse effect. Endocrine workup should therefore be
compared to boys where it occurs later (Tanner III—IV) restricted to girls with progressive forms of puberty.
(Table 16.29). Menstrual periods are irregular in the first
few years before attainment of regular ovulatory cycles. Etiology
It is important to differentiate adrenarche (pilosebaceous Gonadotropin-dependent precocious puberty (GPP) or
development related to increase in adrenal steroids) from precocious puberty is much more common than gonadotro
gonadarche (genital development related to increase in pin-independent precocious puberty (GIPP) (Table 16.30).
GnRH) due to implications in clinical assessment. In more than 90% of these cases, no underlying cause is
Incomplete variants Fig. 16.18: MRI scan of brain showing an isodense mass
Isolated thelarche suggestive of hypothalamic hamartoma
Isolated pubarche (adrenarche)
Isolated menarche
Gonadotropin-independent precocious puberty (GIPP) or
identified. Onset after the age of six years, slow progres peripheral precocious puberty is rare and usually caused by
sion and lack of neurological features suggests idiopathic estrogenic ovarian cysts. Fluctuating pubertal development
GPP. GPP may be caused by a number of CNS pathologies and early vaginal bleeding (due to hyperestrogenic state)
including infection, birth asphyxia, hydrocephalus, is common. The condition is usually self-resolving and
trauma, surgery, radiation and space occupying lesions. there is no need for treatment. Recurrent ovarian cysts
Hypothalamic hamartoma, a neuronal migration defect, is should raise the possibility of McCune Albright syndrome,
the commonest cause of organic central precocious a somatic activating mutation of stimulatory G protein.
puberty (Figs 16.17 and 16.18). The disorder presents with The condition presents with constellation of cutaneous
early onset and rapid progression of puberty, seizures and (multiple dark brown cafe-au-lait spots), skeletal (multiple
uncontrolled laughter episodes (gelastic epilepsy). fibrous dysplasia) and endocrine abnormalities
(hyperthyroidism, rickets and GH excess). Precocious
puberty occurs at an early age and is rapidly progressive.
Advancement of skeletal maturation may trigger GPP.
Prolonged untreated primary hypothyroidism may induce
early puberty due to action of TSH on FSH receptor.
Delayed bone age and growth is characteristic. Estrogenic
adrenal tumor is an extremely rare cause of GIPP.
Evaluation
Aims of evaluation include confirmation of diagnosis,
identification of underlying etiology and determination
of prognosis and treatment.
Clinical: History should include the onset, progression
and extent of puberty. Exposure to steroids, estrogens and
androgens should be enquired. Family history of
precocious puberty and early menarche points towards
idiopathic central precocious puberty. History indicative
of intracranial space occupying lesion, CNS infections,
neurosurgery, radiotherapy and head trauma should be
noted. Features of hypothyroidism should be assessed.
Advanced growth is characteristic of precocious puberty;
growth retardation is indicative of hypothyroidism or
concomitant GH deficiency. Examination of vaginal
Fig. 16.17: Central precocious puberty secondary to hypothalamic mucosa for estrogen effect provides clues regarding the
hamartoma pubertal status of the patient. Red, glistening mucosa
500 Essential Pediatrics
suggests lack of estrogens while pink mucosa with mucus desensitization of pituitary leading to reversal of pubertal
is indicative of estrogen effect. Abdominal examination changes. GnRH analogs should be considered in girls with
for adrenal or ovarian mass should be done. Features of early onset (before 6 years of age) rapidly progressive
McCune Albright syndrome in the form of cafe-au-lait puberty and height compromise (bone age to chronolo
spots, polyostotic fibrous dysplasia, bony deformities and gical age difference more than two years). Triptorelin (60
polyendocrinopathy should be looked for. Hg/kg) or leuprolide (300 |ig/kg) administered as a deep
Investigations: Assessment of pubertal status is based on intramuscular injection every 4 weeks is the most
basal or stimulated gonadotropin levels. Pooled gonado commonly used agent. The treatment is discontinued at
tropin levels are preferred due to their pulsatile secretion. the chronological age of 11 years and bone age of 12.5
LH is a better indicator compared to FSH as LH levels years. This is followed by gradual reappearance of
increase significantly during puberty. LH levels in the secondary sexual characters. Menarche is attained around
pubertal range with LH/FSH ratio more than 1 is 12-18 months following discontinuation of treatment.
suggestive of development of puberty. In unequivocal
situations, LH levels should be measured 30, 60 and 90 Gonadotropin-independent precocious puberty: Thyroxin
minutes after GnRH injection (GnRH stimulation test). replacement results in reversal of pubertal changes in
Ultrasound of abdomen and pelvis helps in diagnosing hypothyroidism. Treatment for McCune Albright
follicular cysts and ovarian and adrenal mass. Thyroid syndrome is directed towards inhibiting estrogen
function should be assessed to rule out hypothyroidism. production (aromatase inhibitors like anastrazole or
Bone age helps in assessing the height compromise and letrozole) or estrogen action (tamoxifen). Treatment of
in predicting final height. MRI of brain should be done in ovarian cysts is guided by size and morphological features.
girls with onset of puberty before 6 years of age, rapid
progression and associated neurological features. Pituitary Precocious Puberty in Boys
functions should be assessed in girls with organic GPP. Precocious puberty is less common in boys, but when
Advanced bone age (more than two years ahead of present is usually associated with significant pathology.
chronological age) is suggestive of progressive precocious This mandates prompt evaluation and treatment of all
puberty, while normal bone age indicates slowly pro boys with precocious puberty.
gressive puberty. Retarded growth and skeletal matu
ration is diagnostic of hypothyroidism. Pubertal LH levels Etiology
are suggestive of GPP and should be followed with an Gonadotropin-dependent and independent precocious
MRI of brain. Girls with GIPP should undergo ultrasound puberty accounts for similar number of cases in boys
of ovary and adrenals (for ovarian cyst and adrenal tumor) (Table 16.31).
and skeletal survey (for fibrous dysplasia in McCune Gonadotropin-dependent precocious puberty (GPP): Th
Albright syndrome).
etiology is similar to girls with the exception that organic
Management etiology is more common. Hypothalamic hamartoma,
craniopharyngioma, hydrocephalus and tubercular
Aims of treatment include treatment of underlying cause, meningitis are important causes. These disorders are
management of associations, suppression of puberty and associated with increase in testicular volume and elevated
achievement of target height potential. The significant basal and GnRH stimulated LH.
long-term consequence of precocious puberty is short
stature. Growth is accelerated at presentation. This is
associated with disproportionately advanced bone age Table 16.31: Etiology of precocious puberty in boys
resulting in premature epiphyseal fusion culminating in Gonadotropin-dependent or central precocious puberty
compromised final height. Significant psychosocial issues Idiopathic
including pubertal development at an early age and CNS tumors: Hamartoma, craniopharyngioma, glioma
practical issues of menstruation in a young girl need to be CNS infections: Tubercular meningitis, meningitis
addressed. CNS injury: Head trauma, surgery, radiation
Gonadotropin-dependent precocious puberty: Treatment CNS malformation: Arachnoid cyst, hydrocephalus
includes management of underlying cause and sup Gonadotropin-independent or peripheral precocious puberty
pression of puberty. Drugs used for pubertal suppression Congenital adrenal hyperplasia: 21-hydroxylase deficiency,
include medroxyprogesterone acetate (MPA), cyproterone lip-hydroxylase deficiency
and GnRH analogs. MPA does not improve height Adrenal tumors: Adenoma, carcinoma
outcome and may be considered in girls with intellectual Testicular tumors: Seminoma, germinoma
disability where final height is not important. Long acting Testotoxicosis-activation of LH receptor
GnRH analogs are the only agents effective in improving hCG secreting tumor: Germinoma, hepatoblastoma
height outcome. They cause sustained stimulation and Exogenous androgen exposure: Testosterone cream
Endocrine and Metabolic Disorders 501
Gonadotropin-independent precocious puberty (GIPP): This is the extent of diagnostic work-up and
in restricting
caused by increased androgen production by testis and counselling.
adrenals in the setting of prepubertal LH levels. Adrenal Isolated thelarche: Isolated breast development may
overproduction due to congenital adrenal hyperplasia is therepresent isolated thelarche or first manifestation of central
commonest cause of peripheral precocious puberty. Rarely precocious
adrenal tumors may present with precocious puberty. and pelvic puberty or GPP. Bone age, gonadotropin levels
ultrasound helps in differentiating the two
Penile enlargement with prepubertal testicular volume is conditions. Normal growth, prepubertal LH, age
characteristic. Human chorionic gonadotropin (hCG) secreting
appropriate bone age and small uterine size suggest
germ cell tumors of the liver, mediastinum or brain may
present with precocious puberty. Testicular volume is only isolated thelarche. Advanced bone age, elevated LH levels
slightly increased as only Leydig cells are enlarged. and increased uterine size indicate precocious puberty and
Testotoxicosis, a disorder associated with constitutional need for GnRH analog therapy.
activation of LH receptor, presents with early onset Isolated adrenarche: Premature adrenarche refers to
gonadotropin-independent precocious puberty. Androgen development of pubic hair and acne in the absence of
secreting testicular tumors present with precocious pubertybreast development or menarche. Most cases are
and unilateral testicular enlargement. physiological variants. Rarely androgen excess due to
Evaluation
adrenal (CAH due to 21-hydroxylase deficiency, llp-
hydroxylase deficiency or adrenal tumor) or ovarian
Evaluation is directed towards confirming the diagnosis (tumor or polycystic ovarian disease) causes may be
and establishing the underlying cause. identified. Normal bone age and absence of virilization
Clinical: History should include age at onset of pubertal suggest premature adrenarche and no treatment. Girls
development, progression of puberty, neurological with virilization and advanced bone age should be
features, family history of precocious puberty and investigated for hyperandrogenic states.
androgen exposure. Detailed anthropometric and Isolated menarche: Menarche in the absence of thelarche is
neurological examination should be performed. Pointers against the diagnosis of GPP. Vaginal bleeding may occur
to CAH (hyperpigmentation and hypertension) should be early in course of estrogen excess states like ovarian cysts,
identified. Estimation of testicular volume forms an hypothyroidism and McCune Albright syndrome. Vaginal
integral part of assessment. Prepubertal testicular volume bleeding without breast development should prompt
(less than 4 ml) is characteristic of CAH and adrenal evaluation of local causes like infection, foreign body,
tumors, while unilateral enlargement is seen in testicular sexual abuse and tumors.
tumors. Pubertal testicular enlargement indicates GPP
while milder enlargement is observed in hCG secreting DELAYED PUBERTY
tumors and testotoxicosis.
Investigations: Initial investigations should include LH, Delayed puberty is more common in boys than girls. Most
FSH and testosterone levels and bone age. All patients children with delayed puberty have constitutional delay
with pubertal LH levels should undergo visual field emphasizing the need for watchful monitoring and
examination and MRI of brain. If CNS pathology is iden conservative approach.
tified, detailed pituitary evaluation should be performed. Delayed Puberty in Girls
In the presence of prepubertal LH levels, imaging for
adrenals (preferably a CT scan) and 170HP levels should Delayed puberty is defined as lack of secondary sexual
be done. hCG levels should be estimated if these characteristics by the age of 17 years. Absence of menarche
investigations are noncontributory. by the age of 16 years or 5 years after pubertal onset also
indicates pubertal delay.
Management
Management includes treatment of underlying CNS Etiology
pathology and GnRH analog therapy. GnRH analog Delayed puberty may be caused by defects in the
should be continued till the age of 12 years and a bone age hypothalamic-pituitary axis, ovaries or genital tract (Table
of 17.5 years is achieved. CAH is managed with hydrocorti 16.32). Patients with anatomical defects present with
sone and fludrocortisone. Surgery is the treatment of choice amenorrhea with normal breast development. Defects in
for adrenal and testicular tumors, while radiotherapy is the hypothalamic-pituitary axis are associated with low
effective in hCG secreting tumors. Aromatase inhibitors gonadotropin levels (hypogonadotropic hypogonadism). This
and antiandrogens are indicated in testotoxicosis. may be related to reversible causes like systemic diseases,
malnutrition, eating disorders, hyperprolactinemia and
Incomplete Variants hypothyroidism. Irreversible defects include destruction
These disorders usually represent normal variants and do of the hypothalamic-pituitary axis by infection, surgery,
not require specific treatment. Their identification helps radiation or tumor. Kallmann syndrome, a neuronal
502 Essential Pediatrics
Table 16.32: Etiology of delayed puberty in girls suggest a defect in the hypothalamic-pituitary axes. Poor
Hypogonadotropic hypogonadism smell sensation is indicative of Kallmann syndrome.
Transient
Patients with amenorrhea with normal secondary sexual
• Systemic disorders: Renal failure, liver disease, celiac disease,
characteristics are likely to have anatomical defects and
renal tubular acidosis, cystic fibrosis should be evaluated accordingly. Neurological
• Nutritional disorders: Malnutrition, anorexia nervosa examination including that for olfactory sensation should
• Endocrine disorders: Hypothyroidism, hyperprolactinemia, be performed. Features of Turner syndrome and
type 1 diabetes hypothyroidism should be looked into. Galactorrhea
Permanent points towards hypothyroidism or hyperprolactinemia.
• Isolated hypogonadotropic hypogonadism
Genetic: KALI, GnRH receptor, LH, FSH, DAX1 mutations Investigations: Initial workup is directed towards excluding
Dysmorphic syndromes: CHARGE, Prader Willi, Laurence systemic disorders such as liver disease, renal disease and
Moon Biedl Bardet syndromes malabsorption. This should be followed by measurement
• Multiple pituitary hormone deficiency of FSH levels. Karyotype should be done if FSH levels are
- Malformations: Holoprosencephaly, septo-optic high. Steroidogenic defects are likely, if karyotype and
dysplasia, midline defects pelvic ultrasound are normal. In patients with low/normal
- Genetic disorders: PROP1, LH gene deletions FSH levels, prolactin and thyroid profile should be
- Brain tumors: Craniopharyngioma, germinoma, glioma measured to exclude reversible causes. Neuroimaging and
- CNS insults: Surgery, infection, radiation, trauma pituitary function tests should be done if these levels are
- Infiltrative disorders: Histiocytosis, autoimmune
disorders
normal.
Hypergonadotropic hypogonadism Management
DISORDERS OF SEXUAL DIFFERENTIATION sex determining region of the Y chromosome (SRY), is one
of the most important regulators of sexual differentiation.
Disorders of sexual differentiation (DSD), previously gene acts
SRY
1
in conjunction with other genes like Wilms tumor
(WT1), SOX 9 and DAX1 to induce testicular
termed as intersex disorders, are rare but constitute a development. In the
medical, social and psychological emergency. Careful develops into ovary. absence of SRY, the bipotential gonad
clinical and laboratory evaluation is essential for identi
fying the underling disorder, need of emergent therapeutic Genital differentiation: Following development of testis,
intervention and decision about sex of rearing. antimiillerian hormone (AMH) secreted by Sertoli cells
induces regression of mullerian ducts. Testosterone
Physiology produced by Leydig cells is responsible for sustenance of
Sexual differentiation is a complex process involving a Wolffian ducts. Dihydrotestosterone (DHT), produced by
close interaction of genetic, phenotypic and psychological action of 5oc-reductase on testosterone, is responsible for
factors. Usually genetic sex guides gonadal sex, which is male external genital development (scrotal fusion and
responsible for the determination of phenotypic mani development of corpus spongiosum and penile corpus
festations and gender identity. Any deviation from this cavernosa). Feminization is the default process of sexual
pattern results in DSD. Sexual differentiation involves development. In the absence of AMH and testosterone,
development of gonads in accordance to the genetic mullerian ducts differentiate into fallopian tubes, uterus
signals, development of internal sexual organs and and the upper third of the vagina. Labioscrotal swellings
secondary sexual characters (Fig. 16.20). and urethral folds do not fuse and give rise to labia majora
and minora respectively. The genital tubercles form the
Gonadal differentiation: Germ cells arise from the celomic clitoris while canalization of the vaginal plate creates the
epithelium of hindgut and migrate to the gonadal ridge lower portion of the vagina. Prenatal exposure to andro
at 4-6 weeks of gestation. These cells combine with gens may lead to labioscrotal fusion, while exposure there
somatic cells to give rise to the bipotential gonad. A after usually causes clitoromegaly alone and no labial
transcriptional factor present on Y chromosome called the fusion.
for inguinal hernia and operated. Intake of progestational Investigations: Initial investigations should include
drugs during first trimester and features of virilization in karyotyping, estimation of electrolytes, 170FIP and pelvic
mother should be enquired. Failure to thrive, polyuria and ultrasound. FISH for Y component provides rapid infor
lethargy indicate 21-hydroxylase deficiency (Table 16.38). mation about the genetic status. Identification of mullerian
Virilization during puberty is suggestive of 5a-reductase structures is an important part of evaluation of ambiguous
deficiency, while feminization indicates AIS. General genitalia. Genitogram is helpful in determination of level
examination should include assessment for facial of fusion, which is of surgical importance. Further investi
dysmorphism and hyperpigmentation. Maternal exami gations are guided by clinical and laboratory evaluation.
nation for features of hyperandrogenism like hirsutism, Mullerian structures with no palpable gonads indicate
acne and change in voice should be done. androgen excess state and need for estimation of 170HP
levels. Absence of mullerian structures is suggestive of
Table 16.38: Pointers to etiology of Disorders of sexual inefficient testosterone action and should be evaluated
differentiation (DSD) with estimation of testosterone and DHT levels. The
Pointer Likely diagnosis
presence of both mullerian structures and palpable gonads
indicate gonadal dysgenesis or ovotesticular DSD. Absent
Pigmentation Congenial adrenal hyperplasia, SF1
gonads and mullerian structure may be caused by
defect
Genital asymmetry Mixed gonadal dysgenesis,
vanishing testis syndrome or dysfunctional intra
ovotesticular DSD abdominal testis. Estimation of levels of AMH and hCG
Hypertension 11a or 17a hydroxylase defect stimulation test are helpful in differentiating the two
Hemihypertrophy WT1 mutation conditions. Children with vanishing testis will have low
Renal failure Denys Drash syndrome levels of AMH and inappropriate response to hCG
stimulation.
Genital examination: The most important step is identi
fication of gonads. Bilaterally rounded structures below Management
the inguinal canal are most likely to be testis. Unilateral Management involves parental counseling, decision about
gonads are suggestive of mixed gonadal dysgenesis. The sex of rearing, timing of surgical correction and gonadec-
labioscrotal region should be evaluated for the extent of tomy. This requires a multidisciplinary team including
fusion (Fig. 16.21). Mullerian structures can be confirmed pediatrician interested in endocrinology, pediatric
by a good rectal examination. The length of phallus and surgeon, geneticist, psychologist and social worker.
number of openings in the urogenital region should be Specific management should be initiated for conditions
recorded. Asymmetrical labioscrotal region is suggestive like 21-hydroxylase deficiency.
of gonadal dysgenesis or ovotesticular DSD. The genitalia Parental counseling: Birth of a child with DSD generates
should be staged according to the classification proposed significant parental anxiety and stress. The most important
by Prader from grades I to V with grade I representing aspect of counseling is reassurance of parents that the child
female with clitoromegaly and V male with cryp is healthy and the condition is amenable to surgical treat
torchidism. ment. Gender specific connotation (his or her, testis, ovary)
should be avoided and neutral terms like gonads and
phallus be used. The process of sexual differentiation
should be explained. This should be followed by explana
tion of child's appearance and possible diagnosis. Future
implications regarding sexual and fertility prospects
should be discussed.
Decision about sex of rearing: Gender assignment should
depend on the potential for future sexual and reproductive
function, anatomical status, feasibility of reconstructive
surgery and social acceptance and norms. Girls with virili
zation disorders usually have potential for fertility and
should be reared as females. Individuals with complete
AIS should also be reared as females. Decision of sex of
rearing is difficult in disorders of inefficient androgen
action. This should depend on genital appearance and
Fig. 16.21: Disorder of sexual development—partial androgen surgical feasibility. There has been a trend of performing
insensitivity syndrome—Note the female appearance of the genitalia early surgeries before gender identity is established. Most
with an underdeveloped buried penis and poorly developed scrotum centers perform clitoroplasty at the age of 1 year with
and testes vaginoplasty reserved during puberty for girls with
508 Essential Pediatrics
vaginal stenosis. Gonadectomy should be done in gonadal Penoscrotal hypospadias and genital ambiguity is
dysgenesis or ovotesticular DSD, if a Y cell line is present. suggestive of disorders of androgen production or action.
Features of dysmorphic syndromes like Prader Willi,
Cryptorchidism (Undescended Testes) Laurence Moon Biedl Bardet, Noonan and DeLange
Cryptorchidism is present in about 3% of full-term infants syndromes are usually evident on examination. The hCG
and 20% of premature infants. In most boys testis descend stimulation test should be done in boys with bilateral
spontaneously by the age of one year with a decrease in nonpalpable testis to differentiate abdominal testis from
the prevalence to around 1%. Spontaneous testicular anorchia.
descent is highly unlikely after the age of one year and
the prevalence in adult population is around 0.8%. Management
Undescended testis is associated with significant compli
Etiology cations like torsion, trauma, inguinal hernia, testicular
Most children with undescended testis do not have an dysfunction and development of malignancy. These
identifiable underlying cause. Endocrine causes account children should be treated early because of the increased
for only a small proportion of boys with undescended risk for malignancy and infertility in later life. The optimal
testis. The possibility of salt wasting 21-hydroxylase time of therapy is before the age of one year. The most
deficiency presenting with sex reversal should be consi commonly used medical treatment is human chorionic
dered in newborns with bilateral cryptorchidism. Unde gonadotropin (hCG) 250 units below 1 year, 500 units
scended testis may be associated with hypopituitarism, between 1 and 5 years and 1,000 units above 5 years
dysmorphic syndromes and disorders of androgen administered twice a week for 5-6 weeks. Good response
production and action. occurs within a month. Alternately GnRH in the form of
an intramuscular injection or nasal spray may be tried.
Evaluation Retraction rate of testes after cessation of therapy is high.
It is important to differentiate true undescended testis from If the response to hCG is poor, patient should be treated
retractile or ectopic testis due to therapeutic and early with orchiopexy.
prognostic implications (Fig. 16.22). Poorly developed
scrotum and inability to bring down the testis to the scrotal Micropenis
sack suggests true undescended testis. Retractile testis is A penis whose length in stretched position is less than 2
an otherwise fully descended testis that has an active SD below the mean for the age is termed micropenis.
cremasteric reflex, which retracts it into the groin. Micropenis may be isolated or may be associated with
Endocrine and Metabolic Disorders 509
genital and structural abnormalities. Most often it is the to multiple organs. Hence diabetes mellitus is the leading
result of primary or secondary testicular failure. cause of end stage renal disease, (ESRD), non-traumatic
leg amputation, and adult blindness.
Etiology The incidence of both type 1 and type 2 diabetes is
Micropenis results from decreased androgen action during increasing worldwide. Sedentary lifestyles and changes
fetal life. It may be due to hypogonadotropic hypogona in dietary habits are believed to be contributing to this
dism as in Kallmann syndrome, Prader Willi syndrome, increase.
septooptic dysplasia, idiopathic hypogonadotropic hypo Classification
gonadism (primary) with isolated micropenis, Klinefelter
syndrome or Robinow syndrome. It may be a manifes Diabetes mellitus is classified based on pathogenic pro
tation of partial androgen insensitivity syndrome or testo cesses that result in hyperglycemia (Table 16.39). Previous
sterone biosynthetic defects. terms of insulin-dependent (IDDM) and non-insulin-
dependent diabetes mellitus (NIDDM) are not used, since
Evaluation many patients with type 2 diabetes eventually require
Penile length should be measured in a fully stretched state insulin to control hyperglycemia. The classification is
based on pathogenesis rather that modality of treatment.
by grasping the glans between thumb and forefinger. A Though most patients with type I diabetes present under
firm ruler or caliper should be pressed against the pubic the age of 30 years, 5-10% individuals develop type 1
ramus to depress the suprapubic fat pad. The measurement diabetes after 30 years. Likewise type 2 diabetes is being
should be made along the dorsum to the tip of the glans increasingly diagnosed in adolescents who are obese.
penis excluding the length of foreskin. Penile size is often
underestimated in boys with obesity (due to the suprapubic
fat) and hypospadias (due to chordee). Investigations Table 16.39: Classification of diabetes mellitus
should include estimation of gonadotropin and testo Type 1 Diabetes mellitus
sterone levels. Boys with low gonadotropin and testo Absolute insulin deficiency resulting from (3-cell destruction
sterone levels (hypogonadotropic hypogonadism) should Type 2 Diabetes mellitus
undergo anterior pituitary hormone tests (IGF-1, IGFBP3, Progressive insulin secretary defect in the background of
serum cortisol, thyroid function tests and urine osmolality) insulin resistance
and MRI of the brain. Elevated gonadotropin levels (hyper Gestational diabetes mellitus (GDM)
gonadotropic hypogonadism) should prompt evaluation Diabetes mellitus manifesting in pregnancy
for testicular dysgenesis, steroidogenic defects or AIS. Other specific types of diabetes mellitus
Genetic defects in (3-cell function or insulin action, diseases of
exocrine pancreas and drug or chemical induced diabetes
Management
All boys with micropenis are treated with a course of low
dose testosterone (25 mg testosterone enanthate or cypionate Most patients can be clearly classified as type 1 or 2
monthly for three doses). The aim of this short course of diabetes mellitus (Table 16.39). However, occasionally an
testosterone treatment is to increase penile length and not adolescent with type 2 diabetes may present with
to induce puberty. Boys with micropenis should be reared ketoacidosis and similarly patients with type 1 diabetes
as males as normal sexual function is usually attainable mellitus may present late and progress slowly appearing
with early intervention. like type 2 diabetes. The correct diagnosis, however,
becomes obvious with time.
Suggested reading
Epidemiology
1. Bajpai A, Sharma J, Menon PSN (eds). Ambiguous genitalia. In:
Practical Pediatric Endocrinology. JP Brothers 2003;97-101. Diabetes has been more commonly diagnosed over the
2. Hutson JM, Hasthorpe S. Testicular descent and cryptorchidism:
past two decades. The prevalence rates of impaired fasting
the state of the art in 2004. J Pediatr Surg 2005;40:297-302.
3. Warne GL, Zajac JD. Evaluation of a child with ambiguous
glucose are also increasing. Type 2 diabetes is increasing
genitalia: A practical guide to diagnosis and management. In: in prevalence more rapidly than type 1 due to increasing
Pediatric Endocrine Disorders. Eds: Desai MP, Bhatia V, Menon obesity and less active lifestyles of children. There is a
PSN. Orient Longman, Hyderabad. 2003;257-276. significant geographic variation in the incidence of
diabetes mellitus. Scandinavia has the highest incidence
of type 1 diabetes mellitus, with Finland having the
DIABETES MELLITUS incidence of 35/100,000/year. China and Japan have a
much lower incidence of 1-3/100,000/year. Indian data
Diabetes mellitus is a metabolic disorder that is char suggest an incidence of 10.5/100,000/year. India would
acterized by hyperglycemia and glycosuria. Hyper have 79 million diabetics by 2030, the highest for any
glycemia resulting from diabetes mellitus causes damage country in the world. The variability in incidence in type
510 Essential Pediatrics
1 diabetes is believed to be due to differences in frequency degraded in the liver. Insulin binds to receptors at target
of high risk HLA alleles in various ethnic groups. Type 1 sites, where glucose transporters are translocated to the
diabetes is uncommon in infants. Diabetes mellitus in the surface (GLUT4) for glucose uptake. Activation of other
newborn period is usually transient, although occasionally receptor signaling pathway induces glycogen synthesis,
a more permanent diabetes is seen. The incidence of protein synthesis and lipogenesis.
diabetes mellitus increases in children with advancing age
all the way to adolescence, with peaks at 5 and 12 years of Pathogenesis
age. Seasonal variation has been noted with a higher Type 1 diabetes develops consequent to immune - medi
incidence in spring and fall. ated destruction of pancreatic (3 cells, resulting in severe
impairment of insulin secretion in genetically susceptible
Diagnosis
children. The immunologic process has often been going
The World Health Organization has outlined diagnostic on for years before endogenous insulin secretion declines
criteria for diabetes mellitus (Table 16.40). to levels resulting in clinical diabetes. Genetic, environ
Random blood sugar of 200 mg/dl or more associated mental and autoimmune factors are believed to result in
with the classic symptoms of diabetes mellitus (polydipsia, the development of type 1 diabetes.
polyuria, and weight loss) is diagnostic. Oral glucose
tolerance is not routinely recommended. Fasting blood Genetics
sugar is also a reliable and convenient test. Elevated Genetic susceptibility to diabetes involves multiple genes.
hemoglobin A1C is diagnostic of diabetes mellitus. The major susceptibility genes are located in the HLA
However, it is not completely reliable when dealing with region on chromosome 6. Polymorphisms in the HLA
mild elevations of blood sugars. complex account for almost 50% of the genetic risk of
developing type I diabetes. This region contains genes that
encode for class II MHC (major histocompatibilty
Table 16.40; Criteria for the diagnosis of diabetes mellitus
complex) molecules. These genes are responsible for
• Symptoms of diabetes and a random blood glucose appropriate presentation of antigen to helper T cells
concentration >ll.lmmol/L (200 mg/dL) or involved in initiating the immune response. Studies have
• Fasting blood sugar 7 mmol/L (126 mg/dL) or indicated that certain haplotypes confer significant risk
• Two hour plasma glucose >11.1 mmol/L (200 mg/dL) of acquiring diabetes while yet others are protective.
during an oral glucose tolerance test Inheritance of diabetes is polygenic. Most individuals
with predisposing haplotypes do not develop diabetes.
Hence most individuals with type 1 diabetes do not have
Screening first-degree relatives with type 1 diabetes. Concordance
Epidemiologic studies indicate that the disease is often of type I diabetes in identical twins ranges from 30-70%.
present for over a decade in patients eventually diagnosed 7% of children whose fathers have type 1 diabetes develop
with type 2 diabetes mellitus. 50% or more patients with type 1 diabetes. Mothers with type 1 diabetes do not confer
Type 2 diabetes have one or more of the complications of a similar risk. Siblings are not at higher risk of developing
diabetes at the time of diagnosis. High risk adolescents type 1 diabetes.
should therefore be screened for diabetes.
Environmental Factors
Insulin Synthesis, Secretion and Action Many environmental agents have been thought to trig
Insulin is produced by the (3 cells of the pancreatic islets. ger the development of type 1 diabetes mellitus. How
Proinsulin is an 86 amino-acid precursor of insulin, which ever, none has been proven to be directly causative. The
is produced by the cleavage of preproinsulin. Proinsulin identification of an environmental trigger has been
is cleaved to produce C-peptide and the A and B insulin difficult since diabetes develops many years after the onset
chains (connected by disulphide bonds). C-peptide is less of pancreatic damage. Triggers of autoimmune damage
degradable by the liver and a useful marker of insulin include viruses, bovine milk protein (presented in infancy
secretion. Glucose is the key regulator of insulin secretion. by the early introduction of cow milk protein) and
GLUT2 (glucose transporter) transports glucose into the nitrosourea compounds.
(J cells. Glucose phosphorylation in the (3 cells is the rate
limiting step in insulin secretion. Glucose 6 phosphate Autoimmune Factors and Autoimmunity
metabolism during glycolysis generates ATP; this ATP, Individuals susceptible to development of diabetes have
inhibits ATP sensitive K+ channels; simultaneously, normal (3 cell mass at birth. Autoimmune destruction
voltage dependent Ca2+ channel are opened and the influx affects only the (3 cells of the islets, even though the a and
of Ca2+ into the cell causes insulin release. Insulin is 5 cells are functionally and embryologically similar to the
released in small secretary bursts of 80-150 minutes and (3 cells. Autoimmune destruction of islets progresses over
also as large bursts following meals 50% insulin is many years resulting in a decline in insulin secretion and
Endocrine and Metabolic Disorders 511
P cell mass. The pancreatic islets are infiltrated with • Reduce and delay the complications
lymphocytes in a process called insulinitis. Once the islet • Achieve a normal lifestyle and normal emotional and
cells are completely destroyed the inflammatory process social development
abates and the islet gets atrophic. The immunologic • Achieve normal physical growth and development
process is thought to be trigged by infectious or environ • Detect associated diseases early.
mental factors. In most patients markers of autoimmune A comprehensive approach is adopted to achieve these
destruction can be measured after the onset of auto goals. Symptoms of diabetes abate with blood sugars <200
immunity and decline once clinical diabetes is established. mg/dL, making the first goal relatively easier to achieve.
Clinical diabetes occurs when the pancreas loses 80% or However, achieving the other goals require focus on
more of its insulin secretory ability. Residual pancreatic (3 diabetes education, medical nutritional therapy (MNT)
cells remain which are functionally active and transiently and well-planned appropriate insulin therapy that is
secrete insulin during the immediate treatment phase customized to the unique needs of each patient. The avail
resulting in the honeymoon phase of diabetes. During this ability of insulin analogs and insulins with long duration
transient, fleeting phase, insulin requirements decrease. of action with minimal/absent peaks allows insulir
This can last for a few days to several weeks. The auto therapy to match glucose excursions with meals and a>
immune process eventually destroys the remaining islet the same time provide baseline insulin for endogenous
cells and the individual becomes completely insulin glucose production without significant hypoglycemia
deficient. Advances in self blood glucose monitoring (SBGM)
Islet cell antibodies (IC A) can be measured in the serum development of insulin pumps for accurate insulin
of 70-80% patients at the time of diagnosis. These include delivery, continuous glucose monitoring systems (CGMS)
antibodies directed at pancreatic islet molecules such as and development of a team approach to the management
insulin, IA-2/ICA-512 and GAD-65. The presence of these of diabetes care has greatly improved diabetes care. These
antibodies predates the clinical presentation of diabetes developments and strategies have allowed many children
and declines after clinical disease has manifested. Auto and adolescents to achieve glycemic goals of near normal
antibody production in Indian children is less pronounced, blood sugars; goals that were previously almost impossi
both in frequency and duration compared to Caucasian ble to achieve, with conventional insulin therapy of twc
children. injections a day.
The current therapeutic regimen, which involves
Clinical Features frequent blood sugar monitoring and multiple insulir
Children and adolescents usually present with symptoms injections or continuous subcutaneous injection infusion
of diabetes that have often been ongoing for a month or (CSII), along with dietary modifications, is called intensive
two prior to seeking physician contact, with an acute insulin therapy. Intensive insulin therapy involves fre
increase in symptoms over the last week. Symptoms of quent communication between the physician and the
type 1 diabetes mellitus include polyuria, nocturia, poly diabetes educator to accomplish insulin adjustments in a
dipsia, recent weight loss, polyphagia and fatigue. Recent timely manner, with the goal of achieving near norma1
acute infection is often noted at presentation. Approxi blood sugar at all times. Intensive therapy results ir
mately 50% children present with acute complication of reduced late complications of diabetes by 39-60%.
diabetes or diabetic ketoacidosis.
Team Approach
Course of Illness Most diabetes centers adopt a team approach to diabetes
Most children respond to insulin therapy. Once insulin is care. In this approach, a group of professionals trained in
initiated, blood sugars gradually decline. Often, after diabetes care provide comprehensive education and care
around a week of insulin therapy, the need for exogenous Diabetes education is the main focus. Individualized goals
insulin declines, due to a transient recovery of insulin are set based on the strengths of the patient and family
secretion. This phase is called the honeymoon phase of The team typically comprises of a pediatric endocrinolo
diabetes. Some children can go completely insulin free gist, a diabetes educator, a dietician, a social worker and
during this time. The honeymoon phase generally lasts a psychologist.
from a few days to a month. It can rarely extend as long
as one year. Insulin needs increase over time till such time Insulin Preparations
as when the pancreas can no longer secrete insulin. At Current insulin preparations are generated using recom
this point the child's daily insulin requirement plateaus binant DNA technology. Animal insulins should no longei
at 0.8-1 unit /kg/day. be used. Amino acid substitutions on human insulin wil!
alter insulin pharmacokinetics and this has been used to
Treatment
synthesize "designer" insulin preparations with particulai
The goals of therapy of type 1 and 2 diabetes mellitus are: desired characteristics. Insulin analogue - Lispro
• Eliminate symptoms related to hyperglycemia (Lys(B28)Pro(B29) human insulin) allows better control
512 Essential Pediatrics
of blood sugar as its onset of action is faster than regular at all times with minimal hypoglycemia. There are two
insulin and duration of action is shorter. Insulin Aspart main classes of insulin regimen: (i) NPH with short acting
also has shorter onset of action but it's duration of action insulin analogues and (ii) long acting insulin, typically
is longer than Lispro insulin. These modifications in insulin Glargine (Lantus) with short acting insulin; as
insulin enable improved glycemic control during fasting depicted in Fig. 16.23.
as well as postprandial state. Table 16.41 provides the In the NPH regimen two to three injections are given
pharmacokinetics and specific characteristics of currently per day routinely: a combination of NPH and short acting
available insulins. before breakfast, short acting at dinner and NPH at dinner
or bedtime. In this regimen usually two-thirds of the total
Insulin Therapy daily insulin is prescribed in the morning prior to breakfast
Insulin requirements generally range from 0.5-1 unit/kg/ and one-third is given in the evening. Pre-breakfast: two-
day. third of the morning insulin is given as NPH and one-
At diagnosis, insulin therapy is initiated with four doses third as short acting insulin. Pre-dinner or pre-bedtime:
of short acting insulin. The dose is evaluated and an 1/2-2/3 of the evening insulin is given as NPH and 1/3—
appropriate home regimen of insulin is planned. The goal 1 /2 of the evening insulin is given as short acting insulin
of therapy is to provide background insulin to maintain prior to dinner. When drawing up a mixed dose of insulin,
glycemic control during the fasting state, and to punctuate short acting insulin is drawn before intermediate acting
this with multiple boluses of short acting insulins to main cloudy insulin. An accidental introduction of longer acting
tain euglycemia during postprandial states in a titrate-able
manner. The rest is a mere detail related to the pharmaco
kinetic characteristics of the insulin being used.
As of now, the most accurate method of achieving gly
cemic control uses the insulin pump. It utilizes insulin deli
very devices to accurately deliver a small baseline
continuous infusion of insulin, coupled with parameters
for bolus therapy - related to food intake and activity
levels. The bolus insulin is determined by the amount of
carbohydrate intake and the blood sugar level.
In most traditional regimens, intermediate or long-
acting insulin is utilized to provide background insulin
to maintain glycemic control during the fasting state. Short
acting insulin is used to provide glycemic control in the
postprandial state. Insulin regimens in varying combi
nations are utilized to achieve near normal blood sugars Fig. 16.23: Intermediate and short acting insulin regimen
insulin in short acting insulin can result in increasing the Lispro and Aspart is 1800/TDD (total daily dose). Example:
duration of short acting insulin. A meal plan, incorpo If a child is on 60 units of daily insulin, correction factor is 30
rating three meals and two or three snacks, is planned. (1800/60). A correction factor of 30 indicates that 1 unit of sh
Insulin is adjusted by reviewing blood sugars. Blood acting insulin will bring a child's blood sugar down by 30 poin
sugars are monitored at least four times a day (prior to Continuous subcutaneous insulin infusion (CSII) via
insulin pump is being increasingly used in the western
meals and at bedtime). It is important to follow the diet
world. The principle involved is essentially a refinement
outlined in the plan and to adhere to meal timings. Varia
tion in meal amounts and timings can result in wide of the regimen above (insulin Glargine. Insulin pumps are
being increasingly used in the western world and are
fluctuations in blood sugars, with high blood sugars from
continuously being improved upon. Use of pumps in India
eating excessively and low blood sugars with insufficient
food intake and delayed meals. Variations in physical has been limited, thus far. The infusion pump has signi
ficant advantages over MDI. These include: (i) the ability
activity and exercise will also affect the insulin/blood
to vary the basal insulin during the day and night by using
sugar dynamic. This plan is typically chosen for children
multiple basal rates allowing adjustment of insulin for
who are young and have difficulty with insulin injections.
nocturnal and daytime requirements; (ii) usefulness in
A child who eats at scheduled times and is able to follow
preventing early morning hyperglycemia secondary to
the meal plan is the best candidate. This regimen does not
dawn phenomenon due to morning hormonal surges; (iii)
generate near normal blood sugars as desired for optimal
control of diabetes. The insulin dose in such regimen allowing alteration of basal rates during exercise and
should be adjusted based on SMBG results. The fasting hence preventing post-activity hypoglycemia; (iv) allow
ing boluses to be given in different wave forms (extended,
blood sugar is primarily determined by the prior evening
dual wave, etc.) to account for variable absorption from
NPH insulin. The pre-lunch insulin is determined by the
different foods. High fat foods takes longer to metabolize
morning short acting insulin. The pre-dinner glucose is
determined by the morning NPH. Insulin doses are and result in delayed hyperglycemia which can be
adjusted by 10-20% of the day's dose. addressed using complex boluses with dual wave infusion
with a greater proportion of insulin given two hours after
A more physiologic insulin regimen utilizes multiple
food intake. Extended boluses are used for food consumed
daily injections of Lispro or Aspart with baseline insulin
over two-three hours or longer in small portions.
levels achieved using Glargine insulin (Lantos). In this
regimen, insulin Glargine is given once daily either in the
The disadvantages of insulin pump therapy are:
morning or evening. Short acting insulin is given withinfection at the infusion site, obstruction of the infusion
every meal and snack. The dose of the short acting insulin
set resulting in unexplained hyperglycemia if site is
is determined by the amount of carbohydrate intake andcompletely obstructed; high cost of care; and the nuisance
the level of blood sugar. The dose of the short actingof the insulin pump which is always attached to the child,
being a constant reminder of diabetes.
insulin is calculated based on a carbohydrate ratio (units
Insulin pumps have been used in conjunction with
of insulin per gram of carbohydrate ingested). Most infants
sensor devices that measure trans-dermal blood sugars.
and young children are on one unit of insulin per 20-30
These measurements enable development of graphs with
grams of carbohydrates, while older children on one unit
trends of high or low blood sugars that provide a more
per 10-15 grams of carbohydrate. Adolescents can require
accurate and detailed and dynamic record of blood sugar
as much as 1 unit of insulin per 5 grams of carbohydrate.
profile.of
Example: If a child’s insulin dose is 1 unit per 15 grams
carbohydrate and he is consuming 60 grams of carbohydrate (1
cup of rice and 1 cup of yoghurt) at a meal, the insulin Medical Nutrition
dose for Therapy (MNT)
this meal will calculate as 60/15=4 units. If the blood sugar
MNT in diabetes is important in preventing and treating
is high, additional insulin, called correction dose, is existing diabetes. The goal of nutritional therapy is to
advised to correct the high blood sugar. The correction match nutritional intake with appropriate insulin. Insulin
dose is dependent on the sensitivity of the patient to therapy and self blood glucose monitoring are integrated
insulin which is suggested by the total daily insulin dose. with appropriate nutrition and caloric intake. Flexibility
If a child is on 100 units of daily insulin the child is less in caloric intake, especially to allow exercise, is desired.
sensitive to insulin compared to another patient who is Nutritional plan which allows deviation in food intake
on 50 units a day. The goal of additional insulin therapy incorporating individuals likes and dislikes is imple
is to correct the high blood sugar to the 120 to 180mg/ dL mented.
range; depending on the age of the child and the time of Nutritional plans are aimed at optimizing blood sugar,
dose. Higher targets are set for bedtime and night, and weight, and lipids. Rigid nutritional plans are no longer
for younger children, particularly those under age 3 years. recommended.
An algorithm/formula for assessing correction dose is An individualized nutritional plan is formulated for
taught to patients. Example Correction Insulin= Blood each patient. The plan takes into account meal and snack
Sugar -140/Correction Factor. Correction factor for insulin times as well as food consumption prior to the onset of
514 Essential Pediatrics
diabetes. A flexible plan is determined to facilitate comp Recommended activities include walking, jogging and
liance with nutritional therapy. Simple sugars are discoura swimming and organized sports.
ged. Foods with a low glycemic index are encouraged. Type 2 diabetes mellitus in children and adolescents
Fiber intake is encouraged. Caloric intake is determined The incidence of type 2 diabetes in children and adolescents
based on the formula: age in years x 100 +1000 (example: is rising and parallels the increase in childhood obesity, at
for a 10 years old child, ideal caloric intake is calculated as least in the West and in the more affluent sections of Indian
10 x 100 + 1000 = 2000 calories/day). Nutritional therapy society. Change in dietary habits and lifestyle changes seem
is based on the insulin regimen selected. to have contributed to this increase. Increase in TV
NPH /short noting insulin regimens: A typical plan includes watching and an increase in time spent playing video
3 meals and 3 snacks (midmorning, afternoon and acquiring games rather than outdoor play have resulted in children
bedtime). Number of servings of carbohydrate, protein and type 1 anda 2 sedentary lifestyle. Distinguishing between
fat are determined for each meal and snack. Food choices 16.42). Often children with children
diabetes in
type 2
can be difficult (Table
diabetes may have weight
are discussed. In general, these plans tend to be less flexible. loss and ketoacidosis as the presenting feature. Sometimes
Basal-bolus insulin regimens (Glargine-multiple injections autoantibodies
and are also measured in children with type 2
pump therapy): Carbohydrate counting is taught to patient diabetes. These children are typically overweight, and have
and families along with basic principles of nutrition. a significant family history of type 2 diabetes. They are
Whole grains and complex carbohydrates are encouraged. noted to have acanthosis nigricans, which is a characteristic
Carbohydrates skin appearance seen typically in the neck crease, axilla,
• 55-60 % of total caloric intake antecubital area, groin and the periumblical area. The skin
• Monitoring carbohydrate by carbohydrate counting or with appears dark, thickened and velvety. Children who present
exchanges is suggested ketosis are treated with insulin initially and transi
tioned
• Refined sugars are reduced to <30 % of total carbohy glucose secretion to oral hypoglycemics once their endogenous
drates. recovers. These children and adolescents
should be evaluated
• Naturally occurring sugars in fruits are not limited; pathy, and nephropathy for hyperlipidemia, diabetic retino
however fruit juices are not encouraged. at diagnosis. It is recommended
that children at risk of type 2 diabetes be screened for
Fiber diabetes. The risk factors include obesity, presence of
M • High fiber diet reduces blood sugar acanthosis nigricans, and first degree relatives with type 2
(J • Intake of 25-35 grams / day is suggested diabetes.
lJ] Protein
I • Intake is evaluated based on kidney function, growth Table 16.42: Distinguishing features of type 1 and type 2
W and glycemic function diabetes mellitus
may be set lower if achievable without complication and ketones greater than 1:2 dilution, serum pH <7.3 and se
risk. Younger children have a higher risk of hypoglycemia. rum bicarbonate <15 mmol/L. In moderate DKA, serum
Pre-pubertal children are at a lower risk for long-term pH is <7.2 and serum Bicarbonate<10 mmol/L. Severe
complication than are post-pubertal children. Therefore, DKA is characterized by serum pH< 7.1 and serum bicar
goals for an acceptable range for blood sugars and for bonate^ mmol/L. It can occur in both type 1 and type 2
glycosylated hemoglobin can safely be set a little higher diabetes. Hyperglycemic hyperosmolar state (HHS) is
for younger children. hyperglycemic state seen primarily seen in adolescents
The goals recommended by the ADA and published in with type 2 diabetes. Both disorders are associated with
2007 practice guidelines are shown below (Table 16.43). absolute or relative insulin deficiency, volume depletion
and acidosis. DKA can occur as the initial presentation of
Table 16.43: Goals of blood sugar and Hb A1C type 1 diabetes. 15-70% of all newly diagnosed diabetic
Toddlers and preschoolers (0-6 years)
children present with DKA. The rate of DKA is inversely
Pre-meal glucose: 100-180 mg/dL proportional to the rate of diabetes in the community. The
Bedtime and overnight: 110-200 mg/dL overall rate of DKA in community has remained consistent
HbAlc: <8.5% at 25%. The prevalence of DKA decreases with age from
School age (6-12 years) 36% in children < 5 years of age to 16% in those > 14 years.
Pre-meal glucose: 90-180 mg/dL Mortality rates in children with DKA vary from 0.15-0.3%.
Bedtime and overnight: 100-180 mg/dL However if cerebral edema occurs, death occurs in 20-
HbAlc: <8.0% 25% patients and there is significant morbidity in survi
Adolescents and young adult vors. Cerebral edema accounts for 60-90% of all DKA
Pre-meal glucose: 90-130 mg/dL related deaths in children.
Bedtime and overnight: 90-150 mg/dL
DKA most commonly occurs in children and adole
HbAlc: <7.5%
scents who are non compliant to insulin therapy. Recently
it has also been seen in patients on insulin pump therapy
Sick Day Care due to acute interruption of insulin due to pump malfunc
Children with diabetes require careful intervention at tion. In young patients with type 1 diabetes, psychological
home when they are ill or ketotic. If timely intervention is problems complicated by eating disorders may be a
not provided they can develop diabetic ketoacidosis contributing factor in 20% of recurrent ketoacidosis. Factors
(DKA) a serious and life-threatening complication of that may lead to insulin omission in younger patients
diabetes. Children who are noted to have high blood include fear of weight gain with improved metabolic con
sugars >240 mg/dL and or are ill should be tested for trol, fear of hypoglycemia, rebellion from authority, and
ketosis. (3 hydroxybutyrate and aceto-acetic acid can be stress of chronic disease. Infection is believed to be one of
measured in blood or urine. Based on the level of ketosis the main precipitating factors.
additional insulin is provided every 2 hours. This ranges Pathophysiology
from 5-20% of the total daily dose as short acting insulin.
Blood sugar is monitored and parents are advised to push The most important factor that contributes to pathogenesis
fluids. If child is vomiting, 30 ml of fluid is given every 15 of DKA is insulin deficiency. This coupled with an increase
minutes. The choice of fluid is dependent on blood sugar in counter-regulatory hormones namely glucagon, growth
level. Sugar containing fluids are given if blood sugar is hormone and cortisol augments glucose production from
normal or low. Scheduled insulin is never omitted. If child glycogenolysis and gluconeogenesis while limiting
is vomiting and unable to drink or eat substantially, the glucose utilization. These hormonal alterations result in
day's insulin is split in small frequent doses. At these times hyperglycemia and lipolysis resulting in increased free
the daily requirement of insulin increases. Parents are fatty acid production. Oxidation of fatty acids in liver
advised to bring the child to the emergency room if the generate (3-hydroxybutyrate and acetoacetic acid (ketones)
child is noted to have altered sensorium, rapid breathing, which results in acidosis and ketosis. Hyperglycemia
fruity odor, signs of dehydration, persistent vomiting and results in osmotic diuresis causing dehydration and
persistent ketosis. hypovolemia and can progress to severe dehydration and
shock. Dehydration also causes lactic acidosis which
COMPLICATIONS OF DIABETES increases acidosis. Ketosis and acidosis results in
electrolyte imbalances and other most diagnostic manifes
Diabetic Ketoacidosis tations of DKA including fruity odor and rapid respi
Diabetic ketoacidosis (DKA) is the most common severe rations (Kaussmaul's breathing). Acidosis causes shift of
complication of diabetes mellitus. DKA is a state of intracellular ions most importantly potassium and
hyperglycemic dehydration and ketotic acidemia. It is phosphate to the extracellular compartment. These are lost
characterized by hyperglycemia, acidosis and ketosis. in urine in excess amounts resulting in total body
Blood sugar is typically over 250 mg/dL, ketonemia with potassium and phosphate depletion. However, serum
516 Essential Pediatrics
Symptoms Physical findings Hypoglycemia is defined as blood sugar less than 60 mg/
dL. Low blood sugar usually occurs when there is mis
Abdominal pain Tachycardia
match of food and insulin or the child has been unusually
Nausea and vomiting Dry mucous membrane/reduced skin
active and insulin and/or food has not been adjusted for
turgor,/hypotension
increase in activity. Counter-regulatory hormones namely
Polyuria/polydipsia Tachypnea/Kussmaul respirations/ adrenalin, glucagon and cortisol are secreted in the body's
respiratory distress attempt to correct the hypoglycemia. Adrenergic symp
Shortness of breath Abdominal tenderness toms such as tremors, pallor, tachycardia, and sweating can
Lethargy/cerebral edema/coma be seen. If left untreated, more severe symptoms from
neuroglycopenia (decreased availability of glucose to the
brain) may rapidly ensue; these include seizures, fainting
Laboratory Evaluation and coma. Prevention of hypoglycemia should be discus
Criteria for confirmation of diagnosis of DKA include sed with the patient and family during diabetes education
blood glucose >250 mg/dL, blood pH <7.3 and serum sessions. Treatment involves a rule of 15, i.e. 15 grams of
bicarbonate <15 mmol/dL. Serum K+ may be elevated or free sugar are given in form of sugar, honey, juice or carbo
normal initially but declines with therapy. Serum Na+ is nated drink, followed by recheck of blood sugar in 15
low and elevated and creatinine are reflective of minutes. If the child is unconscious glucagon is adminis
dehydration. Leukocytosis and hypertriglyceridemia are tered intramuscularly. The dose is dependent on the age
found. In DKA serum ketones are elevated and (3- and weight of the child. (Infants 0.3 mg, child <25 kg: 0.5
hydroxybutyrate is three fold higher than acetoactate. mg and child> 25 kg 1.0 mg). If glucagon is unavailable
Acetoacetate is preferentially detected by ketosis detection intravenous dextrose is given.
reagent (nitroprusside). Serum ketones are present in
significant levels (positive at serum dilution of >1:8). Intermediate Complications
Plasma assays of (3- hydroxybutyrate more accurately Lipoatrophy is fat atrophy at the injection site. This can be
reflect the true ketone body level. prevented by rotation of injection sites.
Endocrine and Metabolic Disorders 517
Table 16.45: Practical guide for assessment and management of diabetic ketoacidosis
INITIAL ASSESSMENT
History
1. New onset diabetes: Evaluate onset and duration of symptoms
2. Known diabetic, evaluate :
• Precipitating factors (insulin dose, illness, stress, dietary indiscretions)
• History of diabetes (date of diagnosis, previous hospital admissions related to diabetes, insulin dose).
• Duration of symptoms
• Recent home glucose levels; duration of urine ketones if tested at home
• Most recent insulin dose and timing
Physical examination
• Vital signs; hydration status; infections
• CNS status—Glasgow coma scale
• Signs of acidosis
Laboratory
• Bedside blood glucose; urine for glucose and ketones.
• Complete metabolic panel, HbAlc, lipid profile, insulin autoantibodies, anti GAD-65 antibodies, anti islet cell antibodies.
• Blood gas and serum electrolytes every 4 hours
• Calcium, magnesium and phosphate every 12 hours
• Appropriate cultures, X-rays
ACUTE MANAGEMENT
A. Fluids and electrolytes (Goal: correct dehydration over 24^48 hours)
1. Initial fluid bolus should be determined based on blood pressure and capillary refill
• Usually 10-20 mL/kg as normal saline bolus is given over the first hour
• Hypovolemic shock—continue fluids for another hour
• Isotonic fluids (normal saline) to be continued till blood sugar 300 mg/dL
2. Calculate fluids based on 10% dehydration.
3. Total fluids must not exceed 4000 ml/m2/day, unless patient is in hypovolemic shock.
4. IV fluids are without glucose until blood glucose (BG) is 250-300 mg/dL. Add 5% dextrose when BG is 250-300 mg/dL and
10% glucose when BG is <180 mg/dL.
5. Potassium (20-40 mEq/L; % KC1 and Vi KP04) is added in fluids after urine flow is established and serum K+ is <5.5 mEq/
L.
B. Use of bicarbonate
1. Bicarbonate is not used routinely in management of DKA
2. To be considered if pH does not improve and arterial pH remains <7.0 (venous pH <6.9) and serum bicarbonate is less than
5-10 mEq/L. Do not use bicarbonate when serum bicarbonate is >10 mEq/L.
3. Plan half correction of deficit in 24 hours. (Assume total bicarbonate 25 mEq/L for arterial and 27 mEq/L for venous
blood.)
4. Calculate deficit as follows: (Normal bicarbonate - actual bicarbonate) x 0.6 x patients Wt in kg = Total deficit.
5. Start correction with adding Vi deficit in IV fluids to run over 24 hours.
6. Discontinue bicarbonate in IV fluids when serum bicarbonate reaches >10 mEq/L and serum pH > 7.1.
C. Insulin therapy
1. Start insulin drip at 0.1 units/kg/hour. If patient is a known diabetic and has received insulin subcutaneously start lower
insulin dose 0.05 u/kg/hr
2. When blood glucose <300 mg/dL, change IV fluids to 5% dextrose with 0.45 saline.
3. If blood glucose drops to <180 mg/dL, inspite of D5 in IV fluids, change IV fluid to 10% dextrose in 0.45 saline.
4. If blood glucose drops to <150 mg/dL, reduce insulin drip in decrements of 0.02 unit/kg/hour.
5. The rate of fall of plasma glucose should be 80-100 mg/hr or 40 mg/hr in the presence of severe infection. If there is no
change in plasma glucose in 2 x 3 hours, increase the insulin infusion (0.15 U/kg/hr).
6. When patient is acidotic and ketotic never decrease insulin infusion below 0.05 U/kg/hr and never discontinue insulin
infusion until after subcutaneous insulin has been given.
7. Monitor blood glucose every 30 minutes when changing insulin drip or if blood glucose drops <150 mg/dL.
8. Insulin must be continued until pH >7.36 or serum bicarbonate >20 mEq/L.
D. Monitoring
• Fluid balance: intake and output hourly to adjust IV rate every four hours.
• Vital signs: every hour; neurological signs: alertness, Glasgow coma scale, pupils every 2 hours; weight daily
• Venous pH, serum HCOj and serum ketones every two hours initially and then less frequently. If acidosis is severe and
bicarbonate is being given, hourly pH is indicated.
• Bedside blood sugar hourly; serum electrolytes every two hours; if stable, every four hours.
518 Essential Pediatrics
Limited joint mobility is typically noted in the hands. This Screening for Chronic Complications
occurs due to flexion contractures of the metacarpophalan in Type 1 Diabetes Mellitus
geal and proximal interphalangeal joints.
Growth failure occurs in children whose diabetes is not well Nephropathy
controlled. Mauriac syndrome occurs with poor control of • Annual screening of microalbuminuria should be ini
diabetes. These children have hepatomegaly, pale skin and tiated once the child is 10 years of age or has had dia
extreme short stature. betes for 5 years.
Delay in sexual maturation is associated with inadequate • Screening is done by testing random spot urine for
control of diabetes. These children have delayed bone age. microalbumin to creatinine ratio.
Hypoglycemic unawareness is caused by frequent hypo
• Abnormal screening test is confirmed with 24 hour
glycemia associated with tight metabolic control of urine microalbumin /creatinine ratio. Patients with
diabetes. It is due to impaired counter regulatory response elevated microalbumin/creatinine ratio are treated
to hypoglycemia. Raising blood sugar targets and with ACE inhibitors.
prevention of hypoglycemia usually causes reversal of Dyslipidemia
hypoglycemic unawareness.
Fasting blood levels of lipids are estimated annually. The
Chronic Complications goal of therapy is to maintain LDL <100 mg/dL.
Retinopathy in diabetes is characterized by microaneur
ysms and proliferative disease. Previously 80-90% of Retinopathy
individuals developed eye disease by 15 years of diabetes. • First ophthalmologic exam is suggested once child is >
With intensive management of diabetes this occurrence 10 years of age and has had diabetes for 3-5 years
is being delayed. Virtually all children and adolescents • Annual follow up is suggested.
with well controlled diabetes have lack of retinopathy in Celiac Disease
the pediatric years.
Nephropathy causes significant morbidity and morta Evaluation for celiac disease involves testing for serum
lity in the adult years. It is defined by leaking of albumin IgA, anti-gliadin antibodies, and transglutaminase
in the urine. It is preceded by microalbuminuria. Treat antibodies. Further evaluation is suggested if these
ment with ACE inhibitors can delay the progression of antibodies are elevated.
nephropathy. Suggested reading
Peripheral neuropathy is unusual in children and Dunger DB, Sperling MA, Acerini CL, Bohn DJ et al. European Society
adolescents. This results in decreased nerve conduction for pediatric endocrinology/Lawson Wilkins Pediatric Endocine Society
velocity and sensory changes are common. An abnor Consensus Statement on diabetic ketocidosis in children and
mality in vibration perception is first noted. adolescents. Pediatrics 2004;113:el33-140.
17 Central Nervous System
nasolabial fold on the ipsilateral side, pulling of the angle The CSF should be examined grossly for its appearance
of the mouth on contralateral side and drooling of saliva and microscopically for number and type of cells. Protein,
indicates paralysis of seventh nerve. Wincing or closing sugar and chloride content estimation is routinely
of eyes in response to noise indicates intact auditory performed. Culture and serology of CSF should be carried
functioning. Ninth and tenth nerve integrity is determined out if infection is suspected.
by gag reflex, nasal twang, nasal regurgitation and
position of the uvula. If the child can shrug his shoulders, Electroencephalogram (EEG)
eleventh nerve (accessory) is intact. In twelfth nerve palsy,
Electroencephalogram is a common and conventionally
the tip of the tongue is turned to the side of the lesion. employed electroneurophysiological test. Electrical
Motor Examination
activity from the surface of the brain is recorded by placing
a set of electrodes in a specific arrangement on the scalp
Best power in all limbs, during spontaneous movement (montages). Recorded rhythms are evaluated by their rate,
and against gravity and resistance should be recorded. amplitude (|iV), symmetry and morphology. The various
Deep tendon reflexes: These are best elicited when the con rhythms include fast activity beta rhythm at 14-20 Hz
cerned muscle groups are relaxed. Exaggerated deep (cycles/sec), alpha rhythm at 8-13 Hz, theta rhythm at 4-
tendon reflexes imply upper motor neuron lesions and 7 Hz and slow rhythm or delta at 1-3 Hz. Activity faster
diminished reflexes are observed in lower motor neuron than beta is an artifact from the scalp muscles. Fig. 17.1
disease, neuropathies, advanced muscle diseases and depicts a normal EEG record.
disuse atrophy. Cerebellar lesions cause pendular jerks.
Plantar response may be normally extensor until the age of
one year.
Developmental Examination
This aims to confirm the milestones stated by the mother.
In infancy, besides tone, posture, neonatal reflexes, head
control, appearance of protective reflexes, and the ability
to attain gross motor functions should be examined, using
standard tests/charts of development to confirm delayed
development in various domains.
INVESTIGATIONS FOR NEUROLOGICAL DISEASES
Fig. 17.1 : Normal EEG, in a 5-year-old child. Note normal posterior
Neurological investigations may serve to (i) confirm the dominant alpha background activity
diagnosis and etiology; (ii) identify the site of lesion; (iii)
rule out other conditions; (iv) review the progress of Indications: EEG is useful in classifying and diagnosing
disease; and (v) evaluate the response to treatment. electrical correlates in epilepsy. The EEG is essential to
distinguish between a seizure and non-seizure state, e.g.
Lumbar Puncture
fainting spells, hypoxic episodes and breath holding spells.
Lumbar puncture is indicated in inflammatory CNS EEG is especially helpful for making the diagnosis of
disorders, neonatal sepsis, neurologic malignancies (to absence attacks, herpes encephalitis and myoclonic epi
determine CNS spread and for therapy), autoimmune lepsies, nonconvulsive status and epilepsy syndromes,
diseases, demyelinating illnesses, slow virus infections and to correlate background rhythm with metabolic/
specially subacute sclerosing panencephalitis (SSPE) (for organ failure. EEG is not indicated in typical febrile con
virological studies, oligoclonal bands and immune vulsions.
response), and certain neurometabolic disorders (for CNS There is no indication to stop anticonvulsants before
metabolites). Lumbar puncture is not indicated in every an EEG, in case the child is already receiving them. A natu
case of febrile convulsions except in infants or if meningo ral sleep record obtained by asking the mother to wake
encephalitis needs to be excluded. the child early on the day of EEG is useful. A sleep depri
Fundus must be examined prior to procedure to vation EEG record is useful where an initial EEG is normal
exclude papilledema, as sudden release of cerebrospinal yet seizures are suspected.
fluid pressure following lumbar puncture may result in
medullary coning and cardiorespiratory arrest. Full Abnormalities: The common abnormalities of background
aseptic conditions should be maintained while doing include slow/abnormal or asymmetric rhythms; these
lumbar puncture to obviate iatrogenic infection. Cerebro may be generalized, localized or lateralized to one side
spinal fluid (CSF) pressure appears low when there is thick and thus help to localize anatomic lesions. In addition,
pus in the subarachnoid space which cannot easily come spikes, sharp waves, polyspikes or hypsarrhythmia may
out of the thin LP needle. be seen in seizure disorders (Fig. 17.2).
Centra! Nervous System 521
and glucose uptake in different parts of brain like conjugate deviation of the eyes. These should be
cerebrum, cerebellum, thalamus and basal ganglia. These distinguished from jitteriness, tremors, startle response
scans are of practical utility in the evaluation of surgically to stimuli, sudden jerks on awakening and tremulousness
resectable lesions in intractable epilepsy, cerebral tumors of the hungry child.
and head injuries. PET scans can be modified to assess Common causes of convulsions are better classified
cerebral blood volume, cerebral blood flow, oxygen and according to the age at onset (Table 17.1).
cerebral glucose metabolism. These have been used as
research tools for assessing brain development, speech and Approach to a Child with Convulsions
vision dysfunction. PET is extremely useful for localization A good description of the seizures including mode of onset,
of an anatomic focus in presurgical work up of intractable details of aura, type of seizure, automatism, associated
epilepsy. behavioral abnormalities and the postictal phase should be
SPECT scans utilizing HMPAO and ECD are now widely obtained. An accurate seizure description is more
available. They are useful to identify perfusion in ictal and informative than detailed neurological examination or
interictal states. Increased perfusion in the ictal phase is investigations. Perinatal, developmental, and family
suggestive of an epileptogenic focus. It has become an history of seizures help in determining the cause. The child
important presurgical investigation of intractable epilepsies. should be examined for evidence of raised intracranial
tension, degenerative, metabolic or congenital disorders.
Others
Digital subtraction cerebral angiography is done to evaluate Table 17.1: Causes of convulsions
cerebrovascular disorders. Carotid Doppler studies can be Early neonatal period
used to study flow patterns. Myelography is used for Birth asphyxia, difficult obstructed labor
investigating compression of the spinal cord. Metrizamide Intraventricular, intracerebral hemorrhage
myelogram can be performed to evaluate compressive Pyridoxine dependency, hypoglycemia, hypocalcemia,
myelopathies on the CT scan. In some cases needle biopsy dysnatremia
of the brain may be obtained for histochemical studies. Inborn errors of metabolism
Psychometric tests are carried out for measuring cognitive Maternal withdrawal of medications
ability and intelligence of patients with suspected mental Injection of local anesthetic into the fetal scalp during the
retardation. paracervical block given to the mother
Neonatal period
Suggested reading Hypocalcemia, hypomagnesemia, hypoglycemia, dyselec-
1. Brett EM. Normal development and neurologic examination trolytemia
beyond the newborn period. In: Brett EM. Pediatric Neurology. Kernicterus
3rd edn. London: Churchill Livingstone 1997; 25-50. Developmental malformations, microcephaly, porencephaly,
2. Swaiman KF, Ashwal S, Ferriero DM. Pediatric Neurology; arteriovenous (AV) fistulae, agenesis of corpus callosum
Principals & Practice. 4th edn. Philadelphia: Mosby 2006 Meningitis, septicemia, tetanus neonatorum, intrauterine
infections
CONVULSIONS __ Metabolic errors: Phenylketonuria, maple syrup urine disease,
galactosemia, urea cycle disorders, homocystinuria
Convulsions are caused by abnormal electrical discharges
from the brain resulting in abnormal involuntary, One month to three years
Early and effective treatment is essential to prevent a the injection (5 mg/mL) or syrup (2 mg/5 mL) form can
refractory status and long-term neurological sequelae. be used. The usual rectal dose for diazepam is 0.2 to 0.5
Many anticonvulsant protocols and treatment guidelines mg/kg. A size 8 feeding tube after lubricating with
are reported from various institutions and groups. Most xylocaine/paraffin is injected per rectum up to 4 cm.
importantly, every institution should have a well- The required dose of the drug is injected through the
established treatment protocol depending upon the local feeding tube and then flushed with tap water. Only a
availability of drugs. A proposed management protocol single prehospital dose of rectal diazepam should be
is shown in Fig. 17.6. given by the caretakers to avoid possibility of respiratory
depression.
Domiciliary Treatment The rectal route of administration is not always
Pre-hospital treatment is advocated for all children with acceptable or convenient. A promising alternative is
recurrent prolonged seizures. Home use of anticonvul midazolam by buccal or nasal route. A few studies have
sants in chronic epileptics can reduces hospitalization found buccal and nasal midazolam to be as effective as
episodes, cost and status. The drug that is most commonly rectal diazepam in the acute treatment of seizures.
used is oral midazolam or rectal diazepam. Diazepam in
Hospital Treatment
Any child who presents actively convulsing to emergency
room should be assumed to be in SE and managed
aggressively. The benzodiazepines are potent first line
agents. The drug routinely recommended is lorazepam or
diazepam. If diazepam is used when treating SE, a long
acting anticonvulsant such as phenytoin must be adminis
History, examination, investigations tered concurrently with diazepam to prevent recurrent
to ascertain cause
convulsions. Diazepam should be administered by the
intravenous (IV) route, if IV line has been expeditiously
Assess and maintain airway, breathing, give oxygen,
establish IV line, estimate blood glucose established. Diazepam stops convulsion within 5 minutes
in 80% of patients. The usual IV dosage for diazepam is 0.1
Initiate specific therapy if indicated to 0.3 mg/kg given at a rate of 1 mg/min. This dose can be
\ / repeated two or three times every 5 to 10 minutes if seizures
Diazepam IV or lorazepam IV, repeat persist up to a maximum dose of 10 mg. Many centers
after 10 min if seizure continues prefer use of lorazepam (0.05-0.1 mg/kg 1/V) as a first line
anticonvulsant as it has a longer duration of action (12-24
Phenytoin or Fosphenytoin (IV) hours), less respiratory depression and repeated doses are
less often required than with diazepam. A second long-
.................... r iiz acting anticonvulsant is also not required because of longer
IV Phenobarbital or IV valproate
duration of action. Maintenance drugs should be added to
control further seizures.
IM/rectal Paraldehyde If IV access cannot be immediately obtained, then other
routes of administration (rectal, oral) should be consi
......... I dered. The intraosseous route requires an invasive
Midazolam infusion
procedure. Rectal lorazepam is not preferred as it has a
-J—1 slower onset of action compared with rectal diazepam.
Pentobartbital coma The liquid formulation of valproic acid per rectally in a
dose of 20 mg/kg can also be used but response to rectal
Fig. 17.6: Algorithm for management of status epilepticus valproate is slower than with rectal diazepam.
Central Nervous System 527
Coupled with potent anticonvulsant properties and the followed by phenytoin or phenobarbitone or both or
ease of administration by intramuscular, nasal or buccal seizure lasting more than 60 minutes after treatment has
route, midazolam may prove to be an important drug for been started, it is labeled as refractory SE. It is associated
the initial management of acute seizure when IV access is with potentially fatal complications including severe
not available. The dose used is 0.1 to 0.2 mg/kg. The safety, hemodynamic and respiratory compromise. Patients with
optimal dosing and the clinical trials of midazolam for refractory SE must be ideally managed in a tertiary health
initial management of SE, however, needs further care center with intensive care unit where facility for
evaluation. artificial ventilation is available. The modalities for
Phenytoin is useful for maintaining a prolonged treatment of refractory SE include barbiturate coma,
antiseizure effect after rapid termination of seizures with midazolam or diazepam infusion, lignocaine, intravenous
a benzodiazepine or when they fail. The loading dose is valproate, propofol, and inhalation anesthesia.
15 to 20 mg/kg infused at a rate of 0.5 to 1.0 mg/kg/min In a recent meta-analysis, midazolam infusion was
(maximum 50 mg/min). A therapeutic effect can be seen found to be a good choice for initial treatment of refractory
in 20 minutes. Saline solution should be used for infusion SE. Compared to pentobarbital, midazolam has fewer
because phenytoin can precipitate in dextrose solution. hemodynamic consequences minimizing the need for
The side-effects include hypotension, cardiac dysarrhy- invasive monitoring. The need for endotracheal intubation
thmia, phlebitis and tissue necrosis from extravasation, and mechanical ventilation is also less frequent with
movement disorder and cerebellar ataxia. midazolam. Patient recovery is also quicker allowing
Fosphenytoin is a water-soluble ester of phenytoin that earlier assessment after SE, and shortening the duration
is rapidly converted to phenytoin by systemic phospha of ICU stay. A bolus dose of 0.15 mg/kg of midazolam is
tases. Fosphenytoin can also be thus administered intra followed by continuous infusion at a rate of 1 |ag/kg/min
muscularly. The dose of fosphenytoin is expressed in increasing by 1 ng/kg/min every 15 minutes until a maxi
phenytoin equivalents (PE) and is 15-20 mg/kg, infused mum of 18 (ig/kg/min or seizure control. The optimum
at a rate of no more than 3 mg/kg/min (maximum 150 rate of infusion at which seizure control is achieved is
mg/min). Phlebitis is less common with fosphenytoin but maintained for a period of 48 hours. Subsequently the
its primary disadvantage is high cost. infusion rate is gradually decreased by 1 |ag/kg/min every
In case of no response to benzodiazepines and two hours. Any seizure activity during the weaning period
phenytoin, phenobarbitone is administered in a loading dose requires an immediate resumption of the infusion to
of 10 to 20 mg/kg at a rate of 1 to 2 mg/kg/min. Potential achieve again a seizure-free period of 48 hours.
side effects include hypotension, respiratory depression, Both pentobarbital and thiopental have been used for
sedation and bradycardia. It must be used with caution barbiturate coma. Patients requiring barbiturate coma
in patients who have already received a benzodiazepine must be intubated and mechanically ventilated with close
because respiratory depression may be exacerbated. hemodynamic and continuous EEG monitoring. Pento
Phenobarbitone is the drug of choice in neonatal seizure, barbital is given in a loading dose of 5 mg/kg followed
hypersensitivity to phenytoin and cardiac conduction by an infusion of 0.5-3 mg/kg/hr. The patient is
abnormality. monitored for a burst suppression pattern by EEG. The
If the patient is already receiving phenytoin or patient remains in barbiturate coma for 12 to 24 hours
phenobarbitone, 5-10 mg/kg of the drug should be given The patient is then weaned and observed for recurrence
before repeating the dose of diazepam or starting another of seizure activity. If seizure recurs, the patient is placed
drug because drug withdrawal is the most likely cause of back into the barbiturate coma and weaning is again tried
SE in such cases. Determine the phenytoin level in the after another 24 hours. Barbiturate coma is advantageous
acute phase to avoid toxicity. over the use of general anesthesia.
Paraldehyde can be administered per rectally (0.3 mL/ General anesthesia with isoflurane or halothane in
kg diluted 1: 3 in olive or coconut oil) or intramuscularly conjunction with a neuromuscular blockade can also be
(0.15 mL/kg deep IM due to high incidence of sterile used for refractory SE. Neuromuscular blockade results
abscesses) in case seizures are continuing. Paraldehyde in muscle paralysis and facilitates mechanical ventilation.
should be given in a glass syringe as it dissolves plastic. If Continuous EEG is necessary to ensure that burst
signs and symptoms of raised intracranial pressure are suppression has occurred when the patient is paralyzed
present, mannitol can be administered in a dose of 5 mL/
kg (20%) IV over 10 minutes to decrease cerebral edema. First Time Seizure: When to Initiate Long-Term
Maintenance therapy should be simultaneously started Anticonvulsant Drugs?
with appropriate AED. The decision for therapy is based on the underlying cause
of the seizure, the results of the head CT or MRI and EEG.
Refractory Status Epilepticus All of these data are rarely available before discharge from
When the seizure has not responded to at least two doses the emergency room, consequently the decision to initiate
of diazepam intravenously or rectally in succession therapy must be based on the predicted risk for seizure
528 Essential Pediatrics
recurrence, which depends on the underlying etiology of important causes of convulsions associated with fever and
the seizure. When no etiology is identified and the EEG can be easily confused with simple febrile convulsions.
findings are normal, the recurrence risk is 24% at 2 years. LP should be performed in the first episode of febrile
Patients who have structural lesion on CT or patients with seizure, in infants below 1 year or where meningitis is
focal seizure that secondarily generalize have a risk of suspected. In all patients with febrile convulsions, a
recurrence of up to 65% and are the group of patients that lumbar puncture is not required routinely. EEG and
probably benefit from initiating long-term anticonvulsant neuroimaging have no role in febrile seizures.
therapy. Treatment: Febrile convulsions are managed by prompt
Suggested reading reduction of temperature with antipyretics or hydro
1. Rosenow F, Arzimanoglou A, Baulac M. Recent developments in therapy to comfort the patient. Supportive therapy, nurs
treatment of status epilepticus: A review. Epileptic Disord. 2002;4 ing in semi-prone position, adequate airway and oxygen
Suppl 2:S41-51. should be assured. An intravenous line should be started
2. Bleck TP. Management approaches to prolonged seizures and to maintain hydration, to give anticonvulsant medication
3.
status epilepticus. Epilepsia 1999;40 Suppl 1 :S59—63.
Bleck TP.Intensive care unit management of patients with status
or to obtain blood specimens for investigation. Possibility
epilepticus.Epilepsia 2007;48 Suppl 8:59-60. of meningitis should be excluded by a lumbar puncture if
4. Brevoord JC, Joosten KF, Arts WF, et al. Status epilepticus: clinical indicated. Aspirin should be avoided because of appre
analysis of a treatment protocol based on midazolam and hension of development of Reye's syndrome. Injection of
phenytoin. J Child Neurol 2005;20:476-481. diazepam (0.2-0.3 mg/kg/dose) slow push IV (maximum
5. Hanhan UA, Fiallos MR, Orlowski JP. Status epilepticus. Pediatr
Clin North Am 2001;48:683-694.
of 5 mg/dose) is given for control of seizures. Pheno
6. Prasad K, Al-Roomi K, Krishnan PR, Sequeira R. Anticonvulsant barbitone is slower acting than diazepam but has a more
therapy for status epilepticus. Cochrane Database Syst Rev 2005 sustained action. When given IV, action starts within 5-
Oct 19; (4): CD003723. 10 minutes but peak concentration in brain is reached in
7. Abend NS, Dlugos DJ.Treatment of refractory status epilepticus:
literature review and a proposed protocol.Pediatr Neurol
30 to 60 minutes.
2008;38:377-390.
Febrile Seizure Prophylaxis
FEBRILE CONVULSIONS Prophylaxis of febrile convulsions is indicated if febrile
episodes are recurrent (30-40%). Prophylaxis may be
Febrile convulsions are the commonest provoked seizures continuous or intermittent.
and 3-5% of children experience them. They are defined
as seizures during fever occurring between 6 months to 5 Intermittent prophylaxis is currently the desirable form of
years age in the absence of infection of the central nervous therapy during episodes of fever. Intermittent drug
system in a neurologically normal child. Febrile seizures prophylaxis is indicated for the first three days of fever as
are frequently genetically determined. The convulsions majority of episodes occur within this period. A drug that
are not related to the degree of temperature rise but are attains drug levels quickly and prevents febrile convul
frequent if temperature rises abruptly. The febrile convul sions should be used. Diazepam and other benzodia
sions may be (i) simple, benign; or (ii) atypical, complex. zepines attain desired levels quickly and may be given as
Simple benign febrile convulsions: The fits occur within a24solution per rectum, suppository or via oral route. Oral
hours of the onset of fever, last less than 10 minutes and diazepam, midazolam and clobazam are effective prophy
are usually single per febrile episode. Convulsions are lactics. Other agents given orally do not attain desired
generalized; 4-18% may show focal convulsions. There is concentrations quickly and are hence unreliable for inter
no post-ictal neurological deficit. There may be a family mittent therapy. Intermittent phenobarbitone is of little
history of febrile convulsions in the siblings. use as blood levels are not achieved by intermittent use.
Atypical febrile seizures: Atypical or complex febrile con Antipyretics, hydrotherapy and meticulous temperature
vulsions should always be distinguished from simple care recording should be advocated for all patients. Domiciliary
febrile convulsions by the clinical criteria enumerated is recommended.
above. Presence of family history of epilepsy, neurodeve- Continuous prophylaxis in the form of antiepileptic drug
lopmental retardation and atypical episodes increase therapy is advocated in the event of failure of intermittent
recurrence risk of febrile episodes and subsequent therapy, especially in recurrent atypical seizures or family
epilepsy. history of epilepsy. Only sodium valproate (10-20 mg/
Convulsions due to neurological damage may also be kg/day) or phenobarbitone (3-5 mg/kg/day) are effective
precipitated by fever, as the cerebral threshold for seizures for febrile seizure prophylaxis. Carbamazepine and
is reduced with the elevation of temperature. These are phenytoin are ineffective. The duration of therapy should
distinct from febrile convulsions, which occur in a be for 1-2 years or until 5 years of age, whichever comes
neurodevelopmentally normal child. earlier.
Differentiation from meningitis : Infections of the central Prognosis: Recurrence risk of febrile convulsions varies
nervous system such as meningitis or encephalitis, are from 30-50% and is greater with younger age, female sex,
Central Nervous System 529
presence of risk factors and atypical prolonged episodes. Table 17.4: Classification of epilepsy
About 1-2% of children with simple febrile convulsions Generalized
and up to 5% of those with recurrent complex seizures Generalized epilepsy may be (i) tonic clonic (grand mal), (ii)
are likely to develop epilepsy. Parents of the child should tonic, (iii) clonic, (iv) absence (petit mal), (v) atonic, akinetic
be reassured that the risk of epilepsy after simple febrile (minor, motor), (vi) bilateral epileptic myoclonus syndromes
seizure is not significantly greater than the general popu Idiopathic, (i) benign neonatal convulsions, (ii) childhood
lation. The risk of developing epilepsy is higher if the sei absence, (iii) juvenile absence, (iv) juvenile myoclonic epilepsy,
zures are atypical, i.e. last more than 15 minutes, are focal, (v) grand mal seizures on awakening, (vi) generalized
electroencephalogram is persistently abnormal, if the child idiopathic
has abnormal neurodevelopment or a family history of Cryptogenic, (i) West syndrome (infantile spasms), (ii) Lennox
epilepsy. Complex partial seizures may manifest after Gastaut syndrome (childhood epileptic encephalopathy), (iii)
several years of prolonged atypical/febrile convulsions. myoclonic-astatic seizures, (iv) myoclonic absences
The role of febrile seizures as an etiological cause for Localized
temporal lobe epilepsy is uncertain. Simple partial (elementary symptoms, no impairment of
consciousness) with (i) motor, (ii) sensory, (iii) autonomic, (iv)
Suggested reading mixed symptoms
1. American Academy of Pediatrics. Practice parameters: Febrile Complex partial (impaired consciousness) (i) simple partial but
seizures. Pediatrics 1996; 97: 769-775. with loss of consciousness; and (ii) with automatism
2. Dube CM, Brewster AL, Richichi C, Zha Q, Baram TZ.Fever, febrile Syndromes
seizures and epilepsy .Trends Neurosci. 2007;30(10):490-6. Epub
2007 Sep 25. Idiopathic. Benign childhood focal epilepsy with centrotemporal
3. RJ.Technical report: treatment of the child with simple febrile spikes or Rolandic epilepsy. Epilepsy with occipital paroxysms
seizures.Pediatrics. 1999;103(6):e86. Symptomatic, (i) Chronic progressive epilepsy; (ii) epilepsia
4. Jankowiak J, Malow B.Seizures in children with fever: Generally partialis continua
good outcome.Neurology 2003 Jan 28;60(2):El-2.
Undetermined syndromes
5. Cendes F.Febrile seizures and mesial temporal sclerosis.Curr Opin
Neurol 2004 Apr;17(2):161-4. Neonatal seizures
Severe myoclonic epilepsy of infancy
EPILEPSY................................................................................... Epilepsy with continuous spike waves during slow wave sleep
Acquired epileptic aphasia
Definition
Epilepsy is characterized by recurrent, episodic, paro
xysmal, involuntary clinical events associated with clonic; (ii) absence fits (petit mal); (iii) atonic, akinetic or
abnormal electrical activity from the neurons. The patient minor motor; and (iv) myoclonic.
may present with motor, sensory or psychomotor pheno
mena, often with alteration in sensorium. Tonic-Clonic Seizures (Grand Mal Type)
Epidemiology
Generalized tonic-clonic seizures are the most frequent
form of childhood epilepsy. Classic form has four phases
Five percent of children are estimated to experience one viz. (i) aura; (ii) tonic; (iii) clonic; and (iv) postictal phase.
or more seizures in childhood, less than 1% have epilepsy.
The incidence is highest in the preschool years. Intra- Aura: A transitory premonitory symptom or aura heralds
familial recurrence of convulsions, especially simple the onset of a seizure. The child may recognize the impend
febrile convulsions, is common. ing seizure by the aura and adopt measures for self
protection. Aura may be sensory, visceral, motor or auto
Classification nomic. Only one-third of patients can describe the aura
Epilepsy is classified by appraisal of (a) seizure type, (b) properly.
etiology and (c) electroencephalographic data. If the Tonic phase: During this phase, skeletal muscles go into a
underlying etiology is identified it is symptomatic epilepsy sustained spasm. Spasm of the laryngeal muscles forces
otherwise it is called idiopathic. In cryptogenic a cause is the air out from the lungs through a partially closed glottis
presumed. A simplified modified version of the classi resulting in a shrill cry. The muscular rigidity is most
fication proposed by the International League Against marked in the antigravity muscles, such as flexors of arms
Epilepsy (ILAE) is given in Table 17.4. and extensors of lower extremities. The child becomes
unconscious and falls on the ground. The face appears
Clinical Features of Epilespy pale, pupils are dilated and eyes are rolled either upward
For the purpose of clinical description epilepsy may be or to the side. There is frothing from the mouth. Urine or
broadly described as generalized or partial (focal). stools may be passed involuntarily. Later, the face appears
Generalized seizures may be (i) tonic, clonic or tonic- suffused. This phase lasts for about thirty seconds.
530 Essential Pediatrics
Clonic phase: It is characterized by rhythmic alternating ii. Complex partial with impairment of consciousness and
contractions of muscle groups, which persist for a few automatisms, psychomotor or limbic system symp
minutes. In many patients, epileptic phases overlap each toms.
other. iii. Partial with secondary generalization.
Postictal phase: The child may complain of headache, Simple partial seizures begin with a focal epileptiform
confusion, perform automatic actions, of which he has little discharge, howsoever brief. The symptoms are generally
recollection later. Rarely, the child develops a transient motor or sensory depending on the cerebral focus. Sensory
paresis, may lose bladder/bowel control or injure himself. symptoms include tingling, pain, sensation of cold,
Unlike in adults, personality changes are unusual in burning or special symptoms. Sometimes visual, olfactory,
children. EEG shows generalized burst of spikes and auditory or taste hallucinations may be complained of.
irregular 4-6 Hz spike-wave complex. Consciousness is not impaired. When the simple seizure
spreads from one area of body to the other according to
Absence Attacks
the representation in the precentral gyrus of the motor
Absence seizures start abruptly in childhood; the peak cortex, it is called a Jacksonian march. Interictal EEG shows
prevalence is between 6-8 years. Even in children, absence focal spikes or sharp waves.
seizures are less common than tonic-clonic seizures. A
typical attack of absence seizures is not preceded by an Complex partial seizures with motor manifestations: Th
aura. The patients have a brief abrupt lapse of awareness events occur secondary to the involvement of parietal or
or consciousness. Patient may show sudden disconti temporal lobe. Partial seizures may be associated with
nuation of the activity being performed with staring spell, automatisms or with loss of consciousness, even if seizures
eye fluttering, or rhythmic movements. The seizure lasts are not generalized. Underlying neurocysticercosis or
less than 30 seconds. There is no loss of posture, tuberculoma is the most important cause.
incontinence of urine/stools or breathing difficulty. Other Complex partial seizures originating from temporal lob
neurological manifestations and postictal phenomena are (psychomotor epilepsy): The clinical profile is protean and
absent and development is normal. Unaware of the nature the episodes are frequently misdiagnosed for absence or
of their illness, schoolteachers may consider them other seizure types, behavior problems or malingering.
inattentive pupils. Brief visceral, olfactory or visual aura are followed by
Postictal drowsiness and confusion do not occur and peculiar posture, tonic jerks of the face and or limbs, or
the patient can resume normal work soon after the seizure. one-sided dystonia. Inappropriate repetitive movements
Hyperventilation for 3 minutes often precipitates the such as lip smacking, chewing and fidgetiness may occur.
attacks. Absence seizures may occur in multiples, every Patients may perform complex automatisms, acts, or
day. Attacks following in close succession indicate petit simply wander aimlessly. There is no memory for the
mal status or pyknolepsy. events and consciousness is impaired. It manifests, as
About half of patients become seizure-free and the rest memory disturbances like forced thinking or dreamy
develop tonic-clonic fits. This is particularly common in states, transitory fear, visual or other hallucinations. Post
children with a very early or late onset of absence fits. ural tone is reduced and the child tends to fall gradually.
Learning disabilities and behavior disorders when present Vasomotor changes such as circumoral pallor are often
are probably related to associated conditions. Electro present. Tonic or clonic movements characteristic of grand
encephalogram shows a characteristic 3 per second spike mal are usually absent but may follow in about 15% of
and slow wave pattern. Absence fits are distinguished cases.
from complex partial seizures by shorter duration (10 The behavior might superficially appear normal, but
seconds), absence of aura and abrupt return of full the child has no recollection of what has happened. In
consciousness. complex-partial seizures associated behavioral abnor
Partial Seizures
malities are more frequent.
Partial seizures account for 60% of seizures in childhood. Benign Childhood Epilepsy with
Common causes include inflammatory granulomas, Centrotemporal Spikes
atrophic lesions, vascular insults, birth asphyxia, head The syndrome has five characteristic features viz., (i) the
trauma and neoplasms. In some geographic areas age of onset is between 2 and 13 years; (ii) there is no
including India, neurocysticercosis has emerged as a neurological or intellectual deficit; (iii) seizures generally
common cause. Neurocutaneous syndrome, arteriovenous occur in sleep, are simple partial with motor signs and
malformations and infarcts are less frequent. Magnetic involve mouth area (abnormal sensation tingling and
resonance imaging may help to clarify the etiology more numbness of tongue and lips). Speech involvement,
accurately than CT scanning. dysarthria and somatosensory symptoms are common;
Partial seizures are classified as (iv) interictal EEG shows a spike focus over the centro
i. Simple partial without loss of consciousness, with temporal or Rolandic area; and (v) may be self-limiting
motor, sensory, autonomic or mixed symptoms. with spontaneous remission around adolescence. These
Central Nervous System 531
seizures account for about one-fourth of cases of epilepsy spike wave discharges (2 per second) are observed on EEG.
in mid childhood. It is most likely to have an autosomal This diffuse form of encephalopathy may result from
dominant inheritance. Treatment with carbamazepine or factors such as head injury, anoxia, cardiopulmonary
valproate controls the attacks. arrest, post-vaccinal encephalopathy and CNS infections.
Drugs of choice are valproic acid, benzodiazepines and
Neonatal Seizures ACTH. Prognosis is often unsatisfactory. Newer anti
Incidence ranges from 1-2% to almost 20% in preterm epileptic drugs, lamotrigine, topiramate and zonisamide
infants. Seizures may be a signal for underlying neuro are promising.
logical diseases severe asphyxia or a metabolic cause
(approximately 25%). Common Errors in Diagnosing Epilepsy
Poor myelination and incomplete dendritic arborization A wrong label of epilepsy may be given to 20-30%
result in clinical manifestations that are different from children reporting to epilepsy clinics. A variety of
older children. Neonatal seizures present in decreasing paroxysmal disorders, which mimic seizures, should be
order of frequency as (i) subtle; (iii) focal clonic; (iii) multi excluded. These include syncope, breath holding spells,
focal clonic; (iv) generalized tonic; and (v) myoclonic. acute psychiatric states, migraine variants, abnormal
Subtle seizures may manifest as eyelid blinking, movement disorders, paroxysmal disturbances of sleep
fluttering or buccal-lingual movement. There may be like night terrors, narcolepsy and lastly hysteria. Careful
pedaling or automatic movements because of subcortical history and EEG are useful to rule out these conditions.
neuronal discharges. The common causes are hypoxic If in doubt, treatment should be deferred until the
ischemic encephalopathy (almost half), sepsis and diagnosis becomes obvious on follow-up of the natural
bacterial meningitis. Metabolic seizures due to hypogly course of the disease. In severe cases, the seizures repeat
cemia, hypocalcemia, dyselectrolytemia and hypomag themselves and in mild cases there is no emergency in
nesemia account for almost one fourth. Intracranial rushing to therapy. Certain types of epilepsies may be
bleeding, developmental anomalies and inborn errors of missed or underdiagnosed, these include brief absence
metabolism need to be excluded. Malformations and dys- spells, mild myoclonus and abdominal epilepsy. Such
genetic states are important causes of tonic or myoclonic cases are relatively uncommon. The vast majority of errors
type of jerks. About one-third are multifactorial and are of overdiagnosis of epilepsy.
idiopathic.
It is important to establish the cause of neonatal Management of Epilepsy
seizures; investigations for hypoglycemia, hypocalcemia,
A chronic illness like epilepsy produces emotional and
hypomagnesemia, hypoxia, sepsis should be performed.
psychosocial disturbances. A physician must therefore
Lumbar puncture for the diagnosis of meningitis is
give due consideration to them besides medical aspects
advised. Clinical trial with intravenous injection of glucose
such as drug therapy, side-effects of drugs and identifying
and calcium is essential, before anticonvulsants are started.
etiology. Child should be protected from injury or
accidents during seizures, yet permitted a near normal
Myoclonic Epilepsies
life. Vocational guidance should be given regarding choice
West syndrome (infantile spasms): The onset is usually of profession with minimal environmental risks. Epilepsy
between 3-8 months of life. It is characterized by a requires management under supervision of a physician
combination of salaam spells (sudden dropping of the for prolonged period extending over 1 to 4 years.
head and flexion of arms), mental retardation and
hypsarrhythmia on EEG (diffuse high voltage slow spike Drug Therapy
and chaotic activity). Common cause of infantile spasms
The first line anti-epileptic drugs (AED) include pheny
are: (i) hypoxic ischemic encephalopathy; (ii) neurocuta-
toin, phenobarbitone, sodium valproate and carbama
neous syndromes specially tuberous sclerosis; (iii) peri zepine. The indications, dose and side-effects of commonly
natal infections; (iv) hemorrhage; (v) injury; (vi) metabolic
used drugs is depicted in Table 17.5. Age, sex, economic
disorders; and (viii) localized structural malformations.
factors and seizure type determine choice of AED.
No cause may be identified in a large number of cases.
The spasms occur in clusters usually on waking. Prognosis Tonic-clonic seizures: Carbamazepine is an effective drug for
for normal mental development is poor. ACTH and partial and generalized tonic-clonic seizures. It has the
corticosteroids frequently help, the course varies from 2- advantage of very few side-effects. Phenobarbitone is the
12 weeks, depending upon response. Vigabatrin is a drug of choice in the first year of life. Almost 20% develop
satisfactory choice, especially in tuberous sclerosis. hyperkinesia and learning disabilities after first year of life.
Lennox-Gastaut syndrome: Onset is usually in late Phenytoin is often used as initial choice if economic
infancy or childhood, is characterized by mixed seizures, constraints exist. Therapy should be initiated with lowest
including myoclonic, atypical absence, generalized tonic- anticonvulsant doses. The drug dose should be increased
clonic or partial seizures. Intellectual regression is gradually. If the seizures control is inadequate or if signs
invariable. Very slow background and slow generalized of toxicity appear, an alternate antiepileptic drug should be
532 Essential Pediatrics
tried and the initial drug tapered. Sodium valproate should Duration of treatment varies from 2-3 years except in
be used as single agent. As a rule, monotherapy should be severe neurodevelopment delay or structural malfor
practiced. Polypharmacy should be discouraged, because mation neurological deficits where risk of breakthrough
doses and side-effects of the individual drugs become diffi and recurrence of seizures is higher. Antiepileptic plasma
cult to monitor. If the above drugs fail to relieve seizures drug level monitoring is not required routinely. It helps
with monotherapy, addition of a second drug is necessary. in better and safer control of therapy: (i) if high dose levels
Central Nervous System 533
are being used; (ii) in mixed seizure disorders; (iii) in psychological profile indicate better prognosis. It is
polydrug therapy; (iv) to assess drug compliance; and (v) difficult to control seizures in children with neuro-
to determine plasma level before discarding a major drug. developmental handicaps and post-traumatic epilepsy.
Drug withdrawal should be attempted slowly over 3 Human conscious behavior requires interplay between the
months, usually after 1-2 years in absence attacks and 2 cerebral cortex and subcortical structures in the dience
year seizure free period in tonic-clonic seizures. Partial phalon, midbrain and upper pons. The anatomic substrate
complex seizures are more difficult to control. Drug comp for this arousal system is the ascending reticular activating
liance is essential. It is difficult to give a precise prognosis. system (ARAS), a portion of the larger reticular formation
Almost 10-15% patients relapse after an adequate course that constitutes the central core of the brain stem and
of AED's. Risk is low if the seizures were controlled easily, extends from the caudal medulla to the rostral midbrain.
certain genetic types, normal neurodevelopment, etc. The ARAS is strategically located and systematically
Relapse rate is low in generalized tonic-clonic seizures and arranged to initiate long-sustained behavioral arousal,
absence fits. Treatment has to be continued lifelong in during which time higher cortical functions can be
juvenile myoclonic epilepsy. Normal neurological and accomplished.
534 Essential Pediatrics
Table 17.6: Causes of coma E. Eye opening: Spontaneous (4), in response to call (3), in
Causes without focal neurological signs response to painful stimuli (2), no response (1).
Cerebrospinal fluid is normal M. Best motor response: Obeys commands (6), localizes (5),
i. Poisonings, narcotic agents, toxins withdraws limb on irritation (4), abnormal flexion of
ii. Metabolic disorders, e.g. hypoglycemia, diabetic acidosis, extremities (3), extensor response (2), no movement (1).
uremia, hepatic encephalopathy
V. Best verbal response: Well oriented (5), confused con
iii. Head injury, concussion
iv. Septicemia versation (4), inappropriate words are spoken (3),
v. Postictal incomprehensible sounds (2), no vocal response (1).
vi. Hyperpyrexia, febrile encephalopathy Score of less than 7 suggest coma, while score of 9 or
vii. Water intoxication more excludes coma. Most cases with score of 8 are also
Cerebrospinal fluid is abnormal comatose.
i. Meningitis
ii. Encephalitis Approach to Diagnosis of Coma
iii. Subarachnoid hemorrhage
iv. Cerebral vein thrombosis The airways, breathing and circulatory status should be
v. Midline cerebral tumors immediately attended. Intravenous access should be
obtained and respiration, blood pressure, capillary refill
Causes associated with focal neurological signs
time recorded. Look for fever, injury, raised intracranial
i. Demyelinating disorders
pressure. A detailed neurologic examination should be
ii. Post-ictal coma
carried out to rule out involvement of cranial nerves,
iii. Intracerebral bleed, vascular malformation
motor deficits and bladder/bowel dysfunction.
iv. Tumors, infarcts, strokes
v. Infections: brain abscess, subdural empyema, encephalitis If respiratory depression or circulatory collapse is
vi. Head injury, intracranial hemorrhage present, prepare for intubation, assisted ventilation and
vasopressor support.
Miscellaneous
Systemic illnesses, hypertension, shock History: A proper detailed history of events preceding
coma, background illnesses, exposure to drugs and toxins
provides useful information. The acuteness of onset,
Four pathophysiologic variables indicate the functional
presence of fever, history of trauma and suggestions of
level, severity of involvement and the rate and extent of
possible bacterial, viral, or parasitic infestations is
the disease process. These functions include pattern of
important. History of immunocompromised states and
respiration, size and reactivity of the pupils, spontaneous
malignancy may suggest opportunistic infections. Family
and induced eye movements, verbal responses and motor
responses. history of tuberculosis, malarial prevalence may be useful
information to elicit. History of headache, vomiting and
Grades of Coma diplopia suggest raised intracranial pressure. Failure to
thrive, vomiting, peculiar skin and urinary odor suggest
Stage I or stupor: The patient can be aroused briefly and
a metabolic cause. Endocrinal dysfunction, dyselectro-
shows verbal or motor responses to stimuli.
lytemia, hypo/ hyperglycemic states, uremia, hyper
Stage 2 or light coma: The patient cannot be aroused easily, ammonemia suggest metabolic basis for coma. History of
except with painful stimuli.
preceding seizure may indicate post-ictal coma.
Stage 3 or deep coma: There is no response to painful stimuli.
Onset: Determine if the loss of consciousness was sudden
The limbs may be kept in a primitive reflex posture.
or preceded by other symptoms. Sudden onset may be
Cortical control over the motor functions is lost. When
due to trauma, poisoning, intracranial vascular episodes,
the brainstem is intact, the arms are flexed on the chest,
post-ictal phase, acute hypoxia, hydrocephalus due to obs
the fists are closed and legs are extended (decorticate
truction of cerebrospinal pathway in cases of brain tumor.
posture). In dysfunction of the midbrain, the comatose child
adopts a decerebrate posture. The arms are rigidly extended Systemic examination: It includes accurate recording of
and pronated and legs are extended. temperature, pulse, respiration rate, blood pressure, pupil
size and reactivity, coma scale, airway patency, pattern
Stage 4 or brain death: All cerebral functions are lost. Pupil
and adequacy of respiration. Skin and mucosa should be
lary reflexes are absent. There is no spontaneous res
inspected for bleeding diathesis, exanthem or systemic
piratory effort. However, local spinal reflexes may be
disease. Organ failures are suggested by associated
preserved.
jaundice, anemia, etc.
Glasgow Coma Scale
Respiration: Periodic or Cheyne-Stoke type breathing indicates
The score is useful for evaluating progress of cases with bilateral damage to the cerebral cortex with an intact brain
disturbed consciousness and is calculated from the figures stem. It occurs in transtentorial herniation, congestive
given in parenthesis. cardiac failure and some metabolic disorders. It is
Central Nervous System 535
attributed to an abnormally increased ventilatory response Flexion of one or both upper extremities with or without
to C02 followed by post-hyperventilation apnea. Hyper extension of the legs (decorticate posture) denotes a
ventilation occurs in metabolic coma with acidosis and in predominantly cerebral cortical and subcortical distur
brainstem lesions. Prolonged inspiratory cramp folloioed by bance with relative preservation of all brainstem
expiratory pause indicates pontine lesions. Irregular or ataxic structures. Decerebrate posturing (extension of all
breathing indicates involvement of respiratory center in extremities) is observed in bilateral cerebral cortical
the medulla. disease with or without brainstem dysfunction as far
Depth of unconsciousness: Presence of yawning, swallowing caudal as the upper pons. Decerebrate rigidity can result
or licking movements of the lips, is an evidence of intact from increased ICP originating in the posterior fossa,
functioning of the brainstem. In these cases deep coma is metabolic disease, cerebral hypoxia, hypoglycemia and
unlikely. If a child resists when his hand is allowed to fall liver dysfunction (Reye's syndrome). Both decorticate and
towards his face, he is not in coma. However flexion, decerebrate posturing is stimulus-sensitive and may
extension and adduction movements may be seen in coma require the induction of pain for their appearance.
tose patients as they are mediated at lower spinal reflex level. Flaccidity occurs when a lesion has abolished cortical
and brainstem function, at least as low as the ponto-
Involuntary movements: Repetitive, multifocal, myoclonic medullary junction.
jerks are seen in anoxic, metabolic or toxic encephalo
pathies. In infections of the central nervous system,
Investigations
multifocal seizures may occur.
Laboratory studies should be carried out to exclude hypo
Pupillary signs: Pupils are generally small, equal and reactive
or hyperglycemia, uremia, hepatic dysfunction, dyselec-
in toxic, metabolic cause of coma. Pupils are moderately
trolytemia and other metabolic abnormalities. Blood
dilated in midbrain damage; they do not react to light but
ammonia, lactate, acid base disturbances, toxins and
fluctuate slightly. Pinpoint pupils indicate pontine lesion or
poisoning should be investigated on suspicion by
morphine poisoning. Bilateral fixed dilated pupils are seen in
preserving appropriate samples. Ferric chloride test shows
terminal states or severe ischemic brain damage, atropine
purple color with ketones and aspirin poisoning. It gives
or belladonna poisoning. Unilateral unreactive dilated pupils
green color with phenothiazine and isoniazid intoxication.
indicate third nerve damage, often associated with
Inflammatory causes of the CNS should be excluded by a
transtentorial herniation of the temporal lobe or traction of
lumbar puncture and blood/CSF culture and a sepsis
third cranial nerve against posterior cerebral artery.
screen. In febrile coma, peripheral smear should be
Eye movements: Stimulation of cortical center for gaze, examined for malarial parasite. Cranial imaging (CT)
results in conjugate eye movements to the contralateral helps to identify intracranial bleeds, infarct raised ICP
side, whereas ablation produces conjugate deviation of meningeal enhancement, hydrocephalus, etc.
the eyes to the ipsilateral side.
Treatment
Doll's eye response: If the head is suddenly turned to one
side, there is a conjugate deviation of eye in the opposite Airway should be kept patent and tongue should be
direction. This response occurs if the brainstem is intact. prevented from falling back. Blood pressure should be
Doll's eye movement is not seen in normal conscious monitored and aspiration should be prevented. Dyselec-
infants and is absent when brainstem centers for eye trolytemia and fluid imbalance should be corrected. In
movements are damaged. situations where inappropriate secretion of antidiuretic
hormone is likely, maintenance fluid may be reduced to
Oculovestibular response: If the external auditory canal is
two-third of the requirement. Hyper and hypothermia
irrigated with cold water, the eyes normally deviate
should be managed. Bladder/bowel care and care of the
towards the stimulated side. This response is lost in
eyes and back to avoid bed sores is imperative. Raised
pontine lesions, labyrinthitis and coma due to drugs such
intracranial pressure should be treated.
as sedatives and phenytoin.
Fever with acute onset coma of uncertain origin with
The hallmark of metabolic encephalopathy consists of
no evidence of meningitis merits treatment for as cerebral
loss of oculocephalic and oculovestibular reflexes with
malaria in endemic areas.
preservation of the pupillary light reflex.
Specific treatment should be given for hypoglycemia
Motor responses: Structural lesions within the cerebral (IV glucose) diabetic coma (see chapter on diabetes
hemispheres involving cortical or subcortical motor mellitus), inflammatory disease of brain or meninges,
centers lead to contralateral hemiparesis and hemifacial metabolic causes or organ failure. Raised intracranial
weakness. In the comatose patient, these motor pressure is treated with IV infusion of mannitol, at a dose
abnormalities may manifest as alternation in muscular of 0.5 g/kg every 6-8 hr for 6 doses. Hypertonic saline also
tone, deep tendon reflex or spontaneous activity when may be used. In some cases especially TBM,
compared with the contralateral side. dexamethasone (0.15 mg /kg every 6-hr) may be used. In
536 Essential Pediatrics
cases of hepatic coma, attempt is made to eliminate may extend from contiguous septic foci, e.g. infected para
intestinal bacteria and their products, such as ammonia and nasal sinuses, mastoiditis, osteomyelitis and fracture of
false neurotransmitter such as phenylethanolamine and the base of skull.
octopomine. Parenteral systemic antibiotics, vitamin and Recurrent meningitis may be associated with pilonidal
non-absorbable synthetic disaccharide lactulose is given sinus, CSF rhinorrhea, traumatic lesions of the cribriform
(10-15 mL/day in divided doses) by nasogastric tube or per plate and ethmoidal sinus or congenital fistulae, besides
rectum. Dietary protein is reduced. Hypoprothrombinemia immune deficiency disorders.
is treated with injectable vitamin K or blood transfusion.
Exchange transfusion, plasmapheresis and peritoneal Pathology
dialysis are indicated in specific situations. Corticosteroids The leptomeninges are infiltrated with inflammatory cells.
have been used in certain metabolic encephalopathies and The cortex of the brain shows edema, exudate and
post-viral encephalopathies, they are contraindicated in proliferation of microglia. Ependymal cells are destroyed
cerebral malaria. The benefit is inconsistent in other states.
and purulent exudate collects at the base of the brain. The
Metabolic coma due to inborn metabolic errors requires subarachnoid space is filled with a cloudy or opaque fluid
specific treatment.
most marked in interpeduncular and chiasmatic cisterns.
Exudates may block the foramina of Luschka and
Suggested reading
Magendie resulting in internal hydrocephalus. Thrombo
1. Giacino JT. Disorders of consciousness: differential diagnosis and
phlebitis of the cerebral vessels may occur leading to
neuropathologic features. Semin Neurol 1997; 17: 105.
2. Kirkham FJ. Non-traumatic coma in children. Arch Dis Child. 2001; infarction and neurological sequelae. Permanent neurolo
85: 303-12. gical sequelae result from infarction, necrosis and
3. Ranjit S. Emergency and intensive care management of a comatose hydrocephalus. In cases of meningococcal meningitis, the
patient with intracranial hypertension, current concepts. Indian illness may be fulminating and death may occur within a
Pediatr 2006 May;43(5):409-15.
few hours because of endotoxic shock.
4. Hailey MK, Silva PD, Foley J, Rodarte A.Loss of consciousness:
when to perform computed tomography? Pediatr Crit Care Med Subcellular pathogenetic mechanisms: Bacterial pathogens on
2004 May;5(3):230-3.
destruction liberate cell wall and membrane active
components (teichoic acids, endotoxins and peptidogly-
ACUTE BACTERIAL MENINGITIS
cans). In response the host cells and capillary endothelia
Acute bacterial meningitis, a major cause of morbidity and produce tumor necrosis factor, cytokines and platelet
mortality in young children, occurs both in epidemic and activating factors. Their interaction with the blood brain
sporadic pattern. barrier and neurons results in extensive host damage.
Cerebral edema (vasogenic) results due to endothelial cell
Epidemiology injury or cytotoxins, leukocyte products and toxic radicals.
Age: Acute bacterial meningitis is commoner in neonates The role of dexamethasone in reducing host damage due
and infants than in older children because their immune to blockage of the above mechanisms has been demons
mechanism and phagocytic functions are not fully trated in both experimental and clinical settings.
matured. The common organisms implicated in the
neonatal period are Escherichia coli, Streptococcus pneu Clinical Features
moniae, Salmonella species, Pseudomonas aeruginosa, The onset is usually acute and febrile. In the initial phase,
Streptococcus fecalis and Staphylococcus aureus. From the age the child becomes irritable, resents light, has bursting
of three months onward to 2-3 years, the infection is most headache either diffuse or in the frontal region, spreading
often due to Hemophilus influenzae, S. pneumoniae and to the neck and the eyeballs. The infant may have projectile
meningococci (Neisseria meningitides). Beyond 3 years, the vomiting, shrill cry and a bulging fontanel.
two most common organisms causing meningitis are S. Seizures are a common symptom and may occur at the
pneumoniae and N. meningitides. onset or during the course of the illness. Varying grades
Host: Patients with diminished host resistance (compli of alterations in sensorium may occur. Photophobia is
ment/immunoglobulin/polymorph function defects) are marked. There is generalized hypertonia and marked neck
predisposed, also malignancies, patients on immuno rigidity. Flexion of the neck is painful and limited. Kernig
suppressive drugs are more susceptible to develop sign is present, i.e. extension of knee is limited to less than
meningitis, specially by fungi, Listeria and Mycoplasma. 135 degrees. Due to spasm and pain in the back of the
thigh or muscles of the back. In Brudzinski sign, the knees
Pathogenesis are flexed as neck of the child is passively flexed. The
The infection spreads hematogenously to meninges from fundus is either normal or shows congestion and
bacterial sepsis or distant foci, etc., e.g. pneumonia, papilledema. Extrinsic ocular palsies may lead to squint,
empyema, pyoderma and osteomyelitis. Purulent diplopia and ptosis. If skin of the abdomen is lightly
meningitis may follow head injury. Rarely, the infection scratched, flushing may be seen (tache cerebrate). The
Central Nervous System 537
muscle power in the limbs is preserved. Reflexes are pyoderma or septicemia. In older children it follows otitis
normal, diminished or exaggerated. Neurological deficits media, mastoiditis, sinus thrombosis, pneumonia, arthritis
like hemiparesis, cranial nerve palsies and hemianopsia and septic lesions of the scalp or skin.
may develop. Respiration may become periodic or
Hemophilus influenzae type B meningitis: It is frequent in
Cheyne-Stokes type often with shock in the late stages of
children between the ages of 3 and 12 months. Subdural
illness.
effusion should be suspected in infants in whom focal
Meningitis in neonates and young infants: Bacterial meningi neurological signs and fever persist even after the CSF
tis in the newborn and the first 4 to 6 months of life has clears biochemically and microbiologically. Convulsions
many atypical features. Neck rigidity and Kernig sign are are common. Residual auditory deficit is a common
seldom prominent. Anterior fontanel may or may not be complication. HiB vaccine is strongly recommended to
bulging. reduce the community prevalence of this infection.
Symptoms and signs, which arouse suspicion of
bacterial meningitis are: (i) presence of sepsis; (ii) vacant
Complications
stare; (iii) alternating irritability and drowsiness; (iv) CNS complications include subdural effusion or empyema,
persistent vomiting with fever; (v) refusal to suck; (vi) poor ventriculitis, arachnoiditis, brain abscess and hydro
tone; (vii) poor cry; (viii) shock, circulatory collapse; (ix) cephalus. CNS complications should be suspected if
fever or hypothermia; (x) tremor or convulsions; and (xi) infants and children fail to respond to treatment, or if fever,
neurological deficits of varying types. focal neurological signs and constitutional symptoms
Newborn babies are at a higher risk for developing recur after a lapse of few days. Long-term neurological
meningitis under the following circumstances: prematu deficits include hemiplegia, aphasia, ocular palsies,
rity, low birth weight, complicated labor, prolonged hemianopsia, blindness, deafness, sensorineural auditory
rupture of membranes, maternal sepsis and babies given impairment (deafness) and mental retardation. Systemic
artificial respiration or intensive care. complications include shock, myocarditis, status epilepticus
and syndrome of inappropriate ADH secretion (SIADH).
Special Features
Diagnosis
Meningococcal meningitis: Epidemics of meningococcal
meningitis are generally caused by serotype A and less Acute bacterial meningitis should be suspected in children
commonly by Type C. Type B generally cause sporadic presenting with a brief history of fever, irritability,
disease. Other serotypes of N. meningitides include D, X, photophobia, headache, vomiting, convulsions and
Y, Z, W-135, etc. Children living in overcrowded houses altered sensorium. Diagnosis should be substantiated by
are specially predisposed. Carrier state is common in examination of the cerebrospinal fluid. Cells should be
children. examined within half an hour and stained to identify their
Besides classical features of meningitis, these children morphology, rather than mere reporting of cell type on
the Neubauer chamber.
show petechial hemorrhages on the skin or mucosa. It is a
good practice to look for petechiae over the conjunctiva if The CSF has elevated pressure, is turbid with an elevated
cell count, often >1,000/mm3 and mostly polymorpho
there are no hemorrhagic spots or rashes on the skin.
nuclear. Proteins are elevated above 100 mg/dL and sugar
Meningococcemia may be associated with acute fulmina
in the CSF is reduced significantly to below 50% of blood
ting illness and adrenal insufficiency. The child is severely
sugar or below 40 mg/dL. Thus, it is desirable to obtain the
prostrated, has hypotension, shock and quickly goes into
blood glucose level concurrently with the CSF glucose.
coma. This is called Waterhouse Freiderichsen syndrome. It
Microscopic examination of the sediment stained with
occurs due to hemorrhage and necrosis in the adrenal
Gram's stain helps to identify organisms. Collect the CSF
glands during the course of meningococcal septicemia.
for culture on a transport medium.
The syndrome may also occur in other types of septicemia.
In partially treated meningitis, CSF may be clear with
Rarely a chronic form of meningococcemia may occur.
predominant lymphocytes; culture is usually sterile.
This manifests with intermittent fever, chills, joint pains
Biochemistry may be variably altered.
and maculopapular hemorrhagic rash lasting for several
CT scan is not necessary for diagnosis, but is useful to
days. Meningococci are very fragile organisms and are
exclude the presence of subdural effusion, brain abscess,
destroyed very easily if there is delay in CSF culture.
hydrocephalus, exudates and vascular complication. It is
Pneumococcal meningitis: Pneumococcal meningitis occurs also useful to distinguish partially treated pyogenic
at all ages except for the first few months of life. It usually meningitis from tuberculous meningitis.
follows otitis media, sinusitis, pneumonia or head injury. Rapid diagnostic tests may be used to distinguish
Exudates are common on the cortex, subdural effusion is between viral, bacterial and tuberculous meningitis based
a usual complication. on antigen or antibody demonstration, e.g. counter current
Staphylococcal meningitis: Neonatal staphylococcal immune-electrophoresis, latex particle agglutination,
meningitis is often associated with umbilical sepsis, coagglutination, ELISA and its modified techniques.
538 Essential Pediatrics
Besides being rapid, they are unaltered by previous gelatinous capsule in India ink preparation. The organism
antibiotic usage. Latex agglutination and ELISA are most grows well on Sabouraud medium.
popular with sensitivity and specificity of almost 80%.
Polymerase chain reaction is used for diagnosis of infection Viral encephalitis: Acute onset with early disturbances of
with herpes simplex, enteroviruses, meningococci, sensorium, raised intracranial pressure and variable
tuberculosis, etc. neurological deficit. The CSF is clear and may show mild
Non-specific tests including C-reactive protein, lactic pleocytosis, mild elevation of protein and normal sugar.
dehydrogenase and CSF lactic acid level may help to PCR for viral antigens and rising CSF antibody titers are
broadly differentiate pyogenic from non-pyogenic useful diagnostic clues.
meningitis. CSF CRP and tumor necrosis factor is also
Poliomyelitis: It should be suspected as a cause of mild
elevated in pyogenic meningitis.
nuchal rigidity during epidemics of poliomyelitis in the
Differential Diagnosis community. CSF shows an increase in protein and
lymphocytes with normal sugar.
Meningism: This may occur in inflammatory cervical
lesions and apical pneumonia. There are no neurological Subarachnoid hemorrhage: Sudden headache and sensorial
signs and the cerebrospinal fluid is normal. Generalized alteration occur without preceding fever. The course of
infection associated with toxemia such as due to H. illness is rapid and signs of meningeal irritation are
influenzae and typhoid fever may be confused with marked. CT scan is diagnostic. CSF reveals many crenated
meningitis. RBCs.
Partially treated bacterial meningitis: If the child has received Lyme disease: It is an infection of central nervous system
prior antibiotics, the cerebrospinal fluid becomes sterile. with Borrelia burgdorferi, a tick-borne spirochete. Patients
Biochemistry may be altered and pleocytosis persists, develop encephalopathy-polyneuropathy, leukoence
though type of cellular response change. It poses a phalitis and hearing loss (ceftriaxone is given IV for two
difficult problem in the differential diagnosis from weeks for treatment).
tuberculous meningitis and aseptic meningitis. The onset,
clinical course, rapid diagnostic tests and other ancillary Treatment
investigations may be useful.
Initial Empiric Therapy
Aseptic meningitis: The clinical and laboratory profile is
Initial therapy recommended is a third generation
similar to pyogenic meningitis. The CSF pressure is
cephalosporins such as ceftriaxone or cefotaxime. A
elevated, shows mild pleocytosis and moderate increase
combination of ampicillin (200 mg/kg) and chloram
in protein with near normal sugar. The CSF lactic acid is
phenicol (100 mg/kg/24 hours) for 10-14 days is also
not elevated. No organisms are cultured.
effective as initial empiric choice. If fever or meningeal
Tuberculous meningitis: The onset is insidious with lethargy, signs persist after 48 hours of therapy, CSF should be
low-grade fever, irritability, vomiting and weight loss. repeated and antibiotics reviewed.
Features of meningeal irritation are less prominent and
course of the illness is prolonged. Neurological features Specific Antimicrobial Therapy
include seizures, gradually progressive unconsciousness, All antibiotics are to be given intravenously.
cranial nerve deficits, motor deficits and visual involve
ment. Features of hydrocephalus and decerebration are Meningococcal or pneumococcal meningitis: Penicillin 4-
relatively common. Evidence of systemic tuberculosis and 500,000 units/kg/day q4 hourly. Cefotaxime (150-200
family contact should be looked for. Mantoux test may be mg/kg/day q8 hourly IV) or ceftriaxone (100-150 mg/
positive and primary complex may be present on chest X- kg/day ql2 hourly IV) are also effective.
ray. Cerebrospinal fluid is clear and a cobweb coagulum
H. influenzae meningitis: Ceftriaxone or cefotaxime IV is
is formed on standing. It appears as a basketball net
used as a single agent. Alternatively, combination of
suspended from the upper end of fluid in the test-tube. ampicillin (300 mg/kg/d IV q6 h) and chloramphenicol
The cell count is in tens to hundreds with majority of (100 mg/kg/day) may be administered.
lymphocytes; the sugar is less reduced than in pyogenic
meningitis. Early stage may pose a diagnostic problem. Staphylococcal meningitis: Vancomycin is the treatment of
choice if methicillin or penicillin resistance is suspected.
Cryptococcal meningitis: It usually occurs in an immuno
Addition of rifampicin to the regime increases the CSF
compromised host. There is low-grade fever, mild cough
penetrance and killing power of these drugs.
and pulmonary infiltration. Meningeal involvement has
a gradual onset with a protracted course. The clinical Listeria: Ampicillin (300 mg/kg/day IV q6 h) and
features are not specific. The CSF shows the fungus as aminoglycoside (gentamicin, amikacin or netilmicin) are
thick walled budding yeast cells, surrounded by a large preferred.
Central Nervous System 539
Pseudomonas: A combination of ceftazidime and an amino Subdural empyema: Drainage of the subdural space along
glycoside is used. Ceftazidime may also be replaced with with intensive antibiotic therapy.
ticarcillin or mezlocillin. Meropenem or cefepime are good
Hydrocephalus: Ventriculomegaly may occur in the acute
broad spectrum agents, useful if above drugs fail.
phase and generally regresses. Ventriculoatrial or
Duration of Therapy ventriculoperitoneal shunt is rarely required.
Generally, patients with bacterial meningitis show distinct Follow-Up and Rehabilitation
improvement in 10 days and treatment is rarely necessary
All cases of bacterial meningitis should be followed up
beyond 10-14 days except for staphylococcal meningitis
for early detection of residual neurological handicaps and
and some patients with Gram negative infection. Routine
provided appropriate rehabilitation. Auditory evaluation
lumbar puncture at the end of therapy is not recommen
should be carried out at the time of discharge and 6 weeks
ded any more. However, in cases with delayed or partial
clinical response, a repeat CSF examination is indicated. later.
Therapy is stopped if child is afebrile, cerebrospinal fluid
Suggested reading
protein and sugar become normal, and the cell count in
the cerebrospinal fluid is less than 30/mm3. 1. El Bashir H, Laundy M, Booy R. Diagnosis and treatment of
bacterial meningitis. Arch Dis Child 2003; 88: 615-20.
2. Tunkel AR: Bacterial meningitis. LWW 2001, Philadelphia USA
Steroid Therapy
3. van de Beek D, de Gans I,McIntyre P, Prasad K. Corticosteroids
Dexamethasone in a dose of 0.15 mg/kg IV 6 hourly for for acute bacterial meningitis. Cochrane Database of Systematic
2-4 days is recommended. The first dose of corticosteroids Reviews 2007, Issue 1. Art. No.: CD004405.
should precede antibiotic use by at least 15 minutes. This 4. Tunkel AR, Hartman BJ,Kaplan SL. Practice Guidelines for the
Management of Bacterial Meningitis. Clinical Infectious Diseases
helps to reduce the incidence of residual neurological
2004; 39:1267-84
complications, such as sensorineural deafness and 5. Maconochie I, Baumer H, Stewart MER. Fluid therapy for acute
possibly internal hydrocephalus, and behavioral distur bacterial meningitis. Cochrane Database of Systematic Reviews
bances. This is especially useful in Hemophilus meningitis. 2008, Issue 1. Art. No.: CD004786.
There is no role of dexamethasone in neonatal meningitis.
TUBERCULOUS MENINGITIS
Symptomatic Therapy
Meningitis is a serious complication of childhood
Increased intracranial pressure: Lumbar puncture should
tuberculosis. It may occur at any age, but is most common
be done very carefully in the presence of increased
between 6 and 24 months of age, there is usually a focus
intracranial pressure. Osmotic diuresis with 0.5 g/kg of
of primary infection with tuberculosis or concomitantly
mannitol as a 20% solution is administered intravenously
with miliary tuberculosis. Mortality rate has reduced but
every 4-6 hours for a maximum of 6 doses.
survivors may be left with serious disabling neurological
Convulsions: Administer diazepam 0.3 mg/kg (maximum sequelae.
5 mg) IV, followed by phenytoin 10 to 15 mg /kg as initial
treatment. Subsequently, phenytoin is given 5 mg/kg/ Pathogenesis
day PO or IV until the antibiotics are continued. The tuberculous infection usually reaches the meninges
Fluid and electrolyte homeostasis: Restricted fluids (two-third by hematogenous route, and less commonly through the
of maintenance) may be required due to inappropriate intracranial lymphatics or the cervical lymph nodes.
ADH secretion in some patients. If unconscious, child may Tubercle bacilli are immobilized in the end arteries and
be fed through the nasogastric tube. lead to formation of submeningeal tubercular foci. These
Hypotension: Fall in blood pressure should be corrected may discharge the tubercle bacilli into the subarachnoid
by intravenous infusion of fluids and vasopressors such space intermittently. The bacilli proliferate and cause
as dopamine and dobutamine. perivascular exudation followed by caseation, gliosis and
giant cell formation. Tuberculous meningitis may occur
Nursing care: The oral cavity, eyes, bladder and bowel
as a part of the generalized miliary tuberculosis, with
should be taken care of. Management of constipation
tubercles in the choroid plexus directly infecting the
prevents atony of the rectum. Retention of the urine is
meninges.
managed by gentle suprapubic pressure or a hot water
bottle. Bedsores are prevented by repeated change of
Pathology
posture in the bed and application of methylated spirit
on the skin to harden it. Soft foam rubber mattress or air The meningeal surface and ependyma are inflamed,
cushion is used to prevent pressure on the bony points. covered with yellow grayish exudates and tubercles. These
540 Essential Pediatrics
are most severe at the base, in the region of the temporal cerebrospinal fluid pressure is elevated to 30-40 cm HzO
lobes and along the course of the middle cerebral artery. (normal 3-4 cm H20). The CSF may be clear and colorless,
The subarachnoid space and the arachnoid villi are spinal block may cause xanthochromia. On standing, a
obliterated resulting in poor reabsorption of cerebrospinal pellicle or a cobweb coagulum is formed in the center of
fluid and dilation of the ventricles, the exudate may block the tube. It is composed of cells and tubercle bacilli
cerebrospinal fluid pathway resulting in hydrocephalus. enmeshed in fibrin. The CSF reveals increased cells 100-
The choroid plexus is congested, edematous and 400/mm3, polymorphonuclear cells may predominate in
studded with tubercles. There is cerebral edema. There early stages but are replaced soon by lymphocytes. The
may be infarcts in the brain due to vascular occlusion. CSF protein is increased above 40 mg/dL, and sugar
Tuberculous encephalopathy results in diffuse edema of usually reduced to about 2/3 of the blood sugar. The
brain simulating postinfective, allergic encephalopathy. chloride level is less than 600 mg/dL. Cerebrospinal fluid
Necrotizing or hemorrhagic leukoencephalopathy may does not confirm the etiological diagnosis, but is adequate
occur in some cases. evidence for starting antitubercular therapy before more
definite evidence of tuberculosis is available. Demons
Clinical Manifestations tration of acid fast bacilli by direct smear, culture and
The clinical course of tuberculous meningitis is described guinea pig inoculation is seldom positive. Bactec and PCR
in three stages. This differentiation is arbitrary as one-stage are useful tests where available.
merges into the other.
CT scan: Computerized tomography is useful in tubercular
Prodromal stage or stage of invasion: The onset is insidious
meningitis and identifies many pathological correlates of
and vague with low-grade fever, loss of appetite and
tubercular meningitis. Basal exudates, inflammatory
disturbed sleep. The child who was active and playful
granulomas, hypodense lesions or infarcts and hydro
earlier becomes peevish, irritable and restless. Vomiting
cephalus both communicating and less commonly
is frequent and the older children may complain of
obstructive type may be seen (Fig. 17.7). X-ray of the chest
headache. He may exhibit head banging and resents
may provide supportive evidence for tuberculosis.
exposure to bright sunlight (photophobia). Constipation
Tuberculin test should be done. A negative reaction does
is usual.
not always exclude the diagnosis.
Stage of meningitis: During this stage, neck rigidity is
demonstrated and Kernig sign is positive. The temperature Serological tests: for the diagnosis of tuberculous meningitis
is elevated, usually up to 39°C and may be remittent or are not very sensitive; ELISA is also not very useful. Bactec
intermittent. The pulse is slow but usually regular in and PCR for tuberculosis carry better sensitivity and
rhythm and volume. Breathing may be disturbed. The specificity. Tests for HIV should be performed on all
patient may be drowsy or delirious. Muscle tone may be suspected subjects.
increased. As the disease progresses, convulsions and
neurological deficits like monoplegia and hemiplegia may Differential Diagnosis
occur; sphincter control is usually lost. Purulent meningitis: The onset is acute with rapid
Stage of coma: This stage is characterized by loss of cons progression. The cerebrospinal fluid is turbid or purulent
ciousness, rise of temperature and altered respiratory
pattern. Pupils are dilated, often unequal, with nystagmus
and squint. Ptosis and ophthalmoplegia are frequent. With
the progression of the disease, the coma deepens; episodic
decerebration is observed which progresses in severity.
The respiration becomes Cheyne-Stokes or Biot type,
bradycardia is common. Untreated illness is lethal in about
four weeks.
According to Udani, et al. the frequency of various
neurological manifestations is as follows: hemiplegia
(20%), quadriplegia (19%), monoplegia (3%), hemi-
ballismus (11%), tremors (6.1%), midline cerebellar
syndromes (4%), cranial nerve palsies (14%), decerebrate
rigidity (13%), decorticate rigidity (3%), and cerebellar
hemispheric lesions (1.0%).
Diagnosis
Lumbar puncture: Lumbar puncture should always be done Fig. 17.7 : Contrast enhanced CT of brain showing communicating
in children with low-grade pyrexia, unexplained recurrent hydrocephalous and periventricular ooze in a child with tubercular
vomiting, unusual irritability and lassitude. The meningitis
Central Nervous System 541
with a significant increase in the number of polymorpho genic or antitubercular therapy should arouse suspicion.
nuclear leukocytes in the CSF. Protein content is elevated Diagnosis is made by demonstration of motile amebae in
and sugar level is markedly decreased. The etiological the fresh CSF preparation. Culture is confirmatory.
agent is demonstrated by the examination of smear,
culture or serology. Prognosis
The prognosis is related to the age of the patient, stage at
Partially treated purulent meningitis: Poses a difficult
which diagnosis is made, adequacy of treatment and
diagnostic dilemma. The clinical picture and cerebrospinal
presence of complications. The prognosis is poorer in
fluid changes are often indistinguishable from tuberculous
younger children. Early diagnosis, adequate and
meningitis. Rapid diagnostic tests to rule out specific
prolonged therapy improves the prognosis. Untreated
bacterial antigens should be performed if available.
cases die within 4 to 8 weeks.
PCR and Bactec provide supportive evidence for tuber
Recovery is a rule in Stage 1 disease. The mortality in
culosis. Treat with a combination of antipyogenic and
Stage 2 is 20-25% and of the survivors, 25% would have
antitubercular regimen for 10 days and repeat the lumbar
neurological deficits. Stage 3 disease has 50% mortality
puncture to evaluate response. Bacterial meningitis cases
and almost all the survivors would have neurological
are likely to improve substantially and the antitubercular
sequelae. The long-term sequelae include mental retar
treatment may then be discontinued.
dation, seizures and motor/cranial nerve deficits. Hydro
Encephalitis: The onset is acute with fever, seizures, cephalus is practically universal. Visual complications and
disturbances of sensorium, drowsiness and diffuse or focal optic atrophy are common. Arachnoiditis, spinal block
neurological signs. The cerebrospinal fluid reveals mild may cause motor and bladder/bowel symptoms.
pleocytosis, normal or mildly elevated proteins and
normal sugar. CT scan is normal. EEG may be abnormal. Treatment
Typhoid encephalopathy: Typhoid patients with severe Antitubercular therapy: The treatment of tuberculous
toxemia may appear drowsy and develop neurological meningitis should be prompt, adequate and prolonged
deficits without meningeal signs. The clinical picture may for at least 12 months. Short course chemotherapy is not
simulate tuberculous meningitis. Cerebrospinal fluid is recommended. At least 4 antitubercular drugs should be
normal. Blood culture is positive for Salmonella typhi and used for initial 2 months comprising (i) isoniazid (5 mg/
Widal test may be positive. kg/day, maximum 300 mg per day); (ii) rifampicin (10
mg/kg/orally, once empty stomach in the morning,
Brain abscess: Patients present with irregular low-grade
maximum dose 600 mg/day); (iii) ethambutol (15-20 mg/
fever, localized neurological symptoms and features of
kg/day); and (iv) pyrazinamide (30 mg/kg/day PO).
raised intracranial pressure. A prior history of congenital
Streptomycin (30^0 mg/kg/day IM) may be used initially
cyanotic heart disease or pyogenic lesions (suppurative
for 2-3 weeks. The first two drugs are continued to
otitis media, mastoiditis, lung abscess, osteomyelitis, etc.) complete one year of therapy.
should be asked for. The cerebrospinal fluid is normal
except when the abscess communicates with the sub Steroids: Parenteral dexamethasone 0.15 mg/kg every 6
arachnoid space; CT scan is diagnostic. hr IV; change to oral drug (prednisolone) once brain
edema settles. Oral corticosteroids may be continued for
Brain tumor: The onset is slow with history of headache, 6 weeks and tapered over next two weeks. Steroids reduce
recurrent vomiting, disturbances of vision and localizing the intensity of cerebral edema, risk of development of
neurological signs. The patients are usually afebrile. CT arachnoiditis, fibrosis and spinal block.
or MRI helps in diagnosis.
Symptomatic therapy of raised intracranial pressure,
Chronic subdural hematoma: There may be a history of head seizures, dyselectrolytemia should be done. The patient
injury or trivial trauma, symptoms of failure to thrive, should be kept under observation for development of
headache, vomiting, localizing neurological signs and papilledema, optic atrophy or increasing head circum
features of increased intracranial pressure. The fundus ference. Decerebration is common in advanced cases in
shows papilledema or choked disks. The sutures may be the acute phase. Ventriculocaval shunt may be required
separated. The cerebrospinal fluid is normal. CT scan or in cases with increasing hydrocephalus and persistent
ultrasound is useful. The subdural tap shows fluid with decerebration.
high protein concentration.
Amebic meningoencephalitis: Free living amebae, i.e. Suggested reading
Naeglaria and Acanthameba can cause meningoencephalitis. 1. Kent SJ, Crowe SM, Yung A, et al. Tuberculous meningitis: a 30
While Naeglaria meningoencephalitis presents acutely, year review. Clin Infect Dis 1993; 17: 987.
2. Shah GV. Central nervous system tuberculosis: imaging
Acanthameba meningoencephalitis presents as chronic
manifestations. Neuroimaging Clin N Am 2000; 10: 355-74.
granulomatous encephalitis. It is more common in 3. Tung YR, Lai MC, Lui CC, et al. Tuberculous meningitis in infancy.
immunocompromised hosts. Non-response to antipyo Pediatr Neurol 2002; 27: 262-6.
542 Essential Pediatrics
exclude treatable causes such as enteric encephalopathy, is crucial for recovery. Prognosis is variable; about half
malaria, shigella, toxins, poisoning, diabetes mellitus and the patients recover after timely therapy.
renal disease. Virological studies should include viral
culture and PCR on CSF and blood. IgM Elisa on CSF serum Suggested reading
should be done for arbo/entero/herpes/measles virus. 1. Shoji H, Azuma K, Nishimura Y, et al. Acute viral encephalitis: the
Rising titers of sera are obtained for antibodies to recent progress. Intern Med 2002; 41: 420-8.
2. Bulakbasi N, Kocaoglu M.Central nervous system infections of
neurotropic viruses, typhoid, etc. Serum lead levels should
herpes virus family. Neuroimaging Clin N Am. 2008 Feb;18(l)
be estimated if there is a possible exposure of the child to 53-84; viii.
lead contaminated environment. 3. Shankar SK, Mahadevan A, Kovoor JM.Neuropathology of viral
infections of the central nervous system.Neuroimaging Clin N Am.
Acute disseminated encephalomyelitis (ADEM): Acute
2008 Feb;18(l):19-39; vii.
immune demyelination of the brain, spinal cord following 4. Fitch MT, Abrahamian FM, Moran GJ, Talan DA.Emergency
a variety of insults to oligodendroglia. Damage is department management of meningitis and encephalitis. Infect Dis
perivenular in location commonly at the gray-white zone Clin North Am. 2008;22(l):33-52, v-vi.
and occurs commonly after infections or vaccination 5. Mizuguchi M, Yamanouchi H, Ichiyama T, Shiomi M.Acute
encephalopathy associated with influenza and other viral
usually a monophasic illness, permanent deficits after the
infections. Acta Neurol Scand Suppl 2007;186:45-56.
initial severe manifestation occasionally. Acute stage is 6. Amin R, Ford-Jones E, Richardson SE et al.Acute childhood
characterized by seizures, sensorial alternation and encephalitis and encephalopathy associated with influenza: a
multifocal neurological signs, raised intracranial pressure prospective 11-year review. Pediatr Infect Dis ] 2008;
visual disturbances, etc. Cerebrospinal fluid usually 27(5):390-5.
normal, mild pleocytosis, mildly elevated protein and
normal glucose. Imaging may be normal, generally reveals REYE SYNDROME
multiple hypodensities in white matter, which enhance
The first description of this syndrome was probably made
with contrast MRI may also show spinal cord, basal
by Najib Khan in Jamshedpur, in 1956 (Jamshedpur fever).
ganglia lesions in addition to white matter involvement.
Reye and colleagues in Australia in 1964 described a
Therapy with pulse corticosteroids is useful.
diffuse fatty infiltration of the liver, to a lesser extent of
the kidney, and cerebral edema with diffuse mitochondrial
Management
injury.
Treatment aims to save life, prevent neurological residua,
relieve symptoms. Pathogenesis
Emergency treatment: Airway should be kept patent and It is an acute self-limiting metabolic insult of diverse
assisted respiration given if necessary. Hyperpyrexia etiology resulting in generalized mitochondrial dysfunc
should be managed with vigorous hydrotherapy and tion due to inhibition of fatty acid (3-oxidation. Salicylates
antipyretics. Shock is managed by infusion of appropriate or viral infections can precipitate this metabolic impair
fluid, dextran or vasopressors. Dopamine or dobutamine ment. An inborn error of coenzyme A dehydrogenase,
are added to the infusion to maintain blood pressure. reduction in medium chain acyl-A and accumulation of
Seizures are controlled by intravenous diazepam and unusual Co-A esters is suspected. Viruses like varicella
phenytoin. Raised intra-cranial pressure is managed by IV and influenza B have been incriminated. Contamination
infusion of 20% mannitol solution (1 g of mannitol/kg body of food with aflatoxin has also been implicated. There is
weight) given in 30 minutes and corticosteroids such as some epidemiological evidence that use of aspirin or
dexamethasone. The role of corticosteroids in most salicylate used for certain viral acute respiratory infections
encephalitides is not proven except in acute disseminated might precipitate Reye syndrome. Neuroglucopenia and
encephalomyelitis and where an autoimmune mechanism hyperammonemia result from mitochondrial and sodium
is postulated. pump failure. Encephalopathy appears to be secondary
to the liver damage.
Herpes simplex encephalitis: Herpes simplex type I virus is
the causative organism. Type II virus causes perinatal
herpes infections. Clinical picture includes fever of sudden Clinical Features
onset, mental confusion, vomiting, meningeal irritation, A mild prodromal illness may be followed by an acute
headache and papilledema. In addition to seizures onset of the disease. The child has vomiting for one or two
neurological deficits are common. Localizing signs (focal days along with anorexia, listlessness, followed by rapid
seizures, focal paralyses, focal EEG changes), presence of disturbances of sensorium, irregular breathing, decerebra
RBCs in the CSF and focal involvement of the temporal tion, pupillary changes and rapidly developing coma.
lobe on CT scan are important diagnostic clues. Diagnosis Seizures occur in more than 80% patients. There are hardly
can be established by CSF culture or PCR. The drug of any focal neurological or meningeal signs. Hepatomegaly
choice is acyclovir (30 mg/kg/day) administered in 3 is present in half the cases. Jaundice is infrequent. The
divided doses per day for a 10 days period. Early therapy clinical features may be described in four stages:
544 Essential Pediatrics
Stage I: Vomiting, anorexia, mild confusion, listless displacement of CSF from the intracranial cavity,
ness, apathy. compensatory hemodynamic changes ensue. Heart rate
Stage II: Delirium, restlessness, irritability, lack of slows, respiratory rate is altered and blood pressure rises
orientation, frightened, agitated states. to maintain the cerebral circulation. Average pressure of
S tage III: Coma, decorticate posture which later becomes cerebrospinal fluid is 180 mm of water is subject to many
decerebrate, patients may die. factors such as patency of the ventricular system, straining,
Stage IV: Flaccidity, areflexia, apnea, dilated pupils not sleep, position and size of the lumbar puncture needle
reacting to light, severe hypotension. and the kind of fluid.
The signs of raised ICT appear early in infratentorial
Laboratory Investigations tumors and are relatively late in supratentorial neoplasms.
There maybe some degree of hypoglycemia with low levels Common clinical features of raised ICT include either one
of glucose in the cerebrospinal fluid. Serum ammonia levels or a combination of the following clinical features.
are elevated. Prothrombin time is prolonged and hepatic Increased head size and/or papilledema: In infants, there is
enzymes are increased. Liver biopsy shows fatty change separation of the cranial sutures, wide fontanels and
and glycogen depletion but no necrosis of the liver cells, increased head circumference. The fontanel should be
EEG shows generalized slow waves. examined with the baby relaxed and placed in the upright
position. A delayed fontanel closure or a tense and non-
Prognosis pulsatile fontanel is significant. Separation of the sutures
Prognosis is poor with 25-70% mortality. Survivors may compensates for increase in the intracranial pressure.
have neurological sequelae. The MacEzven's or crackpot sign indicates raised
intracranial pressure after sutures have closed. Papill
Management edema is unusual in infant unless the increase in
Hepatic failure needs appropriate management. The intracranial pressure is very high. The changes include
patient is given low protein diet with adequate calories. loss of cupping of the disk, absent venous pulsations and
Intravenous infusion of mannitol (20% solution; 0.5 g/kg/ raised disk margins. In severe cases, hemorrhages may
IV q6 hourly) and dexamethasone are used to reduce the be observed. Tests, such as enlargement of the blind spot
brain edema. Hypoglycemia should be corrected by IV on visual field examination are helpful in differentiating
10-25% glucose. Acidosis, hypoxia and dyselectrolytemia papilledema from other conditions.
should be corrected. Double volume exchange transfusion Vomiting: Unexplained projectile vomiting not associated
has been used in Stage III. Vitamin K and fresh frozen with nausea, especially in the morning should arouse
plasma may be required. Surgical decompression of the suspicion of a brain tumor. It is attributed to direct pres
raised intracranial pressure may be required to save life. sure on the medullary centers. Headache may or may not
present.
Suggested reading
Headache: Young children often do not complain of
1. Casteels-Van Daele M, Van Geet C, Wouters C, et al. Reye
headache. Persistent headache in young children,
syndrome revisited: a descriptive term covering a group of
heterogeneous disorders. Eur J Pediatr 2000; 159: 641-8. prominent in early morning is highly suspicious. During
2. Glasgow JF, Middleton B. Reye syndrome—insights on causation the night, when the child is inactive and is lying in a
and prognosis. Arch Dis Child 2001; 85: 351-3. horizontal position, the ventricular pressure above the
3. Schror K.Aspirin and Reye syndrome: A review of the evidence. mass increases and sleep is interrupted because of
Paediatr Drugs 2007;9(3):195-204. headache. During the day, partial obstruction is overcome,
facilitated by the effect of gravity and symptoms may
INTRACRANIAL SPACE OCCUPYING LESIONS________ abate. Parents erroneously impute the early morning
Intracranial space occupying lesions (ICSOL) include brain headache, coinciding with the time of going to school as
tumors, masses of congenital origin and inflammatory malingering and thus delay seeking medical intervention.
disorders such as brain abscess, neurocysticercosis, Diplopia and sixth nerve palsy: Increased pressure displaces
tuberculoma and subdural fluid collection, etc. Brain the brainstem downwards, thus stretching the sixth nerve
edema may also simulate space occupying lesions. ICSOL and resulting in paralysis of the lateral gaze and diplopia.
may present with features of increased intracranial
tension, altered sensorium and/or localizing signs. These Localizing Signs
are detailed below: These signs are helpful to detect the anatomical site of the
lesion.
Increased Intracranial Tension (ICT)
Cranial nerve palsies: Multiple cranial nerve palsies occur
The intracranial space and its contents (brain, CSF & blood) in brainstem lesions along with involvement of pyramidal
are in a state of delicate equilibrium. After closure of tract and cerebellar pathways. Sixth nerve palsy usually
sutures and fontanel the adaptive mechanisms to changes has no localizing value. If 6th nerve palsy is associated
in contents and pressure in the brain is through the with supranuclear seventh nerve involvement, it may be
Central Nervous System 545
suggestive of pontine lesion. In supranuclear hypoglossal blastomas and one-third are astrocytomas of cerebellum. Brain
paralysis, tongue is tilted to contralateral side. In pseudo stem gliomas and ependymomas account for the rest. Most
bulbar palsy, uvula, gag reflex and movements remain of these tumors occur near the midline. Therefore they
intact, though swallowing is affected. Nasopharyngeal commonly obstruct CSF circulation and cause hydro
masses, rhabdomyosarcoma, lymphosarcoma and inflam cephalus early in disease. In adults, infratentorial tumors
matory masses may involve cranial nerves in their course. account for less than 10% of brain neoplasms. Common
Head tilt: Head tilt is seen in superior oblique paralysis, supratentorial tumors are astrocytomas, ependymomas,
cerebellar lesions and posterior fossa tumors. craniopharyngioma and malignant gliomas. Papillomas
of choroid plexus and pineal body tumors are less
Ataxia: Ataxia occurs in cerebellar, spinocerebellar tract,
common. Meningiomas, acoustic neuromas and pituitary
frontal lobe or thalamic lesions.
adenomas are rare in childhood. Ataxia telengiectasia and
Motor deficit: This may occur in cerebral, brainstem and neurocutaneous syndromes are associated with a higher
spinal cord lesions. incidence of brain tumors. Imaging technology is the
Seizures: These indicate cortical or subcortical lesion. mainstay of diagnosis. CT gives adequate information
Intermittent decerebrate posturing may be due to about ventricular size, tumor and surrounding edema. It
infratentorial pathology. is useful for follow-up. MRI provides better information
regarding mass size, infratentorial and spinal cord
Nystagmus : Both irritative and destructive lesions in any extension and tumor detail.
part of cerebello-vestibular system may cause nystagmus
with quick and slow components in opposite direction. Cerebellar Tumors
Unilateral cerebellar lesion may produce bilateral manifes
Medulloblastoma: These are midline cerebellar tumors.
tations because of compression across the midline.
They occur in infancy, are fast growing, malignant,
Brainstem lesions cause vertical nystagmus. The site of
craniospinal spread along neuraxis is common and death
lesion is towards the side of the coarse nystagmus. Nystag
occurs early. They cause truncal ataxia, early papilledema,
mus also occurs with increased intracranial pressure,
unsteadiness in sitting position and a tendency to walk
degenerative syndromes and with toxicity of anti-epilepsy
with a broad base. Radiation, chemotherapy and a VP
drugs such as phenytoin and phenobarbitone.
shunt are generally required.
Vision: It is difficult to evaluate visual acuity and field of
Astrocytoma: These are common in the cerebellar
vision in children. Impaired vision not corrected by glasses
hemisphere. There is ataxia and incoordination more on
should arouse suspicion of lesion near optic nerve,
the side of the lesion. Nystagmus is observed on lateral
chiasma, optic radiations or cortical blindness. Bitemporal
gaze of the child to the affected side. Areflexia and
hemianopsia may indicate compression over chiasma but
hypotonia are present. The head is tilted to the side of
it may also be seen in optic atrophy.
lesion to relieve the increased intracranial pressure caused
Personality disturbances: Infants may become irritable, by herniation of tumor or cerebellar tonsils through the
lethargic and show disturbances of behavior or speech. foramen magnum. Complete surgical excision of the
Loss of cortical sensation as described in supratentorial tumor is often feasible. Chemotherapy with tomustin,
tumors of adults is difficult to interpret in children. There vincristine and cisplatin is advised. Brachytherapy is now
may be a decline in intellectual function. used in a variety of brain tumors to limit radiation necrosis
Personality disturbances, inappropriate sphincter and provide local irradiation to improve prognosis.
control and grasp response suggest localization of tumor
Brainstem Tumors
near the frontal lobe. There may be optic atrophy in the
fundus of the same side and papilledema in the opposite Signs of increased intracranial tension are minimal yet
eye (Foster Kennedy syndrome). vomiting occurs due to infiltration of medullary vomiting
center. Hemiparesis, cranial nerve deficits and personality
BRAIN TUMORS changes are common; reflexes in the lower limbs are
exaggerated. The pontine tumors affect the 6th and 7th
Tumors arising from the brain are the second most
cranial nerves.
common group of neoplasms in children next only to
hematologic malignancies. Metastatic tumors are rare Glioma of the brainstem causes bilateral involvement of the
during childhood. Certain genetic syndrome and familial cranial nerves and long tracts. Cerebellar dysfunction is
factors increase risk of occurrence of brain tumors. Primary often present. The usual age of onset is in the later half of
brain tumors may be malignant or benign. Benign tumors the first decade. Brainstem gliomas carry the worst
may, however, become life-threatening if these are located prognosis. Most children die within 18 months. Surgical
near a vital area of the brain. excision is difficult and not very promising. Hyper
Over two-thirds of brain tumors in children are fractionation radiotherapy is being evaluated. Chemo
infratentorial. About one-third to half of these are medullo- therapy does not have significant role.
546 Essential Pediatrics
Etiology: Anerobic organisms, streptococci, Staphylococcus Clinical features are non-specific. Convulsions, vomiting,
aureus, pneumococci, Proteus and Hemophilus influenzae are irritability and drowsiness are present. There is persistent
the common infecting organisms. The abscesses are fever, anterior fontanel bulges and head size increases. In
observed more often in the cerebrum compared to the newborn period, the skull may show increased
infratentorial compartment. transillumination. CT/MRI or subdural tap establishes the
diagnosis.
Clinical features of brain abscess may be described under 4
broad headings: (i) features of raised intracranial pressure; Treatment: Small collections are absorbed spontaneously.
(ii) manifestations of intracranial suppuration such as Large effusions may need to be aspirated every 24 to 48
irritability, drowsiness, stupor, and meningeal irritation; hours until these become small or are completely dried
(iii) features suggesting toxemia, e.g. fever, chills, and up. Surgical irrigations with indwelling drains may be
leukocytosis; and (iv) focal neurological signs such as focal considered if the effusion persists for more than 2 weeks.
convulsions, cranial nerve palsies, aphasia, ataxia, visual Surgical excision of the subdural membrane is difficult
field defects and neurological deficit. and results are not encouraging.
Suggested reading The CSF is secreted at the choroid plexus within the
ventricles by ultrafiltration and active secretion. It passes
1. Calfee DP, Wispelwey B. Brain abscess. Semin Neurol 2000; 20:
353-60.
from the lateral ventricles to the third ventricle, fourth
2. Goodkin HP, Harper MB, Pomeroy SL. Intracerebral abscess in ventricle exits from Foramen of Luschka and Magendie
children: historical trends at Children's Hospital Boston. Pediatrics. reaches the basal cisterns, and then the cerebral and spinal
2004 Jun;113(6):1765-70. subarachnoid spaces where it is absorbed via the
3. Leotta N, Chaseling R, Duncan G, Isaacs D. Intracranial
arachnoid villi (granulations) into the venous channels and
suppuration.J Paediatr Child Health. 2005 Sep-0ct;41(9-10):508-
12.
sinuses. About 20 mL of CSF is secreted in an hour and its
4. Lu CH, Chang WN, Lin YC et al. Bacterial brain abscess: turnover is 3 or 4 times in a day.
microbiological features, epidemiological trends and therapeutic
outcomes. QJM. 2002 Aug;95(8):501-9. Etiology: Hydrocephalus results from an imbalance
5. Foerster BR, Thurnher MM, Malani PN, Petrou M, Carets-Zumelzu between production and absorption of cerebrospinal fluid.
F, Sundgren PC.Intracranial infections: clinical and imaging Hydrocephalus may be (i) communicating; or (ii) non
characteristics.Acta Radiol. 2007 Oct;48(8):875-93. communicating (obstructive).
Oral glycerol has also been used for similar purpose. A 2. Vertinsky AT, Barnes PD.Macrocephaly, increased intracranial
pressure, and hydrocephalus in the infant and young child.Top
conservative approach is better in most cases.
Magn Reson Imaging. 2007 Feb;18(l):31-51.
If the head size enlarges rapidly, or is associated with 3. Beni-Adani L, Biani N, Ben-Sirah L, Constantini S.The occurrence
progressive symptoms, where vision or life is endangered of obstructive vs absorptive hydrocephalus in newborns and
it is desirable to treat surgically before irreparable damage infants: relevance to treatment choices.Childs Nerv Syst. 2006
occurs. In congenital obstructive hydrocephalus, acquired Dec;22(12):1543-63.
4. Waluza JJ. Management of hydrocephalus.Trop Doct. 2006
hydrocephalus, periventricular ooze with hydrocephalus
Oct;36(4):197-8.
a ventriculo-atrial or preferably a ventriculo-peritoneal
5. Duhaime AC.Evaluation and management of shunt infections in
shunt should be done to drain the CSF directly into the children with hydrocephalus. Clin Pediatr (Phila). 2006
circulation or into the peritoneal cavity. Third 0ct;45(8):705-13.
ventriculotomy by endoscopic approach is another option 6. Matthews YY.Drugs used in childhood idiopathic or benign
particularly in children with obstructive hydrocephalus. intracranial hypertension. Arch Dis Child Educ Pract Ed. 2008
Feb;93(l):19-25.
In cases of bacterial meningitis, an acute hydrocephalus
7. Kesler A, Bassan H.Pseudotumor cerebri - idiopathic intracranial
may set in which is self-limited. Patients with tuberculous hypertension in the pediatric population. Pediatr Endocrinol Rev.
meningitis and progressive hydrocephalus require a 2006 Jun;3(4):387-92.
shunt, specially if it is obstructive.
A variety of shunts are now available. It is usually
NEURAL TUBE DEFECTS
necessary to keep the shunt for the entire life. As the child
grows in size it may be necessary to revise the shunt, using Neural tube defects (NTD) are one of the most common
a longer tube. Blockage and infection are the two most structural congenital anomalies and imply a failure of
common shunt complications. Shunt revision may also be proper closure of neural tube and covering mesoderm and
necessary if there is bacterial colonization of the shunt. ectoderm. These defects occur in about 1.5 per 1,000 live
births; the risk in second sibling is 5 per 100 births. The
Prognosis: Even with the best of treatment, prognosis is
incidence in North India is as high as 3.9-9/1,000 live
guarded. Almost two-third of children have variable
births.
mental and developmental disabilities. Prognosis of
hydrocephalus associated with spina bifida is not Etiology
satisfactory.
Primary neural tube defects have multi-factorial inheri
PSEUDOTUMOR CEREBRI tance. Maternal risk factors include alcohol, radiation
(BENIGN INTRACRANIAL HYPERTENSION) exposure, insulin dependent diabetes mellitus (IDDM),
valproate and carbamazepine, zinc and folate deficiency.
It is a benign self-limiting disorder with generally a favo Chromosomal abnormalities including trisomy 13 and 15
rable outcome. The intracranial pressure is elevated, have been reported.
ventricular system is either normal or small. Generally Maternal malnutrition is an important risk factor for
there are no focal neurological signs. Onset of symptoms development of NTD. Studies until date have shown
of raised intracranial pressure may be sudden or gradual decreased maternal folate levels in NTD affected
extending over a week or so. Visual field shows pregnancies. Periconceptional folic acid supplementation
enlargement of blind spot. has shown to decrease both the occurrence and recurrence
It may follow use of outdated tetracycline, high doses of NTD, though the exact mechanism for this protective
of vitamin A, quinolones, lateral sinus thrombosis effect remains unknown.
(following otitis media, mastoiditis especially on the right
side) and obstruction of venous outflow due to pressure Clinical Features
on superior vena cava. Pulmonary disease with C02
retention may also be responsible. It may occur during The defect is obvious at birth or through fetal sonography.
withdrawal of corticosteroid therapy, Addison's disease, It varies in severity from an occult anomaly to severe life
hypoparathyroidism besides systemic lupus erythemato threatening problem. Lumbosacral region is the
sus. EEG shows excessive slow wave activity. Isotope commonest site, but any part of the spine may be affected.
brain scan, CT or MRI are normal. The patient improves The defect may extend over a variable length of the spinal
spontaneously after a few months. Acetazolamide cord.
(carbonic anhydrase inhibitors) or oral glycerol helps in The spectrum includes spina bifida (meningocele,
symptomatic relief. Dexamethasone may be required. meningomyelocele, spina bifida occulta), anencephaly
Cerebral decompression or optic nerve sheath fenestration (absence of brain calvaria, total or partial), encephalocele
is rarely necessary. (herniation of brain and meninges through defect in
calvaria), craniorachischisis (anencephaly associated with
Suggested reading continuous bony defect of spine and exposure of neural
1. Garg BP, Walsh L. Clinical approach to the child with a large head. tissue) and iniencephaly (dysraphism of occipital region
Indian J Pediatr 2001; 68: 867-71. accompanied by retroflexion of neck and trunk).
Central Nervous System 551
Neural tube defects may be associated with other Surgery includes surgery of the defect and a VP shunt (if
congenital anomalies and dysfunction of organ systems. associated with hydrocephalus). Early closure prevents
Affected children may have lower body paralysis, bladder neurological deterioration. Open lesions draining CSF
and bowel dysfunction, learning disabilities, hydro should be closed within 24 hours. Closed lesions should
cephalus due to Arnold-Chiari Type 2 malformation and be operated within 48 hours. In case, the lesion is infected,
endocrinal abnormalities. Anencephaly is an important the child should be given parenteral antibiotics. Surgery
cause of fetal and infant mortality. Severe cases die in utero, is done only when three 24 hours CSF cultures are sterile.
or in the early neonatal period. Long term sequelae include
Lorber's criteria for selective surgery: Surgery is not
neurological and motor significant physical disability,
recommended if there is severe paraplegia at or below L3
psychosocial maladjustments and increased financial
level, kyphosis or scoliosis, gross hydrocephalus,
burden on family. associated gross congenital anomalies, intracerebral birth
Spina bifida occulta constitues about 5% cases and is injuries and neonatal ventriculitis before closure of back.
asymptomatic. Meningocele or myelomeningocele, Ninety percent would die in the neonatal period.
presents clinically as a raw red fleshy plaque, consists of
meninges, CSF, nerve roots and dysplastic spinal cord. In Prognosis
meningocele, the sac is covered only by skin and generally Delay in intervention causes increase in complications like
there is no neurologic deficit. Arnold-Chiari malformation worsening of neurologic deficit, infection (local or
associated meningomyelocele may have a variety of ventriculitis), progressive hydrocephalus, etc. Late compli
associated CNS anomalies like heterotopias, hypoplasia and cations include: hydrocephalus in 80-90% because of
ventricular abnormalities. Chiari II malformation, urinary tract infections, enuresis,
In meningomyelocele the neurologic deficit includes fecal incontinence or constipation, sexual dysfunction,
varying degrees of flaccid, areflexic paraparesis and intellectual deterioration, delayed neurological problems
sensory deficit in the trunk and legs correspond to the (tethered cord, intradural mass lesions), epilepsy in 10-
involved segments of the dysplastic cord. The cord distal 30%, ocular problems (30%), shunt infection (25%),
to the site of the lesion is severely affected. Involvement psychosocial problems and motor deficits. 2% die during
of bowel and bladder results in fecal and urinary initial hospitalization. 15% die by ten years of age. The
incontinence. Hydrocephalus is usually present in varying mortality rate plateaus by 4 years of age.
degrees and a shunt is required generally. Arnold-Chiari
malformation may cause facial weakness and swallowing Prevention
difficulty. Tongue movements may be impaired and there Primary prevention includes folate supplementation to all
may be laryngeal stridor. prospective mothers including first pregnancy. Food
fortification is another possible approach. Counseling of
Management
family with a previous child with NTD is essential. The
Prenatal diagnosis of myelodysplasia is possible by risk of recurrence is 3.5% with 1 affected child, 10% with
estimating alpha-fetoprotein level in the maternal blood 2 affected children and 25% with 3 affected children.
between 14 and 16 weeks of gestation, or in the amniotic MTHFR polymorphism should be studied. Advise
fluid in early pregnancy where the test is more specific. periconceptional folate and offer prenatal diagnosis in
Additional test in amniotic fluid includes acetyl cholines- subsequent pregnancy. Folate supplementation reduces
terase estimation. Ultrasound pick-up rate is around 100%, recurrence risk by 70%. Zinc and vitamin A supplemen
maternal blood alpha fetoprotein (16-18 weeks) has tation is also advised.
accuracy of 60-70%, amniocentesis for alpha fetoprotein Dose for primary prevention is 0.4 mg per day. A
and acetylcholinesterase has accuracy of 97%. There is no mother who has previously delivered a child with NTD
indication for preinduction cesarian section except should receive 5 mg per day of folic acid in subsequent
craniomegaly, large protruding lesions and obstetric pregnancies. Secondary prevention is imperative after an
indications. index case. Duration of supplementation is 2 months
before and 3 months after conception.
Investigations: They include ultrasound of head and sac (if
possible kidney also), CXR and X-ray spine, culture from
Suggested reading
lesion and draining CSF and complete blood counts.
1. Birnbacher R, Messerschmidt AM, Poliak AP. Diagnosis and
Treatment: Management of NTD requires a team approach prevention of neural tube defects. Curr Opin Urol 2002;12: 461-4.
with the cooperation of pediatrician, neurologist, 2. Lonely J, Watson L, Watson T, Bover C. Periconceptional
neurosurgeon, urologist and orthopedic surgeon with supplementation with folate and/or multivitamins for preventing
assistance from physiotherapist, social worker and neural tube defects. Cochrane Database Sys Rev 2000; 2: CD 00156.
3. Verity C, Firth H, French-Constant C. Congenital abnormalities of
psychiatrist. Parents should be counseled actively. The
the central nervous system. J Neurol Neurosurg Psychiatry 2003;
degree of paralysis, presence of hydrocephalus, kyphosis, 74 : 3-8.
congenital malformation, evidence of infection of nervous 4. Shaer CM, Chescheir N, Schulkin J.Myelomeningocele: a review
system influences decisions. of the epidemiology, genetics, risk factors for conception, prenatal
552 Essential Pediatrics
diagnosis, and prognosis for affected individuals. Obstet Gynecol In mild hemiparesis, when the child is running or
Surv. 2007 Jul;62(7):471-9.
walking, there is circumduction and movements of the
5. Kibar Z, Capra V, Gros P.Toward understanding the genetic basis
of neural tube defects. Clin Genet. 2007 Apr;71(4):295-310.
upper extremities are asymmetric. If the child is pushed
6. Pitkin RM.Folate and neural tube defects. Am J Clin Nutr. 2007 from sitting position the child extends his arm to protect
Jan; 85(1):285S-288S. himself from a fall. This is called lateral propping reaction.
In spastic hemiplegia, this reaction is asymmetric. Absent
ACUTE HEMIPLEGIA OF CHILDHOOD propping reaction in infants after the age 8 to 9 months is
always abnormal.
Acute hemiplegia of childhood is most often due to
Benign intracranial hypertension occurs in lateral sinus
cerebrovascular disorders. The exact cause often remains
thrombosis. Multifocal seizures, raised intracranial
obscure despite modern diagnostic aids and extensive
pressure and vomiting are common in superior sagittal
investigations.
sinus thrombosis. Arterial occlusions generally occur in
Causes the first two years of life. These may be associated with
hemiparesis and seizures, which are difficult to control
1. Occlusive diseases of the cerebrovascular system
with medication. Hemiparesis, cerebral hemiatrophy and
a. Venous thrombosis ofdural sinus: Congenital cyanotic
cerebral porencephaly may result.
heart disease, dehydration, paranasal sinuses,
leukemia Localization
b. Thrombosis (arterial): Sickle cell disease, homo-
Cortical lesions: Cortical lesions are characterized by the
cystinuria, iron deficiency anemia, dysproteinemias,
specific pattern of motor deficit, depending on the vascular
thrombotic thrombocytopenic purpura, Takayasu
distribution of the artery involved. Seizures and cortical
disease, polyarteritis nodosa, lupus erythematosus,
sensory loss are usual.
trauma to internal carotid artery, retropharyngeal
In the left-sided lesion, aphasia is a dominant clinical
abscess, protein C or S deficiency, Moyamoya
feature. The child has difficulty in reading, writing and
disease, NADH coenzyme and reductase deficiency,
comprehension. Organization of space and body image
mitochondrial encephalopathy, stroke syndromes
are affected. In right parietal lesions, the child exhibits
c. Cerebral embolism: Subacute or acute bacterial
lack of attention for objects on his left side. He may ignore
endocarditis, air embolism, fracture causing fat
the left side of a picture placed before him or may not
embolism, umbilical vein catheterization in the
even recognize his left hand. He has difficulty in copying
newborn, sepsis
simple figures (indicating constructional apraxia). He gets
2. Intracranial hemorrhage: Arteriovenous malforma
lost easily and confuses directions given to him because
tions, coagulopathy, platelet vascular defects, hyper
of spatial disorganization.
tension, trauma, intracranial aneurysm, Sturge-Weber
syndrome Corona radiata: The hemiplegia is generally complete and
3. Inflammatory: Inflammatory granulomas seizures are usually absent.
4. Porencephaly: Cerebral abscess, meningitis, encepha
Internal capsule: Hemiplegia is complete, often with
litis, intracranial space occupying lesions
sensory loss.
5. Idiopathic: Mitochondrial disorders also produce
recurrent stroke like episodes and lactic acidosis in both Brainstem
arterial blood and CSF. The stroke does not clearly a. Midbrain: Hemiplegia on the contralateral side and
follow vascular distribution. MR imaging helps in paralysis of 3rd and 4th cranial nerves on the same side
suspecting the diagnosis. (Weber syndrome).
b. Pons: Hemiplegia on the opposite side and involvement
Clinical Features of 6th and 7th cranial nerves on the same side (Millard-
Mode of onset: The rapidity of onset varies with the cause. Gubler syndrome).
Emboli occur abruptly with maximum neurological signs c. Medulla oblongata: Contralateral hemiplegia with
at onset. There is improvement with passage of time. ipsilateral involvement of several cranial nerves.
Seizures are frequently associated. Although intracranial
hemorrhage also occurs acutely, it takes some time before Management
the full clinical picture manifests with headache and
Investigate for the predisposing illness. Platelet count,
nuchal rigidity. Cerebrovascular thrombosis is relatively
hemoglobin, MCV, MCH, serum iron and iron binding
less rapid in onset.
capacity, nitroprusside reaction for homocystinuria, sickle
History and physical examination: History of ear, throat cell preparation of blood, antinuclear antibody tests,
mastoid infection, intraoral or neck trauma, associated protein C and S estimation, APLA, serum lactate/
cardiac disease or hematological disorders may be helpful pyruvate, CSF lactate/pyruvate, chest X-ray and ECG.
in determining the cause. Metabolic tests if indicated.
Central Nervous System 553
Neurological work-up includes CT scan, electro an insidious onset with slowly progressive course and
encephalogram and MR angiography. Lumbar puncture characteristic spinal tract deficit distribution.
is indicated for inflammatory CNS disease. Flaccid weakness may result from spinal cord, nerve
root, nerves and myopathic disorders. Acute onset follows
Treatment: Specific treatment depends on the etiology of
demyelinating polyneuropathy, polio, vascular and
hemiplegia. The role of T-plasminogen activator in child
traumatic spinal cord insults. Chronic causes include
hood stroke is not established. In thrombotic stroke,
spinal muscular atrophy (SMA), peripheral neuropathies
heparin may be indicated. Seizures should be controlled
and myopathies. Table 17.9 enlists the common causes of
and hydration should be maintained. Physiotherapy and
paraplegia and quadriplegia.
speech therapy should be started early.
It should be remembered that symmetrically brisk
Treatment of acute cerebral thrombosis is directed
tendon reflexes with flexor plantar response may be
towards increasing cerebral perfusion, limiting brain
normal in children and do not necessarily indicate any
edema, and preventing recurrences. Salicylates are used
pathological process. In case of doubt between plantar
for preventing recurrence. Calcium channel blockers have
reflex and withdrawal response, the dorsilateral aspect of
been found useful in some. Seizures often persist and
anticonvulsants may be required. Table 17.9: Causes of paraplegia or quadriplegia
Vasodilators and platelet inhibitors have been used in A. Spastic
treatment. Free radical scavengers and coenzyme Q may a. Compressive
have limited utility. Tuberculosis spine with or without paraspinal abscess.
Extradural, e.g. metastasis from neuroblastoma, leukemia,
Prognosis lymphoma; inflammatory process, such as epidural
Prognosis with regard to seizures and mental retardation abscess (usually posterior to the spinal cord), bony
is worse in acute idiopathic hemiplegia below 3 years of abnormalities such as achondroplasia, Morquio disease,
age. Hemiplegic side may be atrophied and post hemivertebrae and occipitalization of atlas vertebra,
hemiplegia athetosis may be seen in these cases. Cerebral atlantoaxial dislocation
Intradural. Neurofibroma and dermoid cyst
hemiatrophy with flattening of the skull and porencephaly
lntramedullary. Glioma, ependymoma, hemato- or
secondary to parenchymal damage may occur.
hydromyelia
Suggested reading b. Non-compressive myelopathies
Vascular anomalies of the spinal cord (AV malformations,
1. Bernard TJ, Goldenberg NA.Pediatric arterial ischemic stroke. angiomas and telengiectasia)
Pediatr Clin North Am. 2008;55(2):323-38, viii.
Spinal cord trauma or transaction of cord
2. Mackay MT, Monagle P.Perinatal and early childhood stroke and
Transverse myelitis/myelopathy. Viral, neuromyelitis optica,
thrombophilia. Pathology. 2008;40(2):116-23.
3. Seidman C, Kirkham F, Pavlakis S.Pediatric stroke: current segmental necrosis due to vascular occlusion, e.g. of
developments. Curr Opin Pediatr. 2007;19(6):657-62. anterior spinal artery
4. Carpenter J, Tsuchida T, Lynch JK.Treatment of arterial ischemic Familial spastic paraplegia, white matter degenerations
stroke in children. Expert Rev Neurother. 2007;7(4):383-92. Lathyrism due to consumption of toxic pulse Lathyrus
5. Carpenter J, Tsuchida T.Cerebral sinovenous thrombosis in sativum
children. Curr Neurol Neurosci Rep. 2007;7(2):139-46. Degenerative spinal cord disease
6. Jordan LC, Hillis AE.Hemorrhagic stroke in children.Pediatr
c. Supra-cord lesions
Neurol. 2007 Feb;36(2):73-80. Cerebral palsy
7. Nelson KB, Lynch JK.Stroke in newborn infants.Lancet Neurol.
Hydrocephalus
2004;3(3):150-8.
Bilateral cortical disease
PARAPLEGIA AND QUADRIPLEGIA Bilateral white matter disease
B. Flaccid weakness
Paraplegia refers to motor weakness of both lower limbs.
Quadriplegia is the nomenclature used for neurological Spinal shock in the initial stages of spinal cord damage, e.g.
after trauma, vascular, inflammatory, neoplastic lesions, or
weakness of all four limbs; the involvement is more in the
transverse myelopathy
upper limbs as compared to the lower extremities.
Acute inflammatory demyelinating polyneuropathy, acute
Neurological weakness may be (i) spastic — spasticity, motor axonal neuropathy
exaggerated tendon reflexes, extensor plantar or (ii) flaccid Acute poliomyelitis
— flaccidity, diminished tendon reflexes, flexor plantar Spinal muscular atrophies
response and muscle wasting. Incomplete paralysis is Demyelinating neuropathies
known as paraparesis or quadriparesis. It may be acute, Motor sensory neuropathy
or insidious in onset and have a variable course. The Botulism, Riley Day syndrome, asymptomatic areflexia
vascular, traumatic and post-infective lesions are usually C. Pseudoparalysis
acute in onset with variable gradual recovery. Compres
Surgery, osteomyelitis, fractures, myositis, metabolic
sive/ neoplastic lesions have insidious onset with myopathy
gradually progressive deficit. Degenerative disorders have
554 Essential Pediatrics
the foot should be stroked (Chaddock maneuver) to obtain is followed by weakness developing in a few days, at first
the plantar response. In lesions above the level of in the legs and then spreading to the upper extremities and
midbrain, jaw reflex becomes brisk. Abdominal reflexes trunk muscles. Weakness is more marked in the proximal
should be elicited by stroking the skin over the abdomen muscle groups. Tendon reflexes are diminished, plantar
close to the umbilicus. Examine patient carefully for reflex is normal and there is hypotonia. Cranial nerve
sensory involvement and sensory level, wasting at the involvement (most often the facial nerve) is seen in three-
segments of the lesion, posterior column involvement and fourths of the cases. Early in disease the involvement may
bladder bowel involvement. at times be unilateral or the degree of weakness may be
different on two sides. Sensory symptoms are subjective
Management rather than objective. Involvement of the autonomic ner
In acute myelitis, high dose of dexamethasone (5 mg/kg/ vous system is indicated by urinary retention, hypertension
day) or IV methylprednisolone pulse therapy for 3-5 days or postural hypotension. Respiratory insufficiency may
maybe useful. In tuberculosis, appropriate drugs, cortico occur if the intercostal muscles are paralyzed. A variant of
steroids and local management suffice. In acute trauma infectious polyneuritis may also present with ataxia.
and paraplegia due to neoplasia the treatment may be
surgical. Diagnosis
Paraplegia is initially flaccid but later becomes spastic The cerebrospinal fluid shows a characteristic albumino-
with development of painful flexor spasms due to the cytological dissociation. The protein is elevated >45 mg/
stimulation of pain fibers. Decubitus ulcers may occur. dL in almost 80% subjects but cell number is normal. The
The child should be frequently turned in bed and nursed rise in protein begins in late first week and maximizes by
on foam mattress. Physiotherapy should be done. Bladder 2-3 weeks. The disorder should be distinguished from
must be emptied regularly by compression or repeated poliomyelitis (asymmetric paralysis and CSF pleocytosis),
catheterization to prevent it being distended and becoming polymyositis (normal CSF, elevated CPK and muscle
atonic. Later bladder may become spastic with frequent pains, no bladder/bowel involvement), transverse
but partial reflex emptying. Urinary tract infection may myelitis (spasticity, exaggerated tendon jerks and extensor
supervene due to inadequate drainage of the bladder. It plantar response after the initial flaccidity for a few days)
should be appropriately treated. In severe spasticity, drugs and cerebellar ataxia. Heavy metal intoxication, porphyria,
that reduce tone provide relief. botulism, spinal cord compression (Froin syndrome), and
post-diphtheric paralysis may mimic Guillain-Barre
GUILLAIN-BARRE SYNDROME/ACUTE syndrome.
INFLAMMATORY DEMYELINATING POLYNEUROPATHY
Treatment
Etiology The natural course of the disease is generally self-limited
The disorder is most likely an autoimmune process. The with gradual recovery in majority of the patients. Few
peripheral lymphocytes are sensitized to a protein patients develop severe paralysis at onset often associated
component of the myelin (p2, neuritogenic peptide); the with respiratory muscle involvement. These patients
basic myelin protein may be altered and rendered definitely require treatment. Recent trials have shown a
immunogenic by the infection. These immune mecha good response with intravenous immunoglobulin,
nisms cause demyelination. Molecular mimicry of administered at a dose of 400 mg/kg/day for 5 days.
bacterial/viral with neuronal gangliosides may cause Response is best if treatment is offered within 3-4 days of
AMAN and AMSAN syndromes. onset. Plasmapheresis is another therapeutic modality
In two-thirds of cases, there is a history of preceding shown to have benefit. Respiratory failure may warrant
viral infection about two or three weeks prior to the illness. assisted ventilation.
Neurologic manifestations usually begin 2-4 weeks after Recovery is complete in most cases, but may take
the viral illness such as infectious mononucleosis (Epstein- 6 months to 2 years for restoration of full function.
Barr virus infection), mumps, measles and those caused Physiotherapy remains the mainstay to prevent handicaps.
by echo, coxsackie and influenza viruses. The conditions
can follow rabies infection, or administration of neural Suggested reading
vaccines for rabies. Campylobacter infections have been
1. Hughes RAC, Cornblath DR. Guillain-Barre syndrome. Lancet
strongly associated with severe forms and acute motor 2005; 366: 1653-66.
axonal neuropathy (AMAN) syndrome. 2. Hughes RAC, Wijdicks EFM, Barohn,R et al. Practice parameter:
Immunotherapy for Guillain-Barre syndrome: Report of the
Clinical Features Quality Standards Subcommittee of the American Academy of
Neurology. Neurology 2003; 61;736-740.
The disorder is characterized by symmetric weakness of the 3. Korinthenberg R, Schessl J, Kirschner J. Clinical presentation and
muscles, diminished reflexes and subjective sensory course of childhood Guillain-Barre syndrome: A prospective
involvement. Pain in the muscles is an early symptom. This multicentre study. Neuropediatrics. 2007;38:10-7.
Centra! Nervous System 555
ACUTE FLACCID PARALYSIS focus on children aged <15 years, it must be flexible to
capture the occasional case that may occur in older
Acute flaccid paralysis (AFP) refers to acute onset (<4
children or adults. It should be noted that AFP in a person
weeks) flaccid, i.e. floppy or limp paralysis of the affected
aged >15 years is unlikely to be polio. Any case of AFP,
limb(s). Tone is diminished on examination by palpation
regardless of the age, should be reported and investigated
or passive movement of joints, but sensation is not
if poliomyelitis is a possible cause.
affected. A case of AFP is defined as any child aged <15
Experience in other parts of the world indicates that at
years who has acute onset of flaccid paralysis for which
least 1 case of non-polio AFP occurs for every 1,00,000
no obvious cause (such as severe trauma or electrolyte
children aged <15 years per year. This is referred to as the
imbalance) is found, or paralytic illness in a person of any
"background" rate of AFP among children. The other non
age in which polio is suspected.
polio causes of AFP, such as Guillain-Barre syndrome
Anatomically AFP can be classified into 4 groups based
(GBS), transverse myelitis, traumatic neuritis, account for
on four levels of motor unit namely muscle, neuro
this background rate, regardless of whether acute
muscular junction, motor fibers, and anterior horn cells.
poliomyelitis exists in the community.
Most of the lesions are acquired often after an acute illness
and has rapidly progressive weakness. Localization of Special effort should be made to obtain 2 stool speci
disorder in the motor unit can be done based on clinical mens from AFP cases within 14 days of paralysis onset.
features (Table 17.10). Outbreak response efforts should be started promptly
Common causes of AFP in our country include polio without waiting for the laboratory results, which might
myelitis, Guillain-Barre syndrome (GBS), transverse take up to 8 weeks. All cases that are classified as
myelitis and traumatic neuritis. Their differentiating "discarded," not polio, require thorough justification and
features are detailed in the Table 17.11. should be reported with the final diagnosis. When a case
of AFP is seen late in the field, stool specimens may be
AFP Surveillance collected up to 60 days after onset of paralysis. The chances
It should be stressed that surveillance is carried out for all of finding poliovirus in the stool after that length of time
cases of AFP and not just for poliomyelitis. Therefore, all are extremely remote. However, it should be noted that
AFP cases should be reported, regardless of the final with a functioning and sensitive surveillance system for
diagnosis. Because paralytic poliomyelitis is one cause of AFP, late detection of AFP cases indicates surveillance
AFP, maintaining a high sensitivity of AFP reporting will failure. The aim should always be to detect AFP cases early
ensure that all cases of paralytic poliomyelitis are detected, so that adequate specimens can be collected.
reported, and investigated, resulting in preventive control Adequate specimen can be defined as 2 specimens, at
measures to interrupt transmission of disease. The aim of least 24 hours apart, collected within 14 days of paralysis
AFP surveillance is to detect poliovirus transmission and onset; each of adequate volume (8-10 g) and arriving at a
the earlier stool is collected the greater the chance that WHO accredited laboratory in good condition. Good
poliovirus may be detected. condition means no desiccation, no leakage, adequate
Historically, poliomyelitis has often been referred to documentation and evidence that the cold chain was
as infantile paralysis. Occasionally, poliomyelitis may maintained. Surveillance is carried out for all cases of AFP,
occur in older children. Therefore, AFP surveillance must not just for poliomyelitis.
Suggested reading usually proximal but may affect fingers, hands, extremities
1. Francis PT. Surveillance of acute flaccid paralysis in India. The and face. The clinical picture may be variable depending
Lancet 2007; 369: 1322-1323. on the severity of the illness. The child may appear clumsy,
2. Field Guide - Surveillance of Acute Flaccid Paralysis. 3rd edition. have mild tick like jerks and deterioration in handwriting.
New Delhi: Ministry of Health and Family Welfare, Government Movements may be limited to one side of the body as in
of India; 2005.
hemiballismus. The movements are aggravated by atten
3. Progress towards interruption of wild poliovirus transmission in
2005. Wkly Epidemiol Rec 2006;17:165-172 18.24. tion, stress or excitement, but disappear during sleep.
Emotional lability, hypotonia and a jerky speech are
SYDENHAM CHOREA (RHEUMATIC CHOREA) common associations.
The following clinical maneuvers are helpful in arriving
Chorea may precede or follow manifestations of rheumatic at the diagnosis:
fever. There is a significant epidemiological association 1. When the hand is outstretched above the head,
of chorea with rheumatic fever. Nearly one-third of these forearms tend to pronate.
patients develop rheumatic valvular heart disease. 2. When hands are stretched forwards, he flexes the
Concurrent association of chorea with rheumatic wrist and hyperextends the fingers.
polyarthritis is rare although authentic cases have been 3. The child relaxes hand grip on and off as if he is
recorded. This is attributed to the fact that chorea generally milking a cow (Milkmaid's grip).
supervenes later in the course of rheumatic activity. 4. The child cannot maintain the tongue in protruded
Chorea is a major criterion for the diagnosis of rheumatic position (darting tongue).
activity. 5. During speech an audible click is heard.
6. The knee reflex may show a sustained contraction
Clinical Features resulting in a hung up reflex. Otherwise there may
Sydenham chorea is more common in girls than in boys. be a pendular knee reflex.
The usual age of onset is 5 to 15 years. Classically, Investigations: The neurological investigations are
choreiform movements are described as irregular, non- generally unrewarding. ASLO titer may not be elevated
repetitive, quasipurposive and involuntary. They are because the onset of chorea is late.
Central Nervous System 557
Prognosis: The disorder is generally self-limiting and may states. Epstein-Barr virus and chickenpox virus have been
last from a few weeks to few months (up to 2 years). implicated.
Relapses or recurrences are not uncommon. The usual age of onset is between 1 and 5 years. Ataxia
Treatment: The child should be protected from injury; may develop within a few hours following a febrile illness.
bedding should be well padded. These children may be The patient has hypotonia, dysarthria, significant ataxia
treated with chlorpromazine, haloperidol, sodium of gait and some incoordination in extremities. The tendon
valproate or carbamazepine. Doses may be determined jerks are often pendular and nystagmus is common. The
by minimum doses required for symptom suppression. cerebrospinal fluid shows mild pleocytosis. Changes in
Aspirin or steroids help to limit the course of chorea and electroencephalogram are minimal. Prognosis is good.
the important modalities of treatment in resistant cases Corticosteroids are useful and a quick response is
not responding to symptomatic therapy. Antistreptococcal observed. Recurrence is uncommon. In the post viral
prophylaxis with penicillin G should be given to prevent group other diagnoses should be entertained in the event
recurrence of rheumatic activity. of recurrence or non-response.
high. These patients should be treated by withholding Toxin: Epidemiological evidence does not support the view
green vegetables (which are rich in phytanic acid that infantile tremor syndrome is due to a toxin.
chlorophyll) from the diet.
Enzyme defect: A transient tyrosine metabolism defect
might lead to interference in melanin pigment production.
Demyelinating/Storage Diseases
Depigmentation of substantia nigra may explain the
Ataxia is an important component of disorders of tremor. This needs further confirmation.
demyelination. Visual involvement, pyramidal tract
involvement and a waxing and waning course may be Clinical Features
observed. Lipidoses can also present with cerebellar
Infantile tremor syndrome occurs in apparently plump
features.
normal or underweight and exclusively breast-fed
children in the age of 5 months to 3 years. Boys are twice
Developmental Disorders
as commonly affected as girls. Most cases occur in summer
Cerebellar ataxia may also occur due to rudimentary months in children belonging to the low socio-economic
development of cerebellar folia. It may be associated with group.
diplegia, both spastic and flaccid, congenital chorea and The prodromal phase lasts for 2 weeks to 2 months. In
mental defect. These are non-progressive and may appear a typical case, the onset is heralded by mental/motor
to improve with physiotherapy. regression characterized by apathy, vacant look, inability
to recognize the mother, lack of interest in surroundings,
Suggested reading
lethargy and poor response to bright and colored objects.
1. Bernard G, Shevell MLChannelopathies: a review. Pediatr Neurol.
There is hyperpigmentation, especially over the dorsum
2008 Feb;38(2):73-85.
of hands, feet, knees, ankles, wrists and terminal
2. Nandhagopal R, Krishnamoorthy SG.Unsteady gait.Postgrad Med
J. 2006 May;82(967):e7-8. phalanges. Pigmentary changes over thighs may be
reticular or honeycomb-like. Hair become light brown,
INFANTILE TREMOR SYNDROME sparse, thin, silky and lusterless. There is mild to moderate
pallor. At times there may be fever, upper respiratory tract
Infantile tremor syndrome as reported from Indian infections, diarrhea, edema, hepatomegaly and a
subcontinent is a self-limiting clinical disorder in infants
tremulous cry.
and young children. It is characterized by acute or gradual The next phase is characterized by abrupt onset of
onset with mental and pychomotor changes, pigmentary tremors, which are usually generalized. Tremors are
disturbances of hair and skin, pallor and tremors. The coarse, fast, 6-12 cycles per second, of low amplitude,
disease is now encountered less frequently. initially intermittent but become continuous later on. Rate
of tremors may vary from one limb to the other. Head is
Etiopathogenesis
tossed from side to side and trunk may show twisting or
The clinical features suggest a disorder of the extra- wriggling dystonic movements. Tremors disappear during
pyramidal system. The course of the illness is self-limiting, sleep and are aggravated during crying, playing or
hence it is unlikely to be a progressive degenerative feeding. Some infants assume a typical bird with wings
disorder. Etiologic possibilities are malnutrition, vitamin spread out posture. Tone is variable. Consciousness is
B12 deficiency and viral infections but none have been retained. Average duration of this phase is two to five
conclusively proven. weeks. Condition remains static for some time before
Malnutrition: Due to its close resemblance with Kahn's disappearing altogether.
nutritional recovery syndrome, malnutrition was During the post-tremor phase, pallor and pigmentation
postulated as a possible etiology but majority of children become less, the child becomes more alert. Improvement
are not malnourished, look chubby and their serum in psychomotor function is relatively slow. This phase
proteins are within normal range. usually lasts for one to six months but the course may be
unduly prolonged with associated infections. Mortality
Vitamin B12 deficiency: A similar clinical entity with low
is never directly related to the disease but may be
vitamin B12 levels, megaloblastic bone marrow and a
attributed to concurrent infections. Subnormal intelligence
prompt response to vitamin B12 therapy was described
is the only long-term sequel.
but not substantiated.
Magnesium deficiency: Low magnesium levels in the serum Investigations
and cerebrospinal fluids are reported in some cases. Laboratory investigations are not pathognomonic. There
Infections: Seasonal incidence and cortical biopsy suggest is mild to moderate anemia with hemoglobin between 6-
that it might be a form of meningoencephalitis, but failure 11 g/dL. Morphology of red cells is variable (normocytic,
to isolate any viral antigen, consistently normal CSF, microcytic, macrocytic or dimorphic). Bone marrow shows
presence of pigmentary changes and pallor do not support normoblastic, dimorphic or megaloblastic changes.
this hypothesis. Cerebrospinal fluid is normal. Histological changes of liver,
Central Nervous System 559
skin, muscle, rectum and nerve are non-contributory. Cor an etiological insult for cerebral palsy is questionable. Most
tical biopsies reveal mild inflammatory changes. Phenu- infants have multiple risk factors. Prematurity is an
moencephalography reveals cortical atrophy. CT scan important risk factor for cerebral diplegia while term
shows no abnormalities or mild atrophy. EEG may show weight babies get quadriparesis or hemiparesis and a
epileptiform activity. Virological studies are negative. poorer mental outcome. The mechanism of CP in a large
proportion of cases remains unclear and primary
Differential Diagnosis neurological aberrations may be unfolded in future. The
Kahn's nutritional recovery syndrome, infection of the importance of role of birth asphyxia has been questioned
central nervous system, chronic liver diseases, hypo by recent data, and asphyxia may be manifestation of the
glycemia, hypomagnesemia, heredofamilial degenerative brain damage rather than the primary etiology.
diseases, phenothiazine toxicity, hyperthyroidism and A variety of pathological lesions such as cerebral
megaloblastic anemia may be considered in the differential atrophy, porencephaly, migration defects, microcephaly,
diagnosis. leukomalacia, degeneration of basal ganglia and cerebellar
lesions may be observed. Gliosis of the contralateral
Treatment hemispheres may result from vascular occlusions.
Cerebral palsy is classified on basis of topographic
Treatment is largely empirical, symptomatic and suppor
distribution, neurologic findings and etiology .
tive. Iron, calcium, magnesium, vitamin B6 supplements
and injectable vitamin therapy is reported to help some Spastic Cerebral Palsy
patients. Phenobarbitone, phenytoin and anti parkinso
This is the commonest form (65%). Depending on
nism drugs do not shorten the duration of tremors.
distribution of spasticity it may be a spastic quadriparesis,
Tremors may considerably diminish after administration
diplegia or hemiparesis. Early diagnostic features of neural
of propranolol. We have successfully used carbamazepine
damage include abnormally persistent neonatal reflexes,
for this condition in a few cases.
feeding difficulties, persistent cortical thumb after
Nutrition should be maintained with dietary supple
3 months age and a firm grasp. On vertical suspension,
mentation. Parents should be reassured. Associated
the infant goes into scissoring due to adductor spasm with
infections and secondary complications must be treated.
an extensor posture and does not flex his knees or thigh.
The stretch tendon reflexes are always brisk. They have
Suggested reading
variable degrees of mental, visual handicaps and
1. Kumar A. Movement disorders in the tropics. Parkinsonism Relate
behavioral problems.
Discord 2002; 9: 69-75.
2. Vora RM, Tullu MS, Bartakke SP, Kamat JR.Infantile tremor Spastic quadriparesis is more common in term babies, and
syndrome and zinc deficiency. Indian J Med Sci. 2002 Feb;56(2): exhibits severe signs including opisthotonic posture,
69-72. pseudobulbar palsy, feeding difficulties, restricted
voluntary movements and multiple deficits.
CEREBRAL PALSY__________________________________
Spastic diplegia is commoner in preterm babies and is
Cerebral palsy (CP) is defined as a non-progressive associated with periventricular leukomalacia. The lower
neuromotor disorder of cerebral origin. It includes hetero limbs are more severely affected with extension and
geneous clinical states of variable etiology and severity adduction posturing, brisk tendon jerks and tendency to
ranging from minor incapacitation to total handicap. Most contractures.
of the cases have multiple neurological deficits and Spastic hemiplegia is usually recognized after 4-6 months
variable mental handicap. The term does not include age. Abnormal persistent fisting, abnormal posture or gait
progressive, degenerative or metabolic disorders of the disturbance may be the presenting complaint. Vascular
nervous system. insults, porencephaly or cerebral anomalies may be
It is difficult to estimate the precise magnitude of the associated.
problem since mild cases are likely to be missed. Approxi Seizures are common in all forms and require therapy.
mately 1-2 per 100 live births is a reasonable estimate of A thorough screen for associated handicaps and develop
the incidence. mental assessment is warranted.
Extrapyramidal CP Diagnosis
The clinical manifestations include dyskinesia such as The diagnosis of cerebral palsy should be suspected if a
athetosis, choreiform movements, dystonia, tremors and child with a low birth weight, perinatal insult has increa
rigidity. Arms, leg, neck and trunk may be involved. These sed tone, feeding difficulties and does not keep pace with
cases account for about 30% of the patients. Mental the anticipated normal range of neurological and beha
retardation and hearing deficits may be present. High tone vioral development. Abnormalities of tone posture,
audiometry should be performed. Early diagnostic indi involuntary movements and neurological deficits should
cators are inability to reach for and grasp a dangling ring be recorded. Evaluation includes perinatal history,
by the age of 6 months. Cerebral damage following biliru detailed neurological and developmental examination and
bin encephalopathy is a classical example, and deafness a assessment of language and learning disabilities. Inborn
common association. errors of metabolism may need to be excluded by
screening of the plasma and urine. CT and MRI help
Cerebellar Involvement delineate the extent of cerebral damage in a case of cerebral
Occurs in less than 5% of the patients. There is hypotonia palsy.
and hyporeflexia. Ataxia and intention tremors appear by
the age of 2 years. Nystagmus is unusual, mental status Differential Diagnosis
may be near normal in some of these patients. Neurodegenerative disorders: Progressively increasing
symptoms, familial pattern of disease, consanguinity,
Mixed Type specific constellation of symptoms and signs are usual
A proportion of the patients have features of diffuse clues for neurometabolic disorders. Failure to thrive,
neurological involvement of the mixed type. vomiting, seizures are significant symptoms. Laboratory
investigations are necessary.
Severity of Lesion
Hydrocephalus and subdural effusion: Head size is large,
Mild cases of cerebral palsy are ambulatory and account
fontanel may bulge and sutures may separate.
for only 20% of patients. Moderately involved patients
achieve ambulation by help. These may be treated at out Brain tumors or space occupying lesions: Lesion is progressive
patient level and 50% of the patients are placed in this and features of increased intracranial pressure are evident.
category. Severely affected and multiple deficit children
account for the rest. Muscle disorders: Congenital myopathies, muscular
dystrophies and muscle-eye-brain diseases can mimic
Holistic Evaluation cerebral palsy. Distribution of muscle weakness and other
features is characteristic, hypotonia is associated with
Eyes: Nearly half the patients may have strabismus,
diminished reflexes. The enzyme creatine phosphokinase
paralysis of gaze, cataracts, coloboma, retrolental fibro
may be elevated. EMG and muscle biopsy are diagnostic.
plasia, perceptual and refractive errors.
Ataxia telengiectasia: Ataxia may appear before the ocular
Ears: Partial or complete loss of hearing is usual in
telengiectasia are evident. But progressive course is
kernicterus. Brain damage due to rubella may be followed
usually evident.
by receptive auditory aphasia.
deficits is important for appropriate physiotherapy and may point to inborn errors of metabolism. Some common
occupational therapy. Symptomatic treatment is prescri causes of neurodegeneration are described below.
bed for seizures. Tranquilizers are administered for
behavior disturbances and muscle relaxants may be used Infantile Gaucher Disease (Type II)
for improving the muscle function. Baclofen and tizanidine It is a metabolic disorder with autosomal recessive
help to reduce spasticity. Diazepam may ameliorate inheritance. The lysosomal enzyme glucocerebroside beta-
spasticity and athetosis. Dantrolene sodium helps in glucosidase is deficient. Glucocerebroside accumulates in
relaxation of skeletal muscles. Local phenol blocks provide various tissues. Foamy reticulum cells are present in the
relief for few months. Plastic orthoses may help to prevent bone marrow. Acid phosphatase is raised in the blood and
contractures, surgical procedures for spasticity and tissues. The deficient enzyme can be identified in
contractures may be required in carefully selected patients. leukocytes/fibroblasts. Most cases terminate fatally before
Botulinum toxin is the new, albeit costly alternative for they are 3 years old. Clinically, these children show a
reducing muscle tone. characteristic triad of retroflexed head, trismus and squint.
Occupational therapy: The beginning is made with simple They may show hypertonia, marked feeding problems
movements of self-help in feeding and dressing with vomiting and dysphagia. Splenomegaly and hepato
progressive development of more intricate activities like megaly are observed later. Enzyme replacement has been
tried for juvenile and adult forms of this disease. It has a
typing.
very different clinical profiles.
Educational: The defects of vision, perception, speech and
learning are managed by adequate special education Tay-Sach Disease (GM2 gangliosidosis)
experiences.
Inheritance is autosomal recessive. A history of consan
Orthopedic support: Light weight splints may be required guinity is usually obtained. It was earlier reported in
for tight tendo-Achilles and cortical thumb. Ashkenazi Jews but has been reported in other racial
Social: The family should be given social and emotional groups also. Several cases have been documented in India.
support to help it to live with the child's handicap. Low serum beta-hexosaminidase level is the characteristic
metabolic defect. As a result GM2 ganglioside accumulates
Rehabilitation and vocational guidance: Parents should help
in the neurons. Death occurs by 2 to 4 years. Initially,
the child to adjust in the society and if possible to become
milestones are delayed. Later, there is retrogression of
self-reliant and independent by proper vocational
development. The baby has an abnormal startle response
guidance and rehabilitation. Several handicapped children
to noise. Convulsions, rigidity of the extensor group of
may need to be institutionalized.
muscles and blindness supervene after the first year.
A cherry red spot is seen over the macular region of
Suggested reading
the retina. The head size increases. Liver and spleen are
1. Rosenbaum P. Cerebral palsy: what parents and doctors want to
not enlarged. Sandhoff disease is described in non-Jewish
know. BMJ 2003; 326: 970-4.
people. It resembles Tay-Sach's disease clinically except
2. Nelson KB, Chang T.ls cerebral palsy preventable? Curr Opin
Neurol. 2008 APr;21 (2):129-35. for later onset, mild visceromegaly and progressive ataxia.
3. Anttila H, Autti-Ramo I, Suoranta J, Makela M, Malmivaara Both hexosominidase A and B are deficient. These cases
A.Effectiveness of physical therapy interventions for children with may show congestive heart failure and enlarged liver.
cerebral palsy: a systematic review.BMC Pediatr. 2008 Apr 24;8:14.
4. O'Shea M.Cerebral palsy.Semin Perinatol. 2008 Feb;32(l):35-41. Metachromafic Leukodystrophy
5. Game E, Dolk H, Krageloh-Mann I, Holst Ravn S, Cans C; SCPE
Collaborative Group.Cerebral palsy and congenital malfor Inheritance is autosomal recessive and the gene is located
mations.Eur J Paediatr Neurol. 2008 Mar;12(2):82-8. on chromosome 22. The characteristic metabolic defect is
6. Jones MW, Morgan E, Shelton JE.Primary care of the child with decreased urinary or leukocyte aryl sulphatase A activity.
cerebral palsy: a review of systems (part II).J Pediatr Health Care.
Clinically, the illness manifests as ataxia, stiffness starting
2007 Jul-Aug;21(4):226-37.
in the second year of life. A little later, signs of bulbar
involvement and intellectual deterioration are observed.
DEGENERATIVE BRAIN DISORDERS
Initially there is hypotonia, but later spasticity supervenes.
A wide variety of hereditary and acquired disorders cause Characteristically, distal tendon reflexes are lost due to
progressive degeneration of the central nervous system. In associated peripheral neuropathy. Progressive intellectual
these disorders, new developmental skills are not achieved. impairment, optic atrophy and loss of speech develop in
As the disease advances, skill already acquired may also be the course of illness. Convulsions may occur in some cases
lost. The degeneration may primarily involve the gray or but are not a prominent feature. These children go into
white matter, resulting in corresponding clinical profile. decerebrate posture terminally. CT scan and MR imaging
Late cases may have common features. A fluctuant reveal abnormal white matter finger like projections, sural
course with recurrent seizures, mental deterioration, nerve biopsy may reveal metachroma tic granules and the
failure to thrive, infections, bad odor, skin and hair changes enzyme (ara-A) is low; parents may reveal a carrier state.
562 Essential Pediatrics
should be managed with phototherapy and/or exchange syndromes is diverse, varying from the mild abortive
transfusion. Cretinism and galactosemia, if diagnosed and forms to severe potentially fatal disorders.
treated in early infancy, have a satisfactory prognosis.
Patients with progressive neurologic disease or severe
Neurofibromatosis
reaction to whole cell pertussis vaccine should receive the Inheritance is autosomal dominant. There are two types:
acellular vaccine instead. Screening of all newborn infants type NF1 (von Recklinghausen disease or peripheral NF1)
for metabolic disorders such as phenylketonuria and and type NF2 (central neurofibromatosis). Deletion or
homocystinuria permits early treatment, averting inactivation of the NF gene in chromosome 17 is
irreversible brain damage. responsible for NFL Gene for NF2 is probably located on
chromosome 22.
Management
NF1: Two or more of the following are present: (i) 6 or
The parents should be counseled together. The diagnosis, more cafe-au-lait spots, each over 5 mm in diameter before
principles of early stimulation and management should puberty or over 15 mm diameter in older persons; (ii) 2 or
be explained, emphasizing the prognosis. Parental guilt more neurofibromas or one plexiform neuroma; (iii)
and the home situation should be discussed. Mentally freckling in axillary or inguinal regions; (iv) optic glioma;
handicapped children need essential basic care as any (v) Two or more Lisch nodules; dysplasia of the sphenoid
other child. Minimal criticism and high appreciation, bone or thinning of the cortex of long bones with or
short-term goals and structured learning results in less without pseudoarthrosis; and (vi) a first degree relative
withdrawal, aggressive and hostile reactions. with NF1.
Associated diseases and dysfunctions, e.g. of musculo
NF2: Presence of bilateral auditory neuroma; unilateral
skeletal system, vision, hearing, locomotion and feeding
auditory neuroma along with a first degree relative with
should be appropriately managed. Anticonvulsive
meningioma, schwannoma or juvenile posterior subcap-
treatment is prescribed for seizures, medications such as
sular lenticular opacity.
phenobarbitone should be avoided. Patients with
hyperactivity often respond to amphetamines including Management: Management comprises of supportive care,
methylphenidate. Specific management of any well- surveillance for and treatment of new manifestations and
defined syndrome such as metabolic or endocrine disease surgical management of spinal deformities. Genetic
should be done. counseling is necessary
Institutionalization should be avoided. Day care centers
Tuberous Sclerosis Complex
and schools, integrated schools, vocational training
centers, sheltered farms and workshops are useful. Classes Tuberous sclerosis is a neurocutaneous disorder inherited
should be taken to educate mothers and families in caring as an autosomal dominant trait. The presenting features
for the handicapped and in trying to develop their vary with age.
potential to the maximum, in an effort to make these Cardinal features are skin lesions, convulsion and
children as independent as possible. mental retardation. Early skin lesions are hypopigmented,
ash-leaf shaped macules (Fig 17.11), red or pink papules
Suggested reading (angiofibromas) called adenoma sebaceum on face .These
appear and also enlarge with age. Other lesions are
1. Sherr EH, Shevell MI. Mental Retardation and Global develop
shagreen patches, subungual fibromas and oral fibromas.
mental delay. In Swaiman KF, Ashwal S Ferriero DM. Pediatric
Neurology Principles & Practice 4th ed. Philadelphia Mosby, 2006.
2. Moeschler JB.Genetic evaluation of intellectual disabilities. Semin
Pediatr Neurol. 2008;15(l):2-9.
3. McDonald L, Rennie A, Tolmie J, Galloway P, McWilliam
R.Investigation of global developmental delay.Arch Dis Child.
2006;91(8):701-5.
4. Shevell M, Ashwal S, Donley D, et al.Practice parameter: evaluation
of the child with global developmental delay: report of the Quality
Standards Subcommittee of the American Academy of Neurology
and The Practice Committee of the Child Neurology Society.
Neurology. 2003 11;60(3):367.
NEUROCUTANEOUS SYNDROMES
There are five major neurocutaneous syndromes viz. (i)
neurofibromatosis; (ii) tuberous sclerosis; (iii) von Hippel
Landau disease; (iv) Sturge-Weber syndrome; and (v)
ataxia-telengiectasia. All of these are inherited disorders Fig. 17.11 : Facial skin showing multiple ash leaf spots in a child with
except for Sturge-Weber syndrome. Clinical profile of these tuberous sclerosis
Central Nervous System 565
Retinal hamartoma may be present. In early life tumors fests with progressive cerebellar ataxia, oculocutaneous
in heart and kidneys may be detected on ultrasonography. telengiectasia, choreoathetosis, pulmonary and sinus
In infancy, myoclonic jerks often lead to detection of this infections, immune deficiency and lymphoreticular
entity and are an important cause of West syndrome; malignancies.
vigabatrine is a useful medication in these cases. Parents Ataxia begins between 12-15 months age and pro
and siblings should be examined for stigmata of tuberous gresses relentlessly making children wheel chair bound
sclerosis. by 10-12 years age. Telengiectasia appears by 2-7 years
on bulbar conjunctiva and even skin. Increased incidence
Sturge-Weber Syndrome
of abnormal movements, vitiligo, abnormal GTT are
Sturge-Weber syndrome is characterized by facial nevus observed. Investigations reveal decreased serum IgA in
flammens (usually in the distribution of first branch of three-fourths of the patients. Alfa-fetoprotein is almost
trigeminal nerve but not limited to it), contralateral focal universally elevated. Increased chromosomal breaks on
seizures, calcification of the cortex and subcortical chromosome 14 are common. Neuroimaging reveals
structures and glaucoma on the same side as the skin cerebellar atrophy. Treatment is symptomatic.
lesions.
Suggested reading
von-Hippel-Landau Disease
1. Kandt RS. Tuberous sclerosis complex and neurofibromatosis Type
In this disorder, there are retinal and cerebellar hemangio- 1: the two most common neurocutaneous diseases. Neurol Clin
blastomas besides the spinal cord angiomas and cystic 2002; 20: 941-64.
tumors of pancreas, kidneys and epididymis. Patients may 2. Leung AK, Robson WL.Tuberous sclerosis complex: a review.
show nystagmus, ataxia and signs of increased intracranial J Pediatr Health Care. 2007 Mar-Apr;21(2):108-14.
pressure. 3. Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG,
Upadhyaya M, Towers R, Gleeson M, Steiger C, Kirby A.Guidelines
Ataxia Telengiectasia for the diagnosis and management of individuals with neuro
fibromatosis l.J Med Genet. 2007 Feb;44(2):81-8.
It is an autosomal recessively inherited disease that has 4. Quigg M, Miller JQ.Clinical findings of the phakomatoses: tuberous
been mapped to chromosome llq. The syndrome mani sclerosis. Neurology. 2005 Nov 22;65(10):E22-3.
18 Neuromuscular Disorders
Fig. 18.1: Molecular architecture of dystrophin and dystrophin-asso Cardiac involvement in DMD is common; the onset being
ciated proteins on the cell membrane usually after the age of 10 years. Almost all patients
beyond the age of 18 years will have some manifestations
of cardiomyopathy. The heart demonstrates fibrosis in the
The diagnosis is suspected, especially if there is a positive
posterobasal portion of the left ventricular wall. Conges
family history of similar illness. Hypertrophy of calf
tive heart failure and cardiac arrhythmias usually occur
muscles may be observed by the age of 4-5 years (Fig.
only in the late stages and especially during times of stress
18.2). The weakness of shoulder girdles is demonstrated
from intercurrent infections. In about 10% of cases, death
by inability to raise the hand above shoulder or comb the
is due to cardiac dysfunction.
hair.
Distribution of the apparently hypertrophied (pseudo- Acute gastric dilatation (intestinal pseudo-obstruction): It
hypertrophied) and atrophied muscles is characteristic. The consists of sudden episodes of vomiting associated with
calf muscles, glutei, deltoid, serrati anterior, brachioradialis abdominal pain and distension, and may lead to death if
and tongue muscles appear large. Sternal head of the not treated appropriately.
pectoralis major and supraspinatus are atrophied. The
condition shows relentless progression, with weakness and Intelligence: The average intelligence quotient is approxi
mately one standard deviation below the mean. One-third
of DMD children have an IQ below 75. Mental retardation
is a pleiotropic effect of dystrophin mutation. The site or
size of deletion has no correlation with severity of
retardation.
A B C<
Figs 18.3A to D: Gower sign. Note how the child with hip girdle muscle weakness climbs up on himself to get to upright position
Cardiorespiratory care: Respiratory exercises should begin 4. Angelini C. The role of corticosteroids in muscular dystrophy: a
critical appraisal. Muscle Nerve. 2007 Oct;36(4):424-35.
as soon as the diagnosis is made. Infections are managed
with appropriate antibiotic therapy and postural drainage.
Cardiomyopathy and congestive cardiac failure are Emery Dreifuss Muscular Dystrophy (EDMD)
managed by conventional approaches. EDMD is an X-linked disorder characterized by a specific
pattern of contractures at elbow, ankle and neck, cardio
Supportive care: Low fat diet is given to prevent obesity as
myopathy, conduction disturbances and slowly pro
these patients would ultimately become non-ambulatory
gressive weakness into adult life. The muscle weakness is
and it is difficult to manage an obese child. Scoliosis is
predominantly proximal in upper limbs (scapulohumeral)
prevented by the use of tight fitting braces. Emotional
and distal in lower limbs (peroneal). CPK levels are
support is given to the patient and the family. Prognosis
moderately elevated. The basic defect in EDMD are
should be explained.
mutations in genes encoding nuclear envelope proteins
Drug therapy: The only drug useful to some extent in DMD (emerin, lamins A & C). The most common X-linked
is prednisolone. Randomized controlled trials have EDMD has been localized to the end of the long arm of
demonstrated improved muscle strength within 3-6 the X chromosome (Xq28)and encodes for Emerin protein.
months of therapy. Prednisolone given in a dose of 0.75 Rarer autosomal dominant and recessive forms have also
mg/kg/day reduces the rate of progression but the disease been described
continues unabated. The drug is continued as long as the
child is ambulatory. Prednisolone may prolong ambu Limb-Girdle Muscular Dystrophies (LGMD)
lation by a maximum of only 2 years. Prednisolone is not These are inherited as either autosomal dominant (LGMD
beneficial in patients with BMD. Deflazacort may be used 1A, IB and 1C) or autosomal recessive (LGMD 2A-H)
as an alternative. Experimental therapies include exon disorders. Autosomal recessive LGMDs are now known
skipping, gene therapy and stem cell therapy. as sarcoglycanopathies.
3. Linksmuchir A, Worman HJ. Emery-Dreifuss Muscular Dystrophy. take the form of a floppy infant syndrome at birth or in
Curr Neurol Neurosci Rep. 2007;7:78-83. early infancy, or may present later with features of muscle
4. Linkspandya S, King WM, Tawil R. Facioscapulohumeral Dystro
weakness. In some children this weakness will be
phy. Phys Ther. 2008;88:105-13.
5. Daniele N, Richard I, Bartoli M. Ins and outs of therapy in Limb predominantly proximal and of girdle distribution, in
Girdle Muscular Dystrophies. Int J Biochem Cell Biol. 2007;39:1608- others it may be more generalized and may also affect
24. facial muscles. Ocular muscles are frequently affected in
6. Straub V, Bushby K. The Childhood Limb-Girdle Muscular myotubular myopathy. Nemaline myopathy has a higher
Dystrophies. Semin Pediatr Neurol. 2006;13:104-14.
7. Linkscardamone M, Darras BT, Ryan MM. Inherited myopathies
incidence of associated dysmorphic features and
and muscular dystrophies. Semin Neurol 2008;28: respiratory deficit.
50-9.
8. Thirion C, Lochmiiller H. Current status of gene therapy for Muscle Diagnosis
Diseases. Drug News Perspect. 2007;20:357-63.
Investigations such as CPK and EMG are not of much help
9. Muntoni F, Wells D. Genetic treatments in muscular dystrophies.
Curr Opin Neurol. 2007;20:590-4.
in diagnosis as CPK levels are frequently normal and the
EMG may be normal or may show mild, non-specific
OTHERMYOPATHIES changes. Muscle biopsy, supplemented by immuno-
cytochemistry, histochemical analysis and electron
Myopathies are congenital or secondary to inflammatory, microscopy, is the only certain way of making an accurate
metabolic and endocrine abnormalities. diagnosis.
Repetitive Stimulation
FLOPPYINFANT
EMG reveals a decremental response of the compound
muscle action potential in response to repetitive Floppy infant is an infant with marked hypotonia of the
stimulation of a motor nerve. Single fiber electromyography muscles and variable associated weakness. This may be
is a more sensitive measure of neuromuscular trans associated with frequent respiratory infections, feeding
mission than repetitive stimulation. difficulties, facial weakness, ptosis, ophthalmoplegia and
574 Essential Pediatrics
Prader-Willi Syndrome
The syndrome presents with profound hypotonia at birth
and marked feeding difficulty but there are no associated
respiratory difficulties. The cry is often weak and high-
pitched. Facies are characteristic with a high forehead,
dolicocephaly, small almond-shaped eyes and an open
576 Essential Pediatrics
triangular-shaped mouth. Such babies are mentally Sural nerve biopsies disclose a loss of myelinated fibers,
retarded and obese. Diabetes mellitus occurs later in life. especially the large myelinated fibers.
Testes may be undescended. It has been shown to be The disease is typically recognized during the first
associated with deletion in the short arm of chromosome decade of life or in early adolescence, but it may be evident
15, especially the paternal chromosome. even at birth. Early onset, although uncommon, usually
results in greater disability later in life than that seen in
Ehlers-Danlos Syndrome individuals with later onset, who are often able to
The basic manifestations are joint hypermobility, skin ambulate and work until old age.
hyperextensibility, dystrophic scarring of the skin, easy HMSN Type I presents with distal lower extremity muscle
bruising and connective tissue fragility. Wound healing wasting. Progressive weakness of the anterior tibialis
is delayed and there are freely movable subcutaneous muscle is associated with the development of the high arch
nodules. Molecular genetics has helped to characterize 11 of the foot or pes cavus. The hammer toe deformities occur
different types of Ehlers-Danlos syndrome, based as the long toe extensors attempt to make up for the foot
predominantly on the associated features. dorsiflexor (anterior tibialis) atrophy and weakness.
Gradual loss of sensation is noted, especially loss of
Suggested reading
proprioception, which causes unsteady gait in darkness
1. Erazo-Torricelli R. Neonatal hypotonia. Rev Neurol 2000: 31: and a positive Romberg sign. Vibration and big toe joint
252-62.
position sense are both diminished. Tendon reflexes are
2. Richer LP, Shevell MI, Miller SP. Diagnostic profile of neonatal
hypotonia: An 11-year study. Pediatr Neurol 2001; 25: 32-7. usually lost early at the ankle and later at the knee. Muscle
3. Bodensteiner JB. The evaluation of the hypotonic infant. Semin wasting and weakness slowly spread proximally. Motor
Pediatr Neurol. 2008; 15:10-20. and sensory conduction velocity is less than 60% of normal
values in infants, and in patients older than 3 years it is
Peripheral Neuropathies
less than 38 m/sec in all peripheral nerves.
The term peripheral neuropathy indicates disease of Treatment is supportive. Early in the course of the
peripheral nerves. Two-thirds of such cases are chronic. disease, strengthening exercises for the feet and legs with
Of the latter group, roughly 70% are hereditary, 20% active stretching of the feet may be beneficial. Using ankle-
indeterminate and 10% acquired. foot orthoses to stabilize the feet and correct the foot drop
may help reduce the likelihood of falls.
Hereditary Neuropathies HMSN Type II: Clinical manifestations tend to develop
These clinically and genetically heterogeneous disorders later than in Type I. Muscle atrophy and weakness are
produce progressive deterioration of the peripheral nerves milder and more prominent than sensory deficits
with secondary muscle wasting and weakness in a distal compared to Type I disorder. Pathology is marked by
distribution. Depending on the predominant clinical axonal degeneration. Nerve hypertrophy and palpable
involvement, hereditary neuropathies are divided in nerve enlargement are not present. Onion bulb formation
broad categories of (i) hereditary motor; (ii) hereditary typical of Type I disease is rarely seen.
sensory and autonomic; and (iii) hereditary motor and HMSN Type III (Dejerine-Sottas disease): Schwann cells are
sensory neuropathies. incapable of forming normal myelin. Histologically, they
are characterized by the presence of thin myelin sheaths,
Hereditary motor and sensory neuropathies (HMSN): Dyck
often with few or poorly compacted myelin lamellae, and
and Lambert's classification divided the HMSN into
by the presence of onion bulbs. Hypomyelination is a
HMSN I-VII and X. Hereditary motor sensory neuropathy
prominent element. In the majority of cases, hypotonia
types I and II are often referred to as Charcot-Marie-Tooth
and delay in developmental milestones or both are noted
disease, which is characterized by weakness of the
within the first year of life. Walking is often delayed
extremities and foot deformities including pes cavus and
beyond the second year, but most HMSN Type III toddlers
permanently flexed "hammer" toes. Variable loss of
eventually do walk, although coordination is never fully
sensations is present. This condition is also referred to as
normal. Ataxia is present in all patients, probably due to
peroneal muscular atrophy, because of the characteristic
a proprioceptive deficit. Distal weakness, more marked
muscle involvement early in the illness. Inheritance is
in the lower limbs, is present.
autosomal dominant, though autosomal recessive and X-
linked forms are also known. Hereditary sensory and autonomic neuropathies (HSAN): At
HMSN Type I: The peripheral nerves are often easily least five clinical entities exist under HSAN including
palpated because they are hypertrophied as a result of hereditary sensory radicular neuropathy, congenital
excessive Schwann cell and fibroblast activity. This sensory neuropathy, familial dysautonomia, congenital
creates redundant wrappings of Schwann cell insensitivity to pain and anhidrosis. All of them are
investments around nerve fibers accompanied by characterized by a progressive loss of function that
excessive collagen deposition, known as onion bulbs. predominantly affects the peripheral sensory nerves.
Neuromuscular Disorders 577
These conditions are less common than hereditary motor cranial nerves are affected. Proximal and distal muscle
and sensory neuropathies. The clinical presentation weakness and muscle tenderness are present.
depends on the population of affected neurons or axons.
Serum sickness: It is a systemic illness resulting from hy
When degeneration of the large diameter afferent fibers
persensitivity to an injected foreign protein, such as teta
occurs, position sense is primarily involved. When the
nus or diphtheria antisera, producing encephalomyelitis,
small afferent and autonomic fibers are affected, an
neuropathy or brachial plexus neuropathies.
increased threshold to nociception and thermal discrimi
nation occurs, accompanied by autonomic and trophic Botulism: Three forms of botulism exist, the most common
changes. being the infantile form that occurs between 1 and 38
weeks of age. A heat-labile neurotoxin is elaborated by C.
Metabolic Neuropathies
botulinum under anaerobic conditions. The toxin produces
Diabetes mellitus: Slowed sensory nerve conduction a presynaptic blockade to prevent the release of
velocities and impaired autonomic function have been acetylcholine from cholinergic nerve endings. The toxin
reported in 25% of diabetic children at the time of seems to block the exocytosis of acetylcholine-containing
diagnosis. Despite multiple daily doses of insulin and vesicles at presynaptic release sites.
good blood sugar levels, peripheral neuropathy is
Infantile botulism: A history of constipation in a 1 -6 month
inevitable in 10% children and adolescents with insulin-
old infant followed by a subacute progression over 4 to 5
dependent diabetes mellitus. Features include mild distal
days of bulbar and extremity weakness with feeding
weakness, loss of touch and pain sensation, and decreased
difficulties, ptosis, hypotonia and respiratory embarrass
ankle tendon reflexes. Changes are bilaterally symmetric
ment should suggest this condition.
and more in the lower extremities.
Classic botulism: It develops 12 to 36 hours after ingestion
Uremic neuropathy: It is rarely diagnosed in children. When
of the toxin-containing food. Early symptoms are blurred
recognized, it is characterized by burning sensations in
vision, diplopia, dizziness, dysarthria and dysphagia
the feet and a symmetric motor sensory neuropathy with
followed by a descending paralysis and dyspnea.
progressive muscle weakness. Motor and sensory nerve
conduction velocities are decreased early in the course of Wound botulism: Wound contamination with C. botulinum
the disease, often before clinical symptoms appear. leads to subsequent production of botulinum toxin after
Proximal nerves are affected earlier. bacterial incubation, producing clinical botulism 4 to 14
days after the wound has been infected.
Acute intermittent porphyria: This rare inborn error of
metabolism, inherited on an autosomal-dominant basis,
is caused by defects in the gene encoding hydroxymethyl- Drug-induced Neuropathy
bilane synthase on the long arm of chromosome 11. Acute, Chloramphenicol can cause mild, primarily sensory
severe, colicky abdominal pain is a typical manifestation peripheral neuropathy after long-term use at relatively
of an acute episode accompanied by central nervous high doses. Nitrofurantoin can cause a severe motor and
system and peripheral nervous system impairment. sensory peripheral neuropathy with an acute to subacute
Peripherally, motor weakness is most striking, but sensory time course. Isoniazid causes an axonal neuropathy
impairment may also occur. A flaccid paralysis resembling responsive to pyridoxine therapy in 1% to 2% of patients.
Guillain-Barre syndrome has been observed. The proximal The primarily sensory neuropathy begins with pares
muscles may be more involved than distal muscles. thesia. Ethambutol occasionally causes a sensory
Reflexes are often diminished or absent. neuropathy associated with optic neuritis. Metronidazole
may also produce neuropathy. Pyridoxine taken in large
Thiamine deficiency: Vitamin B1 deficiency in children
dose can cause a sensory neuropathy with paresthesia,
causes peripheral neuropathy, encephalopathy and high-
diffuse sensory loss, sensory ataxia and autonomic
output cardiac failure.
dysfunction.
Abetaiipoproteinemia: Abetalipoproteinemia is char Peripheral neuropathy may develop after the use of
acterized by progressive ataxic neuropathy, retinitis chemotherapeutic agents to treat neoplasms. Sensorimotor
pigmentosa, steatorrhea, hypolipidemia, deficiency of fat- peripheral neuropathy may develop after high-dose
soluble vitamins and acanthocytosis. cytosine arabinoside therapy. Vincristine is perhaps the
best known chemotherapeutic agent, causing peripheral
Toxic Neuropathies neuropathy and, less commonly, autonomic and cranial
Diphtheria: The onset may occur between 1 to 16 weeks nerve neuropathy. Tingling sensations, absent reflexes
following the infection. Blurred vision and swallowing particularly at the ankles, distal weakness and impaired
difficulties mark the onset of diphtheric neuropathy. A vibration and superficial sensation develop secondary to
generalized motor sensory demyelinating polyneuropathy vincristine use. Cisplatin may cause profound axonal loss
with distal, symmetric involvement is recognized. Lower in peripheral nerves, producing a sensory neuropathy.
578 Essential Pediatrics
Heavy metal neuropathy: Lead toxicity may cause a motor walk independently by 14 to 18 months. By 3 years of age,
neuropathy. Lower extremities are particularly affected. children usually develop a mature walking pattern. By
Other clinical features include abdominal pain, consti the age of 9 years a child usually assumes a well-developed
pation, anemia and encephalopathy. Rarely, arsenic adult type of gait. Generally, limp is a reflex response to
poisoning produces an axonal, primarily sensory weight bearing on a painful weak or imbalanced limb.
neuropathy. Exposure may be by overdose, producing a The time of stance on affected limb is reduced and the
subacute neuropathy, or may be more chronic, causing a stride length of the normal limb is shortened. As a result
slowly progressing neuropathy. Organic mercury the child quickly bears weight on the normal limb.
poisoning in children produces acrodynia or pink disease
consisting of generalized erythema, especially of the Examination
hands, feet and face with swelling of the hands and feet. An attempt is made to localize the cause of the limp in the
Chronic exposure results in sensory and motor neuro spine, hips, knees, ankle or neuromuscular apparatus. The
pathy, encephalopathy, and autonomic dysfunction. differential diagnosis of a limping child depending on the
Accidental ingestion of rat poison or insecticides or part involved is detailed in Table 18.6.
thallium products causes an acute or subacute syndrome A child with painful knee walks with extended knee to
of gastrointestinal disturbance and neuropathy. avoid motion in the joint. In spinal disease, the trunk is
held rigidly. One with septic arthritis of hip refuses to
Suggested reading walk. In Legg-Calve-Perthes disease glutei muscles on the
1. Klein CJ.The inherited neuropathies. Neurol Clin 2007; 25:173-207. affected side cannot keep the pelvis at level when the
2. Reilly MM. Sorting out the inherited neuropathies. Pract Neurol. affected limb bears the weight, so that pelvis is tilted to
2007;7:93-105.
the unaffected side (Trendlenburg gait). The level of pelvis
3. Parman Y. Hereditary neuropathies. Curr Opin Neurol 2007;
20:542-7. is checked by placing a hand on the iliac crest. Diseases of
4. Ouvrier R, Geevasingha N, Ryan MM. Autosomal-recessive and
X-linked forms of hereditary motor and sensory neuropathy in
childhood. Muscle Nerve 2007;36:131-43.
Table 18.6: Common conditions resulting in a limp
5. Jani-Acsadi A, Krajewski K, Shy ME. Charcot-Marie-Tooth
neuropathies: diagnosis and management. Semin Neurol Neuromuscular disorders
2008;28:185-94. Paralysis of muscles, e.g. (acute poliomyelitis, traumatic
6. Young P, De Jonghe P, Stogbauer F, Butterfass-Bahloul T.
neuritis)
Treatment for Charcot-Marie-Tooth disease. Cochrane Database
Syst Rev 2008;1:CD006052.
Hemiplegia, acute hemiplegia of childhood
Myopathies and muscular dystrophies
Hemi-hypertrophy of muscles
LIMPING
A limp in the child is generally of serious concern to the Disorders of bones and joints
parents and the physician. The differential diagnosis for
Hip
a child with lower extremity limb pain or limp is quite Congenital dislocation of hip
diverse; only a few conditions require urgent treatment. Pyogenic arthritis; tuberculosis
Most cases of limp are transient and may improve with Transient synovitis
time without any specific treatment. Trauma
Limp may be the result of disorders in any part of the Rickets
weight-bearing structures including spine, hips, knees, Slipped epiphysis
ankle and feet. Diseases causing tenderness, weakness or Osteochondritis (Perthe's disease)
asymmetry of the weight-bearing apparatus, result in a Knee and ankle
limping gait. Tuberculosis
Rheumatoid arthritis
Transient synovitis
History
Trauma
The diagnosis is based on the history including age of the Osteochondritis
child, time of onset, duration, severity of pain, location of Foot
pain, aggravating factors, posture of the child, history of Painful lesions of the nails, toes and soles, e.g. warts, corns,
trauma, course of illness and accompanying clinical blisters, paronychia, ingrowing toe nail, fracture
features (fever, weight loss, malaise). Certain diagnoses Ill-fitting shoes
are more common at different ages. Osteochondritis
A physician must be familiar with normal motor Spine
developmental milestones and gait pattern and be able to Tuberculosis
appreciate abnormal gait. Most children can "cruise" or Scoliosis
walk holding onto objects before the age of 1 year and Congenital defects
Neuromuscular Disorders 579
neuromuscular system affect walking in several ways The management depends on the specific cause. Besides
because of flaccidity or spasticity. These should be medical and surgical management, acute and long-term
excluded by looking for atrophy, asymmetry or torsion. rehabilitation are also important.
Children who present with an obvious orthopedic
diagnosis such as trauma with suspected fracture may Suggested reading
need nothing more than radiographic studies. At initial
1. Leung AK, Lemay JF. The limping child. J Pediatr Health Care
presentation, however, the history and physical exami 2004;18:219-23.
nation may not be sufficient in eliciting a diagnosis and 2. Abbassian A. The limping child: a clinical approach to diagnosis.Br
certain laboratory and radiographic studies may be J Hosp Med (Lond) 2007;68:246-50.
beneficial. 3. Wyndham M. The limping child. Community Pract 2007; 80:42.
19 Childhood Malignancies
Childhood cancers are rare, but are an important cause of The etiology of ALL remains unknown in a majority of
morbidity and mortality in children younger than 15 years. cases. However, several genetic syndromes have been
Malignancies are difficult to detect in children because the associated with an increased risk of leukemia. In
signs and symptoms are nonspecific and mimic many particular, there is a 10-20 fold increased risk of leukemia
common disorders. Pediatric cancers differ from that in (ALL and AML) in children with Down syndrome. Other
adults since they are more aggressive and consequently genetic syndromes associated with leukemia include
more responsive to chemotherapy. Common malignancies Bloom syndrome, Fanconi anemia, neurofibromatosis,
in children include leukemia (30%), brain tumors (20%) Klinefelter syndrome, immunodeficiency and ataxia
and lymphoma (12%), followed by neuroblastoma, telangiectasia. Exposure to ionizing radiation, certain
retinoblastoma, and tumors affecting soft tissues, kidneys, pesticides and parental smoking are associated with a
bones and gonads. The majority of pediatric cases of acute higher incidence of ALL. Patients having received
leukemia, neuroblastoma, Wilms' tumor, retinoblastoma therapeutic irradiation and aggressive chemotherapy
and primary liver cancer occur below the age of 5-year. (alkylating agents, epipodophyllotoxins) are also at higher
Hodgkin and, non-Hodgkin lymphoma and bone tumors risk of developing acute leukemia.
occur frequently in children over 10-years-old. At all ages,
boys are affected more frequently than girls. Advances in Classification
diagnosis, multi-modality therapy, rational use of
Morphology
chemotherapy and improved supportive care have
improved the survival rates tremendously and over 70% The classification of ALL has evolved over the years from
of all childhood cancers are now curable. one that was primarily morphology based to one which
is currently based on immunophenotyping, karyotyping
and molecular biology techniques. ALL cells can be
LEUKEMIA classified using the French-American-British (FAB) criteria
into morphologic subtypes (Table 19.1). LI lymphoblasts,
Leukemia is a malignancy that arises from clonal the most common in children (80-85%), have scant
proliferation of abnormal hematopoietic cells leading to cytoplasm and inconspicuous nucleoli; these are asso
disruption of normal marrow function and various ciated with a better prognosis (Fig. 19.1). Patients in the
manifestations of leukemia. Leukemia is the most common L2 category, accounting for 15% cases, show large,
cancer in children. There are two main subtypes, acute pleomorphic blasts with abundant cytoplasm and
lymphoblastic leukemia (ALL) and acute myeloid prominent nucleoli. Only 1-2% patients with ALL show
leukemia (AML). A small proportion may have chronic L3 morphology in which cells are large, have deep
myeloid leukemia (CML). cytoplasmic basophilia and prominent vacuolation; these
cells show surface immunoglobulin and should be treated
ACUTE LYMPHOBLASTIC LEUKEMIA as Burkitt lymphoma.
580
Childhood Malignancies 581
of raised intracranial pressure. The diagnosis of CNS splenomegaly and leukocytosis. ALL should be disting
leukemia is made on examination of the cerebrospinal uished from other malignancies (neuroblastoma, non-
fluid; even a single blast is sufficient for this diagnosis. Hodgkin lymphoma, rhabdomyosarcoma, Ewing sarcoma
Overt testicular leukemia may be seen in about 1% of cases. and retinoblastoma) that present with bone marrow
It presents with firm, painless, unilateral or bilateral involvement. Morphologic, cy tochemical, immunopheno-
swelling of the testes; the diagnosis is confirmed by typic and cytogenetic characteristics of the malignant cells
testicular biopsy. Other rare sites of extramedullary should be done. Occasionally patients with ALL may
involvement include heart, lungs, kidneys, ovaries, skin, present with hypereosinophilia or as an emergency with
eye or the gastrointestinal tract. life threatening infections, hemorrhage, organ dysfunction
secondary to leukostasis or signs and symptoms of superior
Differential Diagnosis
vena cava syndrome.
These include infectious mononucleosis, acute infectious
lymphocytosis, idiopathic thrombocytopenic purpura, Management
aplastic anemia and viral infections like cytomegalovirus
and others that result in leukemoid reactions and pancyto The management of acute leukemia needs the combined
penia. Idiopathic thrombocytopenic purpura is the most effort of the pediatric oncologist, radiation oncoloigst,
common cause of acute onset of petechiae and purpura in nursing team, psychologist, medical social worker and
children. Ordinarily children with ITP have no evidence of dietician. Improvements in supportive care and chemo
anemia and have a normal leukocyte count and differential therapeutic regimes has resulted in improved survival
count. Bone marrow smear reveals normal hematopoiesis from <5% before 1965 to 80% for children diagnosed in
and normal or increased number of megakaryocytes. A 2000. The successful treatment of ALL requires the control
bone marrow examination is recommended prior to of bone marrow or systemic disease, as well as treatment
initiation of steroid treatment for presumed ITP, in order (or prevention) of extramedullary disease in sanctuary
to exclude leukemia. ALL must be differentiated from sites, particularly the central nervous system (CNS). The
aplastic anemia, which may present with pancytopenia. cornerstone of this strategy is systemic combination
The condition may also be mistaken for juvenile rheu chemotherapy together with CNS prophylaxis. Various
matoid arthritis in patients presenting with fever, joint regimen have been used to treat ALL like MCP 841 pro
symptoms (limp, arthritis or arthralgia), pallor, tocol, the UK protocol, the BFM protocol, etc. (Table 19.2).
* Intrathecal (IT), in 5 to 10 mL 0.9% sodium chloride injection on days 1, 8, 15 and 22. Dosages are age-adjusted: 1-2 yr (8 mg);
2-3 yr (10 mg); >3 yr (12 mg).
Childhood Malignancies 583
The treatment of ALL is divided into 4 stages: (i) Commonly used agents for intensification therapy include
Induction therapy (to attain remission), (ii) CNS pro high dose methotrexate, L-asparaginase, epipodophyllo-
phylaxis or CNS preventive therapy, (iii) Intensification toxin, cyclophosphamide and cytarabine. Use of these
(consolidation) and (iv) Maintenance therapy (conti medications has resulted in prolonged periods of
nuation). The intensification (consolidation) phase, granulocytopenia and the need for improved supportive
following induction of remission, may not be required in care, liberal use of broad spectrum antibiotics and blood
loiv risk patients, though recent studies suggest benefits products.
in long-term survival with intensification therapy in both
low risk and high risk patients. The average duration of Maintenance (Continuing) Therapy
treatment in ALL ranges between 2-2% year; there is no It has been estimated that approximately two to three logs
advantage of treatment exceeding 3-years. of leukemic blasts are killed during the induction therapy,
leaving a leukemic cell burden in the range of 109-1010.
Induction Therapy Additional therapy is therefore necessary to prevent a
The drug regimen combining vincristine and prednisolone relapse.
induces remission in 80-95% patients with ALL. Since the Once remission is achieved, maintenance therapy is
remission rate and duration are improved by the addition continued for an additional 2-2.5 years. Without such
of a third and fourth drug (L-asparaginase and/or therapy, patients of ALL relapse within the next 2-4
anthracycline) to vincristine and prednisolone, current months. The exception are those with B-cell ALL, who are
induction regimens include vincristine, prednisolone, L- treated with short term (<6 months) high-dose
asparaginase and an anthracycline, with remission chemotherapy. A number of drug combination and
achieved in 95-98% of cases. The induction therapy lasts schedules are used, some based on periodic reinduction,
for 4-6 weeks. others on continued delivery of effective drugs. The main
agents used include 6-mercaptopurine daily and metho
trexate once a week given orally, with or without pulses
CNS Preventive Therapy
of vincristine and prednisolone or other cytostatic drugs.
The concept of CNS preventive therapy is based on the Monthly pulses of vincristine and prednisolone appear to
fact that most children with leukemia have subclinical be beneficial. In intermediate high risk ALL most
CNS involvement at the time of diagnosis and this acts as investigators use aggressive treatment and additional
a sanctuary site where leukemic cells are protected from drugs during maintenance therapy. It is imperative to
systemic chemotherapy because of the blood brain barrier. monitor children for drug toxicity and compliance. For
The early institution of CNS prophylaxis is essential to better outcome, methotrexate and 6-mercaptopurine
eradicate leukemic cells which have passed the blood brain should be given to the limits of tolerance as determined
barrier. CNS prophylaxis has enabled increased survival by absolute neutrophil counts.
rates in leukemia. Most children receive a combination of
intrathecal methotrexate and cranial irradiation. However, Supportive Care
there is considerable concern regarding long term Because of the potential complications encountered with
neurotoxicity and risk of development of brain tumors treatment and the need for aggressive supportive care like
following this therapy. In order to achieve effective CNS blood component therapy, detection and management of
prophylaxis while minimizing neurotoxicity, experts now infections, nutritional and metabolic needs and psycho
recommend a lower dose of cranial irradiation (1800cGy) social support, these children should be treated by a
with intrathecal methotrexate. Other alternative regimens specialist in a cancer center or hospital with all support
for CNS prophylaxis include the use of triple intrathecal facilities. These children should be given cotrimoxazole
therapy consisting of methotrexate, hydrocortisone and as prophylaxis against pneumocytis carinii pneumonia
cytarabine without cranial irradiation. Others propose that They are vaccinated against hepatitis B infection and
cranial irradiation should be limited for patients with high screened for HIV infection. Oral hygiene is taken care of
risk features at diagnosis, including T-cell ALL with by batadine gargles. They are vaccinated against hepatitis
leukocyte count >100,000/mm3, Philadelphia chromo B infection and screened for HIV infection. Oral hygiene
some positive and presence of CNS leukemia. is taken care of by betadine gargles. The survival rates of
children with malignancies are enhanced through access
Intensification (Consolidation) Therapy to state-of-the-art treatment given according to well
This is a period of intensified treatment administered defined protocols in specialized centers.
shortly after remission induction, with administration of
new chemotherapeutic agents to tackle the problem of Treatment After Relapse
drug resistance. There is clear evidence that 'intensi Despite the success of modern treatment, 20-30% of
fication' has improved the long term survival in patients children with ALL relapse. The main cause of treatment
with ALL, especially those with high risk disease. failure in leukemia is relapse of the disease. The most
584 Essential Pediatrics
common site of relapse is in the bone marrow (20%), more complicated, but with intensive myelosuppressive
followed by CNS (5%) and testis (3%). The prognosis for induction and post-remission therapy, about 40-50%
a child with ALL who relapses depends on the site and patients can achieve long term survival.
time of relapse. Early bone marrow relapse before
completing maintenance therapy has the worst prognosis Epidemiology
and long time survival of only 10-20%, while late relapses The ratio of AML to ALL is approximately 1:4. AML can
occurring after cessation of maintenance therapy have a occur at any age but the incidence is more during
better prognosis (30-40% survival). Relapse in extra adolescence; males are affected as frequently as females.
medullary sites, particularly testes, is more favorable in Congenital leukemia (occurring during first 4-weeks of
terms of survival. The treatment of relapse must be more life) is mostly AML. While the etiology of AML is not
aggressive than the first line therapy with use of new drugs known, there is an association following exposure to
to overcome the problem of drug resistance. ionizing radiation. Down syndrome is the most common
Allogeneic bone marrow transplantation offers a better genetic predisposing factor associated with risk of
chance of cure than conventional chemotherapy for developing AML during the first three years of life. Other
children with ALL who enter a second remission after predisposing factors are Fanconi anemia, Bloom syn
hematologic relapse. In addition to the treatment related drome, Kostmann syndrome and Diamond Blackfan
morbidity and mortality, lack of a suitable matched donor anemia. Medications associated with risk of AML include
limits widespread application of allogeneic trans alkylating agents and epipodophyllotoxins.
plantation. Facilities for bone marrow transplantation are
available in all major centers in India including Bombay, Classification
Vellore, Chennai and Delhi. AML can be divided into several subgroups according to
the FAB classification: M0 undifferentiated, Mj acute
Late Effects of Treatment
myeloblastic leukemia with minimal maturation, M2 acute
Long term effects of treatment, which may take years to myeloblastic leukemia with maturation, M3 acute
become apparent, are of particular concern. Continued promyelocytic leukemia, M4 acute myelomonocytic
evaluation of these patients for prolonged periods is leukemia, M5 acute monoblastic leukemia, M6 erythro
necessary. Patients who have received cranial irradiation blastic leukemia, M7 acute megakaryoblastic leukemia.
at a younger age are at risk for cognitive and intellectual About 30—40*%> patients with AML are M, and M2, and
impairment and development of CNS neoplasms. There about same percentage is M4 and M3. M3 type of AML
is a risk of development of secondary AML after the constitutes about 5-10% and M7 is strongly associated with
intensive use of epipodophyllotoxins (etoposide or Down syndrome. Specific chromosomal abnormalities are
tenoposide) therapy. Endocrine dysfunctions leading to found in the various subgroups. Translocation between
short stature, obesity, precocious puberty, osteoporosis, chromosome 8 and 211(8;21) translocation is found almost
thyroid dysfunction and growth retardation (growth exclusively in M, and M2. Almost all patients with M3
hormone deficiency) are reported. Patients having carry the translocation t(15;17) and M5 is associated with
received treatment with an anthracycline are at risk of t(9;ll). Abnormalities of chromosome 16 are seen in
cardiac toxicity. mainly M4 subtype. FAB classification along with the most
commonly employed histochemical stains is usually
Survival Trends in India sufficient to distinguish with AML and its subtypes from
There has been a significant improvement in the outcome ALL. Staining for myeloperoxidase activity and positive
of ALL in India. Multicentric trials suggest a 5-year patient stain with Sudan black B is observed in AML. Auer rods,
survival ranging from 50-60% in our country. Economic needle shaped accumulation of primary granules, are
reasons result in poor compliance and large number of commonly found in M-,, M3 and M5 subtypes of AML (Fig.
dropouts, contributing to the decreased survival. The high 19.2).
incidence of infections, lack of good supportive care and
Clinical Features
poor tolerance to chemotherapy in malnourished patients
also contributes to the mortality. T-cell leukemia and Most patients with AML present with pallor, fatigue,
cytogenetic abnormalities, which predict poor outcome, bleeding or fever as manifestations of underlying anemia,
are more common in Indian patients. thrombocytopenia and neutropenia. Unlike ALL,
lymphadenopathy and massive hepatosplenomegaly is
not very common in AML. However, infants and toddlers
ACUTE MYELOID LEUKEMIA
with AML have more organomegaly, high leukocyte
Acute myeloid leukemia (AML) also termed as acute non- counts and CNS disease at diagnosis. They are mostly M4
lymphoblastic leukemia accounts for 15-20% of leukemia and M5 subtypes. Disseminated intravascular coagulation
in children. AML is much more complex and resistant may occur with any subgroup, but is common in acute
disease than ALL. Progress has been slower and therapy promyelocytic leukemia (M3). Chloromas are localized
Childhood Malignancies 585
Fig. 19.2: A case of acute myeloid leukemia: the blast cells are Fig. 19.4 : Gum hyperplasia is seen in acute myeloid leukemia,
positive for cytochemistry stain myeloperoxidase. This confirms characteristically in subtype AML-M4 and M5
myeloid lineage of the blast cells
collections of leukemic cells seen exclusively in patients anemia, a moderate neutropenia or thrombocytopenia.
with AML. They may occur at any site including CNS, The condition is referred to as a myelodysplastic
bones (typically orbit) (Fig. 19.3) and skin. Gingival syndrome. Some patients may show hypoplastic bone
hypertrophy may be present (Fig. 19.4). Diagnosis must marrow that may develop later into an acute leukemia.
be confirmed by bone marrow examination; the morpho
logic, cytochemical, immunophenotypic and genetic Treatment
characteristics of the blast cells should be determined. Compared to ALL, the cure rate is hampered by a lower
Sometimes the diagnosis of AML is preceded by a remission rate, an increased relapse rate due to the
prolonged preleukemic phase lasting several weeks or development of resistance to multiple chemotherapeutic
months. Usually this is characterized by a lack of one of drugs and a greater risk of death in remission due to
the normal blood cell lineages, resulting in refractory infections and hemorrhage. Nevertheless, during the past
two decades, the long term survival for children with AML
has increased from less than 10% to almost 50%. This is
due to intensification of therapy along with improved
supportive care. The main drugs used for induction
therapy are combination of cytosine arabinoside and an
anthracycline (doxorubicin or daunorubicin). The
induction regimen most commonly used is cytosine
arabinoside (100 mg/m2/day given as continuous
infusion for 7 days) plus daunorubicin (45 mg/m2/day
for 3 days) with or without additional drugs (etoposide,
thioguanine). With the current regimen, remission is
induced in about 70-80% patients. However, without
further therapy most children relapse within one year. Post
remission therapy (consolidation therapy) includes high
dose chemotherapy including cytosine arabinoside and
etoposide. Allogeneic bone marrow transplantation
during early remission is associated with a better long term
survival. Patients with acute promyelocytic leukemia
(M3), which accounts for about 10-15% of patients of AML,
are treated differently with all transretinoic acid or arsenic
and systemic chemotherapy.
Since patients with AML are at high risk for myelo-
suppression following chemotherapy, they require
intensive blood component support including platelet
Fig. 19.3 : Chloroma in a child with AML transfusions and broad spectrum antibiotics for control
586 Essential Pediatrics
of infections. Almost 10-12% patients may die of infection progress to the blast phase of the disease. Leukocyte
and bleeding during induction therapy. alkaline phosphatase activity is low. Philadelphia
chromosome, which involves a reciprocal translocation
Suggested reading between long arms of chromosomes 22 and 9; t(9;22) is
1. Arya LS. Childhood cancer—challenges and opportunities. Indian present in 90% cases.
J Pediatr 2003;70:159-162.
The aim of treatment during chronic phase is to control
2. Magrath T, et al. Treatment of acute lymphoblastic leukemia in
countries with limited resources: lessons from use of a single
the increasing white cell counts. This can usually be
protocol in India over a twenty year period. Eur J Cancer 2005; achieved by single agent chemotherapy with either
41:1570-1583. busulfan or hydroxyurea. However, these agents are being
3. Margolin JF, et al. Acute lymphoblastic leukemia. In: Principles replaced with a-interferon and more recently imatinib
and Practice of Pediatric Oncology. Eds Pizzo PA, Poplack DC.
mesylate. The blood counts returns to normal or near
Lippincott Williams & Wilkins, Philadelphia 2006;538-590.
4. Golub TR, Arceci RJ. Acute myelogenous leukemia. In: Principles normal in almost all patients within 6-8 weeks. Spleen
and Practice of Pediatric Oncology. Eds. Pizzo PA, Poplack DG. size also decreases. With the conventional treatment, the
Lippincot Williams & Wilkins, Philadelphia, 2006; 591-644. average survival is 3-4 years. Survival after development
5. Woods WG. Curing childhood acute myeloid leukemia at the
of accelerated phase is usually less than a year and after
halfway point: Promises to keep and miles to go before we sleep.
Pediatr Blood Cancer 2006; 46: 565-569. blast transformation only a few months. Treatment with
6. Vardiman JW, et al. The World Health Organization (WHO) a-interferon may produce partial or complete remission
classification of the myeloid neoplasms. Blood 2002; 100:2292-2302. in the chronic phase. Recently the invention of imatinib,
7. Creutzig U, et al. Treatment strategies and long term results in
which is a tyrosine kinase inhibitor has shown promising
paediatric patients treated in four consecutive AML-BFM trials.
Leukemia 2005; 19: 2030-2042. results in CML. Imatinib achieves high rates of complete
hematological and cytogenetic remission; the rate of
CHRONIC MYELOID LEUKEMIA progression to accelerated or blast crisis is decreased.
Allogeneic stem cell transplantation is the only docu
Chronic myeloid or myelogenous leukemia (CML) is a mented curative therapy for patients with CML.
myeloproliferative disorder. CML is primarily a disease
of middle age; the peak incidence is in the fourth and fifth Juvenile Chronic Myeloid Leukemia
decade. However, it may occur at any age including
infants and young children. Two main types of well- JCML, also termed as juvenile myelomonocytic leukemia,
differentiated myelogenous leukemia have been recog is an uncommon hematological malignancy accounting
nized. One is clinically and hematologically comparable for less than 2% leukemias in children. Patients with
with the adult form of chronic myelogenous leukemia and neurofibromatosis are at high risk for development of
occurs in children above the age of 4 years. The other JCML (Figs 19.3 and 19.4). Compared to ACML, JCML is
presents earlier in infancy and early childhood usually a disease of infancy and early childhood below the age of
below the age of 4 years, called juvenile chronic myelo 5-years, has a more acute and severe course with relatively
genous leukemia (JCML) has a much more rapid course. more frequent lymphadenopathy, anemia, hepato
The environmental factor implicated in the etiology of splenomegaly, skin involvement (eczema, xanthoma and
CML is ionizing radiation. cafe-au-lait spots), infection and thrombocytopenia.
Peripheral smear shows leukocytosis (usually less than
Adult Variety of CML (ACML) 100,000/mm3) with the full spectrum of granulocytic
Though ACML is one of the commonest leukemias in precursors and increased normoblasts; monocytosis is
adults, it is rare in children accounting for 3-5% cases. often striking. Thrombocytopenia and anemia are com
The natural history is divided into chronic, accelerated mon. The leukocyte alkaline phosphatase score is normal
and blast phases. In the chronic phase, patient has or low and fetal hemoglobin levels are elevated. Bone
nonspecific symptoms such as fever, malaise and weight marrow aspirates show an increased cellularity with
loss. Occasionally, patients present with acute symptoms predominance of granulocytic cells in all stages of matu
such as bone or joint pain or priapism. Splenomegaly is ration; megakaryocytes are normal or decreased. Most
the most common physical finding and is usually massive. patients have normal karyotypes or nonspecific chromo
Mild hepatomegaly and lymphadenopathy may be somal abnormalities. Philadelphia chromosome is
present. Leukocytosis is present in all cases and 80% negative; monosomy 7 is found in 30% patients.
patients have leukocyte counts above 100,000/mm3. The JCML has a fulminant and rapidly fatal course.
differental count shows all forms of myeloid cells from Management involves supportive care including packed
promyelocytes to polymorphonuclear leukocytes; red cell and platelet transfusions, treatment of infections
basophilia is common. Mild anemia and thrombocytosis and allogeneic stem cell transplant if a matched sibling
are common, but thrombocytopenia is rare. Bone marrow donor is present. Even with transplant, there is 30-50%
aspirate demonstrates a shift in the myeloid series to event-free survival rate at 3 year. Cis retinoic acid has been
immature forms that increase in number as patients tried with some benefit in JMML.
Childhood Malignancies 587
Diagnosis
LYMPHOMA
NHL are rapidly growing tumors; prompt diagnosis is
Lymphomas are the third most common malignancy in therefore essential. Almost two-thirds of patients have
children and adolescents, after leukemia and brain tumors. widespread disease at the time of diagnosis, involving
About 60% are non-Hodgkin's lymphoma and 40% are bone marrow, central nervous system or both. Selection
Hodgkin's disease. Lymphomas are uncommon below the of the appropriate lymph node or mass for histological
age of 5 years and the incidence increases with age. diagnosis is necessary. Histology is the primary means
for diagnosis and is supplemented, if possible, with
NON-HODGKIN LYMPHOMA immunophenotypic and cytogenetic studies. If the clinical
condition is not suitable for biopsy, due to a large
Pediatric non-Hodgkin lymphomas (NHL) are different
mediastinal mass causing superior vena cava syndrome,
from lymphomas in adults. Low grade lymphomas, which
the diagnosis may be made with less invasive procedures,
are common in adults are rare in children. Pediatric NHL
e.g. percutaneous needle aspiration of accessible lymph
are high grade, diffuse and aggressive with propensity
node, examination of body fluids or bone marrow.
for wide spread dissemination.
Table 19.3 shows the St. Judes'staging system, which is
applicable to all types of childhood NHL. In newly
Epidemiology
diagnosed patients, a detailed workup and relevant
The relative frequency and incidence of NHL show investigations should be done (Table 19.4).
significant geographic variations. There is male prepon
derance, with male to female ratio of 3:1. In equatorial
Africa, 50% of all cancers are lymphomas (Burkitt
lymphoma being predominant). In United States and Table 19.3: Staging system for non Hodgkin lymphoma
Europe, one-third of childhood NHL are lymphoblastic, Stage I: A single tumor or nodal area is involved, excluding
one-half small, noncleaved cell lymphomas (Burkitt and the abdomen and mediastinum.
non Burkitt or Burkitt like) and the rest are large cell Stage II: Disease extent limited to a single tumor with regional
lymphomas. In India, lymphoblastic lymphoma is more node involvement, 2 or more tumors or nodal areas involved
common. NHL is also characterized on basis of their T- or on one side of the diaphragm, or a primary gastrointestinal
B-cell nature. Lymphoblastic lymphomas are T-cell deri tract tumor (completely resected) with or without regional
node involvement.
ved, while undifferentiated lymphomas (Burkitt and non-
Stage III : Tumors or involved lymph node areas, occur on
Burkitt) are B-cell derived. NHL may follow previous
both sides of the diaphragm. Also includes any primary
chemotherapy for Hodgkin's disease, or be associated with intrathoracic (mediastinal, pleural, or thymic) disease,
immunodeficiency and DNA repair deficiency syndromes extensive primary intra-abdominal disease, or any paraspinal
(Wiskott Aldrich syndrome, X-linked lymphoproliferative or epidural tumors.
disorders, ataxia telangiectasia), acquired immuno Stage IV: Bone marrow and/or central nervous system
deficiency syndrome and organ transplantation (post disease, regardless of other sites of involvement.
transplant lymphoproliferative disease). Infection with
malaria and EB virus are considered risk factors for Burkitt
Table 19.4: Evaluation of patient with non Hodgkin lymphoma
lymphoma.
• Complete blood count.
Clinical Presentation • Surgical biopsy for histology; cytochemical, immunologic,
cytogenetics and molecular studies.
Patients with NHL present with clinical features that
• Bone marrow aspiration and biopsy.
correlate with histologic subtype and stage or extent of
• Cytology: cerebrospinal fluid; if available, pleural,
the disease. Children with NHL typically present with
pericardial or peritoneal fluid.
extranodal disease involving the mediastinum, abdomen
• Liver function tests, renal function tests, electrolytes, LDH,
or head and neck region. Intrathoracic NHL, most often
uric acid.
T-cell lymphoma, might present with cough, dyspnea,
• Chest radiograph; ultrasonography.
dysphagia, chest pain or the superior vena cava syndrome.
• CT scan, MRI of chest and abdomen.
There may be associated pleural and/or pericardial
• Optional: gallium scan, positron emission tomography.
effusion. Cervical lymphadenopathy, abdominal pain,
588 Essential Pediatrics
Management Epidemiology
The dramatic improvement in the survival of patients with The annual incidence of Hodgkin lymphoma is approxi
NHL is because of development of highly effective mately 5-7 cases per million children and it accounts for
chemotherapy and supportive care. Surgery has limited 5-6% malignancies. The age specific incidence of Hodgkin
role in treatment other than for diagnostic purposes. lymphoma exhibits a characteristic bimodal distribution.
Radiotherapy is also restricted to emergency situations, In developed countries, the early peak occurs in the age
e.g. superior vena cava syndrome or spinal cord com group of 20 to 30 years and the second peak after the age
pression due to paraspinal disease. Different chemo of 50 years. In developing countries, however, the early
therapeutic regimens are used for treatment of B- and T- peak occurs before adolescence; it is more common in
cell lymphomas. The regimens for lymphoblastic males. Hodgkin lymphoma is rare before the age of four
lymphoma are usually based on protocols for ALL. Most years. The condition is more common in individuals with
successful protocols are the German BFM (Burlin, an underlying immunodeficiency disease such as ataxia
Frankfurt, Munster) protocols and a modified version of telangiectasia and AIDS.
LSA2L2 protocol. These are intensive protocols that use
combinations of 8 to 10 drugs. Cranial irradiation or Pathology
prophylactic intrathecal chemotherapy is given in stage Lymph nodes are the most common tissue on which the
III and IV diseases. Chemotherapy is given for a period of diagnosis of Hodgkin lymphoma is made. However, liver,
1 to 2 years depending on the stage and extent of the spleen, bone marrow or lung may provide the material
disease. The long term survival in patients with lympho for histologic examination. It is necessary to obtain the
blastic lymphoma with limited disease is 80-90% and for entire node by excision biopsy for proper histologic
advanced disease 70-80%. examination. Fine needle aspiration biopsy and frozen
The chemotherapeutic regimens for B-cell lymphoma section material are not optimal for histology. The
(Burkitt and non Burkitt) is different. Most protocols diagnosis of Hodgkin lymphoma is made with the
consist of short duration (6-months), intensive alkylating identification of the Reed Sternberg cells (large multi
agent therapy (cyclophosphamide or ifosphamide) with nucleated giant cells with abundant cytoplasm and either
high dose methotrexate, vincristine, anthracyclines, multiple or multilobed nuclei). Presence of these cells is,
etoposide and cytarabine; CNS prophylaxis is provided however, not pathognomonic, since they can be seen in
with intrathecal chemotherapy. Long term survival is reactive lymphoid hyperplasia, NHL and non-lymphoid
highly satisfactory with survival in more than 90% patients malignancies.
with limited disease and 75-85% in patients with extensive Hodgkin's disease is divided into four histopathologic
disease. Survival rates in patients with bone marrow subtypes: lymphocytic predominance, nodular sclerosis,
disease have also improved dramatically. The use of anti- mixed cellularity and lymphocyte depletion. Nodular
CD20 monoclonal antibodies (rituximab) directed against sclerosing is the most common type in developed
B-cell antigens has been safely combined with standard countries, whereas in developing countries including
chemotherapy to improve survival. India, the mixed cellularity type is common, accounting
for nearly 60% cases. The WHO classification of Hodgkin
Suggested reading lymphoma recognizes two major subtypes: (i) nodular
1. Link MP, Weinstein HJ. Malignant non-Hodgkin's lymphomas in lymphocyte predominant Hodgkin lymphoma and
children. In: Principles and Practice of Pediatric Oncology. Eds. (ii) classical Hodgkin lymphoma, which includes four
Pizzo PA, Poplack DG, Lippincott Williams and Wilkins, subtypes (nodular sclerosing, mixed cellularity, lympho
Philadelphia, 2006; 722-747. cyte rich and lymphocyte depleted).
2. Cairo MS, Spostos R, Perkins SL et al. Burkitt's and non Burkitt
like lymphoma in children and adolescents. Br J Hematol
2003;120:660-670.
Clinical Features
3. Srinivas V, Soman CS, Naresh KN. Study of the distribution of 289 Children with Hodgkin lymphoma usually present with
non-Hodgkin's lymphomas using the WHO classification among
painless cervical or supraclavicular lymphadenopathy; the
children and adolescents in India. Med Pediatr Oncol 2002 ;39:
40-43. nodes are firm and rubbery in consistency. Cervical lymph
nodes are the most frequent (80%) site of primary
involvement; 50% patients may also have mediastinal
HODGKIN LYMPHOMA
adenopathy (Fig. 19.5). Less commonly, axillary or
Hodgkin lymphoma is characterized by progressive inguinal lymphadenopathy is the presenting feature.
enlargement of lymph nodes. The disease is considered About 20-30% of children present with systemic (B)
unicentric in origin and has a predictable pattern of spread symptoms, as defined by the Ann Arbor staging criteria,
by extension to contiguous nodes. While its etiology is with fever over 38°C, night sweats and unexplained
unknown, the biology of the disease confirms malignant weight loss of >10% body weight at presentation. The
behavior. frequency of these symptoms increases with advanced
Childhood Malignancies 589
*Each cycle to be started on day 29 of the previous cycle, alternating 4 COPP cycles with 4 ABVD cycles. IV intravenous.
Childhood Malignancies 591
Clinical Features
Most patients present with an asymptomatic abdominal
mass detected by their parents or physician during routine
examination. Common features at diagnosis include
hematuria (10-25%), hypertension (25%), abdominal pain
(30%), fever (20%), anorexia and vomiting. Wilms' tumor
should be considered in any child with abdominal mass
(Fig. 19.7). Important differential diagnosis includes
neuroblastoma, other flank masses including hydroneph Fig. 19.8 : CT scan showing bilateral Wilms’ tumor. This poses many
rosis, multicystic kidney, and rarely abdominal lymphoma challenges to the treating team
and retroperitoneal rhabdomyosarcoma.
Stage IV: Metastasis in lung or liver, rarely bone and brain.
Stage V: Bilateral renal involvement.
Treatment
Therapy for Wilms' tumor is based on stage of the disease
and histology. Usually, all modalities of treatment:
surgery, chemotherapy and radiotherapy are required.
Fig. 19.7 : Child with Wilms’ tumor showing marking of mass. The
The immediate treatment for unilateral disease is removal
children are usually asymptomatic so a high index of suspicion is
required to identify these cases. (Courtesy: Dr Sandeep Agarwala,
of the affected kidney. Many experts prefer preoperative
Pediatric Surgery, AIIMS) chemotherapy because it diminishes the size of the tumor
and allows better staging. By preoperative chemotherapy,
Investigations using actinomycin D and vincristine for a period of 4
weeks, 85% of the patients may not require any local
Ultrasonography is the most important investigation since
radiotherapy. Stage I and II tumors with favorable histo
it can differentiate solid from cystic renal mass. CT scan
logy are usually treated postoperatively with vincristine
and MRI provide detailed view of the extent of the tumor
and actinomycin D. The commonly used drugs for
(Fig. 19.8). Intravenous pyelography is seldom necessary.
advanced Wilms' tumor are a combination of vincristine,
An X-ray chest is done to examine for pulmonary
actinomycin D and adriamycin along with abdominal
metastasis. Metastasis in the liver can be detected on
radiation. With the modern therapy, 80-90% of patients
ultrasonography and CT scan. Complete blood counts,
with Wilms' tumor are cured.
urinalysis and assessment of renal and liver function is
done in all cases. Suggested reading
1. Green DM. The treatment of stages I-IV favorable histology Wilms'
Prognostic Factors
tumor. J Clin Oncol 2004; 22:1366-1372.
The prognostic factors are determined by staging: 2. Dome JS, et al. Renal tumors. In: Principles and Practice of Pediatric
Stage I: Tumor confined to kidney and completely excised. Oncology. Eds. Pizzo PA, Poplack DG. Lippincott Williams &
Wilkins, Philadelphia, 2006; 905-932.
Stage II: Tumor extends beyond kidney but completely
excised.
RHABDOMYOSARCOMA
Stage III: Tumor infiltrates renal fat; residual tumor after
surgery. Lymph node involvement of hilum, paraaortic Rhabdomyosarcoma is the most common soft-tissue
region or beyond. sarcoma in children under 15-years of age. Nearly half of
Childhood Malignancies 593
these cases are diagnosed below the age of 5-years and chemotherapy, surgery and radiotherapy. The commonly
two-thirds by 10-years of age. These tumors are associated used chemotherapeutic drugs are vincristine, actinomycin
with several conditions including Li-Fraumeni syndrome, D, cyclophosphamide and doxorubicin. Patients with
neurofibromatosis and the fetal alcohol syndrome. The metastasis show less than 25% long term survival.
histologic classification includes embryonal (60%),
alveolar (20%) variants; the remainder are pleomorphic Suggested reading
and undifferentiated. Embryonal histology is present most 1. Wexler LH, et al. Rhabdomyosarcoma and the other
often in tumors of head and neck and genitourinary areas undifferentiated sarcomas. In: Principles and Practice of Pediatric
Oncology. Eds. Pizzo PA, Poplack DG. Lippincott Williams &
and have good prognosis. Alveolar rhabdomyosarcoma,
Wilkins, Philadelphia, 2006; 971-1001.
which occurs mostly in the extremities and perineal region 2. Stevens MC. Treatment for childhood rhabdomyosarcoma. The cost
in older children is associated with an unsatisfactory of cure. Lancet Oncol 2005; 6:77-84.
outcome.
Rhabdomyosarcoma may occur at any anatomic site
BONE TUMORS
where striated muscle is present. In general, they present
as a mass without antecedent trauma. The most common Osteogenic sarcoma and Ewing's sarcoma are the two
primary site is the head and neck region (35%) (Fig. 19.9) major types of bone tumors in children and adolescents.
followed by the genitourinary tract, extremities, trunk and Both the tumors occur more commonly during second
retroperitoneum. Rhabdomyosarcoma is the most decade of life and show male predominance.
common non-ocular orbital tumor in young children,
Osteogenic Sarcoma
usually presenting with proptosis or swelling of the eyelid.
Parameningeal tumors (nose, nasopharynx, middle ear, The peak incidence of osteogenic sarcoma is during
mastoid and paranasal sinuses) have a tendency for adolescence, correlating with the rapid bone growth; it is
intracranial extension. Genitourinary tumors may present rare below the age of 5-years. The distal femur and
as a pelvic mass, bladder and prostate enlargement or a proximal tibia are the most frequent sites followed by
polypoid mass in the vagina. Extremity and truncal proximal humerus and middle and proximal femur. Flat
primaries are generally of alveolar histology with poor bones, e.g. vertebrae, pelvic bones and mandible may
prognosis. About 25% of patients present with metastasis rarely be involved. Radiation exposure is a documented
at the time of diagnosis, commonly in the lung, bone causal factor for osteogenic sarcoma. Localized painful
marrow and bone. swelling in the bone is the usual presentation which may
Assessing the extent of the tumor is important, because be mistakenly attributed to traumatic or infective
therapy and prognosis depend on the degree to which conditions, delaying the diagnosis by months. Metastasis
the mass has spread beyond the primary site. The optimal occurs early to the lungs and other bones.
therapy involves multimodality approach, including Radiographic examination shows sclerotic or lytic bone
lesions and periosteal new bone formation over the
metaphyseal region. The differential diagnosis includes
osteomyelitis and other bone tumors. Biopsy must be done
to confirm the diagnosis. This is a pleomorphic, spindle
cell tumor that forms extracellular matrix or osteoid.
Imaging studies include CT chest and radionuclide bone
scan to rule out metastasis. MRI provides accurate
assessment of tumor extent.
Successful treatment requires multiagent chemo
therapy with complete surgical resection. Limb sparing
surgery by wide resection of the primary tumor is followed
by replacement of missing bone by a prosthesis. Ampu
tation is rarely needed with present day management
comprising chemotherapy and surgery. Chemothera
peutic agents include doxorubicin, cisplatin, ifosfamide,
cyclophosphamide and high dose methotrexate. The
tumor is unresponsive to radiotherapy. With current
treatments, more than two-thirds of patients presenting
without metastasis have long term survival and are cured.
Ewing’s Sarcoma
Fig. 19.9: Rhabdomyosarcomas are common in the head and neck
region. They usually present as painless soft tissue masses. (Courtesy: Ewing's sarcoma is the second most common malignant
Dr. Sandeep Agarwala, Pediatric Surgery, AIIMS) bone tumor in children and adolescents. Ewing's sarcoma
594 Essential Pediatrics
occurs most often in the second decade, but can occur have a germ line mutation of the retinoblastoma gene (Rb)
below the age of 10-years. They most often arise from flat encoded on chromosome 13ql4. Approximately 10-12% of
bones such as pelvis, chest wall and vertebrae and the unilateral cases have a germline mutation of the Rb gene as
diaphyseal region of long bones. Common sites of well. Of all cases, about 40% are hereditary. The tumor
metastasis are lungs and other bones; bone marrow predisposition is inherited in an autosomal dominant
metastasis is not uncommon. pattern with high penetrance. Germ line mutations of the
The typical presentation is with pain, swelling, a lump Rb gene are associated with increased risk of developing
and/or a limp. Systemic symptoms such as fever and secondary malignancies (e.g. osteosarcoma, soft tissue
weight loss may be present. The duration of symptoms sarcoma), affecting up to 35% of patients 30-years after
varies from few weeks to sometimes more than a year. diagnosis.
Osteomyelitis and Langerhan cell histiocytosis particularly Most patients with retinoblastoma in the developed
eosinophilic granuloma are the differential diagnosis. countries are diagnosed early when the tumor remains
Other small round cell tumors, which metastasize into the intraocular. By contrast, in developing countries including
bone marrow are neuroblastoma, rhabdomyosarcoma and India, late diagnosis is the rule. The most common sign is
NHL. Plain radiographs may show destructive lesions of white reflex, termed leukocoria (Fig. 19.10) of one or both
the diaphysis of bone in the form of lytic or mixed lytic eyes. The next common presenting sign is strabismus
and sclerotic lesions with a classical appearance called followed by painful gluacoma, redness of the eye and dimi
'onion skinning'. Biopsy must be done to confirm the nished vision. In developing countries, retinoblastoma
diagnosis. Chest CT, bone scan and bone marrow biopsy presents very late in its extraocular stage, either with an
are performed to evaluate for metastasis. orbital mass (proptosis) or with distant metastasis in the
These tumors are very well responsive to both bone, bone marrow, lymph nodes and central nervous
chemotherapy and radiotherapy. Local surgery is also an system.
effective way to treat Ewing's sarcoma, however surgical Where possible, both eyes should be examined under
amputation is rarely indicated. Tumor control with general anesthesia. Proper staging requires ultra
radiotherapy requires moderately high doses ranging sonography and CT scan of the orbit and brain, for
from 5500 to 6000 cGy. Multiagent combination chemo assessment of orbital and intracranial extension. Bone
therapy includes vincristine, dactinomycin, cyclo marrow biopsy and CSF examination for cytology is done
phosphamide and doxorubicin. Some investigators add in advanced cases.
ifosfamide and/or etoposide to the above medications. Retinoblastoma is curable when the disease is intra
In localized disease, without metastasis the cure rate is ocular. For intraocular tumors, the standard treatment
nearly 60%, while in metastatic disease it is less than 30%. approach has been enucleation in unilateral cases. In
bilateral cases, enucleation is reserved for eyes with local
Suggested reading loss of vision and/or those with high risk for extraocular
1. Bernstein M, et al. Ewing sarcoma family of tumors. In: Principles spread. In the remaining bilateral cases, the practice is to
and Practice of Pediatric Oncology. Eds Pizzo PA, Poplack DG. rely on local therapy for individual lesions either with
Lippincott Williams & Wilkins, Philadelphia, 2006; 1002-1032.
cryotherapy, photo (laser) coagulation, brachytherapy
2. Link MP, et al. Osteosarcoma. In: Principles and Practice of
Pediatric Oncology. Eds Pizzo PA, Poplack DG. Lippincott
Williams & Wilkins, Philadelphia, 2006; 1074-1115.
3. Carvajal R, Meyers P. Ewing's sarcoma and primitive neuro
ectodermal family of tumors. Hematol Oncol Clin North Am 2005;
19: 501-525
4. Miser JS, et al. Treatment of metastatic Ewing's sarcoma: evaluation
of combination ifosfamide and etoposide - a Children's Cancer
Group and Pediatric Oncology Group study. J Clin Oncol 2004;
22:2873-2876
RETINOBLASTOMA
Retinoblastoma is the most common pri mary ocular tumor
of childhood, a tumor of the embryonic neural retina. It has
an incidence of 11 new cases per million population (age
less than 5-years). About 90% cases are diagnosed by age
3-4 years and 98% by 5 years. Bilateral disease is diagnosed
earlier then unilateral disease. There is increased frequency Fig. 19.10: In the early stages retinoblastoma can be picked up by a
of retinoblastoma in some developing countries especially change in the normal red reflex of the eye to a yellow reflex. This can
Latin America, Africa and Asia including India. Approxi easily be tested using an ophalmoscope/other light source and can
mately 20-30% of cases are bilateral and 10% of patients be part of the well baby examination. (Courtesy: Prof. R.V. Azad,
have family history of retinoblastoma; all these patients Ophthalmology, AIIMS)
Childhood Malignancies 595
(plaque radiation) and/or external beam radiotherapy. X-rays show sharp lytic lesions with nonhealing borders
The use of chemotherapy has previously been reserved (Fig. 19.11). Clinical manifestations include vertebral
for patients with extraocular disease including regional collapse and spinal compression, pathological fractures
or distant metastasis. Several reports have documented in long bones, chronic draining ears and early eruption of
long-term survival of patients with metastatic disease teeth. Other manifestations include seborrheic skin rash
treated with high dose chemotherapy with autologous (Fig. 19.12) in scalp area and back (60%), lymphadeno
bone marrow transplantation. pathy (33%), hepatosplenomegaly (20%) and parenchymal
lung infiltrates (15%). Bilateral infiltration of retroorbital
Suggested reading area may cause exophthalmos. Gingival mucous mem
1. Hurwitz RL, et al. Retinoblastoma. In: Principles and Practice of brane may be involved with lesions, which look like candi
Pediatric Oncology. Eds. Pizzo PA, Poplack DG. Lippincot Williams diasis. Pituitary dysfunction may result in growth
& Wilkins, Philadelphia, 2006; 865-886. retardation and/or diabetes insipidus. Severe disease is
2. Friedman DL, et al. Chemoreduction and local ophthalmic therapy characterized by fever, weight loss, malaise, failure to
for intraocular retinoblastoma. J Clin Oncol 2000; 18: 12-17.
thrive and liver dysfunction. Liver involvement may result
3. Chintagumpala M, et al. Retinoblastoma: review of current
management. Oncologist 2007; 12: 1237-1246. in sclerosing cholangitis and cirrhosis. Bone marrow
involvement may lead to anemia and thrombocytopenia.
THE HISTIOCYTOSES________________________________
Class I Histiocytosis
LCH is a reactive proliferative disease characterized by
abnormal histiocytes, along with lymphocytes, eosino Fig. 19.11 : X-ray skull showing two large osteolytic lesions in
phils, and normal histiocytes to form infiltrates typical for histiocytosis (LCH). (Courtesy: Dr. O.P. Mishra,- Varanasi)
the disease. The hallmark of LCH is the presence of Birbeck
granules on electron microscopy and positivity for S-100
protein and CDla positivity. These infiltrates cause
osteolytic lesions and/or involvement of various other
organs. The etiology of LCH is unknown and its patho
genesis not understood. Currently, the disease is widely
accepted to be a reactive process rather than a malignancy.
The spectrum of LCH (eosinophilic granuloma, Hand-
Schuller-Christian disease, Letterer-Siwe disease) reflects
varying extents of the disease. The course of disease is
unpredictable, varying from rapid progression and death,
to repeated recurrence and recrudescence with chronic
sequelae, to spontaneous regression and resolution.
Patients with disease that is localized (skin or bone) have
a good prognosis and are felt to need minimum or even
no treatment. In contrast, multiple organ involvement,
particularly in young children (under 2-year-old), carries
relatively poor prognosis.
The most common involvement is of the skeleton (80%).
Bone lesions can be single or multiple affecting skull bones,
long bones, vertebrae, mastoid and mandible. The lesions
may be painless or present with pain and local swelling; Fig. 19.1 2: Skin rash and proptosis in LCH
596 Essential Pediatrics
Diagnostic work up should include complete blood compress vital organs like trachea, esophagus or superior
count, liver function tests, coagulation studies, skeletal vena cava. Effusions into the pleural space or pericardium
survey, chest X-ray and urine specific gravity. In addition, may compromise functions of heart and lung. Metastasis
evaluation of involved organ system should be under into the brain may lead to cerebral edema and features of
taken. Bone marrow biopsies are required to exclude raised intracranial tension. Spinal cord tumor involvement
infiltration. by malignancy may lead to cord compression. Bone
Treatment for localized disease or single bony lesion marrow involvement results in anemia, bleeding due to
include curettage and low dose radiation (600 rads). thrombocytopenia or coagulation abnormalities (disease/
Multisystem disease is treated with chemotherapy, com chemotherapy), leukostasis, thrombosis, cerebrovascular
bining vinblastine (weekly IV) and prednisone given daily episodes and infections. Hormonal problems can occur
for 36 months. Other agents include etoposide, metho because of paraneoplastic secretions. Metabolic compli
trexate and 6-mercaptopurine, chlorodeoxyadenosine, cations may occur prior to/at onset of chemotherapy
cyclosporine and interferon. Multiorgan dysfunction is following lysis of tumor cell. Finally, therapy related
associated with poor prognosis. About 10-15% patients complications, include myocardial dysfunction (anthra-
develop diabetes insipidus and require appropriate cyclines), extravasation of drugs (anthracyclines, vinca
screening and follow up. alkaloids), hemorrhagic cystitis (cyclophosphamide),
cerebrovascular accidents (methotrexate, l-asparaginase),
Class II Hemophagocytic Lymphohistiocytoses and pancreatitis (1-asparginase, corticosteroids) may be
encountered. Early diagnosis and urgent management of
The class II histiocytoses are characterized by accumulation
these conditions will save the life of the child and allow
of antigen processing cells (macrophages), which lack
for treatment of the underlying malignancy.
Birbeck granules and CD1 a positivity. Familial erythro-
phagocytic lymphohistiocytosis (FEL) is the only inherited Cardiovascular and Pulmonary Emergencies
histiocytosis (autosomal recessive). Infection associated
Superior vena cava syndrome, cardiac tamponade, peri
hemophagocytic syndrome (IAHS) and FEL both present
cardial and pleural effusions are some serious compli
similarly with fever, weight loss and irritability. Patients
cations, which need early diagnosis and management.
with FEL are younger than 4-year-old and may have severe
immune deficiency. Those with IAHS may present in older Superior Vena Cava Syndrome
children; patients show hepatosplenomegaly, organ
Superior vena cava syndrome (SVC) is the compression
dysfunction and neurological involvement. FEL is a rapidly
of the superior vena cava. Tracheal compression may
progressive fatal disorder. Treatment of any underlying
coexist (superior mediastinal syndrome). Patients may
infection should be undertaken.
present with symptoms of hoarseness, cough, dyspnea,
Class III Histiocytosis orthopnea, headache, lethargy or irritability. Chief signs
include swelling of face, neck and upper extremities, facial
These conditions represent malignancies of the monocyte plethora and cyanosis, chemosis of conjunctivae, promi
macrophage system with proliferation of malignant nent neck veins, stridor and pulsus paradoxus. Malig
histiocytes in many organs. Patients present with fever, nancies implicated include non-Hodgkin lymphoma,
weakness, anemia, weight loss, skin eruptions, jaundice Hodgkin lymphoma, acute lymphoblastic leukemia,
lymphadenopathy and hepatosplenomegaly. Treatment neuroblastoma and germ cell tumors.
is with intensive chemotherapy and CNS prophylaxis. Minimally invasive techniques should be utilized to
establish a diagnosis. Steroids or chemotherapy should
Suggested reading be started immediately; occasionally radiotherapy may be
1. Ladisch S, Jaffe ES. The Histiocytoses. In: Principles and Practice required.
of Pediatric Oncology. Eds. Pizzo PA, Poplack DG. Lippincot
Williams & Wilkins, Philadelphia, 2006;768-785.
2. Gadner H, et al. LCH-I: A randomized trial of treatment for
Cardiac Tamponade
multisystem Langerhans cell histiocytosis. J Pediatrics 2001; This occurs due to massive pericardial effusion, constric
138:728. tive pericarditis from radiation, intracardiac thrombus or
tumors. Symptoms of tamponade include chest pain,
ONCOLOGIC EMERGENCIES cough, and dyspnea while signs include tachycardia,
cyanosis, hypotension and pulsus paradoxus. Treatment
The overall survival of children with cancer has increased includes provision of oxygen, hydration and percutaneous
over the past 25 years as a result of advances in diagnosis pericardial drainage. The fluid must be sent for relevant
and newer therapies including hematopoietic cell diagnostic investigations.
transplantation and use of growth factors. Oncologic
emergencies may come as initial presentation of the Spinal Cord Compression
malignancy, during course of the disease or as a Spinal cord compression is a relatively common compli
consequence of therapy. A solid tumor may invade or cation in the pediatric setting. The tumor encroaches on
Childhood Malignancies 597
the epidural space or subarachnoid space. Magnetic Syndrome of inappropriate antidiuretic hormone (SIADH)
resonance imaging with gadolinium is the investigation secretion may occur due to various chemotherapeutic
study of choice. Steroids should be started immediately; agents (cyclophosphamide, vinca alkaloids, cisplatin) or
occasionally surgical intervention may be required. with certain malignancies (craniopharyngioma, naso
pharyngeal carcinoma). The management consists of fluid
Infectious Emergencies restriction and treatment of cause if possible.
Infectious complications are the most common emer
Gastrointestinal Emergencies
gencies seen in children with cancer. Neutropenia occurs
due to disease and as a consequence of treatment with The main acute gastrointestinal complications include
chemotherapy and/or radiation. Disruption of the skin acute abdomen, ileus, massive hepatomegaly and typhlitis.
and mucosal barriers increases the risk of infection. The These conditions need early diagnosis; usually conser
severity of neutropenia is categorized as mild when the vative management is preferred over surgical intervention.
absolute neutrophil count (ANC) is 1000-1500 cells per Infants with stage IV neuroblastoma may present with
mm3, moderate when the ANC is 500-1000 cells per mm3, massive hepatomegaly sufficient to cause respiratory
and severe when the ANC is less than 500 cells per mm3. compromise. This needs urgent diagnosis and initiation of
The risk of bacterial infection is related to both the severity chemotherapy or irradiation. Typhlitis presents usually
and duration of neutropenia. The child should be evalua with fever, neutropenia and acute abdominal pain. It is a
ted for a focus of infection such as pneumonia, typhlitis, necrotizing colitis caused by bacterial invasion of the cecum
perianal abscess, bacteremia, central line infections, and that may progress to bowel infarction and perforation.
urine or skin infections. Blood cultures and cultures from Typhilitis requires IV antibiotics and aggressive supportive
specific sites of infection must be sent. A chest X-ray care. Hemorrhagic pancreatitis, due to L-asparaginase or
other causes, is treated with IV imipenem, providing
should be obtained. Specific treatment includes intra
parenteral fluids and nutrition, and management of
venous broad-spectrum antibiotics targeted against gram
pain.
positive and negative organisms. Combinations usually
used include an aminoglycoside (amikacin, tobramycin Hyperleukocytosis
or gentamycin) with a broad-spectrum agent (e.g.
ceftazidime, cefoperazone, piperacillin with tazobactum Hyperviscosity associated symptoms are frequent in acute
myeloid leukemia. Presenting symptoms include dyspnea,
or meropenem). The choice of antibiotics should depend
hypoxemia and right ventricular failure; neurological
on culture sensitivity patterns and incidence of organisms
features comprise of blurred vision and altered sensorium;
with extended spectrum P-lactamase production.
priapism may occasionally occur. These patients are at
risk for bleeds in the brain or pulmonary parenchyma.
Metabolic Emergencies
Thrombocytopenia is managed by platelet transfusions;
Common metabolic emergencies include those associated anemia is difficult to manage since transfusions may
with different tumors (e.g. diabetes insipidus, hyper exacerbate symptoms of hyperviscosity. Therapy includes
calcemia, tumor lysis syndrome) or as complications of ensuring adequate fluid intake, and treatment with
treatment (e.g. diabetes mellitus, syndrome of inappro hydroxyurea (10-20 mg/kg) and allopurinol.
priate antidiuretic hormone production).
Urologic Emergencies
Tumor lysis syndrome is caused by cell lysis resulting in
Priapism occurs mostly in chronic myeloid leukemia, and
hyperuricemia, hyperkalemia, hypocalcemia and hyper
is treated with ensuring adequate hydration, and
phosphatemia. This may occur prior to or after initiation
treatment with allopurinol and hydroxyurea. If leuko
of therapy. Burkitt's lymphoma and T-cell lymphoblastic
cytosis and electrolyte problems persist, leukopheresis is
lymphomas are the most common causes. Prevention of
recommended. If priapism does not respond to treatment
tumor lysis syndrome is by ensuring adequate hydration
within 48-72 hours, the child may be left with persistent
(2-4 times maintenance fluid; given intravenously without
deformity.
additional potassium) to enable appropriate urine output,
Obstructive uropathy is seen in patients with bladder
alkalinization (with sodium bicarbonate to maintain urine
rhabdomyosarcomas, large retroperitoneal sarcomas or
pH about 7.5), allopurinol (300 mg/m2 per day, orally)
bulky retroperitoneal lymphomas. A CT scan helps to
and measures to combat hyperkalemia and hyper
confirm the diagnosis. Placement of urinary catheter or
phosphatemia. Hypocalcemia may lead to prolonged QTc stents may be helpful, until definitive therapy of the
interval, however calcium supplementation needs to be malignancy results in resolution of the obstruction.
done carefully in presence of high phosphate levels (to
avoid calcium-phosphate product >60). Patients with Suggested reading
tumor lysis syndrome may require careful management Cohen KJ, Helman LJ. Pediatric emergencies. In: Oncology Emergencies,
of electrolyte balance and occasionally hemodialysis. Oxford University Press, 2002; 239-252.
20 Rheumatological Disorders
APPROACH TO DIAGNOSIS OF ARTHRITIS and must not be confused with a septic arthritis or acute
osteomyelitis. Aspiration of the affected joint results in
Arthritis is a common complaint in children. It is said to
dramatic improvement. Skin traction and judicious use
be present if there is swelling or effusion in a joint or if
of non-steroidal anti-inflammatory drugs (NSAIDs) is
there are any 2 of the following 4 features: limitation of
usually all that is required.
range of motion, pain, tenderness and increased heat. It
can be the manifestation of an underlying illness Reactive Arthritis
(infectious or noninfectious) or may be a primary disease
Reactive arthritis is not as common in children as in adults.
condition in itself. It may not always be easy to differen
It is diagnosed on the basis of Berlin criteria: (i) Typical
tiate these two categories but there are almost always
peripheral arthritis—usually a lower limb asymmetric
important leads which can be picked up from a good
oligoarthritis; (ii) Evidence of preceding infection
clinical evaluation. A convenient way to classify arthritis
(commonly gastrointestinal or genitourinary), usually by
is based on the usual duration of illness at the time of
shigella, chlamydia or yersinia; (iii) Exclusion of other
presentation (Table 20.1).
causes of arthritides.
Transient Synovitis
Arthritic presentation of Acute Leukemia
Transient synovitis is a common condition seen in young
A small proportion of children with acute lymphocytic
children and is characterized by sudden onset of pain in
leukemia may appear to have an 'arthritic' presentation.
the hips, thighs or knees following an upper respiratory
Bone pain (more marked at night) rather than joint
catarrh. It is a self-limiting disorder, lasts only 2-4 days
swelling is the predominant complaint. A bone marrow
examination is mandatory in such cases.
Table 20.1: Classification of arthritis
Arthritis associated with Hypogammaglobulinemia
Acute arthritis (usually <2 weeks)
X-linked agammaglobulinemia (Bruton disease) may
1. Arthritis associated with acute rheumatic fever sometimes be associated with an unusual 'aseptic' arthritis
2. Transient (toxic) synovitis but accompanying respiratory and other infections are also
3. Arthritis associated with Kawasaki disease, Henoch-
present. This arthritis is caused by infection due to
Schonlein purpura
mycoplasma.
4. Septic arthritis (Staphylococcus aureus, Hemophilus
influenzae, Neisseria meningitidis)
Subacute arthritis (2-6 weeks) Legg-Calve-Perthes Disease
neck, (iv) deformed head. Treatment options include the commonest rheumatological disorder of childhood and
femoral varus osteotomies or containment splints. one of the most common causes of disability, chronic
morbidity and school absenteeism in children. While the
Tubercular Arthritis western studies suggest that JRA is more common in girls,
Tubercular arthritis is not very common in our experience. in India the ratio appears to be almost equal.
It can result from an actual infection with the organism
Etiology
Mycobacterium tuberculosis or else may result from an
allergic phenomenon (Poncet's disease). The former type JRA is an autoimmune disease and the immune system is
usually presents as a monoarthritis (e.g. hip or ankle joint) intimately involved in the evolution of the disease. There
while the latter type presents as a polyarthritis with a also appears to be a major histocompatibility complex
strongly positive Mantoux reaction. (MHC) associated genetic predisposition. For instance,
HLA DR5, DR6, DR8 and A2 are linked to early onset
Suggested reading oligoarthritis (seen more in girls), B27 to late onset oligo
1. Cassidy JT, Petty RE. Textbook of Pediatric Rheumatology, 5th edn.
arthritis (seen more in boys) and DR4, Dw4 and DR1 to
Elsevier Saunders, Philadelphia, 2005. rheumatoid factor positive polyarthritis. JRA does not
2. Singh S, Khubchandani R. Pediatric rheumatology in India —in appear to be a single disease entity and the different sub-
need of a joint effort. Indian Journal of Pediatrics 2002; 69:19-20. types may, in fact, be representing separate clinical
3. Salaria M, Singh S, Dutta U, Sehgal S, Kumar L. Arthritis as the
conditions.
presenting feature of hypogammaglobulinemia. Indian Pediatrics
The etiopathogenesis of JRA remains an enigma.
1998; 35:367-370.
4. Salaria M, Singh S, Kumar L. Reiter's Syndrome: A case report. Several environmental triggers (e.g. infection with rubella
Indian Pediatrics 1997; 34: 943-944. virus, parvovirus B19, Mycobacterium tuberculosis,
5. Chaudhuri MK, Singh S, Kumar L. Poncet's Disease- Tuberculous Mycoplasma pneumoniae and enteric organisms; physical
rheumatism. Indian Journal of Pediatrics 1995; 62: 363-365. trauma; psychological stress) have been linked to the onset
of JRA but the exact role that each has to play is not clear.
JUVENILE RHEUMATOID ARTHRITIS (JRA)______________ Complement activation and consumption probably
play an important role in the initiation and perpetuation
The term JRA comprises a group of conditions char
of the inflammatory response. Levels of circulating
acterized by chronic inflammatory changes of one or more
immune complexes (CICs) parallel the activity of the
joints. It cannot be overemphasized that JRA is a clinical
disease and systemic features. Such CICs have been found
diagnosis. The American College of Rheumatology (ACR)
in the synovium and synovial fluid. T lymphocytes in the
has defined it as arthritis of one or more joints with onset
synovium have increased expression of activation markers
below the age of 16 years and persisting for at least 6 weeks,
(i.e. CD3+ IL-2R+). These are believed to secrete
with explicit exclusion of other specific diseases such as
inflammatory cytokines like tumor necrosis factor-a (TNF-
juvenile ankylosing spondylitis (JAS), juvenile psoriatic a) and interferon-y (IFN-y). The cytokine profile of the 3
arthritis (JPsA), arthritides associated with inflammatory types of JRA appears to be quite distinct - increased levels
bowed disease (AAIBD), infectious and postinfectious of IL-la are associated with polyarthritis, TNFa and IL-
arthritis and other rheumatic diseases. The terminology ip with oligoarthritis and IL-6 with systemic onset disease.
used for childhood arthritides is somewhat confusing. For A number of autoantibodies (for instance antinuclear,
instance, the European League Against Rheumatism anti-smooth muscle) may be seen in the sera of children
(EULAR) has suggested the use of the term 'Juvenile with JRA. The classical IgM rheumatoid factor (RF) is
Chronic Arthritis' (JCA) in place of JRA, and the suggested usually negative but it is believed that some children may
cut-off for duration of arthritis is 3 months rather than 6 have hidden RF (especially IgA) in the circulating immune
weeks as in JRA. Moreover, the EULAR definition does not complexes.
exclude conditions like JAS, JPsA and AAIBD. The
International League of Associations for Rheumatology Clinical Features
(ILAR) has recently proposed the use of the term 'Juvenile Three major types of onset are described according to the
Idiopathic Arthritis' and subdivided the group into seven presentation during the first 6 months of disease, viz.
different categories, but this classification is rather complex pauciarticular (4 or fewer joints involved), polyarticular
and more suited for research purposes rather than day to (5 or more joints involved) and systemic (with fever and
day clinical work. The ACR criteria, on the other hand, are rash).
'user friendly' and easy to apply.
It must be clearly understood that JRA is, by no means, Pauciarticular Onset JRA
the pediatric counterpart of adult type of rheumatoid Pauciarticular onset is the most frequent type of JRA
arthritis—the two conditions are quite distinct clinically accounting for about 60% of patients. Four or fewer joints
and biologically. (usually large) are affected and the involvement is often
JRA is not a rare disease—the estimated prevalence asymmetrical. Joint swelling rather than joint pain is the
rates being in the range of 0.4-1.3 per 1000 children. It is usual complaint. Two subtypes are described:
600 Essential Pediatrics
Type I: More common in young girls, typically 3-5 years The illness usually begins as an intermittent fever rising
of age. The knees, ankles, and elbows are commonly up to 3SMrO°C with a characteristic twice daily peak. Fever
affected. Small joints of the hands and feet are not is usually more prominent in the evening hours. Affected
involved. Asymptomatic, and potentially blinding, children have marked irritability which typically decreases
iridocylitis can be seen in 25% of patients by slit lamp with the subsidence of fever. Fever is accompanied by a
examination. Secondary glaucoma and cataract may also characteristic evanescent maculopapular rash with central
occur. clearing. This rash may be seen anywhere on the body
Type II: More common in boys, typically older than but is usually more prominent on the trunk. It can be very
8 years. Large joints of lower extremities are commonly difficult to recognize in individuals with dark skin.
affected. Many children are HLA B27 positive and a Systemic involvement in the form of pericarditis and
proportion of these may go on to develop ankylosing interstitial lung disease may be present. Hepatospleno
spondylitis later as adults. However, sacroiliitis and megaly and lymphadenopathy are common at presen
spondylitis is usually not a significant complaint in the tation and can lead to diagnostic confusion. There is a
pediatric age. Self-limiting acute iritis may occur in some moderate neutrophilic leukocytosis and elevated
patients but it does not progress on to the chronic erythrocyte sedimentation rate. The rheumatoid factor is
iridocyclitis seen in type I. A family history of ankylosing almost always negative.
spondylitis, psoriasis, Reiter's disease and low back pain Laboratory Investigations
may be obtained in these children.
From the pediatrician's point of view it is important that
Polyarticular Onset JRA one learns to recognize the differing patterns of joint
involvement in various types of JRA. This 'pattern
It occurs in 30% of patients and is more common in girls.
recognition' is often the most important diagnostic clue.
Five or more joints (both large and small) are affected
Laboratory investigations seldom help in arriving at a
within the first 6 months of onset of disease. Joint pain
diagnosis. Synovial fluid aspiration for microscopy and
out of proportion to the degree of joint swelling is the usual
culture is indicated in children with monoarthritis because
complaint. Fever and malaise can be significant. Two
septic arthritis may need to be excluded. It must, however,
subtypes are known:
be noted that the joint aspirate in children with JRA would
Rheumatoid factor positive: Age at onset is late also show a predominantly polymorphonuclear response
childhood or early adolescence. The arthritis is symmet with low sugar and decreased complement—a picture not
rical, additive, severe and deforming and typically unlike that of septic arthritis.
involves the small joints of the hand, especially the Full blood counts should be ordered along with an
metacarpophalangeal and the first interphalangeal. erythrocyte sedimentation rate. Acute lymphocytic
Cervical spine and temporomandibular joints can also be leukemia can sometimes have an arthritic presentation and
affected. This subtype is the only category of JRA which such children may be mistakenly diagnosed as having
is somewhat similar to the adult onset rheumatoid JRA. Bone marrow aspiration must, therefore, be carried
arthritis. Rheumatoid nodules are present in some patients out (to exclude leukemia) if use of corticosteroids is being
and they represent the most severe forms of the disease. contemplated for treatment of JRA or else such patients
Rheumatoid factor negative: This subtype may occur may go into partial remission and further complicate
at any age in childhood. The knees, wrists and hips are therapeutic decision making.
the joints usually affected. Small joints of hands and feet C-reactive protein measurements are a surrogate
are less commonly involved and rheumatoid nodules are marker of disease activity and are helpful on follow-up.
not seen. Joint disease in this subtype of JRA is far less Plain radiographs of affected joints are obtained at the time
severe than that seen in rheumatoid factor positive of initial diagnosis and may be repeated for assessment
polyarthritis category. of erosive disease. It should be noted that screening for
RF is not a useful test for diagnosis of childhood arthritis,
Systemic Onset JRA but it is an important prognostic factor.
About 10% of patients with JRA may have an acute onset Treatment
of the disease with prominent systemic features. It may Management of JRA involves many specialities. A good
be noted that these systemic features may precede the joint physiotherapy and occupational therapy team is required
manifestations by weeks or months and consequently this so that the therapy can be tailored to cater to the specific
condition should be considered in the differential diag needs of an individual child. This would not only prevent
nosis of any child with prolonged fever. In infants and development of deformities but would also facilitate
young children it may be a very difficult clinical diagno 'mainstreaming' and rehabilitation. Physical therapy helps
sis to arrive at, especially at the stage when joint symp in relieving pain, enables maintenance of posture and joint
toms are not clearly manifest. Systemic onset JRA can oc mobility, improves muscle strength and prevents fixed
cur at any age and is slightly more common in boys. flexion deformities.
Rheumatolosical Disorders 601
All children with JRA must be assessed initially by an xychloroquin, d-penicillamine and gold salts) were
ophthalmologist so that uveitis can be detected early and believed to have significant DMARD activity. However,
treated appropriately. Children with pauciarticular onset controlled studies have failed to show a significant ben
JRA type I need regular follow-up with an ophthal efit as compared to placebo. Oral weekly methotrexate (15-
mologist as uveitis can develop at any time. Some families 25 mg/m2/week) has revolutionized the management of
find it very difficult to accept the long term implications severe forms of JRA. It is perhaps the only 'true' DMARD.
of a diagnosis of JRA and need psychosocial support. It should be given empty stomach. The drug can be con
tinued for years together if considered necessary. Chil
Medical Therapy dren seem to tolerate methotrexate better than adults and
NSAIDs are the mainstay of symptomatic management. also have fewer side effects. Once the child is in stable
The conventional NSAIDs inhibit both isoforms of the remission, the drug can be tapered off to the minimum
enzyme cyclo-oxygenase, i.e. COX1 (which is constitutive effective dose and then gradually stopped. Methotrexate
and mediates physiologic prostaglandin production should, however, only be given under close medical super
necessary for gastrointestinal mucosal integrity and vision. Periodic testing of liver functions is mandatory
adequacy of renal blood flow) and COX2 (which is while the child is on this drug. Development of hepatic
inducible and mediates pathologic prostaglandin fibrosis is a dreaded side-effect.
production especially at sites of inflammation). The Intraarticular injections of corticosteroids (usually
NSAIDs commonly used in children are naproxen and triamcinolone) are the preferred therapy for children with
ibuprofen. Indomethacin is believed to be of particular pauciarticular onset JRA. In addition, local ocular steroid
use in HLA B27 associated spondyloarthropathies. Doses instillation is done for associated iridocyclitis. Systemic
of commonly used NSAIDs are given in Table 20.2. corticosteroids (usually prednisolone 1-2 mg /kg/ day) are
necessary for severe unremitting arthritis, systemic
manifestations (e.g. pericarditis, myocarditis, vasculitis)
Table 20.2: Doses of commonly used NSAIDs
and rapidly progressive disease. Prednisolone, when used
in this manner, is usually given as bridge therapy for a
few weeks while awaiting the clinical response of
DMARDs. A small minority of children, however, may
require long-term steroids.
Newer modalities of treatment include therapies
targeted against tumor necrosis factor (TNFa). These
include use of a recombinant soluble TNF receptor p-75
fusion protein (etanercept) and a monoclonal antibody
directed to TNF a (infliximab). Both of these are powerful
biological agents and can be very effective in patients with
arthritis which is non-responsive to more conventional
therapy. Leflunomide, an inhibitor of pyrimidine syn
thesis, is a useful 'add-on' drug in adults with rheumatoid
arthritis but experience in children is limited. Cyclosporin
Development of Reye's syndrome is a distinct possi
A is also a useful modality of therapy in difficult cases.
bility while a child is receiving NSAIDs, especially if there
is an intercurrent viral illness. All children with NSAIDs
Course of Illness
must be closely monitored for gastrointestinal side effects.
The recently introduced selective COX2 inhibitor NSAIDs Pauciarticular onset JRA type I usually has a good
(e.g. rofecoxib, valdecoxib) may have lower gastro prognosis but asymmetric growth of limbs with localized
intestinal side-effects but these drugs are not recom deformities can be seen. Blindness due to progressive
mended for use in children. Pseudoporphyria is a peculiar uveitis is a known but preventable complication. Children
side effect of naproxen. Although the mechanism of action with pauciarticular JRA type II can develop spondylitis
of all NSAIDs is the same, idiosyncratic responses are well and sacroiliitis later in life, especially if they are HLA B27
known and a given child may respond to one NSAID and positive.
not to the other. Response to therapy is usually slow and Patients with seropositive polyarticular JRA have a
this fact must be explained to the parents. Treatment must disease pattern similar to adults with rheumatoid arthritis.
continue for at least 4-6 weeks before a decision to switch The arthritis can be erosive and deforming, if not treated
over to another NSAID is made. aggressively. Response to therapy, however, is not predic
Disease modifying anti-rheumatic drugs (DMARDs) table. The prognosis is relatively better for seronegative
need to be started in almost all children with polyarticu polyarticular JRA as remissions are obtained more often
lar onset JRA. In the past a number of drugs (e.g. hydro- and residual joint lesions may be minimal.
602 Essential Pediatrics
The course of systemic disease can be extremely fine needle aspiration cytology from the abdominal fat
variable and the response to therapy is not always pad. Methotrexate and chlorambucil have been used for
satisfactory. Approximately 50% of patients with systemic treatment of secondary amyloidosis.
disease undergo remission with minor residual joint
involvement while others may develop progressive Suggested reading
arthritis or have recurrent episodes of systemic disease. 1. Cassidy JT, Petty RE. Textbook of Pediatric Rheumatology, 5th edn.
The presence of HLA-DR4 is usually associated with Elsevier Saunders, Philadelphia, 2005.
2. Singh S, Salaria M,Kumar L, Datta V, Sehgal S. Clinico-
severe, persistent arthritis.
immunological profile of juvenile rheumatoid arthritis at
Inappropriately treated or untreated patients with JRA
Chandigarh. Indian Pediatrics 1999;36:449-454.
may develop flexion contractures of hips, knees and 3. Jain V, Singh S, Sharma A. Keratoconjunctivitis sicca is not
elbows resulting in permanent disability. Neck stiffness uncommon in children with juvenile rheumatoid arthritis.
is an especially debilitating problem and can result in Rheumatology International 2001;20:159-62.
4. Goraya JS, Singh G, Singh S, Gill SS, Goyal A, Mitra SK, Kumar L.
torticollis. Temporomandibular joint involvement results
Arteriovenous malformation of knee masquerading as juvenile
in restricted opening of the mouth and may require arthritis. Scandinavian Journal of Rheumatology 1998;27:313.
surgical intervention. 5. Beri A, Singh S, Gupta A, Khullar M. Comparison of serum nitric
oxide levels in active juvenile rheumatoid arthritis with those of
Complications patients in remission. Rheumatology International 2004;24:264-266.
cm diameter) or any one of the typical clinical features The malar rash, which is virtually pathognomonic of
(arthritis, meningitis, radiculoneuritis, mononeuritis, SLE, may not be very apparent initially. It involves the
carditis) in the presence of specific antibodies. These cheek, bridge of nose and lower eyelids but spares the
criteria have, however, not been validated in children. It nasolabial folds. Discoid lesions are rare in childhood onset
may be noted that all serological tests may be negative in SLE. Oral ulcerations may involve the buccal mucosa or
the first few weeks of the illness and the treating physician palate and are characteristically painless. Arthritis is
may get virtually no help from the laboratory. Early usually mild and always non-erosive.
disease can be treated with oral amoxycillin (50 mg/kg/ Renal involvement is a dreaded complication of SLE
day) while for disseminated disease or late cases par and one of the commonest causes of mortality in children.
enteral ceftriaxone (100 mg/kg/day) is the drug of choice. Lupus nephritis can be classified as follows:
Duration of therapy is 4 weeks. Children treated late or Class I: Normal; Class II: Mesangial proliferation; Class
incompletely can have a smouldering chronic course often III: Focal proliferative glomerulonephritis; Class IV: Diffuse
resistant to any form of therapy and resulting in consi proliferative glomerulonephritis; Class V: Membranous
derable morbidity. glomerulonephritis; Class VI: Glomerulosclerosis. Class III
and Class IV lesions are associated with the poorest
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) prognosis and require the most aggressive forms of
therapy.
SLE is an autoimmune disorder characterized by inflam
mation of blood vessels and connective tissues resulting Neurological features may include psychosis, seizures
in multisystemic involvement. The clinical manifestations and chorea. There may be no correlation between the
can be extremely variable and the course unpredictable. severity of clinical involvement and findings on neuro
Childhood SLE is usually more severe and has a poorer imaging. Hematologic abnormalities may include a
prognosis than adult SLE. The hallmark of SLE is the Coombs' positive hemolytic anemia, leukopenia, lympho
presence of antinuclear antibodies (ANA). The marked penia and thrombocytopenia. In addition, there may be
female predominance characteristic of adult SLE is usually coagulation abnormalities due to secondary antiphos
not that apparent in young children. pholipid antibody syndrome. Cardiac manifestations may
include a pericarditis, myocarditis, or a verrucous
Diagnosis (Libman-Sacks) endocarditis.
The diagnosis of SLE can be facilitated by the criteria given
Serology
by American College of Rheumatology (ACR) in 1982.
Presence of four of these criteria, either at presentation or Almost all patients with SLE have demonstrable ANA.
sequentially, gives a sensitivity and specificity of 96% in Presence of anti-double-stranded DNA antibodies is
adults. It must, however, be understood that SLE remains highly specific of SLE. The titers of these antibodies usually
essentially a clinical diagnosis—the criteria only provide correlate with disease activity. Anti-histone antibodies are
helpful guidelines for arriving at a diagnosis. In many characteristic of drug-induced lupus (e.g. following
patients (especially children), treatment may have to be dilantin, isoniazid, hydralazine) but in such cases anti-ds
started even when they do not fulfil the requisite number DNA antibodies are usually absent and serum comple
of criteria. The ACR criteria have never been prospectively ment (C3) level is not decreased. Anti-Ro antibodies are
validated in children. The revised 1997 version of the ACR believed to play a role in the development of congenital
criteria is given in Table 20.3. heart blocks characteristic of neonatal lupus syndromes.
These heart blocks are permanent. Anti-Sm antibodies are
Table 20.3: ACR 1997 criteria for classification of systemic believed to be a marker for CNS lupus.
lupus erythematosus
Treatment
1. Malar rash
2. Discoid rash Glucocorticoids form the mainstay of therapy. Predni
3. Photosensitivity solone is usually started in doses of 1-2 mg/kg/day and
4. Oral/nasal mucocutaneous ulcerations then gradually tapered according to disease activity.
5. Nonerosive arthritis Arthritis usually responds to NSAIDs. Sunscreen lotions
6. Nephritis (proteinuria > 0.5 g/day or cellular casts) (with a sun protection factor of 15-20) must be prescribed
7. Encephalopathy (seizures or psychosis) for all such children and should be applied 3-4 times/
8. Pleuritis or pericarditis day. These should be used even on cloudy days.
9. Cytopenia Life-threatening complications (e.g. Class IV lupus ne
10. Positive immunoserology (antibodies to dsDNA/Sm nuclear phritis, mycocarditis, encephalopathy) may warrant use
antigen) or positive finding of antiphospholipid antibodies of intravenous pulses of methyl prednisolone or dexa
(IgG/IgM anticardiolipin antibodies or lupus anticoagulant or methasone for 3-5 days, followed by oral prednisolone.
VDRL)
Use of monthly pulses of intravenous cyclophosphamide
11. Positive antinuclear antibody test
(600-750 mg/m2) has considerably improved the long
604 Essential Pediatrics
term outcome in children with severe forms of lupus muscle and skin and a systemic vasculopathy. Unlike
nephritis. Once remission is achieved, the patient can be adults, pure polymyositis (i.e. in absence of dermatological
put on long-term maintenance azathioprine. Myco changes) is uncommon in children. The diagnosis can be
phenolate mofetil is being increasingly used for the made on the basis of criteria provided by Bohan and Peter:
therapy of severe forms of lupus nephritis in children. 1. Characteristic heliotrope discoloration over the upper
For almost all patients with SLE, low dose prednisolone eyelids
(e.g. 2.5-5 mg/day) has to be continued for many years. 2. Symmetrical proximal muscle weakness
Once a child has been in stable remission for a 'reasonable' 3. Elevated levels of muscle enzymes (AST, ALT, CK,
period of time, hydroxychloroquin (5-6 mg/kg/day) can aldolase)
be started and further tapering of steroids can be carried 4. Electromyographic evidence of myopathy
out under very careful supervision. Maintenance steroids 5. Muscle biopsy showing myonecrosis, myophago-
should only be stopped after careful deliberation. cytosis, and perifascicular atrophy.
Infections must be treated aggressively with appro A 'definite' diagnosis of JDM can be made if a child
priate antimicrobials and the steroid dose hiked up during fulfils the first criterion along with any three of the
such episodes. With appropriate therapy, the long-term remaining four; it is considered 'probable' if two of the
outlook of SLE in children now is quite encouraging. four criteria are met and 'possible' if only one of the four
criteria is met in addition to the first criterion. Other typical
Suggested reading dermatological changes include Gottron's papules
1. Cassidy JT, Petty RE. Textbook of Pediatric Rheumatology, 5th edn. (collodion patches) over the dorsal aspects of meta
Elsevier Saunders, Philadelphia, 2005. carpophalangeal and interphalangeal joints of fingers (toes
2. Singh S, Devidayal, Minz R, Nada R, Joshi K. Childhood lupus usually not involved), edema over eyelids, photosensi
nephritis: 12 years experience from North India. Rheumatol Int
tivity, a truncal rash and calcinosis. From the clinical point
2006; 26: 604-607.
3. Singh S, Devi Dayal, Kumar L, Joshi K. Mortality patterns in of view a child with characteristic dermatological findings
childhood lupus—10 years experience in a developing country. along with proximal muscle weakness can be confidently
Clin Rheumatol 2002; 21: 462-65. diagnosed as having JDM and started on treatment
4. Singh S, Dayal D, Kumar L. Childhood SLE: A single center expe irrespective of the biopsy findings. Magnetic resonance
rience from a developing country. Lupus 2001, 10 (Suppl.): S82.
imaging (MRI) shows characteristic hyperintense signals
on T2-weighted images suggestive of muscle edema and
THE ANTIPHOSPHOLIPID ANTIBODY
inflammation while the Tl-weighted images may show
(APLA) SYNDROME
fibrosis, atrophy and fatty infiltration. Typical findings
The APLA syndrome is a common accompaniment of on MRI may preclude the need for a muscle biopsy.
systemic lupus erythematosus but can be seen in associa Treatment involves use of intravenous boluses of
tion with other rheumatological disorders as well. It was parenteral steroids (methylprednisolone 30 mg/kg/day
first described by Hughes and co-workers from London or dexamethasone 5 mg/kg/day) for 3-5 days followed
in the early eighties. The syndrome can, at times, arise de by oral prednisolone (1.5-2 mg/kg/day). Steroids are then
novo when it is known as primary APLA syndrome. It is a gradually tapered depending on the clinical response. Oral
common cause of hypercoagulable states in children and weekly methotrexate (15-25 mg/m2/week) is now
can manifest with arterial and venous thrombosis, livedo increasingly being used as first-line therapy in combi
reticularis and thrombocytopenia. The presentation can nation with prednisolone. The usual duration of therapy
sometimes be catastrophic and may result in fatality. is 18-24 months. Rapid tapering of steroids may result in
Laboratory diagnosis is based on the detection of anti- disease relapse. The long-term prognosis is excellent.
cardiolipin antibodies (IgM and IgG) and the lupus anti
coagulant test. Treatment is with long term oral anti Suggested reading
coagulation. 1. Cassidy JT, Petty RE. Textbook of Pediatric Rheumatology, 5th edn.
Elsevier Saunders, Philadelphia, 2005.
Suggested reading 2. Singh S, Bansal A. Twelve years experience of juvenile dermato
myositis in North India. Rheumatol Int 2006;26:510-515.
1. Ahluwalia J, Singh S, Garewal G. Antiphospholipid antibodies in 3. Verma S, Singh S, Bhalla AK, Khullar M. Study of subcutaneous
children with systemic lupus erythematosus: a prospective study fat in children with juvenile dermatomyositis. Arthritis Rheu
from Northern India. Rheumatol Int 2005;25:530-535. matism 2006; 55: 564-568.
2. Khetarpal R, Goraya JS, Singh M, Singh S, Kumar L. Pulmonary
hypertension as presenting feature of childhood SLE: Association
with lupus anticoagulant. Scand J Rheumatol 1998, 26:325-326. SCLERODERMA
Diagnosis is confirmed by angiography. Treatment correct diagnosis of KD. Most children have high grade
involves long-term immunosuppression with predni fever and are extremely irritable. In fact, it is this irritability
solone and methotrexate (used in weekly doses). which often provides the first clinical clue to the diagnosis.
Angioplasty procedures are now being increasingly KD must be considered in the differential diagnosis of all
performed even in small children and have shown children below 5 years of age who have fever without
promising results. Cyclophosphamide or azathioprine apparent focus lasting more than 5 days.
may be required in children who fail to show an adequate The basic lesion is a necrotizing vasculitis of medium
response to steroids. Hypertension must be managed ap sized muscular arteries (especially coronaries), which may
propriately. The 5 year survival rates are more than 90%. result in aneurysms, dilatations, and stenoses in untreated
patients.
Suggested reading Treatment involves use of a single dose of intravenous
1. Singh S, Bali HK, Salaria M, Lai S, Pandav SS, Kumar L. Takayasu's immunoglobulin (2 g/kg) and aspirin in anti-inflam-
arteritis in young children—a potentially treatable condition. matory doses (75-80 mg/kg) till the child becomes afebrile.
Indian Pediatr 1999, 36:291-296.
Low dose aspirin (3-5 mg/kg/day) is then continued for
2. Jain S, Sharma N, Singh S, Bali HK, Kumar L, Sharma BK. Takayasu
arteritis in children and young Indians. Int J Cardiol 2000, 75 (S) : a few weeks for its antiplatelet activity. In appropriately
153-57 treated children, the long-term prognosis is excellent with
3. Kakkar N, Vasishta RK, Banerjee AK, Singh S, Kumar L. Pulmonary less than 1% patients developing coronary artery abnor
capillary hemangiomatosis as a cause of pulmonary hypertension malities as compared to 20-30% in the untreated category.
in Takayasu's aortoarteritis. Respiration 1997, 64:381-383.
Table 20.5: Classification criteria for childhood Vomiting occurs in about 60% of patients but hematemesis
polyarteritis nodosa and melena are relatively less common.
Illness characterized by the presence of either a biopsy Most clinical features are self-limiting and resolve in a
showing small and mid-size artery necrotizing vasculitis or few days. Rare manifestations of HSP include CNS
angiographic abnormalities* (aneurysms or occlusions) vasculitis, coma, Guillain-Barre syndrome, pulmonary
plus hemorrhage, carditis and orchitis.
at least 2 of the following:
Laboratory Investigations
1. Skin involvement
HSP is a clinical diagnosis and none of the laboratory
2. Myalgia or muscle tenderness features are pathognomonic. There may be a non-specific
3. Systemic hypertension (based on childhood normative increase in total serum IgA levels. Many children may have
data) microscopic hematuria and proteinuria. Skin biopsy from
4. Abnormal urine analysis and/or impaired renal function the involved sites may show the characteristic leuko-
5. Mononeuropathy or polyneuropathy cytoclastic vasculitis but this is not pathognomonic of HSP.
6. Testicular pain or tenderness On indirect immunofluorescence there are deposits of IgA
and C3 in skin as well as renal biopsies. Ultrasound
7. Signs or symptoms suggesting vasculitis of any other major
examination may need to be repeated at frequent intervals
organ systems (gastrointestinal, cardiac, pulmonary or
central nervous system) for evolving abdominal findings.
PHYSIOLOGICALCONSIDERATIONS different forms. For instance, one of them may code for
black iris, and another for blue iris. Such alternative forms
The pattern of inheritance is determined by the genetic
of a gene are known as alleles. If the alleles code for the
material in the nuclei of cells, which is distributed into 23
same forms, these are said to be present in the homozygous
pairs of chromosomes. The two members of 22 pairs of
state; if they code for different traits, they are in hetero
chromosomes are apparently alike (or homologous) in
zygous state. If an allele clinically manifests itself even in
both sexes. These are called autosomes. The 23rd pair of
the heterozygous state, it is called a dominant gene or
chromosomes is homologous only in females with two
character. Its alternate form or allele which does not
X chromosomes. In the male the 23rd pair of chromosomes
express itself clinically when the other allele from the other
has one X chromosome, and a much smaller Y chromo
parent is normal is called a recessive gene. Recessive genes
some. These are called sex chromosomes.
will manifest features of the disease only when present
Chromosomes are the agents for inheritance of char
on both chromosomes in the pair (homozygous state) or
acteristics and these are derived from both parents in equal
when the specific abnormal gene is inherited from both
number. In the germ cells of both sexes, the cell division
parents. Therefore, clinically manifest characters of an
is not of the usual mitotic variety, but is a reduction divi
individual may not always indicate his or her genetic
sion or meiosis. The cells which are obtained after meiosis constitution since recessive alleles are masked in the
have only one representative of each pair of chromosomes, heterozygous state. The genetic make up of a person is
so that in human beings they have only 23 chromosomes. called the genotype, and the clinically manifest characters
In the course of meiosis, not only is the number of are known as the phenotype.
chromosomes halved, there is also some exchange of Sometimes a gene may express itself in several slightly
genetic material between the two members of a pair. This modified forms without adverse effect on the health of
phenomenon is called crossover. Some of these cells the individual. This is referred to as genetic polymor
(having half the usual quota of chromosomes) form phism.
gametes.
From Chromosomes to Characters
The female gamete (ovum) has 22 autosomes and one
X chromosome, while the male gamete (sperm) can have Chemically, the chromosomes are made up of deoxyribo
two types of chromosomal pattern, 22 + X or 22 + Y. The nucleic acid (DNA) and histones. Only about 3% of DNA
fertilization of an ovum by an X-bearing sperm will result in the human genome symbolizes genes. About 93% has
apparently no clear cut function and is flippantly termed
in a female offspring and by a Y-bearing sperm will result
as "junk DNA". Many copies of the latter type of DNA
in a male offspring. Since the progeny inherits half their
are scattered at random over the chromosomes inter
chromosomes from the father and half from the mother,
mingled with genes. These are called repetitive sequences.
they have some characteristics of both. Since the parents
These are useful for fingerprinting of the human genome.
had also inherited their chromosomes in the same way,
There are about 30,000 genes in the human beings.
and so did their parents, and so on, the chromosomes of
Roughly 20% of these are specific genes which regulate
an individual have the entire ancestral history inscribed
the production of structural or functional proteins. About
on them. The segregation of chromosome pairs at meiosis
80% genes are housekeeping genes responsible for basic
is a random process and occurs independently for each
cell functioning. Highly related genes are clustered in a
pair.
particular region of chromosomes. DNA determines the
The portion of a chromosome which codes for a type of messenger ribonucleic acid (mRNA) that is
'character' is called a gene. The position of a gene on a synthesized by a cell; mRNA is responsible for the type of
chromosome is called its locus. Corresponding loci on the protein manufactured by the cell. The proteins that are
two members of a pair carry genes for the same character. manufactured may be structural proteins or enzymes.
The character coded by the two chromosomes may have Together these determine how the cell looks and what it
609
610 Essential Pediatrics
does. The characteristics of individual cells collectively of the gene product (protein) and the identification of gene
make up the characteristics of the whole organism. follows. In positional cloning identification of the gene
follows the establishment of its position on the genome.
MOLECULAR GENETICS The various markers identified all over the genome on
different chromosomes help in gene identification. Posi
Our understanding of molecular genetics has tremen
tional cloning is used in majority of disorders as the func
dously advanced because of development of new techni
tion of gene products is seldom known. The isolation of
ques. It is now possible to cleave DNA at specific points
the gene is followed by identification of disease causing
by restriction endonucleases derived from bacteria. DNA
mutations.
probes can be made to detect specific base sequences in
the DNA. Southern blotting technique helps in identi Comparative biology of humans and other organisms: Study
fication of small fragments of DNA obtained after the of comparative biology was a major component of HGP.
action of application of restriction endonucleases followed It helps in developing strategies, techniques and infra
by initial separation on agarose gel electrophoresis and structure for studying human DNA. This is based on the
subsequent transfer to a nitrocellulose paper filter (NCP). fundamental knowledge that all organisms are related and
The most fascinating advance in molecular genetics is the share same general type of DNA blueprint and there is
ability to form large number of copies of DNA sequences significant conservation. This approach helps in under
in a short time. This amplification of genetic material is standing gene structure and function.
now possible with polymerase chain reaction (PCR). In
PCR, the double stranded DNA fragment is first denatured Advances in molecular diagnostics: Molecular diagnostics
by heating resulting in two single strands of DNA. These have tremendous scope and usefulness in clinical prac
are annealed by a synthetic primer. Then the enzyme, a tice. The disorders which can be tested are of wide range
DNA polymerase, supplied along with nucleotides, starts which include hereditary, neoplastic and infectious dis
to extend the primer. The primer is extended along the eases. The HGP has and will help in development of mo
length of the DNA fragment of interest, thereby dupli lecular diagnostics in two major ways. Firstly by identifi
cating it. This process (denaturation/annealing/ cation of disease genes and disease causing mutations and
extension) is repeated several times resulting in a million secondly use of wider range of more refined technologies
copies of DNA sequence. There are many more molecular in clinical practice. PCR is being extensively used in clini
genetic techniques available, like high throughput PCR cal practice already. With the availability of high-through-
and microarray techniques through which thousands of put PCR testing hundreds/thousands of PCRs can be per
samples can be analyzed in a very short time. formed in a day. An important discovery is this area is
DNA chips or micro arrays.
The Human Genome Project
Therapeutic benefits: The therapeutic benefits encompass
The Human Genome Project (HGP) began formally in 1990 pre-symptomatic diagnosis and use of preventive mea
and is a 13 year effort coordinated by the US Department sures (like lifestyle alterations and surveillances), prena
of Energy and the National Institute of Health (NIH). It tal diagnosis in lethal or chronic disabling disorders and
finalized almost two years earlier than expected. It was actual therapeutics. The therapeutic advances would in
an enormous task as the aim was to sequence 3 billion clude gene therapy, development of better pharmaco
base pairs and identify approximately 30,000 genes. logical agents. An interesting area in pharmacogenomics
The genome is defined as the total genetic material is studying the genetic basis of drug responsiveness and
contained within the chromosomes of an organism. It can resistance.
be said to be the total genetic information which is carried
by the DNA. Transcriptome is the transcribed messenger Ethical, legal and social implications: There are various is
RNA (mRNA) complement and the Proteome is the sues which need serious thought and discussion. Some of
translated protein constitution. the important ones are as follows:
i. Who should have access to this data
Impact on Human Disease and Clinical Practice ii. Use of genetic information to discriminate people, like
Isolation of disease genes: Many genes are known to cause carriers being stigmatized or health insurance being
human diseases when mutated, but there are others which denied asymptomatic persons.
may have an indirect influence. The major effort of mod iii. Pre-symptomatic diagnosis and susceptibility to dis
ern molecular medicine is to identify association of genes ease (e.g. late onset neurological disorders and malig
with human diseases. nancy predisposition).
Isolation of diseased genes can be done by two major iv. Misuse in prenatal testing.
strategies : functional cloning and positional cloning. In v. Interpretation of tests and pre and post test counsel
functional cloning there is knowledge about the function ing issues.
Genetic Disorders 611
GENETICS AND DISEASE retarded or infertile. At times, only a part of the chromo
some may be deleted or lost, causing less severe genetic
Most disease have a probable genetic and an environ
disturbances. Generally speaking, loss of a whole chromo
mental basis. The genetic component may be the major or
some except that of one X chromosome (as in Turner
the only factor leading to manifestation of the disease, or
syndrome) is lethal. Surveys in still-born or abortuses
it may merely predispose the individual to get a disease
(aborted fetuses) have shown large proportion of
in response to environmental stresses. Different diseases
chromosomal anomalies. Of all live newborns, 0.5% may
can be considered to be at different regions of the spectrum
have a chromosomal anomaly.
between the genetic and environmental reasons in cau
Each chromosome has a short arm (p) and a long arm
sation of the disease. Thus, based on genetic mechanism,
(q) joined by a centromere. Chromosomes are numbered
the disease may be one of five types: (i) chromosomal
based on their size and position of the centromere (Fig.
disorders, (ii) single gene disorders, (iii) polygenic
21.1).
disorders, (iv) mitochondrial disorders and (v) somatic
Chromosomal abnormalities are generally sporadic and
cell (genetic) disorders.
therefore, the risk of their recurrence in the offsprings is
low (except in situation when either parent is a balanced
CHROMOSOMAL DISORDERS
translocation carrier). There are two types of chromosomal
Mechanisms of Chromosomal Anomalies abnormalities—numerical (aneuploidies) and structural.
Chromosomes contain a large number of genes. Loss or There are several mechanisms which lead to chromosomal
gain of a whole chromosome due to abnormalities in cell abnormalities.
division may cause such profound disturbances in the
genetic constitution of the fetus that it may affect its Inversion
survival and the fetus may be aborted. If the fetus is born One or two breaks may occur along the length of the
alive it may die soon after birth. Even if the disturbances chromosome arm. The broken pieces may rearrange
are not lethal, the sufferer may be malformed, mentally themselves in a new way. If there is no loss or gain of
612 Essential Pediatrics
genetic material, there may be no significant clinical translocation is balanced and the person is phenotypically
manifestations. Break point is important if it disrupts a normal. Translocated chromosome may be transmitted to
vital gene. either gamete during meiosis and when it mates with nor
mal gamete, the resulting zygote may either have excess
Isochromosome or deficiency of the genetic material. Such an offspring is
During mitotic cell division, the chromosome divides abnormal. Viability of such zygotes would depend on the
longitudinally. Rarely it may divide transversely across essentiality of the genes carried on translocated portion
the centromere. Half of the chromosome replicates to form of the chromosome.
its complement. Thus instead of normal chromosomes,
two new types of chromosomes are formed—one having Deletion
both the long arms and the other with both the short arms. A segment of chromosome may break off and be lost. Loss
These are known as isochromosomes. Each isochromo of a portion of chromosomal material large enough to be
some thus has excess of some genetic material and seen by light microscope is often lethal or poorly tolerated.
deficiency of some other genetic material, e.g. in some Submicroscopic deletions are detected on special chromo
cases of Turner syndrome. somal staining or fluorescent in situ hybridization (FISH)
(Fig. 21.2). DNA probes have been developed that make
Anaphase Lag it possible for FISH to be used for diagnosis. Gene deletion
In the first meiotic division, the chromosomes are arranged syndromes are characterized by loss of a cluster of genes,
in pairs in the equatorial plane during the metaphase. giving rise to a consistent pattern of congenital anomalies
During anaphase if one of the chromosomes is slow in its and developmental problems. Examples of these are
migration, it might be excluded and thus be lost. William syndrome (7 q 11.23); retinoblastoma with mental
retardation and dysmorphic facies (13 q 14.1); Prader Willi
Nondisjunction syndrome (hypotonia, mental retardation and obesity, 15q
11); Rubinstein - Taybi syndrome (microcephaly, broad
During the first meiotic division, both members of a pair
thumbs and big toes, dysmorphism and mental retar
of chromosomes may move jointly during anaphase to
dation, 16 q 13); and DiGeorge syndrome (congenital heart
either of the daughter cells. Thus, whereas one daughter
defect, hypoplasia of parathyroid and thymus, facial
cell may have both members of a pair of chromosomes;
anomalies, palate anomalies, 22 q 11).
i.e. 22 + 2 or 24 chromosomes, the other cell may have
only 22 chromosomes without any representation of the
erring pair. When such gametes mate with other gametes
Genomic Imprinting
with normal chromosomal complement, the zygote will Maternal and paternal sets of genes are not always
either have 47 or 45 chromosomes. Nondisjunction leads functionally equal. Some genes are preferentially
to aneuploidies. Common aneuploidies seen in live born expressed from maternal or paternal side. Example:
babies include Down syndrome (Trisomy 21), Edward Prader-Willi syndrome (microdeletion on paternal side or
Syndrome ( Trisomy 18), Patau syndrome (Trisomy 13) inheritance of both copies from maternal side) and
and Turner syndrome (monosomy X). Angelman syndrome (microdeletion on maternal side or
inheritance of both copies from paternal side).
Mosaicism
If the nondisjunction occurs in the first mitotic division
instead of meiosis, of the two new cells which are formed,
one has 47 chromosomes and the other cell has 45
chromosomes. The error is perpetuated by repeated
mitotic divisions. Thus, two cell lines with 47 and 45
chromosomes are observed in the same individual. If the
nondisjunction occurs after a few mitotic division have
already occurred, more than two cell lines may be
observed, some with normal and the others with abnormal
complement of chromosomes.
Translocation
A chromosome or a segment of a chromosome may break
off from the parent chromosome and be joined to another
chromosome. This phenomenon is called translocation.
Thus one chromosome may appear shortened in this Fig. 21.2: Fluorescent signals on FISH testing. Reduction or increased
process, no loss or gain of the genetic material occurs, the number of signals indicates aneuploidy
Genetic Disorders 613
Down Syndrome are usual. There is a wide gap between the first and the
second toe (sandle gap). Figures 21.3A and B show
This is the most common chromosomal disorder occurring
characteristic facial features.
with a frequency of 1:800 to 1:1000 newborns. Chromo
some number 21 is present in triplicate, the origin of the
Other Abnormalities
extra chromosome 21 being either maternal or paternal.
In most cases the extra chromosome is from the mother. Congenital heart disease (CHD): About 40% children with
Down syndrome occurs more often in offspring of mothers Down syndrome have CHD. Endocardial cushion defects
conceiving at older age; the risk in the newborn is 1:1550 account for about 40-60% cases. Presence of CHD is the
if maternal age is between 15 and 29 years, 1:800 at 30-34 most significant factor in determining survival. All
years, 1:270 at 35 to 39 years, 1:100 at 40 to 44 years and children with Down syndrome should have a cardiac
1:50 after 45 years. This is attributed to the exposure of evaluation before 9 months of age and it should ideally
the maternal oocyte to harmful environmental influences include an ECHO.
for a longer period since graffian follicles are present in Gastrointestinal malformations: Atresias are present in
the fetal life and exist through female reproductive life. around 12% of cases, especially duodenal atresia. There
The sperm has a short life span and has therefore less is an increased risk of Hirschsprung disease.
chances of an injurious exposure.
Eye problems: There is an increased risk of cataract,
Cytogenetics nystagmus, squint, and abnormalities of visual acuity.
Routine evaluation in first year (or earlier if indicated)
Regular trisomy is found in about 94% cases of Down
and then every year is recommended.
syndrome. Approximately 1% of cases are mosaic and the
rest (5%) are due to translocations, most commonly Hearing defects: 40-60% patients have conductive hearing
involving chromosomes 21 and 14. Karyotype of the parents loss and are prone to serous otitis media (50-70% during
is only required if the affected child has translocation first year). Routine evaluation in first year and then every
Down syndrome. year is advisable. Audiological evaluation at least once
between 5-13 years and then every year is recommended.
Clinical Features and Diagnostic Considerations
Thyroid dysfunction: About 13-54% of children with Down
Patients with Down syndrome have mental and physical
syndrome have hypothyroidism. Thyroid function tests
retardation, flat facies, an upward slant of eyes and
(T3, T4 and TSH) are recommended once in the neonatal
epicanthal folds. Oblique palpebral fissure is obvious only
period/at first contact and then every year. This should
when the eyes are open. The nose is small with flat nasal
ideally include anti-thyroid antibodies specially in older
bridge. Mouth shows a narrow short palate with small
children as etiology is more likely to be autoimmune.
teeth and furrowed protruding tongue. There is significant
hypotonia. The skull appears small, brachycephalic with Atlanto-occipital subluxation: The incidence is variable,
flat occiput. Ears are small and dysplastic. There is a reported in 10-30% of cases. Lateral neck radiograph is
characteristic facial grimace on crying. Hands are short recommended once between 3-5 years, before surgery,
and broad. Clinodactyly (hypoplasia of middle phalanx for participation in special games, or earlier, if signs and
with a single flexion crease of 5th finger) and simian crease symptoms suggest cord compression.
Figs 21.3A and B: Two babies with characterstic features of Down syndrome, showing characteristic flat facies,
upward eye slant and open mouth appearance
614 Essential Pediatrics
Physical growth: Regular follow-up for height and weight natively (if the parents do not want invasive testing) an
is a must. Linear growth is retarded as compared to initial screening may be performed with maternal serum
normal, children tend to become obese with age. Special markers—PAPP-A and free |3hCG in first trimester and
growth charts for Down syndrome children should ideally serum a feto protein, human chorionic gonadotrophin,
be used. unconjugated estriol and inhibin A in second trimester. If
Muscle tone tends to improve with age, whereas the the risk of bearing a Down syndrome child is more than
rate of developmental progress slows with age. The 1 : 250, prenatal fetal karyotyping can be offered.
mainstay of management is early stimulation, physio Fetal ultrasonography helps to detect fetuses who are
therapy and speech therapy. Fortunately, social perfor at high risk for chromosomal abnormalities. Important
mance is usually achieved beyond that expected for mental findings in the second trimester which are markers of
age. Generally they behave as good babies and happy Down syndrome include increased nuchal fold thickness
children, like mimicry, are friendly, have a good sense of (measured over the occiput and not over the spine), short
rhythm and enjoy music. The major cause for early femur and humerus length and duodenal atresia. In the
mortality is congenital heart disease, and almost 50% of first trimester nuchal translucency and nasal bone are very
those with cardiac anomalies die in infancy. Chronic robust markers. Ultrasound findings help in counselling
rhinitis, conjunctivitis and periodontal disease are com specially if the parents have opted for initial screening
mon. Lower respiratory tract infections pose a threat to with maternal serum markers. Both maternal serum
life. They are more prone to develop hematological screening and fetal USG are screening techniques and
malignancies. cannot rule out Down syndrome.
Prenatal karyotyping can be done by various invasive
Counseling procedures. Chorionic villus sampling (CVS) can be
The parents of a child with Down syndrome (DS) should carried out between 10-12 weeks of pregnancy (trans-
be counseled with tact, compassion and truthfulness. cervical or transabdominal). This allows diagnosis in the
Briefly one should: first trimester. The options for the couples who come late
or opt for the initial screening with serum markers and
1. Inform about the disorder as early as possible after
ultrasonography are karyotyping by amniocentesis (16—
diagnosis is confirmed
18 weeks) or transabdominal CVS, or cordocentesis (after
2. Counsel in presence of both the parents in privacy,
18 weeks). The karyotype results are available within a
with the mother holding the baby comfortably
week with cord blood samples and direct CVS prepara
3. Talk in simple and positive language giving hope, and
tions. The results of amniotic fluid cultures take about 2-
allow sufficient time to the parents to ask questions
3 weeks. The risk of fetal loss after CVS is about 3—4% and
4. Discuss known problems and associated disorders
with cordocentesis it is about 3%. Amniocentesis poses
5. Highlight importance of early stimulation
the lowest risk of about 0.5-1%.
6. Not talk about institutionalisation and adoption,
unless asked. Both these options should be discoura Trisomy 18 (Edward Syndrome)
ged
Next to Down syndrome, this is the second most common
7. Ask the parents to contact the local Down syndrome
autosomal trisomy among live births. Frequency is about
association, if one exists
1:3000 births.
8. Talk about genetics only after chromosomal analysis.
This disorder is characterized by failure to thrive,
9. Inform about recurrence risks and possibilities of
developmental retardation, hypertonia, elongated skull,
prenatal diagnosis
low set and malformed ears, micrognathia, shield-shaped
10. Schedule future appointments.
chest, short sternum, joint abnormalities including flexion
Risk of Recurrence deformity of fingers, limited hip abduction and short
dorsiflexed hallux. Congenital heart disease is common -
Women 35 years of age or less who have a child with mostly as ventricular septal defect and patent ductus
trisomy have a 1% risk of having another, which is signi arteriosus. Most subjects have simple dermal arches on
ficantly greater than the general population. The risk is nearly all of the digits. They often have very short fourth
little increased, if any, over the usual maternal age digits with only a single crease.
dependent frequency if the mother at risk is 35 years or The mean maternal age in cases of trisomy 18 is
older. For translocations inherited from the mother, the advanced. Majority of the cases are post-mature with a
risk is about 10%, whereas it is about 4-5% when father is low birth weight. Most infants are usually feeble, and have
the carrier. limited capacity for survival. Resuscitation is often
required at birth, and they may have apneic episodes in
Prenatal Diagnosis the neonatal period. Poor sucking capability may
Parents who wish to get a prenatal diagnosis have a necessitate nasogastric feeding, but even with optimal
number of options. They can directly get a fetal karyotype management they fail to thrive. The median survival is
by chorionic villus sampling or amniocentesis. Alter about 3 months.
Genetic Disorders 615
Klinefelter Variants
As the number of X chromosomes increases beyond two,
the clinical manifestations (mental retardation, impair
ment of virilization, somatic defects such as bony
abnormalities at the elbow leading to restricted supination
and flexion) increase correspondingly.
This syndrome should be suspected in a male with
learning disabilities, language difficulties, attention deficit,
psychosocial problems with hypogonadism, small tests,
infertility and gynecomastia.
Management includes behavioral and psychosocial
Fig. 21.4B: Clinical photograph of a baby with rehabilitation. Testosterone therapy should be started in
trisomy 13 showing polydactyly middle to late adolescence with monitoring of levels.
616 Essential Pediatrics
XYY Males
The incidence of XYY males is approximately 1 in 840
newborns. They are seldom detected in childhood or
adolescence. These individuals have tendency towards tall
stature with dull mentality but IQ is usually within normal
limits. Behavioural abnormalities can be problematic
during childhood and adolescence. The initial belief of
these individuals being more juvenile delinquents does
not seem to be significant. The onset of puberty may be
delayed but most individuals are fertile. Occasionally
cryptorchidism, small penis, hypospadias, radio ulnar
synostosis, and EEG and EKG abnormalities (prolonged
PR interval) have been reported.
Turner Syndrome
Turner syndrome having 45 X chromosomal constitution,
has an incidence of about 1:3000 newborns. However, Fig. 21.5: Turner syndrome in a 10-year-old girl. Note the short neck
chromosomal studies of spontaneous abortions have and wide carrying angle
clearly shown that majority of 45 X fetuses are likely to be
aborted. The precise reason for this is not known. In this The clinical manifestations are milder in Turner
syndrome there is a considerable degree of chromosomal
syndrome mosaicism. It has been suggested that whereas
mosaicism, e.g. 45 X/46 XX. Formation of isochromosome
the loss of a whole chromosome or of the short arm of the
of long arms of X chromosome may also lead to Turner
X chromosome leads to both ovarian dysgenesis and
phenotype with 46 chromosomes because of absence of somatic abnormalities, the loss of only the long arm of the
short arms. The advanced maternal age effect is not
X chromosome results only in ovarian dysgenesis.
apparent. For this reason, it has been suggested that this
syndrome does not arise from gametic nondisjunction. Management
Height monitoring using normal growth charts for Turner
Clinical Features syndrome girls should be done. Cardiac evaluation at
The disorder may be recognizable at birth. Patients have baseline and every year is recommended. Regular
lymphedema of the dorsum of hands and feet, and there measurement of blood pressure and ECHO at baseline and
are loose skin folds at the nape of neck. Manifestations every year is advisable. Growth hormone therapy is useful
include short stature, short neck with webbing and low and may increase the final height by 8-10 cm, but decision
posterior hairline. There are anomalous ears, prominent to treat should be left to the parents as the cost of treatment
narrow and high arched palate, small mandible and is prohibitive. Counseling regarding behavioral problems
epicanthal folds. Chest is broad shield-like with widely due to short stature, amenorrhoea and sterility is an
spaced hypoplastic nipples. There is increased carrying integral part of management. Evaluation for thyroid dys
angle at elbow. Knee anomalies include medial tibial function in infancy and early childhood is recommended
exostosis. Short fourth metacarpals and metatarsals are only if growth is abnormal as compared to normal girls
seen. Later, pigmented nevi may appear. At puberty, with Turner syndrome. TSH measurement every year
sexual maturation fails to occur. Adult stature is less than should be done starting at about 10 years.
145 cm. The phenotype is highly variable. It has been Ovarian hormone replacement should be started
recommended that in all short girls diagnosis of Turner around 14 years. To start with, conjugated estrogen at 0.3
syndrome should be kept in mind. mg/day or ethinyl estradiol 5-10 mg/day used for 3-6
Associated congenital defects are common in the kidney months; then increased to 0.625 mg or 1.25 mg (conjugated
(horse-shoe kidney, double or cleft renal pelvis), heart estrogen) or 20-50 (ig/day (ethinyl estradiol). After 6
(coarctation of aorta) and ears (perceptive hearing defect). months-1 year, cyclical therapy with estrogen and proges
Congenital lymphedema usually recedes in early infancy, terone is started.
leaving only puffiness over the dorsum of fingers and toes. Regular audiometry should done in adults or earlier if
Linear growth proceeds at about half to three-fourths the indicated. Evaluation for renal malformation by USG at
usual rate. Figure 21.5 shows typical features. first contact should be done. Prophylactic gonadectomy
Genetic Disorders 617
in Turner syndrome patients with Y chromosome is recom disorders are generally milder than the recessive
mended due to chances of developing gonadoblastoma. disorders. However, physical examination of other
siblings and the parents should be done to uncover milder
SINGLE GENE DISORDERS___________________________ forms of the disorder. Homozygotes for the dominant
mutant genes usually die prenatally, as in the case of the
Drawing and interpreting a pedigree is an integral part of
gene for achondroplasia. If the child is the only affected
genetic diagnosis. Table 21.1 gives symbols used for
member, it is very likely that the observed mutation has
pedigree drawing.
occurred de novo and is not inherited. In such cases other
siblings are not likely to be affected. However, one-half
Autosomal Dominant Disorders of the offsprings of the affected individual are likely to
Generally, the autosomal dominant mutations cause faults inherit the disorder. New dominant gene mutations are
in the synthesis of structural or non-enzyme proteins, e.g. more likely to occur if the paternal age is high. Examples:
Huntington's chorea and connective tissue disorders. Neurofibromatosis, achondroplasia, Marfan syndrome,
These disorders manifest even if only one of the alleles of Crouzon disease, etc. A typical pedigree is shown in Fig.
the abnormal gene is affected. The autosomal dominant 21.6.
Comments
Contd.
618 Essential Pediatrics
Contd.
Twins attach at the same spot along the inverted T if nonidentical; if identical they branch from a short vertical
line and connected by a line.
• Symbols are smaller than standard ones and individual's line is shorter. (Even if sex is known, triangles are preferred to a
small square/circle; symbol may be mistaken for symbols given in the previous table, especially in hand drawn pedigrees)-
• If gender and gestational age known, write below symbol in that order.
Comments
If ectopic pregnancy, write ECT below
symbol
• Parents who are unaffected and unrelated may be omitted from the pedigree.
• To save space, huge pedigrees are sometimes drawn in circular or spiral form rather than in a rectangular form.
Genetic Disorders 619
that the affected male is seldom born alive. Majority of made between polygenic and multifactorial diseases. The
patients are heterozygous females (Fig. 21.9). former are due to effect of multiple genes, while the latter
have major environmental component. Examples of poly
genic disorders are: neural tube defect, cleft lip, cleft palate,
Hirschsprung disease, congenital hypertrophic pyloric
stenosis, diabetes mellitus, ischemic heart disease, hyper
tension and schizophrenia.
In multifactorial determined disease, the risk to pro
geny and siblings is higher if the malformation is more
severe, because a more severe malformation can be
looked upon as a bigger deviation from the normal
threshold, e.g. the risk of recurrence of Hirschsprung
disease in a family is higher if the aganglionic segment
of the colon is longer. When these diseases have a marked
sex predilection, the risk of recurrence in the family is
higher if the index patient belongs to the less often
affected sex. This is so, because the mutant genes are
likely to be more severe so as to produce the disease in
the sex with an inherent resistance to the disease. For
example, pyloric stenosis has a male to female ratio of 5
MITOCHONDRIAL INHERITANCE to 1. Among the children of female patients, 19% of their
sons and 7% of daughters are likely to be affected,
Mutations within a mitochondrial gene can lead to whereas in case of male patients, 5% of their sons and
phenotypic defects and show a pattern of maternal genetic 2.5% of daughters are prone to suffer from the disease.
transmission. In this type, the inheritance is maternal. All
offsprings born to an affected female will be affected. The
SOMATIC CELL (GENETIC) DISORDERS
reason is that the mitochondria are only present in ovum
and not in sperms. All affected daughters will transmit These include cancers which can arise due to genetic
the disease. Sons will be affected but will not transmit the changes in somatic cells.
disease (Fig. 21.10). Examples : Leigh disease (movement
disorder, regression, respiratory dyskinesia), and THERAPY FOR GENETIC DISORDERS
mitochondrial encephalopathy, lactic acidosis and stroke
Genetic disorders cannot generally be cured completely.
like syndrome (MELAS).
However, symptoms of many disorders can be amelio
rated and the irreversible damage or handicap can be
POLYGENIC INHERITANCE
prevented or reduced through several therapeutic
In a number of conditions, the affected individuals do not approaches.
have a sharp division between the normal and the
1. The deficiency of the metabolic end product may be
abnormal, but merely represent a spectrum of a conti
made up by replacement or administration of the pro
nuously variable attribute. Such conditions are likely to
duct. Thus, thyroxine restores the thyroid function in
be inherited by alterations in many gene loci, each of them
familial goiterogenous cretinism; cortisone suppresses
individually having only a small effect. Many of these
the excess ACTH production and androgen synthesis
conditions are also affected by numerous environmental
in adrenogenital syndrome, and administration of
factors, individually of small effect. A distinction may be
Factor VIII/IX prevents bleeding in cases of hemo
philia.
2. The intake of substances which cannot be metabolized
by the body should be reduced, especially if their
accumulation is potentially toxic; e.g. in galactosemia,
galactose cannot be metabolized adequately. As
9-rO lactose in the milk is hydrolyzed in the body to glucose
and galactose, milk in the diet of the affected infant is
substituted by non-lactose containing dietary
formulae to obviate damage due to excess of galactose
in tissues. The phenylketonuric infants placed on
restricted phenylalanine in the diet may escape
irreversible neurological damage.
Genetic Disorders 621
3. Certain drugs which precipitate adverse symptoms sive disorders. Female carriers of Duchenne muscular dys
in metabolic disorders such as barbiturates in trophy may show high serum levels of the enzyme creati
porphyria hepatica and oxidating agents in glucose-6 nine phosphokinase. Female carriers of glucose-6-phos-
phosphate dehydrogenase deficiency, should never be phate dehydrogenase deficiency can be detected by
administered in these patients. demonstrating relatively low level of enzymes in their
4. Patients with hemophilia and osteogenesis imperfecta erythrocytes. HbA2 levels for (3 thalassemia carrier status
should be protected from trauma and other environ in high risk communities is useful. Molecular techniques
mental hazards to prevent excessive bleeding and are now being increasingly used for carrier detection. In
fractures respectively. dividuals who are more likely to give birth to offspring
5. Surgery helps to reduce the functional or cosmetic with hereditary disorders can be recognized by precise
disability in many structural defects. diagnostic procedures. Genetic counseling for restriction
6. The excretion of certain toxic metabolites can be on selection of the mate or procreation, will limit the
promoted by chelating agents; e.g. penicillamine spread of the genetic disorder.
promotes excretion of copper in patients with Wilson
disease, or desferrioxamine can be used to chelate iron Genetic Metabolic Screening
in cases of thalassemia and hemochromatosis. Newborn infants are screened routinely for some inborn
7. Certain drugs may inhibit production of substances errors of metabolism in developed countries. This is of
which are accumulated, e.g. allopurinol inhibits special value for detecting the affected cases during the
xanthine oxidase and thus reduces the synthesis of uric newborn period, so that the handicap can be prevented
acid, and hence is useful in cases of gout. or minimized by early treatment, e.g. in cases of phenyl
8. Certain enzyme systems which may be immature or ketonuria, galactosemia, familial hypercholesterolemia,
reduced at certain phases of life may be induced or congenital hypothyroidism, tyrosinosis, etc.
stabilized by the use of chemical agents such as pheno- Prevention of neural tube defects (NTD) with the use
barbitone for inducing hepatic microsomal enzymes of folic acid periconceptionally has been proved beyond
like glucuronyl transferase, in cases of neonatal doubt. Four mg of folic acid taken every day one month
hyperbilirubinemia or Crigler-Najjar syndrome. before to three months after conception is recommended
9. In a number of metabolic disorders, enzymatic block for prevention of recurrence. It has also been recom
can be bypassed by administration of large quantities mended that all expectant mothers should consume about
of the coenzyme; for example, pyridoxine in homo- 0.4 mg of folic acid daily to prevent first occurrence of
cystinuria. NTD. Food fortification with folic acid is being consid
10. Enzyme replacement therapy has become a reality ered in western countries.
with the use of deficient enzyme in Gaucher disease, Prenatal diagnosis and selective termination of affected
Hurler syndrome, Morquio syndrome, Fabry disease fetuses is a successfully used modality for preventing birth
and Pompe's disease. The cost of the treatment is of affected babies and reducing the load of lethal/chroni
prohibitive. cally disabling/untreatable/difficult to treat genetic dis
11. Gene therapy is the ultimate goal for genetic disorders. orders in the community.
Though significant research has gone in this field, gene The prenatal screening/diagnostic modalities can be
therapy has been effectively tried only for adenosine noninvasive or invasive. Noninvasive techniques include
deaminase deficiency, familial hypercholesterolemia fetal inspection using ultrasonography (rarely, other
and some cancers. The aim is to introduce the normal techniques like fetoscopy, radiology or MRI are also used).
gene in the affected individual. This is done by using Fetal ultrasonography has became a very important tool
viral or non viral vectors for introducing normal for diagnosing fetal malformation with leaping improve
functioning genes. The therapy can be invivo (i.e. ments in this technology like level II/III scans and 3D
direct introduction in the body/tissues), or exvivo ultrasonography.
(when cells with the normal functioning gene are Maternal serum biochemical screening using triple
grown outside and then introduced), which is the markers test (alpha-fetoprotein, hCG and estriol) in the
preferred mode. As the exact regulation of gene second trimester (16-20 weeks) has a detection rate of
function of single gene disorders is very complex, the about 70% for Down syndrome. First trimester screening
implementation of gene therapy is complicated. using PAPP-A and free beta hCG is also widely studied
and is equally useful. Alpha-fetoprotein and estriol are
POSSIBILITIES OF PREVENTION OF low whereas hCG is high in pregnancies with Down
GENETIC DISORDERS ___________ syndrome fetuses. Alpha-fetoprotein level in maternal
blood is also a very sensitive marker for open neural tube
Carrier Screening defects, the levels being high if fetus is affected. Invasive
It is now possible to detect the carrier state in case of a prenatal testing includes chorionic villus biopsy,
large number of autosomal recessive or X-linked reces amniocentesis and cord blood sampling. The timings,
622 Essential Pediatrics
indications and risks of these techniques are summarized • To help the couples make decision by nondirective
in Table 21.2. counseling.
These samples can be used for chromosomal studies,
The essentials of counseling are:
DNA based tests or enzyme assays. Amniotic fluid is the
1. Precise diagnosis based on a detailed family history,
preferred sample for chromosomal studies and chorionic
constructing a pedigree, clinical examination and
villus tissue for DNA based tests. Many single gene
investigations. History of consanguinity is important
disorders can be diagnosed prenatally. Same examples are
to elicit.
a-thalassemia, sickle cell anemia, hemophilia, duchenne
2. Calculation of the risk of recurrence based on
muscular dystrophy, cystic fibrosis, lysosomal storage
inheritance pattern, empiric risk figures or laboratory
disorders, etc.
tests.
3. Nondirective counseling with good communication
GENETIC COUNSELING
maintaining truth and confidentiality.
Genetic counseling is a communication process, which
Points to remember:
deals with problems associated with the occurrence and
1. Hereditary diseases may manifest at the time of birth
recurrence of a genetic disorder in a family. Counseling
or several years later in life.
should be undertaken by a physician with proper under
2. All congenital defects observed at the time of birth are
standing of the genetic mechanisms. Some important
not necessarily inherited. Some of these may be due to
indications for genetic counseling are as follows:
teratogenic effect of drugs, infections or irradiation
• Known or suspected hereditary disease in a patient or during the first trimester of pregnancy.
family
3. All familial diseases are not necessarily inherited
• Birth defects in previous children
disorders. Children share not only genes, but also the
• Unexplained mental retardation/dysmorphism/
environment.
multiple malformations in a child
4. Different genetic disorders may result in similar clinical
• Consanguinity
picture. Thus several clinical syndromes, which were
• Exposure to a teratogen during pregnancy
once considered as a single entity are now known to be
• Identification of malformation(s) by ultrasonography
caused by several different genes. This is called genetic
during pregnancy.
heterogeneity. It is therefore, necessary to make a
Objectives are: precise diagnosis of the genetic disorder, to provide
• To make precise diagnosis (if possible), explaining the accurate genetic counseling.
cause and course of the disease and treatment options, 5. A degree of clinical variability exists in the presentation
if available. of certain genetic disorders. This variable expression
• To reduce anxiety/guilt. of the mutant gene is attributed to the degree of
• Providing risk figures for future offspring/relatives penetration of the gene. Thus one member of the family
based on genetic facts. may show all the features of a genetic disease, while
• To provide information about prenatal diagnostic his or her siblings may show only mild forms of the
possibilities and the risks involved. disorders with one or the other sign.
* CVS should not be done preferably before 10 weeks of pregnancy. Choice of route is an individual decision. Transabdominal
route can be used before 12 weeks also.
Genetic Disorders 623
6. Difficulty in genetic counseling may arise if the socially special care not to infuse a sense of guilt in the parents.
accepted father is not the real biologic father. In case of X-linked disorders, it will be desirable to
7. Genetic counselor should interpret the anticipated risk temper the blame on the mother, lest she is castigated
of recurrence of the inherited disorder in the future by her husband or in-laws (Indian scenario).
siblings in a meaningful manner, so that the family can
arrive at a rational decision. The counselor has a Suggested readings
particularly important responsibility in reassuring the 1. Rimori DL, Cooner JM, Pyeritz RE, Korf BR. Principles and Practice
parents that the risk of recurrence is low in case of of Medical Genetics, 4th edn., Churchill Livingstone, Philadelphia,
disorders with multifactorial inheritance. In sporadic 2006.
mutations and most of chromosomal disorders, there 2. Harper PS. Practical Genetic counseling, 5th edn. Wright
Publishers, Bristol 2004.
is only a small or no risk of recurrence.
3. Health supervision for children with Down syndrome, American
8. While conveying information to the parents the Academy of Pediatrics Committee on Genetics of Pediatrics.
physician should be extremely cautions. He should take 1994;93:855-859.
22 Inborn Errors of Metabolism
The clinical classification (Table 22.1) gives an insight into APPROACH TO METABOLIC DISORDERS
the manifestations and pathogenesis of neuromuscular
disorders (NMDs). As evident from this classification, the When to Suspect IEM
neurological deterioration can be of intoxication or energy Detection of IEM is usually delayed because the mani
deficiency type. Manifestations may differ in these two festations mimic many of the common pediatric illnesses
types of diseases. Common presentation are as follows: like neonatal sepsis and hypoxic ischemic encephalopathy.
Inborn Errors of Metabolism 625
A physician has to pick up the important clues in history, Table 22.2: Clinical pointers to neurometabolic disorders
physical examination and routine laboratory investi
Cutaneous abnormality: Perioral eruption (multiple carboxy
gations to suspect IEM.
lase deficiency), increased pigmentation (adrenoleuko-
dystrophy, decreased pigmentation (phenylketonuria).
Neonatal Period
Abnormal urinary or body odor: Musty (phenylketonuria),
IEMs should be suspected in a previously well newborn maple syrup (maple syrup urine disease), sweaty feet
presenting with lethargy, poor feeding, persistent (isovaleric acidemia, glutaric acidemia type II), cat urine
vomiting, intractable seizures, tachypnea, floppiness, (multiple carboxylase deficiency), sulphurous (homo-
unusual body/urine odor, failure to thrive, etc. where cystinuria).
other common problems like sepsis, hypoxic ischemic Hair abnormalities: Alopecia (multiple carboxylase defi
encephalopathy and hypoglycemia have been ruled out. ciency), kinky hair (Menke's disease), arginosuccinemic
If undiagnosed, these disorders are frequently fatal. aciduria, multiple carboxylase deficiency.
History of previous unexplained neonatal deaths or Dysmorphic features: Zellweger syndrome, glutaric
parental consanguinity are important clues. acidemia type II.
Ocular abnormalities: Cataract (galactosemia, Zellweger
Physical examination may reveal skin and hair changes, syndrome, homocystinuria), iris heterochromia/retinitis
cataract, hepatomegaly, jaundice, hypotonia, unexplained pigmentosa (Zellweger syndrome), KF ring (Wilson disease)
neurologic signs and coma. Presence of ambiguous Hepatomegaly: Galactosemia, glycogen storage disease
genitalia suggests congenital adrenal hyperplasia (CAH). (GSD) tyrosinemia
Acute metabolic encephalopathy is the term given to a Hepatosplenomegaly: Storage disorders - Niemann-Pick,
syndrome of lethargy, poor feeding, seizures, altered Gaucher disease, mucopolysaccharidosis
sensorium and abnormalities of tone in a child suspected Renal enlargement: Zellweger syndrome, GSD I, tyrosinemia
to be having IEM. Symptoms are absent at birth because
toxic fetal metabolites are cleared by the placenta. • It usually occurs with little warning in a previously
health individual.
Laboratory investigations like persistent/recurrent
• Early signs may be taken as behavioral problem
hypoglycemia, intractable metabolic acidosis, unexplained • Often progresses rapidly
leukopenia, thrombocytopenia (possibility of organic • Consciousness may fluctuate
acidurias) and hyperammonemia are indications for • Usually not associated with focal neurological
evaluation. deficits.
• History of recurrent similar episodes may be present
Older Children
The initial investigations in acute encephalopathy are
The onset of illness may be delayed in intermittent or shown in Fig. 22.1. Examples of acutely presenting IEMs
milder forms of IEM. Recurrent episodes of sensorial are organic acidurias, urea cycle disorders, fatty acid
derangement, vomiting, hypotonia, hypoglycemia and oxidation defects and mitochondrial disorders.
acidosis warrant investigations. Unexplained develop
2. Chronic encephalopathy: Psychomotor retardation/
mental delay with or without seizures, mental retardation,
developmental delay is the commonest manifestation of
organomegaly, coarse facies, cataract, dislocated lenses,
IEM. The retardation tends to be global and progressive.
chronic skin lesions, abnormal hair, abnormal urine color
History of regression of milestones may be present.
on standing and failure to thrive, etc. are also important
Irritability, aggressiveness, hyperactivity and lack of night
clues. Table 22.2 provides a list of some important signs
sleep are commonly associated. In addition retardation is
and symptoms seen in IEMs.
often associated with objective neurological signs like tone
changes, pyramidal or extra-pyramidal deficits. Initial
Clinical Syndromes
approach to a chronic encephalopathy is shown in Fig.
Basically IEMs can present as four types of clinical 22.2.
syndromes—neurologic, hepatic, cardiac and storage and Seizures, visual failure and extrapyramidal distur
dysmorphism. bances are signs of gray matter disease. Seizures occur
early in disease course, are associated with other
Neurologic Syndromes neurologic signs, are usually complex partial or myoclonic
Neurologic syndromes can present as acute encephalo and are resistant to conventional therapy.
pathy, chronic encephalopathy, movement disorders, Involvement of non-neural tissue like hepatospleno
myopathy and psychiatric problems. megaly gives important clue to diagnosis. Hepatospleno
1. Acute encephalopathy: This presents as an acute megaly is commonly seen in lysosomal storage disorders.
emergency and needs to be differentiated from many IEMs commonly presenting as chronic, encephalopathy
acquired conditions. Encephalopathy in acutely include neuronal ceroid lipofuscinosis, storage disorders
presenting IEM has certain characteristics. and homocystinuria.
626 Essential Pediatrics
Hepatic Syndrome
Liver involvement is seen in a number of IEMs. There are
four possible presentations:
• Jaundice may be unconjugated (G6PD deficiency,
Gilbert and Crigler-Najjar syndromes) or conjugated
(galactosemia, tyrosinemia, fructose intolerance).
• Hepatomegaly-asymptomatic hepatomegaly is
common, e.g. GSD, tyrosinemia.
• Hypoglycemia-Galactosemia, GSD.
Fig. 22.1: Approach to a newborn infant with suspected metabolic • Hepatocellular dysfunction-Galactosemia, GSD (IV
defect. NH3 ammonia, PKU phenylketonuria, NKH nonketotic and III), Niemann Pick type B, antitrypsin deficiency.
hyperglycinemia
Fig. 22.2: Approach to IEM presenting as chronic encephalopathy. HSM hepatosplenomegaly; NCL neuronal ceroid lipofuscinosis; MELAS
mitochondrial encephalopathy, lactic acidosis, stroke; XL-ALD X linked-adrenoleukodystrophy; AA aminoaciduria,- OA organic aciduria;
MLD metachromatic leukodystrophy; NPD Niemann Pick disease; MPS mucopolysaccharidosis
Inborn Errors of Metabolism 627
Cardiac Syndromes 1.
Blood investigations: Total and differential counts; blood
Serious cardiac disease has been found to be associated sugar, electrolytes, ammonia, lactate and pyruvate, liver
particularly with fatty acid oxidation defects, mitochon enzymes and arterial blood gases.
drial disorders and GSD II. Syndromes may present as 2. Urine metabolic screen: pH, ketones, odor, reducing
cardiomyopathy (GSD, fatty acid oxidation defects, substances, special urine tests such as ferric chloride,
mitochondrial disorders, methylmalonic acidemia, Fabry dinitrophenylhydrazine, nitroprusside and toluidine
disease, mucopolysaccharidosis, GM1 gangliosidosis) blue spot test.
arrhythmias (Kearns Sayre syndrome, Fabry disease) 3. Specialized tests are required for reaching a conclusive
and coronary artery disease (familial hyperchole diagnosis.
sterolemia). Table 22.3 describes tests required for diagnosis of
acutely presenting IEMs. Based on the results of four
Storage Syndromes and Dysmorphism screening tests, IEM can be classified in major categories
(Table 22.4).
Dysmorphic features in IEM, though not common, may
be characteristic in certain situation. It usually becomes
Biochemical Autopsy
more prominent with age and is associated with ultra-
structural pathological abnormalities. Mucopolysacchari In a severely ill or dying child, where a metabolic disease
dosis and peroxisomal disorders are important examples. is suspected but not diagnosed, parents should be
Storage syndromes may have dysmorphic facies along convinced about the need for a biochemical autopsy for
with organomegaly and skeletal abnormalities. confirmation of diagnosis. After taking informed written
consent, the following material should be obtained post
Laboratory Work-up mortem to facilitate diagnosis.
The investigations should be done during the episode. • Blood: 5-10 mL each in heparin (for plasma) and EDTA
Biochemical tests may be totally normal in between (leukocytes). Keep frozen at -20°C;
episodes when the child is asymptomatic. Initial routine • Urine: Obtain as much as possible (may be taken by
investigations should include: suprapubic aspiration). Keep at -20°C
Table 22.4: Four basic tests for inherited metabolic disorders therapy/peritoneal dialysis, hemodialysis, exchange
transfusion may be done to get rid of toxic metabolites.
Group Acidosis Ketosis Lactate Ammonia Diagnosis
• Specific therapy-special diets, vitamins.
MSUD
Organic Genetic Counseling and Prenatal Diagnosis
aciduria Most IEMs are inherited in autosomal recessive manner
Lactic and risk of recurrence in subsequent pregnancy is 25%.
acidosis
Few disorders are X-linked, autosomal dominant and
Urea cycle
mitochondrial in inheritance. Prenatal diagnosis is
disorder
possible by enzyme assays in chorionic villus biopsy/
NKH, sulfite
oxidase amniotic fluid, metabolites in amniotic fluid and using
deficiency, fetal DNA for molecular tests.The details are discussed in
peroxisomal Chapter 21.
disorders,
PKU, Suggested reading
galactosemia
1. Clarke TR Joe. A Clinical Guide to Inherited Metabolic Diseases.
MSUD maple syrup urine disease, NKH nonketotic Cambridge University Press
hyperglycinemia, PKU phenylketonuria 2. Scriver CR, Beaudet AL, Sly WS Valle D. The Metabolic and
Molecular Bases of Inherited Disease. 8th Edition, McGraw Hill;
Vol. 1 : 2001.
3. Carballo EC. Detection of inherited neurometabolic disorders—A
• Cerebrospinal fluid
practical clinical approach. Pediatr Clin North Am 1992;39: 801-
• Skin biopsy including dermis in culture medium or 820.
saline with glucose at 37°C 4. Leonard JV, Morris AA. Inborn errors of metabolism around time
• Liver, muscle, kidney or heart biopsy should be done of birth. Lancet 2000;356:583-7.
and tissue must be frozen 5. Ogier de Baulny H. Management and emergency treatments of
neonates with a suspicion of inborn errors of metabolism. Semin
• Clinical photograph for dysmorphism
Neonatol 2002;7:17-26.
• Infantogram for skeletal malformations.
which converts tyrosine to melanin. This accounts for 2. NIH Consensus Statement. Phenylketonuria (PKU): Screening and
management. 2000;17:1-33.
blond hair, blue iris and fair skin of the patients. Skin is
more vulnerable to minor inflammatory lesions, rashes
Tyrosinemia
and eczema. Accumulation of phenylacetic acid and other
metabolites causes characteristic musty body odor. Most commonly, there is decreased activity of the enzyme
fumaryl acetoacetate hydrolase. Tyrosine and methionine
Diagnosis levels in the blood are high (Fig. 22.4). The clinical features
include chronic liver disease and disturbances in renal
Diagnostic criteria for PKU are: (i) on a normal diet,
tubular reabsorption. The latter leads to excretion of excess
phenylalanine level in excess of 20 mg/dL/24 hr on two
phosphates in urine, along with glycosuria, proteinuria
occasions, (ii) blood tyrosine level >5 mg/dL, and
and aminoaciduria (Fanconi syndrome). Phosphaturia
(iii) presence of abnormal urinary metabolites of phenyl
results in hypophosphatemia, secondary hyperpara
alanine detected by Guthrie or ferric chloride test. In the
thyroidism and rickets.
newborn period, the diagnosis can be made by routine
These patients develop hepatosplenomegaly, hyper
screening of all neonates.
bilirubinemia and hemorrhages. Acidosis may be present.
Growth is retarded.
Treatment
Phenylalanine should be restricted in the diet of infants. Treatment
However, it should not be completely eliminated as it is
Restriction of phenylalanine, tyrosine and methionine in
necessary for normal growth. If the dietary treatment is
the diet may result in some improvement, but the effect
initiated within a few weeks of birth and blood phenyl
on liver function is not consistent and the progression
alanine levels are carefully monitored, mental retardation
persists. Inhibition of enzyme hydroxyl phenylpyruvate
may be preventable. Biochemical abnormalities, other
deoxygenase by NTBC has been shown to be of help but
neurological signs and pigmentary changes of skin and
follow-up studies are required for long-term effects. Liver
hair improve within a few weeks of starting the therapy.
transplant is the most effective therapy.
Dietary restriction must continue for about 8-10 years.
Albinism
Suggested reading
1. Cederbaum S. Phenylketonuria: an update. Curr Opin Pediatr Albinism is an inherited disorder due to deficiency of the
2002;14:702-6. enzyme tyrosinase with diminished or absent melanin in
630 Essential Pediatrics
the skin, hair and eyes. Melanocytes and melanosomes deposits irritate the articular cartilage, resulting in
are normally present, but the synthesis of melanin is degeneration and osteoarthritis like changes. Inter-
defective. The process may be generalized as in oculo vertebral disks are degenerated, spaces are narrowed and
cutaneous albinism or localized to the eye in ocular albinism. calcification occurs. Ochronotic arthritis commonly
involves shoulders and hips. Pigment deposits in the
Clinical Features kidney manifest as renal stones and nephrosis. The urine
The skin is depigmented. It does not tan but burns on shows a black reaction with Fehling or Benedict reagents
exposure to sunlight. The hair is white and silky in texture but no reaction with glucose oxidase.
and the iris is pinkish or bluish. The light passes through
the iris causing photophobia. Visual acuity is diminished Treatment
and nystagmus is often present. Intelligence remains
normal. No specific therapy is known. Administration of ascorbic
Chediak Higashi syndrome comprises oculocutaneous acid may prevent deposition of the ochronotic material in
albinism, neutropenia and susceptibility to pyogenic the cartilage but has no effect on the basic metabolic defect.
infections. Nitisinone inhibits the enzyme that produces HGA and
may prove useful.
Suggested reading
1. Moss C. Genetic skin disorders. Semin Neonatol 2000;5:311-20. Suggested reading
2. Oetting WS. Albinism. Curr Opin Pediatr 1999;11:565-71.
Phornphutkul C, Introne WJ, Perry MB, et al. Natural history of
3. Russell-Eggitt I. Albinism. Ophthalmol Clin North Am 2001;14:
alkaptonuria. N Engl J Med 2002;347:2111-21.
533^16.
Alkaptonuria Homocystinuria
Alkaptonuria is a rare metabolic disorder due to deficiency Homocystinuria is a relatively common metabolic error
of the enzyme homogentisic acid oxidase in the liver and with autosomal recessive inheritance. In the most common
kidney. This inhibits the breakdown of homogentisic acid, situation, type 1, cystathionine is not synthesized from
which is excreted unchanged in urine. Accumulation of homocysteine and serine because the enzyme cyst
homogentisic acid (HGA) leads to destruction of athionine synthetase in the liver is deficient (Fig. 22.4).
connective tissue. Although the precursor, homocysteine accumulates in the
tissues, it is rapidly oxidized to homocystine. The plasma
Clinical Features level of homocystine is elevated and it is excreted in the
The urine becomes dark on standing, especially if the pH urine. Methionine donates its methyl (CH3) group to form
of urine is alkaline. A black pigment is deposited in the homocysteine. The reaction is catalyzed by an enzyme
sclera (between the cornea and the canthi) and the ear and methyl transferase. The methyl group for this is derived
nose cartilage (ochronosis). It is rarely noticed before the either from N5 methyltertrahydrofolate or betaine which
age of 20 to 30 years. The pigment in ochronosis is is a derivative of choline. Thus methionine level in the
probably a polymer of homogentisic acid. Pigment blood is elevated.
Inborn Errors of Metabolism 631
Clinical pointers to specific organic acidurias administration of non-absorbed antibiotics can reduce the
production of propionate by gut bacteria. The various
• Cutaneous abnormalities: Perioral eruption (multiple
cofactors and adjunctive therapy is detailed in Table 22.5.
carboxylase deficiency)
• Abnormal urinary or body odor: Maple syrup/burnt
sugar [maple syrup urine disease (MSUD)], sweaty feet DISORDERS OF UREA CYCLE
[isovaleric acidemia (IVA)], cat urine (multiple Catabolism of amino acids leads to production of free
carboxylase deficiency)
ammonia. Ammonia is converted into urea through the
• Hair abnormalities: Alopecia (multiple carboxylase
five steps of urea cycle (Fig. 22.5). Two moles of ammonia
deficiency), kinky hair (multiple carboxylase deficiency)
are excreted as 1 mole of urea per cycle, at a net cost of 3
• Dysmorphic features: Mevalonic aciduria and 3-OH-
isobutyric aciduria moles ATP. Urea cycle may be blocked at any stage.
• Hypoglycemia and neurological symptoms: Organic Deficiency of any of the five enzymes in the urea cycle
acidurias including late onset MSUD results in the accumulation of ammonia (> 200 |amol/L)
• Acute ataxia: Late onset MSUD, methylmalonic acidemia and leads to encephalopathy. A defect in the stage III
(MMA), IVA, multiple carboxylase deficiency results in citrullinemia; stage IV defect causes arginino-
• Acute metabolic encephalopathies: Glutaryl-CoA succinic acidemia. Hyperargininemia results from the
dehydrogenase deficiency, IVA, MSUD, MMA, multiple metabolic block in the last stage of the urea cycle.
carboxylase deficiency, propionic aciduria
• Acute hemiplegia and metabolic disease (metabolic Clinical Features
stroke): MMA and propionic acidemia (PA), glutaric
aciduria type 1, methylcrotonyl-CoA carboxylase All metabolic defects of urea cycle, whether due to
deficiency accumulation of ammonia (I and II stage), citrulline (III
Galactose-1 -Phosphate Uridyl glucose is utilized and blood glucose level falls, the
Transferase Deficiency glycogen in the liver is depolymerized, the bonds at branch
It is an autosomal recessive disorder manifesting within a points are split and free glucose is released into the blood
few days or weeks after birth (after ingestion of milk). by hydrolytic dephosphorylation. The final reaction is
The physiological jaundice of the newborn period persists mediated by the enzyme glucose-6-phosphatase. The
longer than usual. The liver is enlarged and cataract series of reactions causing release of glucose are called
appears within a few weeks. There is evidence of liver glycogenolysis (Fig. 22.7).
dysfunction. The children become mentally retarded. Theoretically, there may be a deficient synthesis of
Vomiting, diarrhea and failure to thrive are early and glycogen or glycogen may be stored excessively in the liver
common manifestations. The mechanism of toxicity is and other tissues due to inadequate depolymerization. In
obscure, but cataract is believed to be due to accumulation some types, glycogen may have an abnormal chemical
structure.
of galactitol. Mental retardation and hepatic cirrhosis are
attributed to galactose-l-phosphate. Several well-defined disorders of glycogen metabolism
have been described (Table 22.6). These are numbered
Galactokinase Deficiency
Manifestations are milder. Mental retardation, liver Table 22.6: Enzymatic deficiencies in glycogenesis
damage and cachexia do not occur. The only significant
Type 1 Glucose-6-phosphatase
abnormality is cataract due to accumulation of galactilol.
Type II Lysosomal alpha-1, 4-glucosidase (acid and
neutral maltase)
Treatment
Type III Amylo-1, 6-glucosidase or oligo-1, 4-1,4-glucano-
Galactose free diet, if started early, leads to rapid clinical transferase (debrancher enzyme)
improvement and prevents further damage. Mental Type IV Alpha-1, 4 glucan:alpha-l, 4 glucan-6-alpha
retardation (classical galactosemia), if already present does glucosyl tranferase (brancher enzyme)
not improve with therapy. Type V Muscle phosphorylase
Type VI Liver phosphorylase
Glycogen Storage Disorders Type VII Phosphofructokinase
Type VIII Phosphoglucose isomerase
A major part of ingested carbohydrate is absorbed as
Type IX Phosphorylase kinase
glucose via the portal system. The glucose is phos- Type X Phosphorylase kinase
phorylated to several intermediate compounds (glucose- Type XI 3, 5-cyclic AMP dependent kinase
6-phosphate and glucose-1-phosphate) and is ultimately Type XII Phosphoglucose isomerase
stored as glycogen. Glycogen is an extensively branched Type XIII Triose phosphate isomerase
polysaccharide formed by glucose units linked together Type XIV Phosphoglycerate mutase, M isoenzyme
by alpha 1^4 and alpha 1-6 bonds. When the peripheral
636 Essential Pediatrics
according to the sequence of their discovery. However, it glycemia, because there is no defect of dephosphorylation.
may be more convenient for the physician to consider Prognosis is relatively better. Usually, these patients
these according to the principal organ involved. present with isolated massive hepatomegaly and
deranged liver function. Patients should be treated with
Disorders in which Liver is high protein and low fat diet. Small frequent feeds are
the Main Affected Organ preferable. Intercurrent infections should be treated
These include type I (von Gierke disease), type III (Forbes promptly.
or limit dextrinosis), type IV (amylopectinosis) types VI,
VII, IX and X. Treatment
In type I GSD the usual clinical features include hepato Carbohydrate metabolism in liver is responsible for
megaly, failure to thrive, hypoglycemia, ketosis and acido glucose homeostasis. Treatment is designed mainly to
sis. Hypoglycemia becomes worse after overnight fasting maintain normoglycemia and is achieved by continuous
and is attributed to the inability of the liver to release nasogastric infusion of glucose or oral uncooked starch.
glucose in the blood. Consequently free fatty acids are Depending on the response frequent day time feeds and
mobilized excessively to provide for the energy needs of continuous nasogastric feeding at night may be given.
the body. This results in hyperlipemia in type I. Adminis Uncooked starch acts as a slow release form of glucose.
tration of glucose ameliorates ketosis. In type I, the blood This is specially useful in type I, III and IV but most
glucose level does not rise on administration of glucagon. demanding in type I. Enzyme replacement therapy is
available for type II GSD.
Disorders in which Cardiac Muscle is Affected
Type lla (Pompe disease): Signs and symptoms of this disease Suggested reading
result from lysosomal storage of glycogen in skeletal 1. Clayton PT. Inborn errors presenting with liver dysfunction. Semin
muscles, cardiac muscles and central nervous system. The Neonatol 2002;7:49-63.
heart is enlarged and appears globular. Electrocardiogram 2. Wright EM, Turk E, Martin MG. Molecular basis for glucose-
galactose malabsorption. Cell Biochem Biophys 2002;36:1
shows left axis deviation, short PR interval and large QRS.
15-21.
Heart failure with dyspnea and cyanosis may occur.
Skeletal muscles show hypotonia and marked weakness.
LYSOSOMAL STORAGE DISORDERS
The tongue is large and protruding. Death usually occurs
before the age of 1 year. The diagnosis is suggested by This comprises of a group of about 40 disorders. Deficiency
low levels of the enzyme acid maltase in leukocytes, liver, of a lysosomal enzyme may result in impaired intralyso-
muscles and fibroblasts. Enzyme replacement therapy is somal degradation of exogenous and endogenous macro
available and very effective but the cost is prohibitive. molecules and deposition of these metabolites in several
body tissues. Enzyme deficiencies in the degradation
Disorders with Skeletal Muscle Involvement pathway of glycosaminoglycans cause mucopoly-
Type lib, type III (Forbes or limit dextrinosis), type V sacchariosis, and deficiencies affecting glycopeptides
(McArdle disease), type VII. These patients show muscular cause glycoproteinosis. In glycolipid storage disorders,
hypotonia, weakness, easy fatiguability and muscle sphingolipid degrading enzymes are deficient. About two-
cramps. third of these storage disorders are due to glycolipid
storage. All of these except Hunter syndrome (MPSII) and
Disorders with Abnormal Structure of Glycogen Fabry disease (which are X-linked) have autosomal
In most disorders of glycogen metabolism, the glycogen recessive inheritance.
structure is normal except in two conditions viz. debrancher Accumulation of lipid inside the cells gives them a
enzyme deficiency (limit dextrinosis, Forbes disease type foamy appearance. Foamy cells appear in liver, spleen,
III) and brancher enzyme deficiency (Type IV Anderson lungs and marrow, resulting in enlargement of these
amylopectinosis). In type III or limit dextrinosis, the organs. In some types of glycolipid storage disorders,
enzyme necessary for cleavage of branch point bonds is neurological functions are impaired due to abnormal
deficient. As a consequence, there are excessive branch deposition in the brain. Some of the common disorders
points on the glycogen, which is therefore abnormal. are discussed below. Table 22.7 depicts the enzymatic
In type IV, the brancher enzyme is deficient. As a result deficiencies and important features of common lysosomal
the glycogen molecule has excessively long inner and storage disorders.
outer chains with very few branch points. These patients
do not develop ketosis. Clinical features are primarily Mucopolysaccharidoses (MPS)
related to liver and lead to early cirrhosis. Type III is more Mucopolysaccharides consititute a major part of connec
common than the type IV. Type III may simulate von tive tissue and consist of units of disaccharides, nitrogen
Gierke disease (type I), but can be easily distinguished by and easter sulfate groups. In mucopolysaccharidoses, acid
galactose infusions, which promptly causes hyper mucopolysaccharides are abnormally deposited in the
Inborn Errors of Metabolism 637
tissues and excreted in the urine. Acid muco Inheritance is autosomal recessive in all the types of
polysaccharides yield N'acetyl-hexosamine (a substituted mucopolysaccharidosis except type II which is X-linked
sugar) and uronic acid. Neutral mucopolysaccharides recessive.
comprise N'acetyl hexosamine and a hexose. Major acid
mucopolysaccharides are hyaluronic acid, chondroitin 4- Clinical Features
sulfate, chondroitin 6-sulfate, dermatan sulfate, heparin
Mental retardation is severe in type III and VII, moderate
sulfate and heparin. Keratan sulfate (of cornea or bones)
in type I, mild in type II, rare in type IV (Morquio) and IS
is a neutral mucopolysaccharide. The sulfated muco
(previously called type V). It is absent in type VI
polysaccharides are linked with protein to form macro (Maroteaux Lamy).
molecules. Due to lack of degradation, mucopolysaccha
rides accumulate in the lysosomes causing disorganization Cloudy cornea is observed in types I, IS and VI but it may
of the cell structure and function. Partially degraded occur in some cases of type IV, cloudiness of cornea is
mucopolysaccharides are excreted in the urine. At least 8 minimal in type III, but is not seen in type II.
genetic variants of mucopolysaccharidosis are recognized. Bone changes are most marked in type IV, marked in type
Their clinical features are summarized in Table 22.8. I, II, VI and VII but are mild in types III and IS. The type
of skeletal changes observed include the following:
Metabolic Defect Thickening of the skull, marked deformity of the sella
1. Accumulation of dermatan sulfate and heparan sulfate turcica, broad spatula like ribs, beak shaped vertebrae
in the tissues and their excretion in the urine occurs in especially around the LI vertebra and heavy bones of the
Hurler syndrome (type IH), Scheie syndrome (type IS), hands.
Hunter syndrome (type II) and type VII. In Morquio disease (type IV) the trunk is short with
2. Heparan sulfate accumulates in tissues, and is excreted flattened narrow vertebrae, barrel shaped chest with
in the urine in Sanfilippo disease (type III A and B). sternum protruding forwards. Other features include
3. Keratan sulfate and chondroitin sulfate are excreted in short neck, broad mouth, widely spaced teeth, prominent
the urine in cases of Morquio syndrome (type IV). maxilla and hands reaching up to knees.
4. Dermatan sulfate is excreted in the urine in Maroteaux- Facies are coarse in type IH, the lips are thick, tongue is
Lamy syndrome (type VI). enlarged, teeth are peg-like and widely separated. Bridge
5. Excretion of keratin sulfate like material in the urine of the nose is depressed. The features are very coarse and
and accumulation in the tissue occurs in type VIII. may be mistaken with cretinism.
Hurler/IH + + + + +
Scheie/IS - - - - +
Hunter/II + + + +
Sanifilipo/III + - - - -
Morquio/IV - + +
Maroteaux-Lamy/VI - - - + +
Sly/VII + +
638 Essential Pediatrics
Hepatosplenomegaly is present in types I, II, VI and VII Diagnosis is made by testing urinary excretion of
and multiple sulphatase deficiency. glycosaminoglycans (GAG) and specific enzyme assays.
Figure 22.8 shows a classical facies of MPS I and Fig.
22.9 shows important skeletal changes. Treatment
Enzyme replacement therapy is available for type I and
type VI but the cost is prohibitive. Trials are on for other
types of disease. Bone marrow transplantation has been
found to be effective in MPS I and VI.
Suggested reading
1. Froissart R, Moreira da Silva I, Guffon N, et al. Muco
polysaccharidosis -genotype/phenotype aspects. Acta Paediatr
2002;91:S82-7.
2. Rigante D, Segni G. Cardiac structural involvement in mucopoly
saccharidoses. Cardiology 2002;98:18-20.
3. Saxonhouse MA, Behnke M, Williams JL, et al. Muco
polysaccharidosis Type VII presenting with isolated neonatal
ascites. J Perinatol 2003;23:73-5.
Gaucher Disease
Gaucher disease is a relatively common metabolic disorder
with autosomal recessive inheritance. There is deficiency
of the tissue enzyme glucocerebrosidase which splits glucose
from glucosyl ceramide. As a result, glucosyl ceramide, a
cerebroside, accumulates in the cell of reticuloendothelial
Fig. 22.8: Hurler syndrome system. The cerebroside laden cells are large and have
eccentric nuclei; the cytoplasm appears like crumpled silk
(■Gaucher cells).
Clinical Features
The spleen is always markedly enlarged and there are
signs of hypersplenism, e.g. leucopenia and thrombo
cytopenia. The liver is enlarged and the marrow cavity is
widened, due to deposits of Gaucher cells. Expansion of
the bone is prominent, especially at the lower end of the
femur and humerus. Diagnosis is made by doing
glucocerebrosidase enzyme levels in leucocytes or skin
fibroblasts.
Treatment
This was the first storage disorder for which the treatment
became available. Enzyme replacement is done with
natural or recombinant glucocerebrosidase. It is effective
but expensive. Bone marrow transplantation is another
Fig. 22.9: Typical radiological findings of MPS. Note beaking of treatment option. OGT-918 slows the rate of accumulating
vertebrae and proximal tapering of metacarpals glycolipids and is under trial.
Inborn Errors of Metabolism 639
crenated thorny erythrocytes (acanthocytes), malabsor normal population are PiM type. Their alpha-l-antitrypsin
ption of fats, retinitis pigmentosa and neurological signs level ranges between 0.8 to 1.8 g/L.
of ataxia, tremors, athetosis, and loss of vibration and
position sense. Though fats are normally digested and Deficiency
assimilated through the intestinal mucosa, these cannot
Deficiency leads to retention of abnormal polymerized a-
be transported to plasma from there because of the
1-antitrypsin in hepatocytes; emphysema results from
inability to form chylomicrons. Lipoproteins may be
alveolar damage. At least 24 alleles of the gene have been
necessary for the transport of some essential nutrients to
recognized. PiZ mutant is responsible for majority of cases.
erythrocytes. Therefore their absence may interfere with
The alpha-l-antitrypsin concentration is usually below 0.6
the synthesis of red cell membrane, thus causing g/L in PiZ and nil in those with Pi null. Other homozygous
acanthocytosis. Pathogenesis of the eye and brain changes and heterozygous states have intermediate levels.
is obscure.
Suggested reading
Clinical Manifestations
1. Finch LA, Nowicki MJ, Mitchell TE, et al. Abetalipoproteinemia. J Clinical manifestations in childhood include late
Pediatr Gastroenterol Nutr 2001;32:310,315. hemorrhagic disease of infancy, cholestasis or chronic liver
2. Ohashi K, Ishibashi S, Osuga J, et al. Novel mutations in the disease. Lungs are affected in adulthood. Glomerulo
microsomal triglyceride transfer protein gene causing abetalipo nephritis, vasculitis and panniculitis are the other rare
proteinemia. J Lipid Res 2000;41:1199-204.
manifestations. Diagnosis can be made by estimating
3. Padma MV, Jain S, Maheshwari MC. Abetalipoproteinemia in an
Indian family. Indian J Pediatr 1996;63:263-9. serum levels, genotyping and Pi phenotyping.
PEROXISOMAL DISORDERS
Treatment
Replacement therapy with intravenous a-l-antitrypsin
Peroxisomes are subcellular organelles. A number of
improves the serum levels but is of little benefit in infants
enzymatic reactions such as oxidation of long chain fatty
with liver disease; though it can prevent or treat lung
acids, catalases and phytanic acid occur in these. Zellweger
disease in adults. There are promising early results with
syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and
gene therapy. Efforts are on to move polymerized a-l-
infantile Refsum disease (IRD) are clinically overlapping
antitrypsin from liver to lung where it might be beneficial.
syndromes, collectively called peroxisome biogenesis
Liver replacement therapy has been used successfully for
disorders, with clinical features being most severe in ZS
severe liver injury. An increasing number of patients with
and least pronounced in IRD. Inheritance of these
severe emphysema have undergone lung transplantation.
disorders is autosomal recessive. The peroxisome
biogenesis disorders are genetically heterogeneous, Suggested reading
having at least 12 different complementation groups (CG).
1. Pashankar D, Schreiber RA. Neonatal cholestasis: a red alert for
The gene affected in CGI is PEX1. Approximately 65% of the jaundiced newborn. Can J Gastroenterol 2000;14:67D-72D.
the patients harbor mutations in PEX1. 2. Perlmutter DH. Alpha-l-antitrypsin deficiency. Semin Liver Dis
These multisystemic disorders are characterized by 1998;18:217-25.
invariable neurological involvement. Symptoms include 3. Primhak RA, Tanner MS. Alpha-1 antitrypsin deficiency. Arch Dis
Child 2001;85:2-5.
seizures, nystagmus, hearing defects, progressive upper
motor neuron deficits and neurologic deterioration, optic
atrophy and adrenal atrophy. MRI demonstrates white Wilson Disease
matter changes in brain. Urinary organic acid analysis is Wilson disease is a inborn error of copper metabolism
indeed useful for screening subjects with peroxisomal autosomal recessive inheritance; the defective gene is
disorders. mapped to chromosome 13. Either the lysosomal copper
is excreted in insufficient quantities in the bile or the
Suggested reading binding of copper by metallothionine is increased four fold
1. Barth PG, Gootjes J, Bode H, et al. Late onset white matter disease due to aberrant chemical structure of this intracellular
in peroxisome biogenesis disorder. Neurology 2001;57:1949-55. storage protein copper.
2. Raymond GV. Peroxisomal disorders. Curr Opin Neurol
2001;14:783-7. Copper accumulates in the cytoplasm of liver cells,
reaching a level of 500 to 2000 pg/g of dry weight. Liver
MISCELLANEOUS DISORDERS cells are damaged, copper is released in the serum and
then deposited in other tissues and cells. Red blood cells
Alpha-1-Antitrypsin Deficiency are damaged, resulting in hemolysis. Proximal renal
a-l-antitrypsin, a protease inhibitor (Pi), is synthesized tubules are affected. The toxic effects of copper on the brain
in the liver and protects lung alveolar tissues from cells cause neurologic disturbances. Deposition in the
destruction by neutrophil elastase. Over 70% of people in cornea results in Kayser-Fleischer rings.
Inborn Errors of Metabolism 641
Low serum levels of ceruloplasmin are characteristic. level is less than 20 mg/dL and serum copper concen
This is probably secondary to hepatic damage and not the tration is below 20 pg/dL. More than 100 pg of copper is
primary metabolic defect as was believed earlier. As most excreted in the urine in 24 hours. Urinary copper estima
of the copper in serum is bound to ceruloplasmin, total tion is usually done with a penicillamine challenge. Liver
serum copper level is reduced. copper concentration exceeds 250 pg/g of dry weight.
Liver function tests are abnormal.
Clinical Features Low serum copper and ceruloplasmin levels are not
The clinical presentation can be extremely varied, viz. characteristic of Wilson disease in infants up to the age of
acute or chronic liver disease with or without neurological 6 months and in patients with nephrosis, kwashiorkor or
disease, psychiatric problems, bony deformities, hemolytic severe malabsorption syndrome. Serum copper levels are
anemia and endocrine manifestations. increased in biliary cirrhosis and toxic cirrhosis.
642
Eye Disorders 643
- Sickle cell disease Kays symbols, tumbling E or HOTV card tests where one
- Syndromes with ocular manifestations relies on the child's ability to recognize the shape and match
- Family history of non-traumatic childhood blindness the shape with a similar one on a card. Children
• Signs or symptoms of eye problems reported by the family, 5 years or older can be tested with more conventional vision
health care provider or school teacher testing methods using a Snellens visual acuity chart with
- Defective ocular fixation or visual interactions either alphabets or tumbling E or Landoldts C symbols.
- Abnormal appearance of the eyes Ocular movements and external examination of the eye
- Squinting or tendency to close one eye in certain can be performed by using adequate illumination with a
situations torch and aided by toys or colorful pictures to capture the
child's attention and interest to cooperate with the
- Any obvious ocular alignment, movement abnor
examiner. Pupillary reactions must be tested and fundus
mality, head tilt or nystagmus
examination should be attempted with a direct ophthal
- Large and/or cloudy eyes
moscope through the undilated pupil to view the disc and
- Drooping of the eyelids
macula. In case required, for more detailed eye exami
- Lumps or swelling around the eyes nation of the fundus and retinal periphery, the pupils can
- Persistent or recurrent tearing, sticky discharge, be dilated with mydriatic eye drops such as 2.5% phenyle
redness, itching or photophobia phrine or short acting cyloplegic-mydriatic drops such as
- Learning disabilities or dyslexia tropicamide 0.5% or cyclopentolate 1% eye drops. The
retina is best viewed with an indirect ophthalmoscope as
Guidelines for Examination this gives the maximum field of view and the examination
Children are best examined in a comfortable and friendly can be completed efficiently. In general, as far as possible,
environment. Very young children can remain in the lap most of the examination should be completed without
of their mother while older children can be distracted with touching or going too close to the child so that the child is
toys and colorful objects. When the child first enters the comfortable and does not feel intimidated. Once, one has
room, simple observation of behavior, fixation, movement gained the trust and confidence of the child, one can
and general awareness of the surroundings are good attempt further examination such as digital assessment of
indicators of the child's general visual status, and any the intraocular pressure, eversion of the lids, slit lamp
examination, etc. In certain situations, an examination
gross abnormalities can be detected.
Steady fixation and uniform steady alignment of the under anesthesia is required and should be done only after
eyes develops in the first 4-6 weeks. Visual acuity obtaining the parents' informed consent after explaining
assessment in children less than 6 months of age is limited why the procedure is to be done and what exactly is
to seeing if the child attempts to fix and follow light. A planned.
child 6-12 months of age can follow and even reach out
CONGENITAL AND DEVELOPMENTAL
towards colorful objects and this permits a very crude
ABNORMALITIES_________ __________________________
assessment of gross visual ability. A more objective
assessment can be made with electrophysiological tests This group of diseases may or may not manifest at birth.
using a pattern-induced visual evoked response using If the disease is detected at birth it is 'congenital' such as
chequered patterns of varying degrees of resolution lid coloboma, severe corneal opacity, total cataract with a
(pattern VER) or by observing the optokinetic response white opaque lens, etc. Sometimes the disease is present
or nystagmus induced by the child's attempt to view a at birth, but detected later on, for example a partial cataract
striped pattern on a moving drum (OKN nystagmus). or mild congenital glaucoma. Sometimes the disease is a
Both these tests are an assessment of the resolution acuity defect of development but manifests later, such as
or power of the eye to distinguish patterns of varying developmental cataract or juvenile glaucoma.
degrees of separation or width. However, both tests are
Disorders in Development of the Whole
expensive and not readily available in routine clinics so
Eyeball (Globe Abnormalities)
are practically only used at tertiary levels of care. For
most preverbal children up to the age of 3 years, a simple A child may be born with a small eye (microphthalmos or
observation of fixation pattern and behavior, ability to nanophthalmos), absent eyeball (anophthalmos) with or
see, follow or pick up small objects like toys or candy without an orbital cyst, or more complex abnormalities
beads, preferential looking tests using Teller acuity cards associated with craniofacial dysgenesis.
or preferential looking cards are used to estimate the
visual status. Unilateral loss is also tested for by observing Abnormalities of Development of the Orbit,
if the child resists closure or occlusion of one eye over Eyelids and Adnexa (Lacrimal Drainage System
the other. and Glands)
Vision of children 3-5 years of age can be assessed using Children are sometimes born with the eyes completely
picture tests and symbols with matching cards such as the covered by the eyelids so that the globe is not apparent or
Eye Disorders 645
Musculoskeletal, Neurodegenerative
Diseases and Phakomatoses
Fig. 23.4: ‘Leokocoria’ or white pupil in an infant. Note the white
Marfan and Ehlers-Danlos syndromes may be associated appearance is seen to be from a structure more posteriorly, has a
with subluxated lenses and possible consequent secondary slight yellowish pinkish tinge due to vascularization and the
glaucoma. Marfan syndrome is usually associated with appearance is unlike that seen due to a cataract. An ultrasonography
upward and outward displacement of the lenses and can confirm the diagnosis straight away as to the site of origin and the
myopia with consequent blurred vision. Retinal detach nature of the lesion. The diagnosis is retinoblastoma and this
appearance should not be mistaken for a cataract. An immediate
ments are also common. Surgical lens removal becomes
referral to a tertiary care centre with an explanation to the parents
necessary if the vision is non-correctible with spectacles
about the possible etiology is mandatory to ensure prompt diagnosis
or contact lenses. Leukodystrophies and demyelinating
and treatment of this potentially life-threatening disease. A CT scan
diseases may be associated with extra-ocular muscle to demonstrate calcification and map the extent of the tumor,
weakness, ptosis and optic neuropathy. Phakomatoses like screening of the other eye and siblings will form part of the
neurofibromatosis, Sturge-Weber syndrome and nevus of management protocol. Depending on the size, extent and spread of
Ota may be associated with cafe au lait spots and plexiform the tumor, treatment options include enucleation, local treatment with
neurofibromas of the lids and orbit, Lisch nodules on the laser or radiotherapy, and systemic chemotherapy
iris and glaucoma.
Local muscular dystrophies or degenerations such as
prescribed accordingly. Associated amblyopia or
chronic progressive external ophthalmoplegia result in
strabismus must be taken care of and any additional
ptosis and restriction of eye movements. Duchenne
features like nystagmus or extraocular muscle imbalance
muscular dystrophy may be associated with cataracts.
ruled out. Patients need to be carefully monitored with
respect to improvement of vision with spectacles and
Tumors and Neoplastic Diseases
compliance with follow up. Failure to show an improve
Benign tumors include dermoids of orbit, lids or on cornea; ment of vision with spectacles warrant further investi
hamartomas, osteoma, vascular malformations or heman gations to rule out any associated subtle pathology such
giomas of various types and neurofibromas. Malignant as microstrabismus, retinal macular degeneration, retinitis
intraocular tumors are confined to retinoblastoma, pigmentosa, congenital hereditary cone dystrophy,
juvenile xanthogranuloma, medulloepithelioma and delayed visual maturation, dyslexia, Leber's amaurosis,
metastatic lesions from neuroblastomas, Ewings sarcoma, etc.
leukemias and lymphomas. Orbital tumors include
rhabdomyosarcoma, Langerhans cell histiocytosis, STRABISMUS AND AMBLYOPIA____________
extraocular spread of retinoblastoma, metastatic spread
Strabismus is defined as the condition when the visual
of Ewings sarcoma, neuroblastoma, leukemias and
axes of the two eyes do not meet at the point of regard. In
lymphomas (Fig. 23.4).
other words, the motor and sensory alignment of the two
eyes and their images in the brain are not synchronized.
REFRACTIVE ERRORS______________ ________________
The cause may be a basic abnormality of development as
An abnormality in the refractive and focusing apparatus in essential esotropia or exotropia (concomitant or
of the eye thereby making it difficult for parallel rays of comitant squint when the angle of deviation or separation
light from the distance to be accurately focused on the of the two eyes is uniform, irrespective of the direction or
retina is a deviation from the normal emmetropic state position of gaze) or secondary to extraoocular muscle
and is termed as 'ametropia' or refractive error. This paralysis, i.e. paralytic squint, local orbital space
manifests usually as poor or blurred vision which may be occupying lesion, myositis or orbital inflammation as in
noticed by parents, relatives, friends, school teachers or orbital pseudotumor syndrome, orbital musculofascial
reported by the child as a difficulty in viewing clearly. abnormality like Duane's retraction syndrome or Brown's
Sometimes, indirect evidence is reported as 'eye rubbing', superior oblique tendon sheath syndrome (incomitant or
'squinting', 'going too close to the television, holding non-concomitant squint where the deviation is more in
objects too close to the eyes, etc. An assessment of visual certain positions and less or even absent in some positions
acuity followed by cycloplegic refraction and fundus of gaze).
evaluation is required in addition to routine ophthalmic An inward deviation of the eye is termed esotropia and
evaluation. Refractive errors may be myopia, hyper outward deviation is termed exotropia. The child initially
metropia and astigmatism and spectacles must be suffers diplopia due to the different images being
Eye Disorders 649
presented to the visual cortex by the two eyes, but learns years old as there are significant problems of change in
to suppress one image eventually developing amblyopia lens power requirements as the maximum growth of the
or a 'lazy eye' with a loss of binocularity and stereopsis. eyeball takes place during the first two years of life as
Very young children will not report their symptoms and also higher risk of complications of glaucoma and
presence of an intermittent or constant squint or intraocular inflammation and fibrosis. In very young
misalignment of the eyes should be indications for referral children, therefore, a capsule rim is left for subsequent
to an ophthalmologist. secondary IOL implantation and temporary optical
Amblyopia or 'lazy eye' is a condition of subnormal rehabilitation is provided with spectacles or contact lenses
vision defined as two lines less than normal or less than supplemented with patching for amblyopia in unilateral
the fellow eye on the visual acuity chart with no cases (Fig. 23.5).
anatomical cause detectable on examination, i.e. no media
opacity and a normal fundus. Amblyopiogenic factors GLAUCOMA
have their maximum impact on the immature developing
Primary congenital and developmental juvenile glaucoma
visual system, i.e. during the first 6 years of life and
are now recognized to be inherited diseases. Primary
include sensory deprivation or abnormal binocular
congenital glaucoma is associated with CYP1B1 gene
interaction. The former would refer to a corneal opacity
(2p21) which had a predominantly autosomal recessive
or cataract which, even if taken care of surgically, do not
mode of inheritance, and mutations in the myocillin
indicate good chances of restoration of normal vision.
(MYOC) gene. Photophobia, blepharospasm, watering
Similarly abnormal binocular interaction occurs in the
and an enlarged eyeball are classic symptoms. Suspicion
presence of strabismus or anisometropia (difference in the
of glaucoma or buphthalmos warrants urgent referral to
refractive power of the two eyes), in which case, one eye
takes over and the visual cortical neurons meant to
receive stimuli from the other eye are unable to develop
normally leading to a 'lazy eye'. These changes are
potentially reversible with appropriate therapy in the first
decade, but become irreversible and permanent if left
uncorrected. Treatment involves first restoration of clear
vision with correction of any refractive error with
spectacles, removal of any media opacity if present such
as corneal opacity (by corneal transplantation) or cataract
(cataract removal with intraocular lens implantation or
other appropriate optical correction), patching therapy by
part time patching of the 'good' eye to enable the 'lazy'
eye to catch up and strabismus surgery to restore ocular
alignment if required.
CATARACT_________________________________________
A visible lenticular opacity in the eye is termed as a
cataract. It is congenital if present since birth,
developmental if appears later on and traumatic if occurs
after an episode of eye trauma. A central opacity is
onsidered visually significant if it impairs visual acuity
and on clinical assessment is obstructing a clear view of
the fundus. A cataract may be unilateral or bilateral and
then symmetric or symmetric. In view of the risk of sensory
deprivation amblyopia, visually significant cataract
should be treated surgically as soon as possible after birth. Fig. 23.5: A child with bilateral developmental cataract. Note that
Functional success is highest if operated within the first the cataract is partial so as the child had some vision, the parents did
not notice the problem till it was pointed out by the school teacher
few weeks after birth, provided the child is medically fit
to have the eyes tested. The child has a cataract in both eyes visible
to undergo general anesthesia. Unilateral cataracts must
as a whitish opacity behind the pupil. Also note that the child has a
be supplemented with postoperative patching therapy to
convergent squint. The child also has impaired hearing and congenital
take care of any amblyopic effect. Optical and visual heart disease, suspected to be due to congenital rubella syndrome.
rehabilitation for the aphakic state resulting from lens Proper immunization of the mother for rubella would have prevented
removal includes the implantation of an intraocular lens this disabling ocular and systemic disease and further emphasizes
(IOL) for children above two years of age. Generally the importance of proper community coverage by immunization
intraocular lenses are avoided for children less than two programs.
650 Essential Pediatrics
an ophthalmologist. An examination under anesthesia is in the exposed uveal tissue hitherto protected from direct
required to measure the corneal diameter, the intraocular access to lymphatic drainage (Figs 23.6A and B).
pressure and visualize the optic disc. Once glaucoma is
confirmed, medical therapy to lower the pressure is started RETINAL DISEASES
and patient prepared for surgery. If the cornea is clear
Children can be affected by a wide variety of retinal
enough to allow visualization of the angle structures, a
diseases. Retinal detachment can occur secondary to
goniotomy is attempted. If the glaucoma is more severe
trauma or spontaneously in cases with high or patho
or the cornea very edematous, a glaucoma drainage
logical myopia. Classical symptoms such as sudden loss
procedure for opening of alternative aqueous drainage
of vision with floaters and photopsia may not be reported
channels such as a trabeculectomy and trabeculotomy is
by children and the detachment may not be detected till
undertaken. If the cornea fails to clear after adequate
much later. Retinal detachment requires surgical treatment
control of the intraocular pressure, a corneal transplan
and the sooner the surgery is performed, the greater are
tation is required to restore vision and prevent irreversible
the chances of functional recovery of vision. Other diseases
sensory deprivation amblyopia.
that can affect the retina in childhood include degenerative
Children can also develop secondary glaucoma due to
and hereditary conditions like retinitis pigmentosa and a
chronic use of topical corticosteroid eyedrops, following
variety of different forms of macular degeneration such
eye trauma particularly if associated with traumatic
as Stargardt's disease. These diseases lead to gradual,
hyphema (blood in the anterior chamber) or angle
painless, bilateral diminution of vision in the first or
recession, after surgery for developmental cataract and
second decade of life which may be accompanied by
after chronic uveitis.
defective dark adaptation or abnormal color vision. No
EYE TRAUMA AND TRAUMA RELATED PROBLEMS______ specific treatment modalities are available, but refractive
correction, low vision aids, visual rehabilitation and
Eye injuries in children, especially in developing countries, genetic counseling are ancillary measures which must be
most commonly occur as the result of lack of supervision undertaken.
or carelessness on the part of the adult care provider. The Vascular abnormalities of the retina such as heman
eye being a very small and delicate structure, apparently giomas, arteriovenous malformations and exudative
minor trauma can also have serious consequences. Eye vitreoretinopathies like Coat's disease maybe seen. Retinal
injuries are considered to be an important cause of
preventable blindness and every effort must be made to
educate the community in general and mothers in parti
cular about the importance of not allowing children to play
with sharp pointed toys like bows and arrows and fire
crackers, chemicals including colors during Holi festival or
other chemicals like edible 'chuna'. Sharp and dangerous
household objects like knives, scissors, needles, etc. and
chemicals like cleaning liquid, acid, whitewash paint and
edible 'chuna' should be kept out of reach of children.
In case an injury is sustained, the child should be taken
to the nearest health centre without delay. In case a
chemical has entered the eye, every effort should be made
to immediately wash the eyes thoroughly with locally
available clean water such as drinkable water, and then
rush to the nearest hospital without delay.
Perforating injuries of the globe require surgical repair
under general anesthesia under cover of systemic and
topical antibiotics and tetanus prohylaxis. The child should Fig. 23.6A: The sequelae of ocular trauma. The child sustained an
be told not to rub the eyes and given only fluids while injury to the eye with a wooden stick from an ordinary broom which
rushing the child to hospital so that there is no unnecessary was being used to play a game of bows and arrows with friends. The
delay in preparing the patient for general anesthesia and child had a corneal perforation which was repaired as an emergency
and associated traumatic cataract was surgically removed and an
planning surgery on reaching the hospital. Meticulous
intraocular lens implanted during a second surgery performed 6 weeks
repair of the wounds should be undertaken as soon as
later. Note the irreversible anatomical damage with corneal scar,
possible to minimize the risk of secondary complications
distorted iris and pupil and lens capsular opacification. Permanent
such as endophthalmitis, expulsion of intraocular contents functional handicap includes astigmatism, loss of accommodation
and later risk of sympathetic ophthalmitis or an inflam requiring the use of spectacles with near correction for reading, glare
matory panuveitis in the normal other eye due to sensi and photophobia from the pupil damage, and a long-term risk of
tization of the immune system to the sequestered antigens secondary glaucoma
Eye Disorders 651
Fig. 23.6B: The long term consequences of chemical injury. The child was playing with a packet of edible 'chuna' dispensed in a thin plastic
pouch at the local ‘paan’ shop. While squeezing the packet the thin cellophane plastic covering burst and the ‘chuna’ squirted into the child's
eye. Though the parents tried to wash the eye with water, the child would not let them wash the eye thoroughly due to severe pain and
burning. The parents delayed seeking medical attention until the next morning. A thorough irrigation of the eye with normal saline was
performed in the emergency department and an examination under anesthesia was required with double eversion of the upper lid to remove
residual chunks of solid ‘chuna’ from underneath the upper lid hidden in the superior fornix. The child was treated with topical antibiotics to
prevent secondary infection of the raw inflamed ocular surface, topical steroids to control inflammation, topical cycloplegic, topical ascorbate
and citrate drops to replenish ascorbate levels, promote collagen synthesis and promote corneal healing. Supplementary therapy with amniotic
membrane transplantation to restore the ocular surface and prevent excessive scarring and vascularization was also undertaken with subsequent
use of preservative-free topical lubricants. Note that despite the best efforts and successful clinical result considering the severity of injury, the
long-term sequelae include residual conjunctival inflammation with limbal stem cell deficiency and a scarred, irregular and opacified corneal
surface. Further therapeutic options include limbal stem cell transplantation by an autograft from the fellow eye or an allograft from an HLA-
matched relative
vasculitis may be seen in Eales' disease and other inflam Suggested reading
matory disorders. Diabetic retinopathy and hypertensive For a review of relevant anatomy, physiology, optics and description of
retinopathy can occur if these systemic disorders are important diseases, differential diagnosis and management in keeping
present in sufficient grade of severity predisposing to with the undergraduate syllabus: Parsons diseases of the eye. 20th edn.
Eds Ramanjit Sihota R, Tandon R. Elsevier India, Delhi.
these manifestations for an adequate duration of time.
24 Skin Disorders
Morphology of Lesions
Primary Lesions
The basic or characteristic lesions of a disease are the
primary lesions.
Figs 24.2A and B: (A) Papule: solid lesion, <0.5 cm. (B) Nodule:
solid lesion, > 0.5 cm
652
Skin Disorders 653
Fig. 24.3: Plaque: area of altered skin consistency, the surface area of
which is greater than its depth
Figs 24.8A and B: Erosions and ulcers: (A) Erosions are due to
Fig. 24.10: Burrow: serpentine, thread-like, grayish curvilinear lesion,
complete or partial loss of epidermis without loss of dermis. (B) Ulcer
diagnostic of scabies
is a defect in the skin which extends into the dermis or deeper and
heals with scarring
Fig. 24.11: Comedones: keratin plugs that form within follicular ostia
Clinical Features
The clinical features of various forms of ichthyosis are
shown in Table 24.2.
Genodermatoses are the group of inherited single gene
cutaneous disorders that manifest themselves wholly or Treatment
in part in the skin, mucous membranes, hair and nails.
Symptomatic treatment
Ichthyosis • Hydration (by immersing in water), and immediate
lubrication with petroleum jelly or urea containing
Ichthyosis are a heterogeneous group disorders char
creams and lotions, form mainstay of treatment.
acterized by the presence of fish-like scales.
• Keratolytic agents (hydroxyacids, propylene glycol and
Classification salicylic acid) when moderately severe.
• Oral retinoids (acetretin) given in collodoin baby and
• Ichthyosis vulgaris (IV)
severe cases of lamellar ichthyosis and epidermolytic
• X-linked ichthyosis (XLI)
hyperkeratosis.
• Lamellar ichthyosis (LI)
• Non-bullous ichthyosiform erythroderma (NBIE) Treatment of complications: Short course of topical steroid-
• Epidermolytic hyperkeratosis (EHK) antibiotic combination in eczematized skin.
Fig. 24.13: Ichthyosis vulgaris: large scales on extremities Fig. 24.14: Collodion baby: baby is ensheathed
which are attached at the center and turned up at the edge in a shiny lacquer-like membrane
Skin Disorders 657
Specific measures
• Gene therapy, especially for junctional variant.
• Phenytoin is of doubtful value in autosomal recessive
EB.
• Empirical use of vitamin E.
Surgical measures
Surgery is required for release of fused digits, correction
of limb contractures and esophageal strictures.
INFECTIONS________________________________________
Bacteria, viruses and fungi can cause infections of the skin.
Pyodermas
Classification: Based on predisposing factors, pyodermas
Fig. 24.15: Lamellar ichthyosis: large pasted scales with continuous
are classified as:
rippling around ankle
Primary: When there is no underlying skin disease.
Secondary: When there is an underlying skin disease, e.g.
Classification
scabies, pediculosis, dermatophytic infection, atopic
Inherited EB dermatitis or miliaria.
- EB simplex: autosomal dominant; Based on morphology, pyodermas are classified as shown
defective keratin gene, in Table 24.4.
- Junctional EB: autosomal recessive
Localized pyoderma
- Dominant dystrophic EB: autosomal dominant;
- Bullous impetigo Staphylococcus aureus
defective collagen 7 gene
- Impetigo contagiosa S. aureus, S. pyogenes, both
- Recessive dystrophic EB: autosomal recessive
- Ecthyma S. aureus, S. pyogenes, both
Acquired EB • Spreading pyodermas
- EB acquisita immune mediated.
- Erysipelas S. pyogenes
- Cellulitis S. pyogenes
Clinical Features (Table 24.3)
• Follicular pyodermas S. aureus
Treatment
Predisposing factors
General measures • Underlying skin disease (scabies, pediculosis, fungal
• Avoiding friction and trauma, wearing soft well
infection)
ventilated shoes, gentle handling of child.
• Poor hygiene
• Wound management.
• Carrier states
• Nutritional support.
• Infection control. • Systemic diseases: diabetes.
Clinical features
Clinical features of different types of pyodermas are
discussed in Tables 24.5 to 24.7.
Treatment
General measures
• Local hygiene.
• Rest and limb elevation in case of spreading pyodermas
• NSAIDs, if pain and constitutional symptoms are
present.
Specific measures
• Topical antibiotics like mupirocin, sodium fusidate and
nadifloxacin, for localized lesions.
• Systemic antibiotics for wide spread lesions, presence
of constitutional symptoms and lymphadenopathy and
Fig. 24.16: EB dystrophica: Bullae heal with scarring. Note loss
spreading infection.
of nails
- Antistreptococcal antibiotics (e.g. injectable procaine
penicillin) for erysipelas and cellulitis.
Table 24.4: Classification of pyodermas - Erythromycin group for impetigo contagiosa and
Superficial Deep ecthyma.
Non- Localized Impetigo Ecthyma - Antistaphylococcal antibiotics (e.g. cloxacillin) for
follicular contagiosa, bullous impetigo and follicular infections.
Bullous • For recurrent infections, rule out underlying skin
impetigo disease, evaluate for carrier state and treat accordingly.
Spreading Erysipelas Cellulitis
Follicular Folliculitis Superficial Deep Staphylococcal Scalded Skin Syndrome (SSSS)
folliculitis folliculitis Etiology
Perifolliculitis Furuncle Carbuncle SSSS is mediated by hematogenously spread exotoxin
produced by S. aureus present in infection at a site distant
Sites of Face, especially around the mouth Face and other parts of body Buttocks, thighs, legs
predilection and nose
Folliculitis Furuncle
Clinical features Erythematous follicular papules, often Firm red follicular nodules which discharge pus
surmounted by pustules (Fig. 24.19). and heal with minimal scarring.
Sites of predilection Face, lower extremities Buttocks, lower extremities
from the involved, skin, (e.g. otitis media, pneumonitis) peeling of skin in thin sheets, giving the appearance of
and rarely in skin. scalding (Fig. 24.20). Constitutional symptoms are
minimal.
Clinical features Treatment
• Usually seen in newborns and infants <2 years of age. • Supportive measures.
• Erythema and tenderness is followed by superficial • Antistaphylococcal antibiotics, administered initially
parenterally then orally.
Cutaneous Tuberculosis
Clinical features
Clinical presentation is highly variable and depends on
immunity of the individual as well as route of inoculation
of organism.
Fig. 24.19: Folliculitis: erythematous follicular papule often Fig. 24.20: Staphylococcal scalded skin syndrome (SSSS): etythema
surmounted by pustules and superficial peeling of skin in thin sheets
660 Essential Pediatrics
Clinical features
Skin lesions: Macules, plaques and nodules which can be
hypopigmented, anesthetic/hypoesthetic. Skin append
ages (hair, sweating) on the lesions are reduced and there
Fig. 24.21: Lupus vulgaris: solitary, well defined annular plaque with is epidermal atrophy.
central scarring
Nerve involvement: Nerves can be thickened and tender
and there may be associated sensory and motor impair
Scrofuloderma ment.
• Occurs by contiguous spread from tubercular lymph Acid-fast bacilli (AFB): AFB can be demonstrated in some
nodes, bones or joints. forms (usually LL, BL and less frequently BB).
• Manifests initially as firm subcutaneous nodules which The profile of different clinical types of leprosy is discussed
break open to form sinuses. The mouth of the sinus is in Table 24.8.
serpiginous with undermined edges.
Lepra reactions
Tuberculosis verrucosa cutis Two types of acute episodes are seen in course of leprosy.
• Presents at trauma-prone sites.
• Type 1 lepra reaction:
• Single papule with a violaceous halo which evolves to
- Is due to alteration in host's CMI
warty, firm plaque having clefts and fissures that
- Occurs in borderline spectrum (BT, BB, BL).
discharge pus. There may be scarring at center.
- It can be an upgrading (reversal reaction) with
Diagnosis improvement of CMI or a downgrading reaction (as
Diagnosis is confirmed by histopathology. seen in natural course of disease) when CMI
decreases.
Treatment - Characterized by edema and erythema of preexisting
Intensive phase: of 8 weeks with lesions and neuritis which may result in sensory and
• Isoniazid 5 mg/kg motor impairment.
• Rifampicin 10 mg/kg • Type 2 lepra reaction (erythema nodosum leprosum)
• Ethambutol 15 mg/kg - Is an immune complex reaction.
• Pyrazinamide 30 mg /kg - Occurs in BL and LL.
- Characterized by several tender erythematous,
Maintenance phase: of 16 weeks with
transient nodules on face, flexures and legs. It is also
• Isoniazid 5 mg/kg
associated with neuritis, orchitis, iridocyclitis,
• Rifampicin 10 mg/kg arthralgia and fever.
Skin Disorders 661
Treatment
• The patient (and parents) needs reassurance, counseling
regarding treatment and care of hands, feet and eyes.
• For the purpose of treatment, leprosy is classified into
paucibacillary and multibacillary leprosy. Multi drug
therapy (MDT) is instituted based on number of lesions
(Table 24.9).
• Newer drugs: Newer drugs are required in case of
resistance or intolerance to conventional therapy. These
include ofloxacin, sparfloxacin, minocycline and *Not to be used in girls in the reproductive age group.
clarithromycin. NSAIDs non-steroidal anti-inflammatory drugs
• Treatment of reactions
Acute lepra reactions may be of variable severity and
are managed as depicted in Table 24.10. • Verruca plana: Trichloroacetic acid touches, retinoic acid
(0.025-0.05%) locally at night.
H Viral Infections • Palmoplantar warts: Wart paint after soaking in water
U Several viruses infect the skin, either primarily or as part to soften skin and protecting surrounding skin,
I of the viremia. cryotherapy and formalin soaks.
• Filiform ivarts: Electric cautery and radiofrequency
Verruca (Warts)
ablation.
Etiology
Caused by human papilloma virus, of which there are Molluscum Contagiosum
more than 100 types. They are transmitted by close contact Clinical features
and auto-inoculation. • Morphology: Multiple pearly white, dome-shaped
Clinical features papules with central umbilication (Fig. 24.26). Cheesy
material can be expressed from the lesion.
In children, nongenital warts are common, with an
incidence of upto 10%. The main features of various types
• Site: Seen on any part of the body. Widespread lesions
are seen in atopies and immunocompromised patients.
of warts are given in Table 24.11.
• Course: Usually self limiting, clears within a year's time.
Treatment • Complications: Secondary infection.
Several modalities of treatment used, depending on the
type of wart: Treatment
• Verruca vulgaris: Cryotherapy, electric cautery and Application of wart paint and mechanical removal under
radiofrequency ablation. cover of topical anesthetic EMLA.
*In children < 10 years of age, dose is given according to weight. Rifampicin: 10 mg/ kg body weight; clofazimine: 1 mg/ kg body
weight daily, 6 mg/ kg monthly; dapsone: 2 mg/ kg body weight.
Skin Disorders 663
Fungal Infections
Superficial fungal infections are common in childhood.
Dermatophytoses (Ringworm)
Etiology
Three genera of fungus cause dermatophytoses Tricho
phyton, Epidermophyton and Microsporum. The infection is
given different names depending on the site affected.
Dermatophyte infection of glabrous skin is known as
tinea corporis, of groin as tinea cruris, of hands as tinea
manuum, of feet as tinea pedis, of nails as tinea unguium,
and of scalp as tinea capitis.
Clinical features
Classical lesion of tinea is an annular or arcuate plaque
with the active edge showing papulovesiculation and scal
ing and a clear centre. These features are modified by
site.
664 Essential Pediatrics
Tinea capitis
Is common in preadolescent children and three patterns
are seen:
Non-inflammatory or epidemic type: Caused by anthro-
pophilic organisms and so is responsible for epidemics. It
presents as a patch of alopecia with marked scaling at
periphery (Fig. 24.27). Flair break off easily and inflam
mation is minimal.
Inflammatory type or kerion: Caused by zoophilic organisms
and so does not cause epidemics. It presents as a boggy
swelling which drains pus from multiple openings (Fig.
24.28). Hair is easily pluckable without pain. Usually
associated with occipital lymphadenopathy.
Favus: Caused by T. schonleinii, presents as yellowish, foul
smelling cup-shaped crusts with matting of hair.
Tinea corporis
• Shows classical features of tinea and is usually
inflammatory in children.
Tinea corporis
• Localized lesions treated with topical therapy (azoles
available as clotrimazole, miconazole or ketoconazole
in lotion, gel and cream formulations)
• Widespread lesions require systemic antifungal
therapy with griseofulvin (for 4 weeks) or terbinafine
(2 weeks).
Candidiasis
Candida albicans, a normal commensal, becomes patho
genic in the presence of predisposing factors such as
Fig. 24.27: Tinea capitis: area of non-scarring alopecia with minimal moisture, obesity, diabetes and immunocompromised
inflammation states. Less frequently, other species like C. glabrata.
Clinical features
• Most frequently seen on exposed parts. In children candidiasis may present as oral thrush,
• Tinea faciale (tinea of face) common in children. vulvovaginitis, intertrigo, candidal diaper dermatitis or
paronychia as seen in chronic mucocutaneous candidiasis.
Diagnosis
KOH test is simple, quick, inexpensive and sensitive test. Oral thrush
Culture is confirmatory and required for identification of • Seen in new born breast fed infants.
species. • Presents as soft, creamy white to yellow, elevated
plaques, that are easily wiped off to leave an erythe
Treatment matous, eroded or ulcerated surface.
Tinea capitis • Buccal mucosa (most frequently), tongue, palate and
• Griseofulvin (15 mg/kg/day of ultramicrosized gingiva.
formulation for 8 weeks) is drug of choice.
Candidal intertrigo
• Terbinafine (5 mg/kg/day for 4 weeks) is effective in
Occurs in skin folds as erythematous, moist, macerated
non-inflammatory tinea capitis. Longer treatment (8
lesion with a frayed irregular edge with satellite lesions.
weeks) needed for kerion.
• Washing with ketoconazole shampoo helps to reduce Candidal diaper dermatitis
transmission. Also avoid sharing combs and other head • Begins in perianal region, spreading to perineum, upper
wear. thighs, lower abdomen and lower back.
Skin Disorders 665
DRUG ERUPTIONS
Diagnosis
• Diagnosis is based on clinical features and temporal
relation to drug use. Though any drug can cause a
reaction after any length of treatment, some drugs are
more suspect and the most recent introduction most
likely cause.
• Prick tests and in vitro tests are of little value. The role
of drug provocation test is controversial but may be
needed to find the culprit drug in patients on multiple
drugs as well as to find safe alternative drugs.
Treatment
'Withdrawal of drug: Is most effective approach hut is not
always easy as the child may be taking several drugs or
the suspected drug may be difficult to withdraw as it is
essential. Sometimes chemically unrelated drug substitute
may not be available.
Symptomatic therapy
• Urticaria: Antihistaminics.
• Anaphylactic reactions: Airway maintenance,
adrenaline, chlorpheniramine maleate, hydro
cortisone.
• Exanthematous reactions: Topical, and if severe,
systemic steroids.
• SJS-TEN complex: Supportive treatment including
fluid-electrolyte balance. Role of systemic cortico
steroids controversial.
Exanthematous eruptions Commonest drug eruption. Symmetric erythematous Penicillins, sulphonamides, anti
macules and papules surmounted by scales. convulsants, antitubercular drugs,
Erythroderma Entire skin surface becomes erythematous, Penicillins, sulphonamides, barbiturates,
(exfoliative dermatitis) scaly and edematous. isoniazid and gold.
Stevens Johnson syndrome- Initial lesions targetoid, followed by diffuse, Sulphonamides, pencillin, quinolones,
toxic epidermal necrolysis intense erythema. Flaccid blisters, followed by barbiturates phenytoin, frusemide,
(SJS-TEN) complex large areas of skin denudation. Mucosae always hydralazine, NSAIDS.
involved.
Fixed drug eruption Well demarcated, erythematous plaques, recurring at Phenolphthalein, barbiturates, sulpho
same site each time implicated drug is taken. namides, tetracyclines, salicylates.
Subside with hyperpigmentation.
Photosensitive eruption Pruritic papules and plaques on sun-exposed areas. Thiazides, sulphonamides, tetracyclines,
quinolones, phenothiazines, psoralens.
Vasculitis Can manifest as palpable purpura, urticarial vasculitis, NSAIDS, phenytoin, sulphonamides,
necrotic ulcers nodular vasculitis. tetracyclines, ampicillin.
Urticaria and angioedema Can occur independently or as a part of a severe Aspirin, indomethacin, opiates,
generalized reaction with bronchospasm and sulphonamides, pencillin.
circulatory collapse (anaphylaxis).
ECZEMATOUS DERMATITIS
Atopic Dermatitis
Atopic dermatitis (AD) is an acute, subacute or chronic
relapsing, endogenous eczema, characterized by dry skin
and pruritic, recurrent, symmetric dermatitic lesions.
Etiology
• Genetic predisposition is an important factor but the
inheritance pattern has not been ascertained.
• Immunological changes include elevated IgE levels,
Fig. 24.30: Verrucous epidermal nevus: multiple brown papular increased levels of specific IgE to allergens and
lesions arranged linearly abnormalities of lymphocytes.
- Side effects like dry skin, cheilitis, and dry eyes (seen Treatment
in all patients) are treated symptomatically. Careful Single or feiv lesions of <6 months duration: Observed,
monitoring of liver function tests and lipid profile is
as spontaneous recovery common.
essential at baseline and every 6 weeks.
Single or few lesions of >6 months duration: Treated with
Cyproterone acetate following:
- Should not be used in boys. - Topical corticosteroids.
- Used cyclically in combination with ethinyl estradiol - Intralesional triamcinolone acetonide.
in girls who have a polycystic ovary disease. - Topical minoxidil.
- Topical psoralens in combination with UVA/sunlight.
Physical modalities Extensive lesions
Intralesional corticosteroids for stubborn cysts and laser - Oral corticosteroids.
therapy, cryotherapy, dermabrasion and collagen - Oral psoralens with UVA/sunlight.
injections are used for treatment of scars. - Induction of allergic contact dermatitis with agents such
as diphencyprone.
Alopecia Areata
Miliaria
Etiology
Etiology
Autoimmunity is the most likely cause of alopecia areata.
Miliaria is due to obstruction and rupture of eccrine sweat
Clinical Features ducts resulting in spillage of sweat into adjacent tissue.
• Affects children and young adults. Clinical Features
• Typically discoid areas of noncicatricial alopecia with Milaria occurs at any age and depending on level of
exclamation mark hair at periphery (Fig. 24.38). rupture 3 different morphologically variants seen:
• Most commonly occurs on the scalp, eyelashes and Miliaria crystallina: Usually seen during high fever.
brows. Alopecia totalis is total absence of terminal Characterized by tiny, non-inflamed vesicles.
scalp hair while alopecia universalis is total loss of Miliaria rubra: Characterized by small erythematous
terminal hair from body and scalp. Ophiasis is a band papules commonly surmounted by vesicles.
like pattern of hair loss from the periphery of scalp. Miliaria profunda: Characterized by large erythematous
• Course: Spontaneous remission is common. Initially, papules.
the regrowing hairs are grey, but regain color over
Treatment
period of time. Poor prognostic features include onset
in childhood, ophiasis, association of atopy and • General measures are avoiding humidity, wearing cot
widespread alopecia. ton clothes.
• Calamine lotion and mild topical steroids are useful.
DISORDERS OF PIGMENTATION
Vitiligo
Vitiligo is chracterized by depigmented macules. It affects
both sexes equally and peak incidence is seen between
10-30 years.
Etiology
Genetic factors: 20-30% of patients have a positive fam
ily history.
Autoimmune hypothesis: Association with autoimmune
disorders, e.g. thyroid disorders and alopecia areata,
presence of antibodies to melanocytes and lymphocytes
in early lesions points to autoimmune etiology.
Neurogenic hypothesis: In some patterns of vitiligo.
Clinical Features
Fig. 24.38: Alopecia areata: non-cicatricial, non Morphology: Characterized by depigmented (chalky
inflammatory discoid lesions with exclamation mark hair white or pale white) macules which are sharply
at periphery marginated. The outline of macules is scalloped and these
Skin Disorders 673
PAPULOSQUAMOUS DISORDERS_____________________
Etiology
Unknown. An eruption resembling lichen planus and
termed lichenoid eruption is seen after intake of drugs
like chloroquin and as a manifestation of graft-vs-host
disease.
Clinical Features
Morphology: Characterized by pruritic, polygonal, viola
Fig. 24.39: Acrofacial vitiligo: involvement of face and acral parts ceous and flat-topped papules (Fig. 24.40) with white
674 Essentia! Pediatrics
Etiology
Etiology is unknown but several factors are incriminated:
Heredity: Psoriasis is polygenic trait.
Triggers: Physical trauma, infections ((3 hemolytic
streptococci, HIV infection) and drugs (lithium, NSAIDS,
antimalarials).
Immunological factors: T cells play a pivotal role in
pathogenesis of psoriasis.
Classification
• Chronic
- Psoriasis vulgaris
Fig. 24.40: Lichen planus: plane polygonal, violaceous papules
- Erythroderma
• Acute onset
streaks (Wickhams striae) on the surface (visualized best - Acute guttate
with hand lens after application of mineral oil). - Pustular psoriasis
Sites of predilection: Lesions seen on wrists, around ankles
and may appear at sites of trauma (Koebners pheno Clinical Features
menon).
Psoriasis vulgaris
Variants: Several variants like linear, actinic, hypertrophic,
Morphology: Characterized by well demarcated,
follicular.
indurated, erythematous scaly (silvery, loose) lesions.
Mucosal membranes: Mucosal involvement seen 25%
Lesions become polycyclic due to confluence and annular
patients in form of reticulate lacey pattern on buccal because of central clearing.
mucosa, tongue and gingiva or superficial erosions on
Sites of predilection: Symmetrical involvement of knees,
tongue and buccal mucosa, annular lesions are seen on
elbows and extensors, lower back, scalp and sites of
genitalia.
trauma (Koebners/isomorphic phenomenon). Face and
Scalp lesions: Scarring alopecia.
photo-exposed areas generally spared.
Nail changes: Longitudinal grooves, tenting of nail plates
and pterygium formation. Bedside tests
- Grattage test: Accentuation of scales on grating lesion
Diagnosis with a glass slide.
Diagnosis is based on clinical features and can be - Auspitz sign: Removal of scales by scraping with a glass
confirmed by histopathology. slide reveals a glistening white membrane (Burkleys
membrane) and on removing the membrane, punctate
Treatment bleeding points become visible.
Localized lichen platius: Topical steroids and oral Guttate psoriasis
antihistamines. • Occurs in children and adolescents.
Extensive lichen planus: PUVA, oral steroids and • May be precipitated by streptococcal tonsillitis.
acitretin • Crops as small erythematous scaly papules.
Lichen planus of nails: Oral steroids • Predominantly on trunk.
Lichen planus of scalp: Oral steroids
Pustular psoriasis
Mucosal lichen planus: Dapsone + steroids in ora-
Two rare variants described in children:
base, oral steroids, acitretin
Annular pustular psoriasis. Characterized by sudden
Psoriasis onset of fiery red erythema rapidly covered by cluster of
very superficial creamy white pustules which in children
Psoriasis is a chronic, recurring dermatosis which may
form circinate/annular lesions (Fig. 24.41).
have onset in childhood/adolescence (type I psoriasis)
and in adults (type II psoriasis). Type I psoriasis is Infantile and juvenile pustular psoriasis. Rare; seen in
characterized by: infants as annular/circinate lesions (Fig. 24.42). Runs a
Skin Disorders 675
TUVA: Psoralen + UVA. Patient ingests 8 methoxypsoralen, 0.6 mg/ kg and exposes after 2 hours to gradually increasing doses
of UVA (provided either from artificial sources or from sunlight PUVAsol**) after applying an emollient on the lesions. Should
not be used in children <6 years of age.
Figures 24.10, 24.14, 24.16, 24.28 and 24.34 in this chapter are reproduced from Khanna, N: Illustrated Synopsis of Dermatology and Sexually
Transmitted Diseases, 2/e, with permission of the publishers, Elsevier, New Delhi.
25 Poisonings, Injuries and Accidents
676
Poisonings, Injuries and Accidents 677
Table 25.3: Clinical clues to nature of poisoning cyanide. Measurement of anion gap and osmolal gap
detects accumulation of unmeasured ions and osmotically
Features Toxin
active agents in blood.
Bradycardia Digoxin, organophosphorus compounds,
P-blockers Gastric Aspirate
Tachycardia Atropine, salicylates
Acidotic breathing Salicylates Addition of two drops of 30% hydrogen peroxide and
Hypertension Phenylpropanolamine deferoxamine (0.5 ml, 125 mg/ml) to 1 ml of gastric fluid
Hypothermia Barbiturates leads to color change in iron poisoning.
Fever Atropine, salicylates, theophylline, Efforts to identify the poison should not jeopardize
quinine general measures, which are effective in most cases.
Ataxia Phenytoin
Paralysis Botulism, heavy metals Laboratory Evaluation
Miosis Organophosphates, opioids, barbiturates
Poisoning is associated with accumulation of toxins in the
Mydriasis Atropine, amphetamines
Jaundice Acetaminophen, carbon tetrachloride body. The aim of laboratory evaluation is to identify the
Cyanosis Methemoglobinemia, carbon monoxide toxin, assess the amount of exposure and detect organ
Flushed Carbon monoxide, cyanide dysfunction and metabolic derangements produced by the
appearance (red) toxin. Initial samples in any child with suspected poison
Characteristic smell Acetone, cyanide, alcohol, kerosene ing should include vomitus or gastric aspirate for identi
fication of the incriminating agent and urine and blood
for qualitative and quantitative assessment respectively.
Bedside Tests for Toxin Identification Hemogram with complete blood count, ECG, chest
X-ray, liver and renal function tests and blood gas analysis
These tests provide an idea about the possible toxin before should be performed in all children with significant
the reports of other tests are available. intoxication. The effect of toxins on metabolism may
produce characteristic abnormalities that may help in
Urine Tests
identification of the toxin (Table 25.5).
Urine should be examined for abnormal color. In phenol
poisoning, smoky dark green color occurs on standing.
MANAGEMENT ______ ___
Oxalate crystals indicate the possibility of ethylene glycol
poisoning. Ferric chloride test may help in identifying the Early suspicion and appropriate management forms the
incriminated toxin. Add 5-10 drops of freshly prepared mainstay of therapy. General measures should be
10% ferric chloride solution to 10 ml of boiled and acidified instituted immediately, since early treatment is associated
urine. Change of color to red suggests exposure to with improved outcome.
salicylates; purple green and violet indicate phenothiazine If the child is brought in the pre-toxic phase, deconta
and phenol exposure respectively. Ketones in urine mination is the highest priority and treatment is based on
suggest exposure to acetone, salicylate and isopropyl history. The maximum potential toxicity based on greatest
alcohol. possible exposure should be assumed. During toxic phase,
the time between the onset of poisoning and the peak
Blood Tests effects, management is based primarily on clinical and
Blood appears chocolate color in patients with methe laboratory findings. Resuscitation and stabilization are the
moglobinemia. This turns pink on addition of potassium first priority. During resolution phase, supportive care and
Table 25.5: Laboratory pointers to identification of toxins cations. Indications for intensive care include: (i) evidence
of severe poisoning, coma, respiratory depression, hypo
Observation Possible toxin
tension, cardiac conduction abnormalities, arrhythmias,
Hypocalcemia Ethylene glycol, oxalate hypothermia or hyperthermia; (ii) need for antidote or
Hypokalemia Beta agonists, diuretics, theophylline enhanced elimination therapy; and (iii) progressive clinical
Hyperkalemia Beta blockers, digoxin, alpha agonist
deterioration.
Hyperglycemia Acetone, theophylline, calcium channel
blockers Prevention of Further Absorption of Poison
Hypoglycemia Oral hypoglycemic agents, ethanol,
quinine, salicylates These measures target preventing absorption of the toxin
Increased anion Methanol, ethanol, ethylene glycol, and depend upon the site and route of poisoning and
gaP salicylate, isoniazid patient's age and general condition.
Decreased anion Lithium, bromide
Dilution: This involves application of water in an effort to
gap
Increased Mannitol, ethylene glycol, isopropyl reduce the duration of exposure to the toxin. The
osmolal gap alcohol, glycerol, acetone, sorbitol mechanism depends upon the site of exposure.
Pulmonary edema Carbon monoxide, cyanide, irritant gas In patients with corrosive burns and organophos
Radiopaque Calcium, heavy metal phorous poisoning (readily absorbed from skin), all clothes
density should be removed and the contaminated area washed
Bradycardia, Beta blockers, digoxin, calcium channel with liberal amount of water and soap. Neutralization of
AV block blockers an agent (using alkali for acid exposure or vice versa) is harmful
Prolonged QRS Hyperkalemia, membrane active agents and contraindicated. Skin cleaning should be done irres
complex
pective of duration of exposure to the toxin. Lubricating
solutions like grease or cream may cause poison to stick
monitoring should continue until clinical and laboratory
on to skin.
abnormalities have resolved.
Oral and ocular mucosa is washed with plenty of water.
Airway Maintenance Eyes should be irrigated with lids fully retracted for at
least 20 minutes. This may be achieved by keeping normal
Establishing airway may be difficult in children with
saline bottle and infusion set near the eye. In patients with
poisoning due to caustic and thermal upper airway
corrosive ingestion, liberal amounts of water or clear fluid
injuries, neck and facial injuries, or angioedema. In any
(5 ml/kg) should be given orally as soon as possible. It is
child with altered mental status, respiratory depression and
contraindicated in poisoning due to tablets as it may cause
pupillary constriction, a trial of naloxone should be given before
increased absorption.
intubation. Bag and mask ventilation is associated with a
higher risk of aspiration. This can be minimized by Gastrointestinal decontamination: Gastric emptying is a
synchronized and gentle ventilation, Sellick's maneuver cardinal principle of management of ingested toxins. The
and aspiration of gastric contents prior to ventilation. desired outcome is prevention of continued absorption
of poison from the gut into the bloodstream in
Breathing asymptomatic children.
Adequacy of breathing should be assessed by respiratory The procedure of choice for decontamination, if needed,
effort, chest movement, air entry and oxygen saturation. is activated charcoal, with whole bowel irrigation being
used for a few indications. Ipecac induced emesis and
Circulation
cathartics are not recommended as gastric emptying
Fluid boluses, repeated if needed, under monitoring for procedures. Orogastric lavage may be considered for
fluid overload, constitute the initial management of shock uncommon situations.
particularly in poisoning due to cardiotoxic agents and Routine administration of syrup of ipecac in the
children with cardiopulmonary diseases. In an unrespon emergency department in children with poisoning may
sive shock, dopamine is the agent of choice except in remove 30 to 40% of ingested toxin when administered
poisoning due to tricyclic antidepressant or MAO inhibi soon after the ingestion. It has been abandoned except as
tors. Exposure to myocardial depressant or vasodilator a home remedy before child is transported to emergency
toxin or concomitant conditions like visceral injuries, room. Other emetics like apomorphine, detergent, raw egg
pulmonary embolism, ruptured aortic aneurysm, sepsis or and dry mustard powder are also not used.
severe acidosis makes the hypotension refractory to these The role of gastric lavage in children is not clear. It is
measures. contraindicated in corrosive poisoning. The procedure
should be reserved for conditions where a potentially
Supportive Therapy
lethal toxin has been recently (within 60 minutes) ingested.
The goals of supportive therapy include maintenance of Gastric lavage should be performed with a large tube with
homeostasis and prevention and treatment of compli multiple lateral holes at the distal end and funnel at the
Poisonings, Injuries and Accidents 679
proximal end. Size of tube is selected according to age agents, ingested crack vials and drug packs. The procedure
(neonates 28 Fr, older children 36 Fr). Narrow tubes are is not helpful in the management of ingestion of rapidly
ineffective in removing solid substances. absorbed drugs, liquids, parenteral drugs and caustics.
Gastric lavage should be performed only after the gag Whole bowel irrigation can be achieved with adminis
reflex has been assessed. In patients with impaired tration of 500 ml/hour of polyethylene glycol over 4-6
consciousness and absent gag response, intubation should hr. The procedure is safe, with rare side effects of rectal
be performed before gastric lavage. The length of lavage itching and vomiting.
tube should be measured before insertion. The child should
be kept in lateral decubitus position with lowering of head end. Enhancing Elimination
Lavage should be done with 15 ml/kg of normal saline Procedure directed towards enhancing elimination is
until clear fluid is drained. Activated charcoal should be indicated in patients with significant delay following
instilled after the lavage is completed. poisoning or when methods for prevention of absorption
are ineffective or not applicable. Diuresis, alteration of
Binding agents: Activated charcoal, clay and
urine pH and dialysis are commonly used for enhancing
cholestyramine may be helpful in reducing absorption of
drug elimination.
ingested toxins. Activated charcoal is produced by
destructive distillation of organic materials like wood, Manipulation of pH and diuresis: The rate of elimination of
coconut and petroleum. The distillate is treated at high ingested substances can be increased by increasing GFR
temperature using steam. These procedures increase the or altering urine pH for the toxins that are excreted by
adsorptive capacity of the compound by increasing surface kidneys. Acidification of urine to enhance elimination of
area, removing adsorbed material and reduction in weak bases should be avoided. Alkalization of urine may
particle size. Activated charcoal acts by binding and be used in patients with poisoning due to weak acids like
elimination of the toxin. The total surface (adsorptive) of salicylate, phenobarbital and herbicides. This is achieved
activated charcoal is 1600 to 1800 m2/g making it ideal as by administration of sodium bicarbonate at a dose of 1-2
binding agent. mEq/kg given every 3-4 hr, in order to maintain urine
Activated charcoal is used at a dose of 1-2 g/kg. The pH between 7 and 8. Sodium bicarbonate is also effective
drug is available as a 400 mg tablet and should be crushed in reducing the toxicity of tricylic antidepressants, quinine
before administration, made into slurry and administered. and some antiarrythmic drugs.
Under most circumstances, a single dose is effective.
Dialysis: The indications of dialysis are given in Table 25.6.
Multiple doses of activated charcoal (every 4-hr) have been
The mode of dialysis depends upon clinical condition,
shown to decrease elimination half lives of drugs through
available resources and type of ingestion.
gut dialysis. The greatest benefit is within one-hr of
ingestion. Multiple doses may be indicated in patients with Peritoneal dialysis is more effective in children due to larger
massive ingestion of toxin and desorption of toxin from peritoneal surface in relation to body surface area. It
activated charcoal. enhances elimination of compounds like alcohol, lithium
Activated charcoal is an effective nonspecific adsorbent and salicylates. It has the disadvantages of gradual
and should be considered in all cases of poisoning, removal of toxins and decreased efficacy in hypotensive
irrespective of interval since ingestion. It should be subjects. The procedure may however be a temporizing
avoided in patients with corrosive ingestion, ileus, measure before hemodialysis or hemoperfusion.
intestinal hemorrhage and patient with unprotected
Hemodialysis is the preferred method for removal of
airway at risk of aspiration. Other binding agents
compounds like bromide, chloral hydrate, ethanol,
including various attapulgite, bentonite, fuller's earth,
methanol, ethylene glycol, lithium and salicylates. In
kaolin-pectin are less effective. The burnt toast in universal
addition to removing toxins, it also rapidly corrects
antidote possesses little, if any adsorption capacity, and
metabolic abnormalities and fluid overload. The proce
has been abandoned. Cholestyramine has been found
dure has risks of bleeding or thrombosis, hypotension,
effective in paracetamol and digitalis toxicity but it is less
nosocomial infection and possible elimination of agents
well tolerated.
like folinic acid and ethanol, administered therapeutically
Cathartics: Routine use of cathartics either alone or with during acute poisoning.
activated charcoal is not recommended.
Hemoperfusion is the procedure (of pumping blood through
Whole bowel irrigation with polyethylene glycol has been a cartridge containing activated charcoal or carbon with
used in patients with poisoning and drug overdosage. It large surface area) and is effective in removal of substances
is the only procedure, which decontaminates beyond the adsorbed by activated charcoal. The procedure has
pylorus without inducing emesis or causing fluid overload the advantage of being not limited by protein binding and
and dyselectrolytemia. It is, however, not a substitute for is the preferred method for elimination of carbamazepine,
activated charcoal. It is particularly useful following phenobarbital, phenytion and theophylline. Substances,
ingestion of sustained release drugs, slowly dissolving which are not adsorbed by activated charcoal,
680 Essential Pediatrics
like alcohol, lithium, many heavy metal poisons are not children is to limit the access to poison. In households
removed. The procedure may be associated with compli where children live or visit, alcoholic beverages,
cations like thrombocytopenia, leukopenia and hypo medications, household products (automotive, cleaning,
calcemia. fuel, pet-care, toiletry products), non-edible plants and
Exchange transfusion may be performed in neonates and vitamins, should be kept out of reach or in locked or child
infants. It removes poisons affecting the red blood cells proof cabinets. Poison prevention education should be an
(as in methemoglobinemia or arsine-induced hemolysis). integral part of all well child visits, even before a child is
The elimination of heavy metals is enhanced by chelation mobile. Counseling parents and other caregivers about
and removal of carbon monoxide can be increased by potential poisoning risks, how to "poison-proof" a child's
hyperbaric oxygen. environment, and what to do if a poisoning occurs
diminishes the likelihood of serious morbidity or mortality
Table S5.6: Indications of dialysis in a patient from an exposure.
with suspected poisoning Adolescents with suicidal poisoning or drug addiction
need proper counseling before discharge. Unless pedia
Patient related Toxin related
tricians are aware, the likelihood of early diagnosis and
Anticipated prolonged Satisfactory membrane appropriate management of suspected cases of poisoning
coma permeability or drug abuse are dramatically decreased. A potentially
Hepatic and renal Correlation between plasma con healthy adulthood is irreparably harmed.
failure centration and toxicity
Serious underlying Plasma levels in fatal range COMMON POISONINGS
illness Significant quantity of agent
Acetaminophen (Paracetamol)
metabolized to toxic substances,
e.g. barbiturates, chloral hydrate, It is the most common analgesic, antipyretic used in
ethylene glycol, theophylline, children. The toxic dose is usually >200 mg/kg in children
salicylates, heavy metals <12-yr-old. Overdosage is treated with N-acetylcysteine
used orally within 16-hr after ingestion at a loading dose
of 140 mg/kg diluted to 5% solution orally, followed by
Administration of Antidotes
70 mg/kg q 4-hr for another 2 days.
Antidotes counteract the effects of poisons by neutralizing
them or by antagonizing their physiologic effects Organophosphorous Compounds
(activation of opposing nervous system activity, provision (Insecticides and Pesticides)
of metabolic or receptor substrate). Antidotes significantly Pesticides are the most important poison throughout the
reduce the morbidity and mortality, but are potentially tropics, being both common and associated with a high
toxic. Their safe use requires correct identification of mortality rate. Pesticides include insecticides, herbicides,
specific poisoning or syndrome. Table 25.7 lists the fungicides, nematocides, rodenticides, fumigants, Bacillus
common antidotes used for management of poisonings. thuringiensis and unconventional pest control agents (e.g.
sulphur). Exposure in children may be acute or chronic.
Prevention of re-exposure
Chronic exposure may be dietary or nondietary.
Poisoning is a preventable illness: The elegance and delicacy Aggregate exposure refers to total exposure to a single
of the development of a human from conception through pesticide through food, water and non-dietary exposure.
adolescence affords particular windows of vulnerability Cumulative exposure is the summated exposure to
to hazards. The best approach to prevent poisoning in multiple pesticides with a common mode of action.
Poisonings, Injuries and Accidents 681
Children are at higher risk in view of higher body sur depends on its volatility, viscosity or surface tension. The
face area and high body mass ratio; significantly greater lower the viscosity, higher is the risk of pulmonary aspi
minute ventilation rates in young children result in increa ration. Thus substances with low viscosity and volatility
sed pulmonary exposure. These agents are absorbed (mineral oil, kerosene, furniture polish) have a higher risk
through the skin and mucosa. Symptoms of excessive para of aspiration. Substances with high volatility and low
sympathetic activity including blurring of vision, head viscosity (benzene derivatives like toluene, xylene used
ache, giddiness, nausea, pain in the chest, profuse in solvents and degreasers, gasoline, naphtha in lacquer
salivation and sweating occur within a few hours. Pupils diluent) may also act as toxins through inhalation,
are constricted and papilledema may occur. Carbamates manifesting with neurological depression.
are less toxic than organophosphorus pesticides. Death is Kerosene and paraffin oils are common household
usually due to respiratory failure. energy sources in the developing world. Often kept in
Treatment includes reduction of dermal contact and unsafe containers (soft drink and beer bottles), these oils
gastric emptying. Atropine sulphate is the primary anti are a major cause of accidental poisoning among young
dote (0.03-0.04 mg/kg IV; ampoule 1 mg/ml); the dose is children. The incidence of kerosene ingestion has decrea
repeated after 15 minutes and then every hour until sed to less than half. Respiratory symptoms, as a result of
atropinization (maximum 1 mg/kg in 24-hr). Atropine, a chemical pneumonitis, restlessness, fever and abdominal
competitive antagonist of muscarinic receptors, reverses distension are common. Convulsions and coma may occur.
the peripheral symptoms (secretions and airway resis Radiological changes, which might occur within one-hr
tance) and arrests the early phase of convulsions when include basilar infiltrates, emphysema, pleural effusion
given within 5 minutes of exposure. It is a satisfactory and pneumatoceles. Management is symptomatic with pre
antidote for mildly affected victims as an anti-sialogogue servation of the airway in unconscious patients. Gastric empty
or as a peripheral parasympatholytic. This agent does not ing is contraindicated and is done only when large
cross the blood-brain barrier and is ineffective for those quantities of turpentine have been ingested or the
with symptoms involving central nervous system. It is hydrocarbon product contains benzene, toluene,
an effective antidote, but causes profound neurological halogenated hydrocarbons, heavy metals, pesticides or
effects, including sedation. aniline dyes. Mortality ranges from 2-10% and is higher
Pralidoxime aldoxime methiodide (2-PAM) hydrolytically in malnourished children. Steroids have no role in
cleaves the organophosphate from the enzyme, acetyl treatment.
cholinesterase restoring enzymatic function. It is given at
a dose of 25-50 mg/kg IM to a maximum of 2000 mg/hr Iron Intoxication
every 12-hr (maximum for infants 0.25 g). It is highly Ingestion of tablets of ferrous sulfate may cause acute
effective in reversing nicotinic effects (e.g. muscle fasci- poisoning, characterized by GI toxicity, followed by a
culations, weakness, respiratory depression). It is not period of relative stability and then circulatory shock with
given in carbamate poisoning alone. Common untoward metabolic acidosis and myocardial dysfunction. Hepatic
effects include dizziness, transient diplopia, and blurred necrosis and gastric scarring are long-term effects. The
vision. Dose adjustment in individuals with renal lethal dose is 300 mg/kg of iron. The child may develop
insufficiency is required, because 2-PAM is excreted complications within a few hr or after a latent period of
almost entirely unchanged by the kidneys. Rapid IV 1-2 days.
administration can cause laryngospasm and rigidity. Treatment includes gastric emptying, followed by
Hypertension is the most serious untoward effect at higher stomach wash with sodium bicarbonate. IV sodium
doses. Intravenous fluids are given if needed. bicarbonate (3 ml/kg diluted twice with 5% dextrose) is
Toxicity with DEET (diethyl toluamide, the component given for treatment of acidosis. Fluid resuscitation may
of most insect repellant creams) may occur through be necessary. Iron is chelated with IV infusion of
covered skin surfaces or ingestion. Seizures are the most deferioxamine (dose 15 mg/kg/hr) until the serum iron
severe manifestation but are most often self limited. is <300 mg/dl or until 24-hr after the child has stopped
For DDT poisoning, phenobarbitone is given for passing 'vine rose' colored urine. In case of renal failure,
convulsions. Cholestyramine, an anion exchange resin dialysis to remove deferioxamine-Fe complex may be
should be administered to all symptomatic patients of required.
DDT poisoning.
Dhatura (Belladona) Poisoning
Hydrocarbon Poisoning Accidental ingestion of dhatura seeds cause delirium,
Aliphatic hydrocarbons, including kerosene, turpentine, confusion, visual disturbances, photophobia, dilated
lubricating oils and tar, have the greatest risk of aspiration sluggishly reacting pupils, dryness of skin and mouth,
and pulmonary symptoms. Aromatic compounds include fever, tachycardia and urinary retention. Treatment is by
benzene compounds and have mainly neurological and gastric lavage and physostigmine at a dose 0.1 mg/kg
hepatic toxicity. The type of toxicity with a hydrocarbon (max 2 mg) IV slowly.
682 Essential Pediatrics
Chemical Burns soothing effect and restricts fluid and heat loss from the
The burnt area is flushed with plenty of running cold burn surface. It can cause skin rash, leukopenia and
water. If an eye is burnt by chemical especially an acid or thrombocytopenia. Silver nitrate is not an effective antibac
an alkali, it is flushed gently but thoroughly with tap water terial agent because of poor penetration of the burn eschar;
for long time. The burn wound should be kept as clean as it can cause hyponatraemia, hypokalaemia, hypochloremia
possible, protected from dirt, dust and flies. and hypocalcemia. Mafenide acetate penetrates the burn
eschar effectively; its application can be painful and may
Management be associated with skin reaction and metabolic acidosis
(being a carbonic anhydrase inhibitor). Daily dressing
Estimate Burn Size
changes are required after thorough cleansing. Maintain
The primary determinant of survival in patients with burn ing such dressings intact in a young child is difficult over
injury is patient age below 4-yr and the size and depth of the face and hands. MEBO (moist exposed burn ointment)
the burn wound. Young children do not tolerate thermal is promising in this regard. A judicious combination of
injury as well as adults. The Berkow body surface area topical therapy, eschar excision and skin grafting helps in
chart and the rule of nines, used to estimate surface area quick healing. Decompressive escharotomy of circum
of burn injuries in adults, are not applicable to children. ferential burns of the chest, abdomen and extremities must
The Lund and Browder modification, which divides the be performed without delay at the bedside
body into small portions and takes into account childhood
differences in body proportions, is preferred. Analgesia
Adequate control of pain and anxiety is essential to
Hospitalization
minimize the stress response in burn injury. Narcotics are
Minor burns can be treated at home with topical the commonest form of analgesia in major burns.
ointments. Indications for hospitalization are patients Requirement for analgesia is generally higher in adults
having: (i) 5% total body surface area (TBSA) third-degree with burn injuries.
burns, (ii) 10% TBSA second- and third-degree bums, or
(iii) burn injuries involving the face, hands or genitalia. Nutrition
Principles of therapy include: (i) adequate fluid Attention to the nutritional needs of a burned child is an
replacement, (ii) correction of hypoxia and ventilatory essential component of management. High caloric and
disturbances, (iii) prevention of hypothermia and (iv) nitrogen intake is crucial for survival. Adult nutritional
management of pain and anxiety. Patients with inhalation calculation formulas are not well suited to children.
injury are managed by endotracheal intubation and Calorie requirements are best estimated by the following
supportive ventilation; hyperventilation with 100%
formula
oxygen shortens the half-life of carbon monoxide • Infants: 2100 Cal/m2 + 1000 Cal/m2 burn surface area
elimination from 4 hr to 40 minutes. • Children: 1800 Cal/m2 + 1300 Cal/m2 burn surface area
• Adolescents: 1500 Cal/m2 surface area and burn surface
Adequate Fluid Replacement
area.
The goal of fluid resuscitation is to restore and maintain Adequate protein (2-3 g /kg body weight), supple
perfusion and tissue oxygen delivery at optimal levels in mentation of trace elements, vitamins and minerals is
order to protect the zone of ischemia in burned tissues necessary. Whenever feasible, particularly in patients with
without overloading the circulation. Oliguria occurs as a less than 15-20% burns, nutrients should be administered
result of several factors, including excessive secretion of by the enteral route. Tube feeding is started on the first
antidiuretic hormone. Urine output should be maintained day of admission with rapid advancement towards intake
between 0.7-1 ml/kg/hr. Isotonic solutions (normal saline goals. In children with more extensive burns, inhalation
or Ringer lactate) should be administered initially at a rate injury or prolonged paralytic ileus, parenteral nutrition
of 20 ml/kg/hr until calculation of appropriate replace is considered.
ment can be made. Potassium is not administered during
the first 12-24 hr, or until normal kidney function is Others
demonstrated. Assessment of physical abilities and enabling full range
of joint movements by physical and occupational therapy
Topical Therapy and play therapy is encouraged. Family support and
Sixty-five per cent of pediatric burns heal spontaneously, evaluation of the child's social environment should not
without the need for skin grafting, with topical therapy be overlooked.
alone. The most commonly used topical agents are 0.5%
DROWNING
silver sulphadiazine, 0.5% silver nitrate and mafenide
acetate. These agents limit bacterial proliferation but do not Drowning is a form of asphyxial death in which the access
sterilize the wound. Silver sulphadiazine offers advantages of air to the lungs is prevented by the submersion of the
in small children; its application is painless, it has a body in water or other fluid medium. In India, drowning
Poisonings, Injuries and Accidents 685
is an important cause of child mortality. Though drowning Most of the injuries can be prevented by ensuring
occurs most frequently in natural bodies of water like discipline, an attribute that has not received sufficient
ponds, lakes, river, deaths due to drowning in swimming emphasis in injury prevention. Discipline may not prevent
pool and bath tubs are increasing. The risk of drowning is a toddler from getting into trouble, but it can prevent an
directly related to physical development of a child and older child from becoming involved in accidents. It
his aquatic skills. includes immediate stopping of all dangerous practices
such as door banging, throwing objects around the room,
Aspiration, Suffocation
playing on the stairs, etc. Even a young child of 1 to VA
Many young children die every year due to suffocation years can be trained to keep away from the kitchen stove
caused by ingestion of foreign objects. Safety pins lead or electrical connections. Parents should not tolerate any
the list of ingested object in infants. More than 50% dangerous habits such as turning on the gas taps that are
accidental deaths among infants were caused by aspiration done for attention seeking. However, they should be
of food during or after feeding. Peanuts are mostly aware that excessive discipline and over-strictness may
responsible for aspiration related suffocation fatalities in force their children to rebel against restrictions making
2-4 yr-olds. Eating rapidly, improper chewing, running them vulnerable to injuries.
with food in mouth or holding a potential foreign body in
the mouth (such as a pin, nail or small toy) is responsible Suggested reading
for such mishaps. Less common reasons include accidental
1 Riordan M, et al. Poisoning in children. General management. Arch
suffocation due to pacifier cords, cords of cradles, small Dis Child 2002;87:392-396.
chains, necklace and rarely by being crushed by adults 2. Riordan M, et al: Poisoning in children 3: Common medicines. Arch
sleeping in the same bed as a young infant. Dis Child 2002;87:400-402.
26 Pediatric Critical Care
INTRODUCTION _____ physician staff can observe all the patients. There should
be adequate space for various utilities and storage.
While neonatal and adult intensive care is well advanced,
The ICU should also have various equipments for
pediatric intensive care is still a developing area. In tertiary
cardio-respiratory monitoring, ECG monitoring, pulse
care hospitals, 5-10% of total pediatric beds should be for
oximeters, devices for oxygen therapy, mechanical venti
ICU and this should be greater if the hospital has surgical
lators, nebulizers, devices for IV therapy including infusion
units.
pumps, weighing scales and plenty of disposables.
Instability of homeostatic mechanisms, functional
More important than anything else, it is the ICU team
immaturity of vital organs and occurrence of multiple
that has a key role in care of critically ill children. The
problems simultaneously in critically ill children lead to
team consists of physicians trained in intensive care and
a complex picture. In addition, children have special
well versed with resuscitation and intravascular access,
needs. In order to optimize resource utilization, it is
and well trained and dedicated nursing staff. It is desirable
essential to understand indications of admission into the
to have a multidisciplinary team.
PICU (Table 26.1).
The ICU should have access to laboratory facilities,
preferably relying on micro-methods. Rapid diagnostic
Table 26.1: Indications for admission into PICU tests for glucose estimation and for determination of
• Hemodynamic instability, shock, cardiac arrhythmias or various compounds in the urine should be available in
cardiorespiratory arrest the ICU. There should be facility for complete blood counts
• Severe anemia or hemorrhage and blood gas and electrolyte estimations. Portable X-ray
• Acute poisoning units and ultrasonography are desirable.
• Respiratory failure: Impending or established Care of a child in ICU requires regular assessment and
• Altered sensorium, encephalopathies, status epilepticus or monitoring (particularly the trends). This relies heavily
raised intracranial pressure on physical examination and use of various monitoring
• Hepatic failure and complications equipments. However, the equipments are not a substitute
• Renal failure and complications to clinical methods. In fact, intensive care is labor intensive.
• Severe metabolic abnormalities such as severe hyper- or The decision making in the ICU goes in the continuous
hypokalemia, severe hyper- or hyponatremia, hypoglycemia cycle of evaluation, intervention and re-evaluation. The
or diabetic ketoacidosis
success of intensive care is greatly dependent on early
• Severe infections like severe malaria
identification of a sick child.
• For procedures such as peritoneal dialysis, exchange
In addition to caring for the primary disorder, particular
transfusion, central venous carunulation
attention should also be paid to nutrition, sedation and
• For postoperative monitoring and care.
analgesia and infection control.
Suggested reading
The optimal number of beds in an ICU is 6-10. Proper
attention has to be paid to the ICU layout; 200-250 square Consensus guidelines for pediatric intensive care units in India:
feet area should be provided per bed. This area will Indian Pediatr 2002; 39: 43-50.
provide space for the bed and various equipments. The
ASSESSMENT/IDENTIFICATION OF
unit should have an uninterrupted power supply. The unit
A SERIOUSL ILL CHILD
preferably should be air-conditioned. The type and
arrangement of beds should be such to allow rapid access In order to improve the survival of seriously ill children,
to the head end for airway management. A crash cart it is mandatory to recognize a sick child at the earliest.
containing all the drugs and necessary equipment for This early identification is required on arrival to the
resuscitation should be ready at all times. In addition, the emergency services and also in children already admitted
unit should have a central station where the nursing and in the hospital. Such an assessment will ensure provision
686
Pediatric Critical Care 687
of more intensive care to these children, which should the work up should be tailored according to the clinical
improve the survival. profile.
Identification of a critically sick child relies on obser Once a sick child is identified and assessed completely,
vation of the child, history and physical examination. At appropriate interventions are performed and the child
first contact, the ABCs are quickly assessed-patency of periodically reexamined to assess improvement or
Airway, adequacy of Breathing and Circulation (this worsening even with intervention and also to identify any
aspect is discussed in the section on pediatric life support). fresh problems.
If there is an abnormality in any of these, life support/ For management of a critically sick child it is mandatory
resuscitation must be initiated. to have good clinical skills; there is no substitute for these.
The important symptoms in seriously ill children Once the child is examined, it is important to identify the
include: problems; for this, a sound knowledge of normal and
• Drowsiness abnormal is required. Appropriate intervention is then
• Seizure activity performed and the child reassessed in the same cycle.
• Excessive irritability
• Decreased activity MONITORING _______
• Difficulty in breathing Monitoring of critically ill children is an essential
• Cold extremities (particularly in the absence of cold component of management. The purposes of monitoring
environment) are:
• Decreased feeding/decreased intake of fluids i. To measure intermittently or continuously key physio
• Decrease in the urine output (e.g. less than 4 wet logic indices that help in diagnosis and management,
nappies in the previous 24 hours) ii. To provide alarms that notify the health care team that
• Apneic episodes/cyanosis important changes have occurred in the child's
• Bilious vomiting. condition, and
These features are predictive of a serious illness, iii. To create and evaluate trends that would help in the
particularly in young infants. In addition, the history assessment of treatment and prognosis.
should identify any underlying chronic illness.
An assessment of whether a child appears to be well or Respiratory Monitoring
ill can also be made on grading the degree of compromise Physical examination: The child should be observed for
in a variety of age-specific behavioral and activity para respiratory rate and pattern, chest retractions, nasal
meters. Various clinical scoring systems are available for flaring, use of accessory muscles and color. On auscul
describing the severity of illness. The parameters tation, check for asymmetry of air entry, type of breath
objectively evaluated in some of these scores include: the sounds and presence of stridor, rhonchi or crepitations.
respiratory effort, level of activity, color, temperature,
Use of monitors: Respiratory rate can be monitored
playfulness, quality of cry, reaction to parental stimu
continuously by impedence pneumography, which
lation, and hydration status. Some of the scores are Yale
requires the presence of three electrodes over the chest.
Observation Score, Young Infant Observation Scale, and
One must be aware about the normal rates at different
Severity Index Score. These scores help in objectivising
ages to be able to detect abnormality (Table 26.2).
the assessment; however, none of these are 100% sensitive
and specific.
Examination is targeted at picking up abnormalities in Table 26.2: Respiratory rates (RR) and heart rates (HR)
various organ systems. As mentioned earlier, it begins at different ages
with assessment of ABCs. Pulse rate, character of the pulse,
respiratory rate and effort, temperature, capillary refill
time, and oxygen saturation (if available) should be
accurately measured. In addition, one should look for
pallor, icterus, edema, wasting and signs of dehydration;
examine the central nervous system for alteration of
sensorium, any neurological deficits, and signs of
meningeal irritation; and assess the renal function by
recording the urine output.
If facility is available for pulse oximetry, the same
should always be included in the assessment of a child. In
a sick child, commonly performed investigations include:
complete blood counts, blood glucose and electrolytes, * Figures in parentheses give the range
and if feasible, arterial blood gas estimation. The rest of
688 Essential Pediatrics
Pulse oximetry has made it possible to non-invasively microcirculation. This helps in diagnosing hemodynamic
measure percent oxygen saturation of hemoglobin. The compromise earlier than drop in arterial blood pressures.
technique is based on Beer-Lambert law and the ratio of Another way of determining adequacy of the peripheral
oxyhemoglobin to the sum of total hemoglobin (reduced perfusion is noting the core-peripheral temperature
hemoglobin and oxyhemoglobin) estimated by measuring gradient. A gradient of more than 5°C indicates hypo
absorption at wavelengths of 660 nm (red) and 940 nm perfusion.
(infrared). Pulse oximetry is fairly reliable in most settings. Abnormality in the intensity of the heart sounds and
However, some conditions lead to inaccuracies: dyshemo- the presence of murmurs may indicate underlying heart
globinemias (methemoglobin), dyes and pigments disease.
(methylene blue), poor peripheral perfusion, increased
Continuous ECG monitoring is mandatory in critically ill
venous pulsations, and optical interference with external
children admitted in ICU.
light sources like phototherapy unit or fluorescent light.
Transcutaneous blood gas monitoring is now feasible Central venous pressures (CVP) are monitored by placing a
and it makes continuous monitoring of pC02 and p02 catheter through a large vein into the right atrium. This
possible. However, it has the limitations of need for pressure gives information about the venous return and
frequent calibration, high cost, and occasional burns. the preload. Normal right atrial pressure is less than 6
Capnography is the graphic waveform produced by mm Hg. If the pressures are low in a child with
variations in C02 concentration throughout the respiratory hypotension, it signifies a low intravascular fluid volume.
cycle as a function of time. A sidestream or mainstream On the other hand, CVP may be increased due to
sampler samples the gases inspired and expired by the myocardial dysfunction, fluid overload or increased
patient. C02 is estimated in these samples by infrared pulmonary artery pressures.
spectroscopy. End-tidal C02 can be used as a substitute In some children, particularly after cardiac surgery,
for PaC02. Also, it has a role in determining endotracheal monitoring of cardiac output and pulmonary artery
tube placement, dead space, and mechanical ventilation pressures may be useful. Echocardiography is a non
failures. invasive modality to assess cardiac structure and function.
In mechanically ventilated children, respiratory In addition, vital organ perfusion can be assessed by
mechanics help in better understanding of respiratory monitoring urine output, which is a surrogate marker of
pathophysiology. renal perfusion and function. Urine output less than 0.5
Apart from these continuous monitoring modalities, ml/kg/hr in a child with normal kidneys signifies poor
chest radiography and arterial blood gas analyses are renal perfusion or excessive ADH. Poor perfusion may
performed periodically. be due to depletion of intravascular volume or conditions
like congestive cardiac failure or shock. Monitoring of the
Hemodynamic Monitoring sensorium and neurologic status also gives information
about vital organ perfusion.
Hemodynamic monitoring provides information about
perfusion of a child's vital organs. Monitoring of Other Organ Systems
Physical examination: Repeated examination of a critically Other monitoring depends on the child's diagnosis and
ill child is the cornerstone of hemodynamic monitoring. the affected organ systems. This would include monitoring
The rate and character of pulse should be examined. The of the hepatic, renal and hematologic parameters.
heart rates are dependent on the age and one must be Level of consciousness can be assessed by Glasgow
aware of these to pick up abnormalities. Coma Scale (GCS). Modified GCS can be used in small
Blood pressure can be monitored by noninvasive or kids upto 5 years of age (Table 26.3).
invasive methods. The pressures may be determined
manually using sphygmomanometers or by use of Suggested reading
automated systems. Invasive methods rely on placement
1. Robertson MA, Molyneux EM. Triage in the developing world—
of a catheter in an artery and pressure measurement by can it be done? Arch Dis Child 2001;85:208-13.
manometer. In children with hemodynamic compromise, 2. Nolan T, Angos P, Cunha A], Muhe L, Qazi S, Simoes EA et al.
blood pressures may not drop significantly until the Quality of hospital care for seriously ill children in less-developed
compromise is severe. countries. Lancet 2001; 357: 106-10.
The state of microcirculation can be assessed by 3. Cheifetz IM Venkataram ST, Hamel DS. Respiratory monitoring.
In Nichols DG. Roger's Textbook of Pediatric Intensive Care.
capillary filling time. Firm pressure is applied over
Baltimore, Lipincott Williams and Wilkins 2008;662-85.
sternum or forehead by ball of the thumb for 5 seconds-
4. Hailey GC, Tibby S. Hemodynamic monitoring. In: Nichols DG
this leads to blanching. On removal of pressure, the color Rogerts Textbook of Pediatric Intensive Care. Baltimore. Lippincott
returns and the time taken for complete return of color is Williams and Wilkins 2008;1039-63.
noted. The normal capillary filling time is 3 seconds or 5. Talman A, Warren A, Development of modified pediatric coma
lesser. Any prolongation signifies impairment of scale in intensive care practice. Arch Dis Child 1997;77:519-21.
Pediatric Critical Care 689
1. Assess responsiveness
Table 26.3: The Glassgow Coma Scale
2. Airway
3. Breathing
4. Circulation.
Assess Responsiveness
The pediatrician should quickly assess the presence and
extent of injury, if present and determine the level of
consciousness (whether the child is responsive or not). The
child who has sustained head or neck trauma should not
be shaken. A child, who is responsive but having
respiratory distress, will require opening of airway to
optimize the ventilation and circulatory support. If the
child is unresponsive, seek help and be prepared for
BLS. If second rescuer is present during assessment, he
can initiate the BLS activation of emergency system to get
proper medical help.
Airway
Infants and children are at a higher risk of having respira
tory obstruction and failure due to following reasons:
smaller size of upper airway in comparison to adults; large
size of tongue in relation to the size of oropharynx; smaller
and compliant subglottic area more prone for collapse
and/or obstruction; relatively compliant chest wall and
rib cage; and limited oxygen reserve.
SEQUENCE OF CPR/BLS
To maximize survival and intact neurological status in
post-resuscitation stage strict adherence to the BLS
sequence is needed. Basic life support (BLS) guidelines
give a series of skills performed sequentially to assess and
restore effective ventilation and circulation to the child
with respiratory or cardio-respiratory arrest. Evaluation
and interventions in pediatric BLS should be simultaneous
processes. The sequence for BLS is described as Fig. 26.1: Head tilt-chin lift maneuver
690 Essential Pediatrics
Jaw thrust: Two or three fingers are placed under each side
of lower jaw at its angle to lift the jaw upwards and
outwards (Fig. 26.2). If this method is unsuccessful, the
head may slightly be extended and another attempt is
made. This method should be used in all victims with
blunt trauma, craniofacial injury and those having
Glasgow Coma Scale score of less than 8. This method is
no longer recommended for lay rescuer because it is
difficult to learn and perform, is often not an effective way
to open the airway, and may cause spinal movement.
visible chest rise. Excessive expansion may compromise Advanced Life Support (ALS) is available. Chest
cardiac output, increasing the chances of regurgitation by compressions provide circulation as a result of increase
distending stomach and increases chances of air leak. In in intrathoracic pressure and/or direct compression of the
patients with small airway obstruction like asthma, heart and should be provided with ventilation in infants
bronchiolitis, excessive ventilation volume may lead to and children. One should compress the lower half of
air leak and compromised cardiac output. In patients with sternum to a relative depth of approximately one third to
head injury or cardiac arrest, excessive ventilation may half of the antero-posterior diameter of chest at a rate at
adversely affect neurological outcome. least 100 compressions per minute in infants and 80 per
The self-inflating bag delivers only room air unless it minute in children. The xiphoid process should be avoided
is connected to an oxygen source. Pediatric bag-valve while providing chest compression and compression
device without any reservoir if connected to an oxygen should be adequate to produce a palpable pulse during
inflow of 10 L/min delivers 30% to 80% of oxygen to the resuscitation. To provide optimum chest compression,
patient. If used with a reservoir it may deliver 60% to 95% victim should be lying supine on a hard and flat surface.
of oxygen and oxygen inflow of 15 L/min is necessary to In an infant with no signs of head or neck trauma, CPR
provide an adequate oxygen volume in the reservoir. may be successfully done supporting the infant's back
with palm of one hand while the other hand gives the
Techniques ofbag-mask ventilation: Bag-mask ventilation can
chest compression.
be as effective as endotracheal intubation and safer when
providing ventilation for short periods. But bag-mask Chest Compression in Infants (<1 Year)
ventilation requires training and periodic retraining. One
Two-finger technique: If you are alone or you cannot
should select a bag with reservoir and mask of proper size
physically encircle the victim's chest, compress the chest
for the patient. The mask must cover the patient's nose
with 2 fingers. Place two fingers of one hand vertically
and mouth completely without covering the eyes or
over the sternum just below the inter-mammary line
overlapping chin. The bag-mask system is connected to
(between the two nipples) ensuring that the fingers are
oxygen supply, the airway is opened and a proper face
not over xiphoid process. One can keep one hand under
mask seal is ensured. When no signs of neck trauma are
the infant supporting the body and head and the other
present, victim's head is to be tilted back to a semi
hand can perform the compression.
extended position to keep airway open. If trauma is
suspected, no head and neck movement is to be done. One Two-thumb technique: Encircle the infant's chest with both
should place the thumb and index finger in a 'C' shape hands; spread your fingers around the thorax, and place
over the mask and exert downward pressure on the mask your thumbs together over the lower half of the sternum
to achieve air seal. The jaw lifting and mask-face seal are avoiding xiphisternum. Forcefully compress the sternum
done by one hand, which is called as 'E-C clamp' with your thumbs as you squeeze the thorax with your
technique. After applying the mask to face properly, the fingers for counter pressure. The 2 thumb-encircling
ventilation bag is compressed with the other hand to hands technique is preferred because it produces higher
achieve visible chest rise. Two rescuers can achieve better coronary artery perfusion pressure, more consistently
bag-mask ventilation; one maintains the proper airway results in appropriate depth or force of compression, and
patency and mask-face seal while the other rescuer may generate higher systolic and diastolic pressures.
delivers ventilation. Gastric distention can be reduced by Provider should perform chest compressions while the
the placement of an orogastric or nasogastric tube. other maintains the airway and performs ventilations at a
ratio of 15:2 with as short a pause in compressions as
Circulation
possible. Do not ventilate and compress the chest
After opening the airway and providing 2 effective rescue simultaneously with either mouth-to-mouth or bag-mask
breaths, heart rate is checked to determine whether the ventilation.
patient is in cardiac arrest and requires chest compression.
Pulse check can be taken as a sign of circulation. Carotid Chest Compression Technique
artery is palpated in children and brachial artery is in the Child (1-8 Years Age)
palpated in infants. This should not take more than 10 Heel of one hand should be placed over lower half of
seconds. sternum avoiding pressure over xiphoid with fingers lifted
Indications for chest compression are absence of signs of above the chest wall to prevent compression of rib cage
circulation after delivering rescue breaths (no spontaneous (Fig. 26.4). Rescuer should place/position him/herself
breathing, coughing, movement or pulse) or the child is vertically above the victim's chest.
pale or cyanosed or heart rate/pulse rate <60 beats per
minute with signs of poor perfusion after rescue breaths.
Chest Compression for Large Children
Chest compressions are serial rhythmic compressions
and Above 8 Years of Age
of the chest that cause blood flow to the vital organs (heart, Two-hand method for chest compression should be used
lungs and brain) in an attempt to keep them viable until to achieve an adequate depth of compression in these
692 Essential Pediatrics
Components of PALS
• Basic life support (BLS)
• Use of equipments and techniques to establish and
maintain effective oxygenation, ventilation and
perfusion
• Clinical and ECG monitoring with arrhythmia detection
and management
• Establishing and maintaining vascular access
• Identification and treatment of reversible causes of
cardiopulmonary arrest
children. This is achieved by placing heel of one hand over
• Emergency treatment of patients with cardiac and
the lower half of sternum and heel of the other hand over
respiratory arrest
the first hand, interlocking the fingers of both hands with
• Treating patients with trauma, shock, respiratory
fingers lifted above the chest wall. Compress the sternum
failure or other pre-arrest conditions.
to depress approximately one third to half of the
anteroposterior diameter of chest. After compression, Adjuncts for Airway and Ventilation
release the pressure without taking off the fingers or
All fluids from patients should be treated as potentially
thumb from the surface of chest wall. Chest compression
infectious and standard universal precautions be followed.
should be delivered in a smooth fashion with equal time
Oxygen should be given to all seriously ill or injured
in compression and relaxation phases.
children with respiratory insufficiency, shock and trauma.
Ventilations are relatively less important during the first
During mouth-to-mouth rescue breathing, 16-17% oxygen
minute of CPR for victims of sudden arrhythmia induced
is delivered with alveolar oxygen pressure of 80 mm Hg,
cardiac arrest than they are after asphyxia-induced arrest,
and optimal external chest compressions provide only a
but even in asphyxial arrest, a minute ventilation that is
fraction of cardiac output resulting in reduced tissue
lower than normal is likely to maintain an adequate
perfusion and oxygen delivery. Ventilation-perfusion
ventilation-perfusion ratio because cardiac output and,
mismatch during CPR and underlying respiratory
therefore, pulmonary blood flow produced by chest
conditions causes right to left shunting resulting in
compressions is quite low.
reduced oxygenation. Oxygen can be administered by
The lay rescuers should use a 30:2 compression-
facemask, nasal cannula, pharyngeal mask, laryngeal
ventilation ratio for all (infant, child, and adult) victims.
mask and tracheal tubes with ventilation.
For one healthcare provider, the compression-ventilation
ratio should be 30:2 for all age groups and for two rescuers, Endotracheal Intubation
the compression-ventilation ratio should be 30:2 for all
If used properly, this is the most effective and reliable
adult CPR and 15:2 compression ventilation ratio for infant
method of ventilation. The advantages of endotracheal
and child up to the start of puberty.
intubation are: (a) ensures adequate ventilation, (b)
Two or more rescuers should rotate the compressor role
reduced risk of aspiration of gastric contents, (c)
approximately every 2 minutes to prevent fatigue and
inspiratory time and peak inspiratory pressure can be
deterioration in quality and rate of chest compressions.
controlled, (d) suction can be done to keep airway patent,
The switch should be accomplished as quickly as possible
and (e) positive end-expiratory pressure can be provided.
(ideally in less than 5 seconds) to minimize interruptions
Indications for endotracheal intubations are excessive
in chest compressions.
work of breathing leading to fatigue, inadequate CNS
External chest compression in children and infants
control of ventilation leading to apnea or poor respiratory
should always be accompanied by rescue breathing.
effort, functional or anatomical airway obstruction, need
Reassess the victim after 2 minutes or after 5 cycles.
for higher peak inspiratory pressure or positive end-
If signs of spontaneous circulation have reappeared,
expiratory pressure to maintain effective alveolar gas
chest compression should be stopped and only ventilation
exchange, lack of airway protective reflexes, and for
to continue till return of adequate spontaneous breathing.
prolonged duration CPR. Airway in the child is more
compliant with relatively large tongue, anteriorly placed
PEDIATRIC ADVANCED LIFE SUPPORT (PALS)
glottis and proportionately smaller airway, making it
Pediatric advanced life support (PALS) refers to the different from adults. As the subglottic area is the
assessment and support of pulmonary and circulatory narrowest part of the pediatric airway, uncuffed
Pediatric Critical Care 693
endotracheal tubes are used in children <8 years of age. Depth of insertion (cm) = Internal diameter of the tracheal
In certain circumstances (e.g. poor lung compliance, high tube (in mm) x 3.
airway resistance, or a large glottic air leak) a cuffed tube In newborn the depth of insertion of endotracheal tube
may be preferable provided that attention is paid to depends on the birth weight:
endotracheal tube size, position, and cuff inflation Depth of insertion (cm) = birth weight (kg) + 6
pressure. The cuff inflation pressure should be kept <20 In children >2 years of age:
cm H20. Depth of insertion (in cm) = (age in years/2) + 12.
Size of the tracheal tube and suction catheter for the While intubating, the black mark on the tracheal tube
tube can be determined according to the age of the child/ should be kept at the level of vocal cords to place the tube
infant as per the following chart (Table 26.4): in proper position.
Beyond 1 year of age, the size of tracheal tube can be After intubation, the position of the tracheal tube should
estimated according to the formula: be assessed to ensure adequate ventilation and avoiding
Tracheal tube size (in mm) complications like segmental collapses. Chest rise should
be bilaterally symmetrical with equal air entry in both axil
= (Age in years/4) + 4 in case of uncuffed tube lae. Breath sounds should be checked over upper abdomen
= (Age in years/4) + 3 in case of cuffed tube to rule out esophageal intubation and due to close proxi
mity breath sounds may be heard over chest in infants and
In general, tubes of size 0.5 mm smaller and 0.5 mm
young children. Check for exhaled C02 if there is a perfus
larger than the estimated should be available for use. The
ing rhythm. If the child has a perfusing rhythm and is
size of suction catheter (in Fr) is usually twice the internal
<20 kg, one may use an esophageal detector device to check
diameter of the tracheal tube in mm, i.e. 8 Fr suction
for evidence of esophageal placement. Check oxygen
catheter for tracheal tube of size 4 mm.
saturation with a pulse oximeter. Following hyper
oxygenation, the oxyhemoglobin saturation detected by
Table 26.4: Selecting the sizes of ET tube and suction
pulse oximetry may not demonstrate a fall indicative of
catheters in newborn and infants
incorrect endotracheal tube position (i.e. tube displace
Age Tracheal tube Suction catheter
ments) for as long as 3 minutes. If there is uncertainty about
size (in mm) size (in Fr)
the tube position, direct laryngoscopy can be performed to
Premature newborn 2.5 5
visualize the tube passing between the vocal cords.
<1 Kg Tracheal tube position should be confirmed by chest
Premature newborn 3.0 5-6
radiograph.
1-2 Kg
Newborn 2-3 kg 3.0-3.5 6-8 Establishing and Maintaining Vascular Access
Newborn > 3 kg 3.5-4.0 8
Tracheal route may be used for administration of lipid- severe hemorrhagic shock who remain in shock even after
soluble drugs like lidocaine, epinephrine, atropine and infusion of 40-60 ml/kg of crystalloid. Dextrose solutions
naloxone (LEAN) until vascular access is established. should not be used for initial resuscitation as they don't
According to the data from animal models and adult expand the intravascular volume effectively and may cause
human studies, the suggested dosage for tracheal use is hyperglycemia leading to osmotic diuresis setting a vicious
approximately 10 times of IV dose. cycle of polyuria and hypovolemia. Recommendation
Administration of resuscitation drugs into the trachea cannot be made about use of colloid solutions in fluid
can result in lower blood concentrations than the same resuscitation of infants and children due to lack of studies.
dose given intravascularly. Furthermore, recent animal Hypoglycemia, if suspected or documented, should be
studies suggest that the lower epinephrine concentrations managed readily with intravenous glucose with measures
achieved when the drug is delivered by the endotracheal to prevent recurrence.
route may produce transient (3-adrenergic effects. These
effects can be detrimental, causing hypotension, lower Drugs used for Cardiac Arrest and Resuscitation
coronary artery perfusion pressure and flow, and reduced Table 26.5 shows the commonly used drugs during
potential for return of spontaneous circulation. Thus, resuscitation.
although endotracheal administration of some resus
citation drugs is possible, IV or IO drug administration is Arrhythmias
preferred because it will provide a more predictable drug Most pediatric arrhythmias are the consequences of
delivery and pharmacologic effect. hypoxemia, acidosis, hypotension but children with
Non-lipid-soluble drugs (e.g. sodium bicarbonate and myocarditis, cardiomyopathy and after cardiac surgery
calcium) may injure the airway and should not be are at increased risk of primary arrhythmia. Drugs in
administered via the endotracheal route. therapeutic or toxic doses can lead to arrhythmia. About
10% of pediatric cardiac arrest patients have VF or
Fluid Therapy pulseless VT.
Early restoration of the circulating blood volume is
important to prevent progression to refractory shock or car Bradyarrh ythmias
diac arrest. Volume expansion is best achieved with iso Hypoxemia, hypothermia, acidosis, hypotension, and
tonic crystalloid fluids, such as Ringer lactate or normal hypoglycemia depress the sinus node function and slow
saline. Blood replacement is indicated in patients with conduction through the myocardium. In addition to these,
excessive vagal stimulation, raised intracranial pressure First 3 episodes should be given in rapid successions with
or brain stem compression may cause bradycardia. Sinus pauses to check the presence of VF. Simultaneous
bradycardia, sinus node arrest with junctional or correction of hypoxia, acidosis, and hypothermia should
idioventricular rhythm, AV blocks are usual pre-terminal be done if present to improve the outcome of defibrillation.
rhythms observed in infants and children. All slow After failure of 3 attempts, trial of defibrillation should be
rhythms resulting in hemodynamic instability require given after epinephrine and CPR for 30 to 60 seconds. After
immediate treatment. Adrenaline or epinephrine is the the 4th failed defibrillation, use amiodarone (5 mg/kg
most useful drug in treating symptomatic bradycardia bolus), lidocaine (1 mg/kg) or high dose epinephrine
unless due to heart block or vagal overtone. For suspected followed by defibrillation with 4 J/kg within 30 to 60
bradycardia due to vagal overtone, atropine is the drug seconds after each drug if VF/VT persists.
of choice. If no positive or transient effect is observed after In cases of children > 8 years of age those who weigh
ventilation and oxygenation, continuous infusion of >50 kg, adult dose defibrillation should be used. Increase
epinephrine or dopamine should be considered. in the dose is not indicated when defibrillation is initially
successful but rhythm reverts back to VF. Adjunctive
Pulseless Electrical Activity (PEA) medications (amiodarone, lidocaine, sotalol) with defibril
It is a state of electrical activity observed on a monitor or lation may improve the outcome. The reversible causes
ECG in absence of detectable cardiac activity. This is often of VF/VT (hypoxia, hypothermia, hyper/hypokalemia,
the pre terminal state preceding asystole representing the hypovolemia and metabolic disorders) should be looked
electrical activity of a hypoxic and acidotic myocardium. for and treated accordingly.
Occasionally the PEA may be due to sudden impairment
Suggested reading
of cardiac output with normal ECG rhythm and heart rate
increased or rapidly decreasing. Pulses or other evidence 1. Guidelines 2005 for cardiopulmonary resuscitation and emergency
cardiovascular care: Pediatric basic life support. Circulation 2005;
of cardiac output are absent and child appears lifeless.
112 (suppl part 11): 156-66.
This category of PEA is called electromechanical 2. Guidelines 2005 for cardiopulmonary resuscitation and emergency
dissociation (EMD). The reversible causes of EMD are 4H's cardiovascular care: Pediatric advanced life support. Circulation
and 4T's. The 4 H's are severe hypovolemia, hypoxia, 2005; 112 (suppl part 12):167-87.
hypothermia, hyperkalemia and other metabolic imbalan
ces whereas the 4 T's are tension pneumothorax, toxins RESUSCITATION IN TRAUMA: BASIC PRINCIPLES
and drugs, pericardial tamponade, pulmonary thrombo
A large number of children are injured in accidents both
embolism. Treatment of PEA and EMD are same as
in and outside the home. While minor injuries can be
treatment of asystole with identification of reversible
managed easily, serious injuries need expert care to
causes and treating accordingly.
improve the outcomes. As with other emergencies, it is
Please refer to section on tachyarrhythmia for treatment
of supraventricular tachycardis, ventricular tachycardia mandatory to start with the assessment of ABC. A few
specific considerations are given here.
and fibrillation.
Airway
Defibrillation
Often, children injured in road traffic accidents or due to
Defibrillation is the asynchronous depolarization of a
fall from height have cervical injury and improper
critical mass of myocardium that successfully terminates
handling may lead to irreparable damage. In such cases,
VF or pulse less VT. It is successful in cases of sudden
the cervical spine should be immobilized with a semi-rigid
onset VF having oxygenated normothermic myocardium
cervical collar. Ensure that head is in neutral position.
without significant acidosis. Larger size defibrillator
Cervical collar should not be removed till radiographs and
paddles, i.e. 8-10 cm in diameter are recommended in
physical examination have ruled out the spine injury.
children weighing more than 10 kg weight to maximize
Always inspect for foreign body, blood or broken teeth in
the current flow. Smaller paddles are used in infants and
the upper airway. For airway stabilization, head-tilt/chin-
children weighing less than 10 kg. One paddle is placed
lift procedure is contraindicated because of converting an
over the right side of the upper chest and the other one
incomplete spinal cord injury into a complete one. Crico-
over the apex of the heart (to the left of the nipple over the
thyrotomy may be required in the presence of severe
left lower ribs). Alternatively electrodes may be placed in
orofacial trauma.
anterior-posterior position with one placed to left of
sternum and the other one over back.
Breathing
Optimal electrical energy dose to defibrillate is not
conclusively established in children but the available data The considerations for endotracheal intubation and
suggests an initial dose of 2J/kg. If this is unsuccessful, ventilation are the same as discussed earlier. Inspect for
energy dose should be doubled and repeated if needed. pneumothorax or hemothorax.
696 Essential Pediatrics
Mediators of Tissue Damage in Shock tachycardia, mild tachypnea, slightly delayed capillary
Altered oxygen metabolism: Hypoxia and ischemic (oxygen refill (>2-3 sec), orthostatic changes in blood pressure or
and substrate deficiency) injury occurs at some time pulse and mild irritability. But early septic shock reveals
during all types of shock. Cellular hypoxia results from increased peripheral pulses, warm and over perfused
either atmospheric low oxygen input abnormal lungs with extremities, widened pulse pressure and hyper dynamic
V/Q mismatch, stagnant anoxia, anemic hypoxia. precardium.
Reduced ATP production, depressed mitochondrial If the shock state continues, the compensatory mecha
function, intracytoplasmic calcium, dysfunction of Na+ K+ nisms are not enough to maintain the metabolic needs of
ATPase pump lead to cellular edema which subsequently the tissues. The cellular ischemia and inflammatory
causes release of lysosomal enzymes resulting in tissue mediators released affect the microcirculation to reveal
the signs of brain, kidney and cardiac compromise. Incre
damage.
ase in tachypnea due to metabolic acidosis leads to
Microcirculatory abnormality: Spasm of precapillary reduction in PaC02 and respiratory alkalosis. Skin shows
sphincters and arterioles cause anoxia and damage to features of reduced capillary refill and mottling.
capillary endothelium. This leads to blockage of capillary Hypotension and oliguria sets in with hypothermia.
bed with platelet aggregation and fibrin deposit further Mental changes in the form of agitation, confusion, stupor
compromising the tissue circulation. and finally coma may occur.
I
preventing nitric oxide production. Although there was
much optimism that these agents would reduce the morbi
Start dopamine or
dity and detrimental effects of inflammatory mediators,
Observe in PICU
dobutamine at subsequent animal and human studies have revealed
10 |jg/kg/min mixed results. In fact some of these studies have been
Insert CVP line Start
arterial pressure monitoring
associated with an increased mortality. Naloxone hydro
chloride, an opioid antagonist, may block the endorphin
effect that occurs in sepsis and may improve the
Dopamine/dobutamine resistant shock
hemodynamics in patients with septic shock. However,
its routine usage is not recommended. Inhibition of nitric
Warm shock Cold shock oxide release by methylene blue has been shown to
improve the mean arterial pressure in adult patients with
septic shock.
Start norepinephrine Start epinephrine
diaphragm, and abdominal wall). Tube-like structures are This equation shows that PA02 can be increased by
conduits for gases; their mechanics can be characterized increasing the FiOz. The other way, not commonly used,
by the relationship of the gas flow through the tube (F) is to administer oxygen at higher pressures i.e. hyperbaric
and the pressure difference (P2-Pi) that produces the flow. oxygen therapy.
Bag-like inflatable structures contain gas; their mechanics Ventilation perfusion mismatch is usually due to
are characterized by the relationship between the con atelectasis or poorly ventilated alveolar units (these act as
tained gas volume (V) and the pressure difference displac R—> L shunt). These units can be recruited by increasing
ing the wall. the mean airway pressure (MAP). This recruitment
Lungs are a combination of both types of structures. reduces the mismatch and also increases the end expi
To simplify the matters, lung can be viewed as a single ratory volume, thereby improving the compliance of the
compartment, consisting of a single, cylindrical flow- lung. The MAP is dependent on the peak inspiratory pres
conducting tube (i.e. the conducting airways) connected sure (PIP), positive end expiratory pressure (PEEP),
to a single, spherical, elastic compartment (i.e. alveoli). inspiratory time (Ti), expiratory time (Te), and the
The transrespiratory pressure (Ptr) necessary to achieve characteristics of the waveform (k).
inflation has two components: MAP= k [ (Ti X PIP) + (TeX PEEP)]/(Ti + Te)
i. the transairway pressure (Pta) necessary to overcome From this equation, one can predict the effects of change
the resistance to flow, and in PIP, PEEP, Ti, etc. on the MAP.
ii. the transthoracic pressure (Ptt) which is the pressure
required to deliver the tidal volume against the elastic Alveolar Ventilation
recoil. The PaC02 depends on the C02 production and the
alveolar ventilation. While the C02 production can be
When a patient is ventilated, the Ptr is equal to the
manipulated by dietary modifications and modification
airway pressure (Paw)
of the metabolic rates, the same cannot be done for effect
Paw = Ptt + Pta
ing acute changes in PaC02. So, for practical purposes the
changes in the PaC02 depend on alveolar ventilation.
The change in Pta is proportional to the change in flow
Alveolar ventilation = [Tidal volume (VT)-dead space
rate (F) and the constant of proportionality AP/AF is
volume (VD)] x Respiratory frequency (f).
resistance (R). The change in the lung volume is directly
Therefore, the PaC02 can be altered by regulating VT
proportional to the corresponding change in the Ptt. The
and frequency. In a mechanically ventilated child, efforts
constant AV/ AP is called compliance (C), and its reciprocal
should be made to minimize the dead space , e.g. ET tube
elastance. If a system is highly compliant, it means that
should be cut short, ventilator circuit dead space should
only a small change in pressure is required to achieve
be minimized. Usually an increase in VT would decrease
inflation; on the other hand if compliance is reduced, a
PaC02. However, this will depend on the dead space and
larger change in pressure is required to produce the same
changes in the metabolic rate.
change in volume. Therefore, the equation of motion of
At end of this discussion it is clear that to improve
the respiratory system for inspiration is: Paw = V/ C + F
oxygenation, the following can be done: increase Fi02, or
R. The equation of motion for expiration is: V/ C = - F R,
PIP, or PEEP, or Ti. To reduce PaC02, increase the VT or
as during passive exhalation, the elastic component of the
the frequency (f). VT in turn is dependent on the driving
lungs (i.e. the elastic recoil) provide the necessary pressure
pressure i.e. PIP-PEEP, the resistance, compliance, and the
to drive the flow.
Ti.
Mechanical Ventilators cycle variables, i.e. the patient performs the triggering
Mechanical ventilators are designed to assist or replace work, the ventilator completes the rest. Assisted
the work of the respiratory muscles and the thorax to ventilation aims at reducing patient effort and optimizing
maintain the gas exchange function of the lungs. There comfort. Modes of assisted ventilation can be used in large
are many types of ventilators available. Chatburn number of situations to work in synchrony with patient
developed a useful classification, which is easy to effort. This is because most ventilated patients continue
understand. This is based on the equation of motion: to breathe on their own except if their CNS is highly
Pressure= (Volume/compliance) + Flow x Resistance. damaged, if their PaC02 is maintained lower than the
The main headings to describe a ventilator are: apnea threshold, or if they are deeply sedated or
a. Power input, paralyzed. These modes are also used during weaning.
b. Power transmission, Assist control ventilation (ACV): ACV is a mode of
c. Control scheme, mechanical ventilation where the ventilator provides a
d. Output waveform, and preset VT or pressure in response to every patient-initiated
e. Alarms. breath. If the patient fails to initiate a breath within a
preselected time period, the ventilator delivers the VT or
Modes of Mechanical Ventilation
pressure at the predetermined frequency. Since every
A mechanical ventilator can allow/ deliver 4 different patient inspiratory effort that is detected by the machine
types of breaths: mandatory, assisted, supported, or results in a mechanical breath there is a risk of hyper
spontaneous; or a combination of these. ventilation and respiratory alkalosis.
movements / expansion, air entry, breath sounds, and the essential to provide adequate nutrition early in course of
color of the skin. Pulse oximetry is useful adjunct. The severe illness in order to improve the outcomes.
patient ventilator interaction should be evaluated carefully Two routes are available for administration of nutrients:
and efforts should be made to improve synchronization. enteral and parenteral. Enteral route is the preferred one,
After a short time of stabilization, ABGs should be provided the intestines are functioning. It is safer and more
measured and necessary adjustments should be made. cost effective than total parenteral nutrition (TPN). Enteral
nutrition helps in maintaining the gut barrier and prevents
Continuing Ventilatory Support and the ulcerative complications. It also preserves the indi
Weaning from Mechanical Ventilation genous flora and prevents the overgrowth of the
pathogens there by reducing the risk of bactermia and
Most children need ventilatory support for a few days
pneumonia. The enteral feeding prevents the gut mucosal
only; however, a small number require mechanical
atrophy so that the early resumption of full oral feeds is
ventilation for prolonged periods. After starting mechani easier during recovery period.
cal ventilation, subsequent adjustments are made after Elemental and non-elemental diets are available.
evaluating the child's disease status, spontaneous effort, Simplest kind of feed is a milk based feed. Various com
and ABGs. In case of worsening, the settings have to be mercial formulas are available. The elemental formulae
increased (as discussed earlier). Usually one variable is contain carbohydrates as oligosaccharides, maltodextrins
modified at a time and then its effect seen on ABGs. or hydrolyzed cornstarch; nitrogen as peptides or free
However, if worsening is severe or or acute, multiple amino acid and lipids as various oils or medium-chain
variables, e.g. FiOz, rate, PEEP, etc. may have to be triglycerides. In addition, special formulae are also
adjusted to achieve improvement in oxygenation and/or available, e.g., low lactose or lactose free diets. Start with
ventilation. 10-15 ml/kg/d of feeds and increase by 10-15 ml/kg/d
Weaning is basically the process of liberation from till target categories are achieved. Enteral feeds may be
ventilator. As the child improves the need for ventilatory delivered directly into the stomach by nasal/oral routes.
support decreases. A child's condition has to be carefully Small-bowel feedings are useful in cases of gastroparesis.
followed so that our support keeps pace with the child; Supplementation of vitamins and minerals is best done
decreasing support earlier than indicated imposes greater with enteral route.
work of breathing while delaying this would delay The disadvantage of enteral route is, most patients with
sepsis may have the septic ileus, which would take 3-7
extubation.
days to resolve precluding the early administration of
enteral route. The other common clinical conditions where
Suggested reading
the enteral feeding is contraindicated are severe GI
1. Lodha R, Kapoor V, Kabra SK, Mechanical ventilation. In: Kabra
hemorrhage, recent GI surgery, intestinal obstruction. The
SK, Lodha R, eds. Essentials of Pediatric Pulmonology. Nobel
Vision 2006;233-257.
complications of enteral feeding are intolerance,
2. Heulitt MT, Wolf GK, Arnold IH. Mechanical ventilation. In Nichols misplacement of the feeding tube, esophagitis and
DG (ed). Roger's Textbook of Pediatric Intensive Care. Baltimore. esophageal ulceration. There can be reflux which may lead
Lipincott Williams and Wilkins. 2008;508-31. to pulmonary aspiration. Diarrhea may occur because of
hyperosmolar formulae, infection, or malabsorption.
NUTRITION IN CRITICALLY ILL CHILDREN ____________ Rarely there can be nutritional recovery syndrome in a
child who is severely malnourished and is given high
A critically ill child is particularly prone to develop caloric and protein diet.
malnutrition. Decreased intake, accelerated demands Parenteral nutrition refers to the delivery of all the
brought by severe illness, and increased needs associated nutrients directly into the blood stream: amino acid
with growth contribute to malnutrition. In sick children, mixtures, lipids, glucose, and trace mineral and vitamins.
reduced nutrition intake can have deleterious effects. As These may be infused into a peripheral or central vein.
children have less energy and substrate reserves, they are The use of peripheral veins is limited by the osmolality of
more dependent on substrate supply than adults. infusate (should be < 700 mOsm/1). Thus, for delivery of
Malnutrition in hospitalized patient is increasingly being adequate calories, central venous access is essential.
recognized as an important factor determining outcome The goal for calories is age dependent. For infants, the
of the disease. Children with any grade of malnutrition need is about 100 cal/kg. Glucose infusions are started at
are at increased risk of mortality with acute severe illness. about 5-6 mg/kg/minute and increased gradually; insulin
There is growing evidence that early and appropriate goal may be used if there is hyperglycemia. Amino acids are
oriented nutritional support in the ill child aids recovery. begun at lg/kg/d; then increased over 2-3 days to 2.5 g/
Stress results in increase in resting energy expenditure, kg/d. Lipids are infused at 0.5 g/kg on day 1 and increased
proteolysis, gluconeogenesis, urinary nitrogen loss, to 2-2.5 g/kg/d over 4-5 days. Appropriate combination
glucose intolerance and resistance to insulin. Provision of can be achieved by considering fluid requirements. Trace
glucose alone does not suppress 'auto-cannibalism'. It is elements and vitamin preparations are added.
704 Essential Pediatrics
Use of TPN requires regular monitoring blood glucose underlying medical problems, medication use, allergies
thrice a day; serum electrolytes and urea twice a week; and time and nature of last oral intake.
and serum chemistry, triglycerides, and complete blood Monitoring is very important during sedation. The
counts once a week. Weight is recorded daily, other child's face, mouth and movement of chest wall must be
anthropometric measurements recorded once a week. continuously observed. The vital regions should be
The complications include catheter related infections, measured before, after the administration of the drugs,
liver dysfunction, hyperglycemia, hyperlipidemia, on completion of the procedure, during recovery and at
acidosis, and electrolyte imbalances. completion of recovery. ECG monitoring and pulse
Once parenteral nutrition is started, enteral feeds are oximetry are useful adjuncts. The sedation and procedure
added as soon as gut function improves. room should have all the equipment for airway
management and the essential drugs for resuscitation.
Immunonutrition Table 26.10 summarizes the details of commonly used
The use of enteral formulae supplemented with immuno- drugs for sedation and analgesia. Table 26.11 lists various
nutrients has been demonstrated to modulate gut function, clinical scenarios requiring sedation/analgesia. For
inflammatory and immune responses. In critical illness, children undergoing mechanical ventilation, continuous
it is desirable to have reinforcement of mucosal barrier infusion of midazolam/diazepam may be used for better
and cellular defense and some down-regulation of local control of ventilation. In addition, intermittent doses or
or systemic inflammatory response. This may be achieved continuous infusion of fentanyl or morphine may be used
by use of immunonutrients: glutamine, arginine, w-3 fatty for pain control.
acids, nucleotides, taurine, cysteine, certain complex
carbohydrates and probiotic bacteria. Use of immuno Neuromuscular Blocking Drugs
nutrition has been shown to reduce morbidity and the risk The use of neuromuscular blocking drugs (NMBD) drugs
of infectious complications in critically ill patients. is common in intensive care units. Various drugs are now
available to allow the clinician to tailor a regimen to child's
Suggested reading specific needs. Succinyl choline is the only depolarizing
1. Biolo G, Grimble G, Preiser JC, et al. Metabolic basis of nutrition in muscle relaxant available. The non-depolarizing drugs
intensive care unit patients. Intensive Care Med 2002; 28:1512- 20.
include pancuronium, atracurium, vecuronium, rocuro-
2. de Carvalho WB Leite HP. Nutritional Support in the critically ill
nium.
child. In Nichols DG (ed). Roger's Textbook Pediatric Intensive
Care. Baltimore. Lippincott Williams and Wilkins. 2008;1500-15. The possible indications for use of neuromuscular
3. Briassoulis G, Zavras N, Hatzis T. Malnutrition, nutritional indices, blocking drugs in intensive care units are as follows:
and early enteral feeding in critically ill children. Nutrition. 2001;
17: 548-57. Short Term
i. Facilitation of airway instrumentation
SEDATION, ANALGESIA, PARALYSIS_______________
ii. Facilitation of invasive procedures
The management of acute pain and anxiety in children
undergoing therapeutic and diagnostic procedures Long Term
outside the operating theater has improved substantially. i. Facilitation of mechanical ventilation, to overcome
The goal of sedation is safe and effective control of pain, patient-ventilation dyssynchrony, and to facilitate
anxiety, and motion so as to allow a necessary procedure ventilation at high settings.
to be performed and to provide appropriate amnesia or ii. Reduction of work of breathing/metabolic demand.
decreased awareness. The need for sedation and analgesia iii. Treatment of agitation unresponsive to maximum
is significantly higher in intensive care units. sedation and analgesia
The state of sedation varies from conscious sedation to iv. Treatment of tetanus
deep sedation to general anesthesia. In conscious sedation, v. Facilitation of treatment of status epilepticus under
the consciousness is depressed but the protective airway continuous EEG monitoring.
reflexes are maintained and the child can respond Limiting asynchronous patient-ventilator interactions
appropriately to verbal command or physical stimulation. has been one of the major indications of use of NMBDs in
Deep sedation refers to a medically controlled state of intensive care units. However, improved ventilator
depressed consciousness from which the child is not easily techniques and development of ventilators that can
aroused. This is accompanied by partial or complete loss synchronize with child's own inspiratory efforts have
of protective reflexes and the child cannot respond reduced the use of NMBDs.
purposefully to physical stimulation or verbal commands. Table 26.12 shows the characteristics and doses of
For safe sedation, it is essential to have skilled personnel various neuromuscular blocking drugs.
capable of rapidly identifying and treating cardio Children receiving neuromuscular blocking drugs
respiratory complications. The child should be carefully should be monitored very carefully. Particular attention
assessed before sedation. This includes evaluation of should be paid towards position of artificial airway and
Pediatric Critical Care 705
adequate ventilation. Sedation should always be given to muscle atrophy and joint contractures. This can be reduced
any child who is requiring paralysis. by passive movements and splinting of joints in functional
The use of these drugs is associated with some position. Pressure sores and skin ulcers are likely to
complications. Prolonged usage of NMBDs can cause develop because of immobilization and impaired skin
706 Essential Pediatrics
perfusion. Absence of eye blink may lead to corneal in an ICU is an important determinant of nosocomial
drying and abrasions. This can be avoided by use of infection. The use of invasive devices (endotracheal tubes,
lubricating ointment and artificial tears and gentle closing intravascular catheters, urinary catheters) has an
of the eyelid. If a child is receiving NMBDs, he/she should important role in development of nosocomial infections.
simultaneously receive a sedative and analgesic for It is observed that about 90% of all bloodstream infections
overcoming anxiety no pain. Some children experience occurred in children with central venous lines, 95% of
prolonged muscle weakness after discontinuation of nosocomial pneumonias occurred in those on mechanical
NMBD. Use of succinyl chloride may lead to vagal- ventilation and 75% of UTIs in children with urinary
mediated bradycardia, sinus arrest or functional rhythms; catheters. These figures highlight the important role of
larger doses may lead to tachycardia, ventricular various devices in nosocomial infections.
arrhythmias and hypertension. Nosocomial infections may be caused by organisms that
originate from exogenous sources in hospital or from endo
Suggested reading
genous sources such as child's own flora. Because of
1. Krauss B, Steven SM. Sedation and analgesia for procedures in alteration of child's flora associated with the illness and
children N Engl J Med 2000; 342: 938-45.
hospitalization, such distinction may not be easy. The
2. Young C, Knudsen N, Hilton A, Reves JG. Sedation in intensive
care unit. Crit Care Med 2000; 28: 854-66.
altered flora mainly included gram-negative bacilli and
3. Martin LD, Bratton SL, O'Rourke PP. Clinical uses and contro Staphylococcus aureus, which were often antibiotic
versies of neuromuscular blocking agents in infants and children. resistant.
Crit Care Med 1999; 27: 1358-68. The hospital environment may contribute to acquisition
4. Nair MNG, Jatane SK. Sedation Analgesia in Pediatric Intensive
and spread of most endemic nosocomial infections. Even
Care. Indian J Pediatr 2004;71;145-49.
if environmental surfaces are contaminated with microbes,
they can be spread to patients by hand contact only.
NOSOCOMIAL INFECTIONS IN PICU Occasionally, environment may be responsible for life
Nosocomial or hospital acquired infections are all threatening nosocomial infections such as aspergillus in
infections that occur during a patient's hospitalization and immunocompromised individuals.
not present or incubating at admission. Also any infection It is estimated that the overall mortality attributed to
that appears to have been acquired in hospital but does nosocomial infections is about 10%. The mortality is
not manifest until after discharge is judged to be a associated with nosocomial infections is multifactorial;
nosocomial infection. Therefore, all infections diagnosed some of these factors are the type of patient, the number
48 hours after admission till 72 hours after discharge of altered organs, and the microbes responsible for the
should be considered as nosocomial. infection. Blood stream infections caused by Klebsiella
Nosocomial infections are a significant problem in pneumoniae or the fungi have mortality range of 18-20%.
pediatric intensive care units. The infections in pediatric The nosocomial infections increase the duration of stay in
intensive care units (PICU) are more widespread than in hospital and also the cost of therapy.
general pediatric wards. The increased risk of infection
probably results both from the greater severity of the Strategies to Reduce the
underlying disease and from the frequent interventions Incidence of Nosocomial Infections
and use of devices that bypass natural barriers to infection. For reducing the incidence of nosocomial infection, each
The estimated rate of infection is 10-20 nosocomial PICU should have an infection control program. There
infections per 1000 patient days for pediatric ICUs. The should be a written description of the goals, objectives,
overall nosocomial infection rates in the PICUs are reported and structure of program. A team of health professionals
to be 6-10%. These rates are lower than those seen in adult should ensure implementation of the policies and
intensive care units. The primary bloodstream infections compliance on the part of the PICU team. Well-directed
are the commonest nosocomial infections (25-30%) in infection control activities can reduce the nosocomial
PICUs followed by the lower respiratory tract infections infection rates by up to 50%.
(20-25%) and urinary tract infection (UTI) (15-20%). In The importance of hand washing and hand disinfection
adults, UTI is the commonest nosocomial infection is well understood. The appropriate hand washing
followed by surgical infection and lower respiratory tract technique includes wetting the hands, taking soap,
infections. Staphylococcous aureus, coagulase negative rubbing hands to produce a lather, and performing wash
staphaylococci, E.coli, Pseudomonas aeruginosa, Klebseilla, movements that include rubbing palm to palm, right palm
enterococci and Candida are the significant pathogens in over left dorsum and vice versa, palm to palm with fingers
pediatric services in the various sites examined. interlaced, backs of fingers to opposing palm with fingers
The risk of nosocomial infections in a PICU is the direct interlocked, rotational rubbing of right thumb clasped in
consequence of the severity of illness, the level of invasive left palm and vice versa, rotational rubbing with clasped
monitoring, the indiscriminate use of anti-microbial and fingers of right hand in palm of left hand and with changed
the nature of diagnostic procedures. The duration of stay roles (Fig. 26.6). The whole procedure should not take less
Pediatric Critical Care 707
technique of insertion and maintenance of the catheter plasma and platelet components by differential centri
throughout its life, (ii) type of solution being administered fugation. Automated apharesis procedures can be used
through the intravenous line, (iii) number of "break ins" to collect platelets, granulocytes or plasma. Cryo
into the catheters system and intravenous tubing, (iv) the precipitate may be prepared from a plasma unit. Plasma
presence of infection elsewhere in the body. The following proteins such as albumin, anti-D immune serum globulins,
measures may help in reducing catheter-related infections: intravenous immunoglobulins and concentrated coagu
• Selection of subclavian, basilic or cephalic vein site lation factors are prepared by more expensive processing
rather then femoral or internal jugular vein. of large polls of donor plasma obtained from whole blood
• Using maximal aseptic technique for catheter or plasmapharesis donations.
"insertion"
RBC Transfusion
• Mupirocin ointment may reduce the risk of bacterial
colonization of catheters but may increase colonization
Indications for Transfusion of RBCs
rate of fungi. Small volume transfusion
• Using cotton gauze rather than transparent dressing. 1. Infant with hematocrit <20% and asymptomatic with
reticulocytes <100,000/cu mm.
• Having an experienced physician insert the catheter.
• Avoid use of TPN catheters for other than infusion of 2. Infant with hematocrit <30%
TPN. requiring oxygen <35%;
requiring CPAP or mechanical ventilation;
• Have adequate staff for management of patients with
and significant apnea or bradycardia;
central venous catheters.
heart rate >180/min or respiratory rate >80/min
persisting for >24 hours; or
Prevention of Nosocomial Urinary Tract Infections
weight gain <102g/day observed over 4 days while on
The catheterizations should be kept to a minimum. The >100 cal/kg/d or undergoing surgery.
need for catheterization must be strictly evaluated and
3. Infant with hematocrit <35%
catheterization must be replaced by closed condom
if receiving oxygen >35% or
drainage whenever possible. When thought to have
getting mechanical ventilation.
fulfilled their need the catheters must be immediately
removed. Strict asepsis should be maintained during Transfusion in children
insertion of the catheter using sterile gloves, drapes, and 1. Hb 4 g/dL or less (Hematocrit 12%) irrespective of the
local antiseptics. clinical condition group
Closed drainage must be strictly maintained and this 2. Hb 4-6 g/dL (Hematocrit 13-18%) with
has been shown to bring down the rates of infection. The
Features of hypoxia, acidosis causing dyspnea or
closed drainage must be maintained with the collection
impaired consciousness
tubing and bag below the level of the patient's bladder
3 Hyperparasitemia in malaria (>20%)
and the tubing must always be above the level of the bag.
When in place the closed drainage system must be handled 4 Features of cardiac decompensation.
and manipulated as infrequently as possible. Antibiotic Transfusion for acute blood loss
prophylaxis does reduce the frequency of infections but If patient is not stabilized after 2 boluses of 20 mL/kg of
is not universally recommended as it selects multidrug isotonic crystalloid and the suspected blood loss is >30%.
resistant strains when the infection occurs.
Transfusion for chronic anemia
Suggested reading Children with chronic anemia usually tolerate Hb levels
as low as 4 g/dl and the underlying cause of anemia
1. Lodha R, Natchu UCM, Nanda M, Kabra SK. Nosocomial infections
in pediatric intensive care units. Indian J Pediatr 2001;68:1063-1070. should be detected for better therapy as only transfusion
2. Banerjee SN, Grohskopf LA, Sinlowitz-Cochran RL, Jarvis WR, is not the definitive therapy. So the patient should be
National Nosocomial infections Surveillance Systems; Pediatric investigated and monitored for any evidence of abnormal
Prevention Network. Incidence of Pediatric and neonatal intensive physical signs of cardiovascular decompensation, which
care unit-acquired infections. Infect Control Hosp Epidemiol
indicates transfusion. Along with transfusion the
2006;27;561-70.
definitive therapy should also be given to improve the
outcome and reduce the need of further transfusion.
BLOOD TRANSFUSIONS
Blood component transfusion is an integral part of the Choice of Blood Group
treatment plan of many children and adolescents cared For RBC transfusion, the choices are based on the principle
for in an ICU. Blood products are prepared from collected that the recipient plasma must not contain antibodies
whole blood or apharesis donation. Donated whole blood corresponding to donor A and /or B antigens. For plasma
units are separated as required into red blood cells (RBC), and platelet transfusion, donor plasma must not contain
Pediatric Critical Care 709
A /B antibodies corresponding to recipient A/B antigens. Immediately following collection from a normal donor,
Patients who are RhD antigen positive may receive RhD plasma contains approximately 1 unit/ml of each of
positive or negative RBCs but patients who are RhD coagulation factors. Coagulation factors V and VIII are
negative should receive only RhD negative RBCs. Ideally labile and are not stable in plasma stored at 1-6°C. Plasma
the same blood group RBC which is compatible with the frozen within 8 hours of donation contains at least 0.7 u/
recipient plasma should be transfused. The acceptable ml of factor VIII and is called fresh frozen plasma (FFP).
choices of ABO blood groups for RBC, plasma and platelet Plasma after 24 hours of donation contains <15% of factor
transfusions are shown in the following Table 26.13. V and VIII. FFP may be stored for 12 months at tempera
ture -18°C or colder.
Table 26.13: Possible choices of ABO blood groups for Use of FFP is limited exclusively to the treatment or
RBCs, plasma and platelet transfusions prevention of clinically significant bleeding due to
Recipient Acceptable ABO group of blood component deficiency of one or more plasma coagulation factors and
blood group to be transfused such situations can be:
RBCs Plasma Platelets • Use of vitamin K antagonist
o O O A,B,AB O A,B,AB • Severe liver disease
A A, O A, AB A, AB • Disseminated intravascular coagulation (DIC)
• Massive/large volume transfusion
B B, O B, AB B, AB
• Isolated congenital coagulation factor deficiency.
AB AB, A, B, O AB AB
1. Risk of serious hemolytic transfusion reaction There is a risk of bacterial proliferation or loss of function
2. Transmission of infections agents including HIV, HBV, in blood products once they have been removed from the
HCV, Syphilis, Malaria, CMV. correct storage conditions.
hospital temperature is between 22°C to 25°C. In case of based on initial progression and severity of illness, effort
high ambient temperature shorter out of refrigeration can be made to rationalize the admissions to intensive care
times should be used. unit. This helps channelising the resources for both patient
care and resource management. Moreover once the clinical
Platelets and laboratory parameters have been assigned specific
As soon as they have been received and should be values, it becomes easy to analyze the data for the purpose
completed in about 20 min. of cohort comparison and medical audit. To sum up, role
of predictors of outcome in intensive care in today's
FFP scenario is to draw an association between a dependent
In adult FFP one unit 200-300 ml in 20 min (start within and independent variable in the form of a mathematical
30 min) and in children depending on the clinical equation for the purpose of comparative audit, evaluative
condition. research and clinical management.
These products should be infused through a new, sterile
Determining the Predictors of Outcome
blood administration set containing an integral 170-200
pm filter and should be changed 12 hourly if multiple Once admitted in to intensive care unit, the parameters
transfusions are needed. which would decide the final outcome of the patient are:
For platelet transfusion a fresh set primed with saline the illness, its severity, the care received in the intensive
should be used. care unit and the complications of care thereafter. When
The child should be monitored frequently during it comes to determine as to which factors would seem
infusion of blood or blood products. applicable, the two parameters which come into the
picture are physiological criteria and laboratory
Massive Transfusion parameters at the time the patient is admitted to the
The replacement of blood loss equivalent to or greater than intensive care unit.
the patients total blood volume with stored blood in less Illness can be assessed in terms of parameters that are
than 24 hours (70 ml/kg) in adults and 80-90 ml/km markers of severity of illness and organ dysfunction.
children/infants).
Scoring Systems
The complications of massive transfusion are acidosis,
hyperkalemia, citrate toxicity and hypocalcemia, depletion For ease of application to routine clinical care simple
of fibrinogen and coagulation factors, depletion of method to objectivise the severity of illness has been
platelets. DIC, hypothermia, reduced 2,3 DPG and devised. Scoring systems enable matching of patients for
microaggregates. evaluation of treatment protocols and new drugs, defining
criteria for admission to special care facilities by
Suggested reading identifying life threatening clinical situation and
1. Lacroix J, Luban NLC, Wong ECC. Blood Products in PICU. In. prognostication of outcome. The rising cost of medical
Nichols DG (Ed). Roger's Textbook of Pediatric Intensive care. services in recent years has created the need to evaluate
Baltimore Lippincott William and Wilkins 2008;584-99. cost effectiveness of different medical facilities and
2. Easley RB, Brady KM, Tobias ID. Hemotologic to Emergencies. In.
treatment modalities again stressing the need for an
Nichols DG (Ed). Roger's Textbook of Pediatric Intensive Care,
Baltimore Lippincott William and Wilkins 2008;1725-58. objective measure of disease severity.
The commonly used scoring systems are PRISM, PRISM
III, TISS, and PIM. The PRISM (Pediatric Risk of Mortality)
PREDICTORS OF MORTALITY AND SCORING SYSTEMS
score was developed and validated in intensive care unit
Severity of illness assessment has been crucial from time setting by Pollack et al. This scoring system assesses the
long-for a wide range of pediatric, neonatal and intensive severity of illness according to 14 physiological and
care users, including quality assessment, controlling for laboratory parameters. The parameters are: heart rate,
severity of illness in clinical studies and study of intensive systolic and diastolic blood pressure, respiratory rate,
care unit resource utilization and management. Pa02/Fi02 ratio, PaC02, Glasgow coma score, pupillary
The basic aim of intensive care is highest possible reactions, prothrombin time, total bilirubin, potassium,
quality. Quality of care cannot be improved in the absence calcium, glucose, and bicarbonate. Each variable is then
of objective predictors of outcome; the reason being that assigned a particular score and further age dependent
clinical effectiveness of critical care cannot be evaluated. variables are individually categorized. Thereafter, the sum
Outcome of a patient in intensive care unit which can be total of all scores is fed into a predecided equation and
assessed in terms of mortality, morbidity, functional health the final PRISM score is used for mortality and dynamic
status and quality of life is possible only if baseline and objective risk assessment. There are some problems with
data thereafter is comparable, which in the absence of PRISM. Because it is calculated from the most abnormal
appropriate case mix and objective assessment of severity values of 14 variables over a 24 hour period, it is very
of illness would seem irrelevant. In resource poor settings, difficult to collect the large amount of information needed
712 Essential Pediatrics
to calculate PRISM, so that many pediatric intensive care Some parameters which have not been included in the
units do not calculate it routinely. Later this score was scoring systems mentioned above namely infection status
refined and PRISM III score was developed and validated. (focus of infection, counts, c-reactive protein); malnutrition
Shann et al developed and validated PIM (Pediatric (nutritional parameter assessment -weight, height, weight
index of mortality) and PIM2. PIM2 is a simple model for height, etc.); underlying illness also need to be
based on eight explanatory variables collected at the time evaluated.
of admission to the intensive care unit starting from
Suggested reading
whether admission to intensive care unit was elective or
1. Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated
not, presence of underlying high risk diagnosis, acid base
pediatric risk of mortality score. Crit Care Med 1996; 24:743-752
parameters-Pa02, FiOz, base excess, systolic blood 2. Pollack M. Severity-of-illness scoring system. In. Nichols DG (ed).
pressure, need for mechanical ventilation, and pupillary Roger's Textbook of Pediatric Intensive Care. Baltimore. Lippincott
reaction. Williams and Wilkins. 2008;106-13.
27 Common Medical Procedures
REMOVAL OF ASPIRATED FOREIGN BODY_____________ 1-yr of age, abdominal thrusts (Heimlich maneuver) may
be performed, with special care in younger children
The management of foreign body aspiration in children
because of concern about possible intra-abdominal organ
varies according to the presentation and age of the patient.
injury (Fig. 27.2).
If the child presents with acute signs and symptoms of
When initial interventions fail, a jaw thrust should be
upper airway obstruction and can cough, breathe, or
performed, with the hope of partially relieving the
speak, the child should be encouraged to utilize his or her
obstruction. If the foreign body can be visualized, it should
cough to dislodge the foreign body. However, if the child
be manually removed, using Magill or other large forceps.
is observed to have either complete obstruction or partial
In the unconscious, nonbreathing child, a tongue-jaw lift
obstruction with either cyanosis or poor air exchange, or
can be performed by grasping both the tongue and lower
if the child's cough is ineffective in expelling the foreign
jaw between the thumb and finger and lifting. For children
body, then the rescuer should intervene. Blind finger-
who present with signs and symptoms suggestive of
sweeps should be avoided in infants and children because
bronchial foreign body aspiration beyond the oropharynx,
the foreign body could be pushed back into the airway,
endoscopy should be performed by those experienced
causing further obstruction.
with the procedure.
A choking infant younger than 1-year-old should be
placed face down over the rescuer's arm, with the head INSERTION OF NASOGASTRIC TUBE
positioned below the trunk. Five measured back blows
Indications
are delivered rapidly between the infant's scapulas with
the heel of the rescuer's hand (Fig. 27.1). If obstruction 1. Decompression of the stomach and proximal bowel for
persists, the infant should be rolled over and five rapid obstruction or trauma.
chest compressions performed (similar to cardio 2. Gastric lavage in the child with upper gastrointestinal
pulmonary resuscitation). This sequence is repeated until bleeding or accidental ingestion.
the obstruction is relieved. In a choking child older than 3. Administration of medications or for nutrition.
Fig. 27.1 : Back blows in a choking infant Fig. 27.2: Heimlich maneuver in a child
713
714 iential Pediatrics
ARTERIAL CATHETERIZATION
iii. The needle is inserted at an angle of 10-15° from the and sponge in widening circles until an area of 10 cm in
vertical, away from the joint space (caudad for the diameter has been cleaned and allow it to dry. The child
proximal tibia, cephalad for the distal tibia and femur). is draped beneath his or her flank and over the back with
Apply pressure and a to-and-fro rotary motion. As the spine accessible to view. Local anesthesia should be
the needle passes into the marrow, a "give away" will used in children older than 1-yr of age. The site is
be felt. The needle should stand without support. anesthetized by injecting 1% lidocaine intradermally to
iv. Evidence for successful entrance into the marrow in raise a weal, then the needle is advanced into desired
cludes (a) the lack of resistance (or a "give way") after interspace injecting anesthetic, being careful not to inject
the needle passes through the cortex, (b) the ability of it into a blood vessel or spinal canal.
the needle to remain upright without support, (c) as The spinal needle is checked to ensure that the stylet is
piration of the bone marrow into a syringe, and (d) secure. One should grasp the spinal needle firmly with
free flow of the infusion without significant subcuta the bevel facing "up" toward the ceiling, making the bevel
neous infiltration. Aspiration of bone marrow into the parallel to the direction of the fibers of the ligamentum
intraosseous needle is not always possible, especially flavum. The patient's position should be checked again
in a very dehydrated patient. to ensure that the needle's trajectory is midsagittal to his
v. One should then remove the stylet. Proper placement or her back. The needle is inserted into the skin over the
is confirmed by aspiration of bone marrow into a 5- selected interspace in the midline sagittal plane. The
ml syringe or freely flowing heparinized saline flush. needle should be inserted slowly, aiming slightly cephalad
vi. The needle is connected to the desired intravenous toward the umbilicus. When the ligamentum flavum and
tubing and solution. then the dura are punctured, a "pop" and decreased
resistance are felt. One should then remove the stylet and
vii. One should observe for extravasation of fluids into check for flow of spinal fluid. If no fluid is obtained, one
the surrounding soft tissue. This indicates superficial should reinsert the stylet, advance the needle slowly and
needle placement or that the bone has been pierced check frequently for the appearance of CSF.
posteriorly. About 1 ml of CSF is collected in each of the three sterile
Complications
tubes. The CSF is sent for routine culture, glucose and
protein determination and cell count. Additional tubes are
Potential complications include osteomyelitis, sub collected as indicated. One should then reinsert the stylet
cutaneous abscess, extravasation of fluid into sub and remove the spinal needle with one quick motion. The
cutaneous tissue, epiphyseal trauma and fat embolism. back is cleansed and the puncture site is covered.
LUMBARPUNCTURE Sitting Position
Indications The infant is restrained in the seated position with
To obtain cerebrospinal fluid (CSF) for the diagnosis of maximal spinal flexion (Fig. 27.6B). The assistant should
meningitis, meningoencephalitis, subarachnoid hemor hold the infant's hands between his or her flexed legs with
rhage and other neurologic syndromes. one hand and flex the infant's head with the other hand.
Drapes are placed underneath the child's buttocks and
Procedure
on the shoulders with an opening near the intended spinal
puncture site. One should choose the interspace as noted
Lateral Decubitus Position earlier and follow the procedure as outlined for the lateral
The patient is restrained in the lateral decubitus position position. The needle is inserted such that it runs parallel
as shown in Fig. 27.6A. The spine is maximally flexed to the spinal cord.
without compromising the upper airway. Frequently, in
young infants, the patient's hands can be held down Complications
between the flexed knees with one of the assistant's hands. Lumbar puncture may be associated with headache, local
The other hand can flex the infant's neck at the appropriate back pain and infection. Brainstem herniation may occur
time. The spinal cord ends at approximately the level of in the presence of symptomatic intracranial hypertension.
the LI and L2 vertebral bodies. Caudal to L2, only the
filum terminale is present. The desired sites for lumbar THORACOCENTESIS
puncture are the interspaces between the posterior
elements of L3 and L4 or L4 and L5. One should locate Indications
these spaces by palpating the iliac crest. An imaginary Thoracocentesis is performed to evacuate fluid from the
"plumb line" is followed from the iliac crest to the spine. patient's pleural space.
The interspace encountered is L4 to L5.
The skin is cleansed with povidone iodine solution and Diagnostic
alcohol. One should begin at the intended puncture site Pleural effusion or empyema.
718 Essential Pediatrics
B A
Figs 27.6A and B: Lumbar puncture with the child in (A) decubitus
position (B) sitting position. Arrow indicates site for needle insertion
Therapeutic
When large collections of pleural fluid compromise
ventilatory function, the procedure should be done
carefully in subjects with uncorrected coagulopathy.
Persistent inability to draw fluid suggests a loculated
effusion, and the operator should withhold further
attempts until the procedure can be performed under
radiographic guidance (i.e. CT scan, ultrasound).
Technique
The first step in thoracocentesis is to ensure that fluid is
present in the area of thoracocentesis by clinical and B
radiological methods. Decubitus films are helpful in
demonstrating free fluid that shifts with movement. The
procedure (Figs 27.7A to C) is carried out with the patient
appropriately sedated and properly positioned. Standard
positioning for the patient is with the patient positioned
upright and leaning forward. The procedure is carried out
under aseptic precautions. The site of entry is anesthetized
with local anesthetic. The landmark for evacuation of the
fluid is the angle of the scapula that corresponds
approximately to the eighth rib interspace. An appropriate
catheter is used over the needle. The needle is introduced
immediately above the superior edge of the rib to avoid Figs 27.7A to C: Thoracocentesis: (A) The landmark for thoraco
puncturing the intercostal artery and vein. Once the centesis is the angle of the scapula that corresponds approximately
pleural space is entered and fluid is aspirated, the catheter to the eighth rib interspace. (B) The needle is introduced immediately
is advanced as the needle is withdrawn. The catheter is above the superior edge of the rib to avoid puncturing the intercostals
connected to a three-way stopcock and syringe (10-20 ml). vessels. (C) After inserting the catheter in the pleural space, the
It is important to control the aspiration of fluid such that catheter is connected to a three-way stopcock and a syringe
719
air is not allowed to enter the pleural space from the technique and at an angle perpendicular to the skin.
outside. Continued aspiration of the needle is used until peritoneal
fluid is aspirated. Approximately 10-15 ml of fluid is
Complications aspirated for studies, which include culture, Gram stain
i. Intercostal artery puncture with severe hemorrhage. and cytology; levels of amylase, lactate dehydrogenase
ii. Development of pneumothorax or hemothorax. (LDH), bilirubin, albumin and protein are estimated. If
iii. Malpositioned needle, leading to abdominal viscera the paracentesis is performed for therapeutic purposes, a
or lung parenchymal injury. catheter should be placed.
Complications
ABDOMINALPARACENTESIS
The complications of abdominal paracentesis are
indications
hemorrhage, fluid leak, intestinal or bladder perforation
Diagnostic and hypotension, if large volumes are removed.
Determine etiology of ascites; diagnose peritonitis.
CATHETERIZATION OF BLADDER
Therapeutic
Indications
Remove large volumes of ascitic fluid (if causing Bladder catheterization is done in bedridden patients who
respiratory compromise). need short-term assistance. It is also required in patients
Technique with (i) polytrauma, especially for evaluation of the
The patient is placed in a supine position, and the bladder urinary tract in an unconscious child; (ii) shock; (iii) acute
is emptied. The common sites for paracentesis are shown urinary retention; and (iv) to obtain a urine specimen for
in Fig. 27.8. These sites are chosen to avoid puncture of urinalysis.
underlying vessels or viscera. Usually the left lower Complications
quadrant is preferred to the right in critically ill children Injury to urethra or urinary bladder, and inadvertent
because they may have cecal distention. Following local catheterization of the vagina may occur. Absence of aseptic
infiltration of xylocaine, the skin is then tiled anteriorly precautions might result in urinary tract infection.
so that further infiltration into the subcutaneous tissue is
in a different plane (Z tracking). A needle or over-the- Procedure
needle catheter is then advanced using the Z tracking
Restrain the patient as necessary. Prepare the urethral
meatus and penis or the perineal area by cleansing with
povidone iodine solution; select a Foley catheter of the
appropriate size (8 Fr in the newborn, 10 Fr in most
children and 12 Fr in older children). The catheter tip
should be well lubricated to minimize local trauma.
Male
Gently grasp and extend the penile shaft to straighten out
the urethral pathway. Hold the catheter near the distal
tip and advance it up the urethra unless resistance or an
obstruction is encountered. If resistance is encountered,
select a smaller catheter. The catheter should be passed
into the bladder all the way to the Y-connection; this is
important because urine may begin to flow while the
catheter is in the proximal urethra, and inflation of the
balloon in the urethra may lead to complications. Inflate
the balloon after advancing the catheter all the way to the
Y-connection. Tape the catheter to the child's leg.
Female
In the female, the principles of catheterization are similar
Fig. 27.8 : Sites for abdominal paracentesis. The preferred sites are to those in the male. Have an female assistant carefully
the linea alba (midway between the umbilicus and the pubic spread the labia. Introduce a well-lubricated, pretested
symphysis) and lateral to the rectus abdominis muscle. Arrowheads Foley catheter into the bladder. Again, advance the
(<) indicate common sites for paracentesis catheter its entire length before inflating the balloon. A
720 Essential Pediatrics
catheter that is passed in its entirety has not been inadver Transjugular venous biopsy of the liver is used in
tently located in the small vagina of the young girl. After patients with risk of bleeding. Surgical liver biopsy obtains
withdrawing the catheter until a dunking sensation is liver tissue via laparotomy or laparoscopy and is utilized
appreciated, secure it with tape. in instances when the percutaneous technique is contra
indicated. The surgical methods allow for better
LIVER BIOPSY______________________________________ hemostasis when the patient has a coagulopathy.
Liver biopsy is used to determine the cause of "acute or RENAL BIOPSY_____________________________________
chronic liver disease," assess prognosis, determine
response to therapy and monitor effects of hepatotoxic The usual indications are children with steroid resistant
drugs. Analysis of the biopsy specimen can include nephrotic syndrome, rapidly progressive glomerulo
histology, metal content, biochemical or enzyme assay, nephritis, recurrent gross hematuria with significant
culture for viral, bacterial or fungal pathogens, and proteinuria, and unexplained acute renal failure. In most
electron microscopy. instances, a percutaneous biopsy is done using a spring-
Liver biopsy can be performed percutaneously at the loaded biopsy needle that is guided with ultrasonography.
bedside or with ultrasound guidance. The latter is prefer In children, the procedure can be done with sedation. The
red because of lower complication rate and the opportu procedure is relatively safe in experienced hands. The
nity to visualize the liver and target focal lesions. The tissue obtained is processed with standard histochemical
biopsy can be performed by either an anterior, subdia- stains, and examined by light, immunofluorescence and
phragmatic or right lateral approach, the last being the electron microscopy.
most commonly used. The biopsy site is typically just Suggested reading
anterior to the right midaxillary line, at about the tenth
intercostal space. Absolute contraindications include 1. Dieckmann RA, Fiser DH, Selbst SM editors: Illustrated textbook
of pediatric emergency and critical care procedures 1st edn,
inability to remain still and maintain expiration for the Philadelphia, Mosby, 1997.
procedure, or a bleeding tendency. Relative contra 2. Carlson DW, Digiulic GA, Gennitz MH, Givens TG, Handler SD,
indications include severe anemia, peritonitis, marked Hodge D, et al: Illustrated techniques of pediatric emergency
ascites, high-grade biliary obstruction and a subphrenic procedures. In Fleisher GR, Ludwigs editors: Synopsis of pediatric
or right pleural effusion. Major complications (e.g. intra emergency medicine; 4th edition, Philadelpha; Williams and
Wilkins, 2000.
abdominal hemorrhage, bile peritonitis, lacerated liver) 3. Fuhrman BP, Zimmerman JJ editors: Pediatric critical care, 3rd edn,
are rare. Philadelphia, Mosby, 2006
28 Rational Drug Therapy
INTRODUCTION _________ ___________________________ Key words: M2 = square meter of body surface; PO= per
Drugs play a vital role in protecting, maintaining and oral; SC = subcutaneous; PR = rectal; T = topical; IM =
restoring the health of people, if used rationally. Most intramuscular; IV= intravenous; ITH= intrathecal; Wt.=
drugs are chemicals and their indiscriminate consumption weight; D = day; h = hour; Y = age in years; g = gram; kg
may lead to toxicity and adverse reactions. Expected = kilogram; mg = milligram. Names of some popular
benefits and possible side effects of the drug should always proprietary preparations are given in parenthesis.
be kept in mind. It is better to use those drugs with which
the physician is familiar. Indiscriminate and injudicious ANALGESICS, ANTIPYRETICS AND
use of drug may be potentially harmful. Some general NON-STEROIDAL ANTI-INFLAMMATORY
guidelines for rational drug therapy are given below. DRUGS (NSAIDS) _____________ _________
i. There should be a genuine indication for the use of a Non-Narcotic Analgesics
drug in the patient.
ii. A minimum number of appropriate, familiar and Aspirin: Anti-inflammatory dose in rheumatic disease: 90-
inexpensive drugs of good quality should be used. 130 mg/kg/day PO q 4 h. Antipyretic dose: 30-60 mg/
iii. Drugs should preferably be prescribed by generic kg/day PO q 4-6 h. Salicylates should be avoided on
name. empty stomach. Side effects: Hypersensitivity, hypopro-
iv. The dosage of the drug should be optimum to achieve thrombinemia. There is an epidemiologic association
the desired clinical benefits. between salicylate use and Reye's encephalopathy.
v. It is desirable to administer drugs as far as possible Therefore its use for upper respiratory tract infection and
through oral route in children. fevers of undetermined origin in children is not advisable.
vi. Adverse drug reactions should be anticipated, Paracetamol: 40-60 mg/kg/PO q 4-6 h. Injection 5 mg/
monitored and appropriately managed. kg IM. Side effects: Skin rashes, hepatotoxicity. Occasionally
Examples of true synergism are rare; the most notable renal damage.
exception being cotrimoxazole incorporating trimetho
prim and sulphamethoxazole. Combination of antibiotic Ibuprofen: 20-30 mg/kg/day q 6-8 h oral Avoid in infants
agents may be necessary when the causative agent is not < 6 months age. Side effects: Nausea, vomiting, rashes.
known. Multidrug therapy is indicated to prevent bacterial Nimesulide: 5 mg/kg/day q 8-12 h. Side effects: Hepatic
resistance to individual drugs during long-term manage enzyme elevation. Use with caution in hepatocellular
ment of tuberculosis and leprosy and also to reduce
toxicity of individual drugs. Bactericidal drugs ordinarily disease or when combining with another hepatotoxic
act best when the organism is actively multiplying. drug. Safety not established in children under 6 month of
Therefore, bacteriostatic drugs are not the best agents to age.
combine with bactericidal drugs.
The response to different drugs may vary at different Narcotic Analgesics (Opioids)
ages due to developmental factors and may depend on Fentanyl: 0.5-5 |ig/kg/dose q 1-4 h IV, may be adminis
the genetic factors controlling their metabolism. Doses of tered as a continuous infusion 1-5 |ug/kg/h. Potent
drugs need to be modulated according to the individual narcotic analgesic, 0.1 mg dose possesses an equivalent
responses. The dosages of the drugs may vary in specific analgesic activity to 10 mg of morphine.
disease, e.g. meningitis, subacute bacterial endocarditis,
pyogenic arthritis, etc. All doses given below are approxi Pentazocine: 0.5 to 1 mg/kg per dose 4 times a day. (30-
mate doses used in common practice. The reader is 60 mg IM equivalent to 10 mg of morphine. Orally 50 mg
advised to consult the prescribing information on the drug equals 60 mg of codeine). Contraindications. Head injury,
package. raised intracranial tension, porphyria.
721
722 Essential Pediatrics
Codeine: For pain: 3 mg /kg/D PO q 4 h. For cough: 0.2 reverts or hypotension develops; maintenance 5-10 mg/
mg/kg/dose 4 hourly. kg/D q 12 h PO. For status epilepticus: loading 15-20 mg/
Pethidine: 1-2 mg/kg/dose IM or IV.
kg IV, do not exceed 1-3 mg/kg/min. Maintain with 5-8
mg/kg/D PO or IV q 12-24 h. Side effects: Gum hyper
Morphine: 0.1-0.2 mg/kg/dose q 4 h (max. 15 mg) IV, trophy, hirsutism, hypersensitivity, megaloblastic anemia,
IM or SC. Caution: Keep naloxone (0.01 mg/kg IV) ready osteomalacia, vestibulocerebellar syndrome.
as antidote in case of respiratory depression. Procainamide (Pronestyl): 2 mg/kg/dose IV followed by
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
0.5 mg/kg/h by constant IV infusion. PO dose 50 mg/
kg/D q 3-4 h. Side effects: Thrombocytopenia, coomb's
Quick acting positive hemolytic anemia, lupus like syndrome.
a. Salicylates Contraindication: Heart blocks, myasthenia gravis.
b. Ibuprofen, 20-30 mg/kg/D q
Propionic acid derivatives;
Propranolol: 0.01-0.25 mg/kg/dose IV. May repeat in 15
6 h for fever; 30 mg/kg/D for Juvenile rheumatoid minutes. Then 4-8 hrly. Orally 0.5-1 mg/kg/D q 6 h.
arthritis (JRA); ketoprofen and naproxen 5 mg/kg per
Side effects: Life threatening increase in pulmonary
dose two times a day resistance, fatigue, bradycardia.
c. Anthranilic acid derivatives (mefenamic acid 8 mg/kg/
dose three times a day). Quinidine: Test dose 2 mg/kg PO followed by 30 mg/
d. Aryl acetic acid derivatives (diclofenac sodium 2-5 mg/ kg/D PO q 6 h. Side effects: Thrombocytopenia, tinnitus,
kg/day q 8h PO). hypotension, blood dyscrasias. Contraindicated in heart
e. Indole derivatives (indomethacin 3 mg/kg/D PO q 8h, blocks, congestive heart failure.
for ductus closure use 0.2 mg/kg/dose for 3 doses IV Verapamil: 2-4 mg/kg/D q 8 hr PO, 0.1-0.2 mg/kg IV
or PO). over 2 min in infants and 0.1-0.3 mg/kg IV over 2 min in
Slow acting children. Contraindication: Cardiogenic shock, AV block,
a. Hydroxychloroquine 5-10 mg/kg/D. children below 2 years of age.
b. Penicillamine 15 mg/kg/D q 8 h; (c) gold 3-6 mg single
dose daily of auronofin. Refer to Chapter 19, on juvenile ANTIMYASTHENIC AGENTS
rheumatoid arthritis, for details of dosages. Edrophonium chloride (Tensilon): Initial dose: 0.04 mg/
kg dose (maximum 1 mg for <30 kg). If no response after
ANTIARRHYTHMICS 1 min, may give 0.16 mg/kg/dose for a total of 0.2 mg/
Adenosine: 0.05-0.2 mg/kg/dose rapid IV (over 1-3 secs), kg (total maximum dose is 5 mg for <30 kg).
if no response in 1-2 min, double the dose and continue Neostigmine bromide (Prostigmin): Neonate 1 mg q 4 h,
to double the dose 1-2 min until response occurs. Max 30 min before feed. Children 1-3 mg/kg/D PO q 4-6 h.
single dose 0.25 mg/kg. Indicated for supraventricular Begin with lower dose and increase gradually till
tachycardia. Side effects: Transient chest pain, dyspnea, symptoms disappear. Use with atropine for non
flushing, bronchospasm. depolarizing neuromuscular blocking agents. Side effects:
Atropine sulfate: 0.01 mg/kg/dose SC or IV. The dose Cholinergic.
can be repeated after 2 h (max 4-6 times a day). Antidote Pyridostigmine (Mestinon): 7 mg/kg/D PO q 4—6 h. Start
to organo-phosphorus poisoning: 0.02-0.05 mg/kg every with lower dose and increase gradually.
10-20 min until atropine effect, then every 1-4 hourly for
at least 24 hours. Side effects: Dry mouth, blurred vision, DRUGS USEFUL AGAINST INFECTIONS
tachycardia, urinary retention, constipation, dizziness,
hallucinations, restlessness. ANTIBIOTICS
E. Alter protein synthesis and result in cell death: Amino Ampicillin and sulbactam sodium
glycosides. 150 mg/kg/D q 8 h IM or IV. Contains 100 mg ampicillin and
F. Antimetabolities: Sulphonamides and trimethoprim. 50 mg sulbactam.
G. Nucleic acid analogs: Acyclovir.
Anti-pseudomonas penicillins
H. Inhibitors o f D N A gyrase: Quinolones.
Carbenicillin 50-500 mg/kg/D IM or IV q 6 h
Penicillin Ticarcillin 50-300 mg/kg/D IV infusion q4-6h
Common nucleus of natural or semi-synthetic penicillin Piperacillin 100-300 mg/kg/D IV infusion q 4-8 h.
is, 6-aminopenicillanic acid (6-APA). Benzyl penicillin is
still the drug of choice for Gram positive and Gram
negative cocci. Gram negative bacilli such as Listeria, Cephalosporins
Clostridia and spirochetes also respond to penicillin G. These groups of antibiotics have a common peptide
Bacterial resistance to penicillins is due to production of nucleus, 7-aminocephalosporanic acid. These antibiotics
beta-lactamase by the bacteria. Beta-lactamase (peni resist hydrolysis by beta-lactamase (penicillinase).
cillinase) splits the beta-lactam ring and inactivates the First generation cephalosporins have similar spectrum
penicillin. Addition of a side chain to the basic structure as penicillin. More recently introduced cephalosporins
of penicillin reduces the effect of beta-lactamase on the have greater activity against Gram negative bacilli.
antibiotic. By altering the chemical structure of penicillin, Approximately 10% of penicillin-hypersensitive patients
a range of broad spectrum antibiotics have been show allergy to cephalosporin and even a fatal anaphy
developed. laxis may occur. Oral cephalosporins cause gastro
Penicillin may cause hypersensitivity reactions in about intestinal symptoms such as loss of appetite, nausea,
1% of individuals. Hypersensitivity reaction may be vomiting and diarrhea. Some parenteral cephaloridines
immediate (lgE mediated type IV- T cell mediated). may cause serious renal toxicity. First and second genera
Symptoms include urticaria, angioneurotic edema, tion cephalosporins have anti- staphyloccal activity.
anaphylactic shock, asthma, laryngeal edema, hypo However, third generation are not effective against
tension. Delayed reactions are fixed drug eruption, serum staphylococci.
sickness, hemolytic anemia, and recurrent arthralgia.
Drug Dosage
Penicillins (Penicillinase-sensitive) (mg/kg/day)
Benzyl penicillin G (sodium or potassium) First generation cephalosporins
4.00.000 units PO q 6 h Cephalexin 25-50 PO q 6 h
50,000-60,000 units/kg/D IM q 6 h Cefazolin 50-100 IM or IV q 6-8 h
2.00.000^1,00,000 units/kg/D (meningitis) IV q 4-6 h Cefadroxil 30 PO q 12 h
Benzathine penicillin G 1.2 mega units IM once in 3-4 weeks
Procaine penicillin G 4,00,000 units IM q 12-24 h Second generation cephalosporins
Cefaclor 20-40 PO q 6-8 h
Cephamandole 50-150 IM or IV q 8-12 h
Acid-resistant penicillins
Cefuroxime 50-100 IM or IV q 6-8 h
Phenoxy-methyl-penicillin V
(Pencillin V) 10 mg/kg/D PO q 6 h Third generation cephalosporins
Cefotaxime 100-150 IM or IV q 8-12 h
Pencillinase resistant penicillins Cefoperazone 50-200 IM q 8-12 h
Methicillin sodium 100 mg/kg/D IM or IV q 6h Ceftriaxone 80-150 IV q 12-24 h
Oxacillin 50 mg/kg/D PO or IV q 6h Ceftazidime 100-150 IV q 8-12 h
Cloxacillin 50-100 mg/kg/D PO cr IV q Ceftizoxime 100-150 IV q 8-12 h, IM
6h Cefixime 8-10 PO q 12 h
Broad spectrum penicillins Third generation drugs attain high CSF concentrations and are
(aminopenicillins) widely used in meningitis.
Ampicillin 50-100 mg/kg/D PO or IV q Fourth generation cephalosporins
6h Cefpirome 30-60 IM or IV 12 h
For meningitis 200^100 mg/kg/D IV q 4-6h Cefpodoxime 8-10 PO q 12 h
Amoxycillin 25-50 mg/kg/D PO q 8 h
species of streptomyces. Gentamicin is fermented from gray color due to cyanosis and peripheral circulatory
Micromonospora purpura. Amikacin and netilmicin are collapse with death occurring in half of cases.
semisynthetic aminoglycosides prepared from kanamycin
and sisomicin. These antibiotics are bactericidal and Chloramphenicol 50-100 mg/kg/D PO, IM or IV q 6 h
mainly useful against Gram negative bacilli. Organisms Ophthalmic ointment 0.5 and 1%
may become resistant to aminoglycosides by mutation.
Streptomycin has auditory and vestibular toxicity. Macrolides
Hypersensitivity can also occur. Rashes and drug fevers Macrolides are bacteriosatic. These can be used for infec
occur in about 5% of patients. Kanamycin may show tions with Staphylococcus aureus, streptococci, Mycoplasma
ototoxicity (cochlear damage). Gentamicin and other pneumoniae, Chlamydia, Corynebacterium diphtherae
aminoglycosides cause vestibular damage and reversible bacilli, B. pertussis and Campylobacter jejuni. Erythromycin
kidney dysfunction (proteinuria and azotemia). is generally safe with occasional gastrointestinal side effects.
Drug Dosage (mg/kg/day) Azithromycin has increased activity against Gram negative
Streptomycin 30^0 IM q 12 h organism and is better tolerated as compared to
Gentamicin 5-7.5 IM or IV q 8-12 h erythromycin.
Amikacin 15-20 IM or IV q 8-12 h Drug Dosage (mg/kg/day)
Tobramycin 6-7.5 IM or IV q 6-8 h
Netilmicin 6-7.5 IM or IV q 8 h Erythromycin 30-50 PO q 6-8 h
Sisomicin 5-7.5 IM or IV q 8 h Roxithromycin 5-8 PO 12 h
Azithromycin 10 PO 24 h
Clarithromycin 15 PO q 12 h
Dosage should be reduced and interval between dosage
should be increased in case of renal damage and raised
urea and creatinine levels. Quinolones
These act by inhibiting the enzyme DNA gyrase and are
Tetracyclines useful in a wide variety of enteric, urinary, respiratory,
Tetracyclines are deposited in growing teeth and bones. skin, bone, joint and systemic infections. Except nalidixic
If the drug is used in children between the ages of 2 months acid (used widely for dysentery), none of the quinolones
and 8 years, both deciduous and permanent teeth may are officially recommended for use in children.
show irreversible staining, hypoplasia of enamel and Drug Dosage (mg/kg/day)
proneness to caries. Deposition in bones may lead to
stunting. Doxycycline does not bind to calcium as Nalidixic acid 50-60 PO q 8 h
intimately. Tetracyclines are not recommended in children Ciprofloxacin 20-30 PO q 12h
below 8 years of age. 10-20 IV q 12 h
Gatifloxacin 10 PO 24 h
Drug Dosage (mg/kg/day)
Norfloxacin 10-15 PO q 12 h
Levofloxacin 10-15 PO or IV 24 hr
Tetracyclines 25-50 PO q 6 h Ofloxacin 15 PO q 12 h
15-25 IM q 8-12 h 5-10 IV q 12 h
Doxycycline 2-5 PO q 12-24 h Pefloxacin 12 PO q 12 h
Sparfloxacin 4 PO q 24 h
Chloramphenicol
It is a bacteriostatic drug. Indicated in H. influenzae Sulphonamides
meningitis and enteric fever. Most important toxicity is Cotrimoxazole
bone marrow depression after prolonged administration
of the drug and is dose related. It may reverse on stoppage It is a mixture of trimethoprim and sulphamethoxazole.
of drug. A more serious type of aplasia may occur due to Its antibacterial action results from the action of two-
idiosyncracy to the drug and may follow a single dose or sequential steps in the synthesis of tetrahydrofolic acid.
prolonged therapy. Incidence varies between 1 in 10,000 Toxic Side effects are blood dyscrasias, exfoliative
to 1 in 50,000. This toxic reaction is unpredictable and may dermatitis, serum sickness, drug fever, etc. Each tablet
terminate fatally. Drug fever, skin rashes and angio contains of 80 mg of trimethoprim and 400 mg of sulpha
neurotic edema may occur as hypersensitivity reaction. methoxazole. Dosage is 5-8 mg of trimethoprim equiva-
GI disturbances are also seen. Newborn infants especially lent/kg/D PO q 12 h.
prematures on full dose of chloramphenicol develop grey-
baby syndrome, resulting in abdominal distension, Anti-Leprosy Drugs
vomiting, refusal to suck and dyspnea. The baby develops Refer to Chapter 24.
Rational Drug Therapy 725
therapy is to inhibit hepatitis B viral replication, long-term Dacarbazine DTIC: 2-4.5 mg/kg/IV. Side effects:
control of hepatic necrosis resulting inflammation, Pancytopenia, paresthesia, flushing.
prevention of cirrhosis, and malignant transformation of Daunorubicin: 25-50 mg/M2 IV max dose 550 mg/M2.
hepatocytes. Side effects: Pancytopenia, cardiotoxic, rashes, red colored
Therapy with 2.5-10 million units generally given daily urine.
for about one week, then 3 times weekly for a total 1-6 Doxorubicin: 60-75 mg/M2 IV max dose 550 mg/M2. Side
months in patients with chronic infection has been effects: Same as daunorubicin.
associated with a response rate of improvement 25-40%
of cases. Other data also suggest that IFN alfa can produce Hydroxyurea: 20-30 mg/kg/D PO. Side effects: Bone
clinical, biochemical, and serologic remissions with marrow suppression, megaloblastic changes, impairment
hepatitis B virus-related renal injury. IFN alfa has also been of renal function.
used along with acyclovir and vidarabine, steroids and 6-mercaptopurine: 2.5 mg/kg/D PO. Side effects: Bone
other lymphokines in an attempt to improve response marrow depression, jaundice, hepatotoxic, hematuria.
rates.
It is also tried in management of some malignancies Methotrexate: Standard dose 2.5-5 mg for children PO
(chronic myeloid leukemia). 2.5-10 mg for adults PO. Higher doses of 30 mg/M2 have
been used three times a week. Side effects: Bone marrow
ANTICANCER DRUGS________________________________ depression, ulceration of mouth, megaloblastic anemia,
diarrhea, hepatoxic.
Doses of anti-cancer drugs are modified by different
workers for specific uses. Consult current protocols. Mustine hydrochloride: Total dose 0.4 mg/kg or 6-10
mg/M2 given in 2 or 4 daily consecutive IV injection. Side
Actinomycin D: 10 to 15 mg/kg/day for 5 days. Side effects: 13 one marrow depression, tinnitus, vertigo,
effects: Thrombocytopenia, agranulocytosis, myalgia, deafness.
erythema, nausea, vomiting.
Procarbazine: 50 mg/M2/D PO during first week
L-asparaginase: 1000 units/kg/D IM or IV for 10 to 20 followed by 100 mg/M2/D. Side effects: Bone marrow
days. Side effects: Uremia, CNS disturbances, hyper depression, somnolence, depression, agitation, peripheral
glycemia, pancreatitis. neuropathy.
Azathioprine: 1-5 mg/kg/D q 24h PO. Side effects: Vinblastine: 2.5 mg/M2 IV increased by 1.25 mg/M2
Leucopenia, fever, liver damage, pancreatitis. weekly to a maximum of 7.5 mg/M2. Side effects: Bone
Bleomycin: 12-20 mg/M2 once or twice weekly 300 mg/ marrow depression, headache, depression, psychosis,
kg, SC, IV or IM. Side effects: Rash, pruritus, vesiculation, neuromyopathy, peripheral neuritis, convulsions.
pulmonary fibrosis. Vincristine: 1.5-2 mg/M2 IV weekly. Side effects: Same as
Busulphan: 60 pg/kg/D PO. Side effects: Thrombo vinblastine, bone marrow depression less common.
cytopenia, cataract, pulmonary fibrosis, hyperpigmen
tation. ANTICOAGULANTS_________________________
Chlorambucil: 200 mg/kg/D. Side effects: Bone marrow Acenocumarol (Sintrom): Dose is 1-8 mg/day PO single
depression. dose. Maintain prothrombin time 1.5 times of normal.
Cisplatin: 15-20 mg/M2/D for 5 days. Side effects: Bone Heparin: IV: 50 u/kg IV bolus followed by 10-25 u/kg/
marrow depression, nephrotoxic, ototoxic. hr as IV infusion or 50-100 u/kg/dose q 4 hr IV. SC: 25-
50 u/kg q 12 hr*. DVT prophylaxis: 5000 u/dose SC q 8-
Cyclophosphamide: 2-3 mg/kg/U PO or IV is a 12 hr until ambulatory.
conservative dose for susceptible neoplasms. Fligher dose Antidote: Protamine sulfate (1 mg neutralizes 1 mg: heparin).
of 4-8 mg /kg IV for 6 days followed by oral dose of 1-5 Side effects: Skin rash, alopecia. Contraindicated in
mg/kg may be used. Side effects: Leucopenia, alopecia, ulcerative colitis, shock, hidden hemorrhage.
hemorrhagic cystitis.
Cyclosporin A: 10-25 mg/kg/D PO. IV dose 5-6 mg/kg/ Phenindione: 0.5 to 4 mg/kg/day q 12 hr oral.
D in slow infusion. Side effects: Nephrotoxic, gastro Warfarin: 0.05 to 0.34 mg/kg/day oral or parenteral.
intestinal disturbances, hirustism, gum hypertrophy, Adjust the dose to maintain desired prolongation of
angioedema. prothrombin time.
Cytarabine (cytosine arabinosides): 2 mg/kg/D IV. Side
effects: Granulocytopenia, megaloblastic anemia, *The dose is adjusted by maintaining clotting time at twice the
neurotoxic, nephrotoxic, flu-like syndrome. normal.
Rational Drug Therapy 729
ANTICONVULSANTS _____ ___________ __________ Promethazine theoclate: 0.5 mg/kg/dose q 8-12 hr oral.
Refer to Chapter 17. Administer first dose 1-2 hr before travel. Indications:
Motion sickness. C/I: children <2 yrs; asthma, sleep apnea.
ANTIDOTES ___ Triflupromazine (Siquil): 0.5 mg/kg/day q 8 h PO. IM
dose is half. Side effects: Drowsiness, hypotension.
Ipecac syrup: < 1 yr 5-10 mL/dose, others 15-20 mL/dose.
Do not use in semi-comatose child or after charcoal ANTIHISTAMINICS__________________________
administration. Most antihistaminics are histamine HI blocking agents
Deferoxamine (Desferal): 20 mg/kg IM or IV. Slow and exert their action by competing with HI receptors.
subcutaneous infusion every 6 h; dose to be adjusted These do not prevent release of histamine but have varying
depending upon the response. Side effects: Hypotension, degrees of anticholinergic and antiserotonergic activity.
shock, cramps, diarrhea. Contraindicated in renal Astemizole (Stemiz, Astelong): 2 mg/10 kg body weight.
insufficiency. Below 6 yr not recommended. Single daily dose. Should
Dimercaprol (BAL): 2.5 mg /kg PO every 4 hours on the be taken half an hour before meals. Side effects: Weight
first day, every 6 hours on the next 2 days, every 12 hours gain with prolonged use.
for the next 10 days and thereafter 24 hourly for the next Cetrizine (Alerid): Non sedating long acting. Dose 0.2
10 days. Side effects: Burning sensation, muscle aches, fever, mg/kg once day PO.
hemolysis in G-6-PD deficiency.
Clemastine (Tavegyl): 1 to 3 yrs: 0.25 mg - 0.5 mg BD, 3-
Edetate calcium disodium: 12.5-30 mg/kg/dose IV 12 6 yrs: 0.5 mg BD, 6-12 yrs: 0.5-1 mg BD; > 12 year: 1 mg
hourly for 5 days. Side effects: Proteinuria, hematuria. BD. Avoid below 1 year of age. Useful for urticaria, contact
Methylene blue: 1-2 mg/kg/dose IV (in 5 minutes). dermatitis.
Nalorphine (Lethidrone): 0.1 mg/kg/dose IM or IV. Chlorpeniramine maleate: Children 0.35 mg/kg/day q
Naloxone (Narcan): 0.01 mg/kg/dose IM or IV. Repeat if 4-6 hr. According to age: 2-6 yrs: 1 mg, 6-12 yrs: 2 mg,
needed. >12 yrs: 4 mg q 4 to 6 hrly. Side effects: Hypotension,
sedation, urinary retention, oculogyric spasms may occur
Penicillamine (Cuprimid): Infants 5 mg/kg/dose 3-4 c with higher doses and after a few days of therapy.
times daily. Side effects: Nephrotoxic, hepatotoxic, leuco-
penia, thrombocytopenia, cataract, bleeding diathesis. Cyproheptadine hyprochloride: 0.25 mg/kg/D q 8 h PO.
Side effects: Same as chlorpheniramine.
Digoxin specific Fab antibody (Digibind) is a recently
introduced preparation for digoxin poisoning. Given by Dimethindene maleate: Children >12 yrs; 1-2 mg q 8 hrly
IV infusion. Approximately 60 mg binds 1 mg of digoxin. or 2.5 mg SR twice a day.
Diphenhydramine hydrochloride: 5 mg/kg/day q 6 hr
ANTIEMETICS..._.... ................. ... ............... ...... ..... ............... oral, maximum dose 300 mg/24 hr. For anaphylaxis or
Dimenhydrinate: 5 mg/kg/day q 6 hr oral, IM or IV. phenothiazine overdose 1-2 mg /kg IV slowly.
Avoid in children below 2 years. Maximum dose 2-6 yrs: Fexofenadine: 30 mg BD for children < 12 years and 60
75 mg/day, 6-12 yrs: 150 mg/day. mg BD or 120 mg OD for children >12 yrs.
Domeperidone (Domstal): 0.3 mg/kg/dose PO, IM may Hydroxyzine hydrochloride: 2 mg/kg/day q 6 hrly oral;
be repeated after 4 to 8 hours. Side effects: Mild extra- 0.5-1 mg/kg/dose q 4-6 hr IM.
pyramidal symptoms. Ketotifen: 1 mg twice daily for children. Indicated in
Metoclopramide (Perinorm, Reglan): 0.5 to 2 mg/kg/D prophylaxis of allergic bronchial asthma, symptomatic
PO, IM q 6-8 h. Side effects: Extrapyramidal symptoms. treatment of allergic rhinitis and conjunctivitis. Side effects:
Ondansetron hydochloride: Oral dose <4 yr: 2 mg q 4 hr, None.
4-11 yrs: 4 mg q 4 hr, >12 yr: 8 mg q 4 hr. IV dose for >3 Loratadine: It is a long acting selective periheral HI
yrs old 0.15-0.45 mg/kg/dose at 30 min before and 4 and antagonist with minimal sedation. Above 3 yrs upto 30
8 hr after emetogenic drugs. Indicated in chemotherapy kg weight 5 mg oral per day; 12 yrs 10 mg once a day
and radiotherapy induced emesis (not indicated below 4 oral.
years of age).
Methdilazine hydrochloride: >3 yrs 4 mg q 6-12 hrly.
Cisapride: 0.5 mg/kg/D PO q 6-8 h. Indicated for
gastroesophageal reflux, chronic constipation. Pheniramine maleate (avil): 0.5 mg/kg/D PO, I.M or IV
q 8h. Side effects: Same as chlorpheniramine.
Prochlorperazine (Stemetil): 0.5 mg/kg/D PO q 8 h. IM
dose is half of oral dose. Side effects: Bone marrow Promethazine hydrochloride (Phengran): 0.1 mg/kg/
depression, CNS depression, extrpyramidal symptoms. day q 6 to 8 hr and 0.5 mg/kg/dose at HS oral PRN.
730 Essential Pediatrics
Nausea and vomiting or sedation : 0.25-1 mg/kg/dose ml of 1:10 diluted antivenin. In subjects with hyper
q 4 to 6 hr oral, IM, IV or PR. sensitivity careful desensitization is undertaken. Side
Motion sickness: 0.5 mg/kg/dose q 12 hr oral (1st dose effects: Serum sickness, anaphylaxis.
30 minutes before journey). Diphtheria antitoxin: For Schick test positive contacts. One
Side effects: Same as chlorpheniramine. dose of diphtheria toxoid should be given in one arm and
Pseudoephedrine: Children <12 yrs 4 mg/kg/day q 6 to 500-2000 units of diphtheria antitoxin IM in other arm.
8 hr oral, >12 yrs: 30-60 mg/dose q 6-8 hr PO. Maximum Six weeks later, give prophylactic toxoid in order to
dose 240 mg per day. complete the course of active immunization in form of 3
doses of toxoid at monthly intervals. For treatment, the dose
ANTIHYPERTENSIVES is not related to age and weight of the patient: Pharyngeal
or laryngeal diphtheria of 48 hours duration 20,000-40,000
Refer to Chapter 13. units IV. Nasopharyngeal diphtheria, 40,000-60,000 units
IV. Extensive disease of more than 3 days duration with
ANTISPASMODICS neck swelling, 80,000-1,20,000 units IV.
Dicyclomine hydrochloride (Cyclominol, Colimex): Human normal immunoglobulin: For prophylaxis and
Infants below 6 months: 5-10 drops (colimex) 15 min treatment of viral diseases, bums, bacterial infections, and
before feeds, 6 month to 2 yrs: 10-20 drops 15 min before primary immunodeficiency disorders:
feeds, above 2 yrs 1 ml every 6 hr. Side effects: Dry mouth, Primary immunodeficiency disorders 0.2 mL/kg IM
urinary retention. every 4 weeks.
Hyoscine butylbromide (Buscopan): 6-12 years 10 mg q Attenuation of disease among close contacts of Measles.
8 h PO, 10-20 mg IV or IM bolus. 0.25 mL/kg IM within 6 days of exposure; Hepatitis A.
0.02-0.04 mL/kg/IM of a 10% solutions.; Hepatitis B
Oxyphenonium bromide (Antrenyl): 0.8 mg/kg/day q 6 (Hepatitis B immune globulin). 0.06 mL/kg IM to maximum
hr oral. Give 5-10 drops in preschool children and 10-20 of 3-5 mL given within 7 days of exposure. Repeat 30 days
drops in older children q 6 hr. Side effects: Dry mouth, after exposure. Side effects: Coagulopathy, thrombo
blurred vision, retention of urine, dizziness, fatigue, cytopenia. Contraindicated in IgA deficiency and allergy
tremors. to human immunoglobulin.
Pipenzolate methyl bromide: 2.5-5 mg every 8 hr oral. Human tetanus specific immunoglobulin: Prophylactic:
Below 6 months 4 drops, 6 month to 1 year 8-10 drops, 1- 250 IU IM; Therapeutic: 30-300 IU /kg IV; Intrathecal: 250-
3 yrs 16 drops before feed. 500 IU single dose.
Intravenous immune gamma-globulin (IVIG): Dose 0.4
ANTITOXINS AND IMMUNOGLOBULINS
to lg/kg/D IV infusion over 2 hours daily for 5 days or 2
Anti-Rh D immunoglobulin: For prevention of rhesus g/kg IV infusion over 10-12 hrs as a single dose. Possible
sensitization of Rh negative mother. The baby or abortus uses, (i) Idiopathic thrombocytopenic purpura, (ii)
should be Rh-positive and indirect Coomb's test during Kawasaki disease, (iii) myasthenia gravis, (iv) auto
pregnancy should be negative. For antenatal prophylaxis immune neutropenia, (v) systemic lupus erythematosus,
^ give 300 meg IM at 28 weeks and 34 weeks of gestation or (vi) juvenile rheumatoid arthritis, (vii) Guillaine-Barre
I a single dose within 72 hours of delivery. In twin syndrome, (viii) dermatomyositis, (ix) psoriasis, and (x)
n pregnancy, give double the dose. In case of abortion, atopic allergy.
(1 evacuation, procedures (CVS, amniocentesis, external Human rabies specific immunoglobulin: 20 units/kg.
I cephalic version) and trauma give 250 meg IM. Half for infiltration at the site of bite and half IM over
^ Antisnake venom: It contains a mixture of four enzyme- gluteal region if patient presents within 24 hours. The total
refined lyophilized polyvalent antisnake venom serum dose is given IM, if patient presents between 1-7 days.
(common Krait, Cobra, Russell's viper and saw-scaled The rabies vaccine should be administered simul
viper). The total dose of antivenin serum is around 5 vials taneously.
(50 ml) for mild, 5-15 vials for moderate manifestations Tetanus antitoxin: Prophylactic: 3,000-5,000 units SC, IM;
and 15-20 vials (150-200 ml) for severe cases. Smaller Therapeutic: 10,000 units IM or IV; Intrathecal: 250-500
children may require one and half times of this dose units q 24 h for 3 days. Side effects: Serum sickness,
because they receive larger dose of venom per unit body anaphylaxis.
weight. The antivenin is given IV diluted in 250 ml of one-
fifth saline. It is safe to maintain an infusion rate of 20 ml/ Varicella zoster immunoglobulin (VZIG): 125 units/kg
kg/hr. Use steroids and antihistamines in addition. IM within 48 hours or at least within 96 hours of exposure
Exclude horse serum allergy by injecting intradermal 0.02 to varicella.
Rational Drug Therapy 731
BRONCHODILATORS AND ANTI-ASTHMA AGENTS L/min delivering 2-5 micron size particles. Side effects:
Headache, tremor, irritability.
Adrenaline: 0.01 mL/kg/dose (maximum 0.5 mL/dose)
of 1 : 1000 solution SC. Repeat the dose after 15-20 min. Salmeterol: 1-2 puffs twice a day. Maximum 4 puffs twice
Side effects: Palpitations, anxiety.
a day or rotacap once or twice a day. It is long acting and
provides prolonged bronchodilation. (Not recommended
Aminophylline: 5-7 mg/kg/dose PO every 8 h. For status for children below 4 years of age).
asthmaticus 5-7 mg/kg loading dose IV followed by 0.9 Sodium cromoglycate: Initiating dose is 1-2 puffs (5 mg
mg/kg/h. If patient is already receiving oral amino per MDI dose) 3-4 times/d or 1 rotacap (20 mg/cap) 3-4
phylline do not use loading dose. For apneic attacks in times/d. Maintenance dose; 1 puff 3-4 times/day or 2-3
preterm infants 5 mg/kg loading dose slow IV followed rotacaps per day. Adults 2 puffs 4 times daily. Continuous
by 2 mg/kg PO or IV q 8 h. Side effects: Irritability, prophylaxis is required, may take 4-6 week for evident
convulsions. beneficial effect.
Bambuterol: An oral long acting prodrug of terbutaline Terbutaline (Bricanyl): 0.1-0.15 mg/kg/D q 8 h orally.
with 24 hr duration of action. 2-5 yr: 5 mg, 6-12 yr: 10 mg 0.005 to 0.01 mg/kg/D SC, IM or slow IV divided doses 8
single dose. May be useful in nocturnal asthma. Presently hourly. Inhaler 1-2 puffs of 250 pg every 6-8 h. Side effects:
recommended for use in children above 2 yrs of age. Same as salbutamol.
Beclomethasone dipropionate (Beclate inhaler): Inhala Zafirlukast: 40 mg/d in 2 divided dose for prophylaxis
tion of 50-100 pg of beclomethasone 3-4 times per day and treatment of asthma in children older than 12 years.
(maximum 10 inhalations in 24 hours) in children with Note: Metered dose inhalers should be used with spacers.
chronic asthma requiring corticosteroid therapy for 10- For infants MDI with spacer can be used with a baby face
12 weeks. mask. Rotacap dose is double of the inhaler dose. Rotacaps
Budesonide (Pulmicort inhaler): Inhalation of 100 pg of are administered using Rotahaler.
budesonide 2-3 times a day (maximum 8 inhalations in
24 hours). Meter dose inhalers are used with a spacer, CARDIOTONICS
while rotacaps with a rotahaler. Baby mask can be used
in infants. Inotropic Agents
Ciclosonide: Long acting steroid one (80 meg) or two (160 Dobutamine (Dobutrex): 2.5-25 pg/kg/min IV conti
meg) puff/day. Not to be used below 12 years of age. nuous infusion. Side effects: Tachycardia, hypertension,
arrhythmias.
Formoterol fumarate: 12 meg inhalation twice daily. It is Dopamine: 2-5 pg/kg/min IV continuous infusion
a long acting selective beta-2 adrenergic stimulant. Not increased slowly to 20 pg/kg/min. Adjust the dose for
for treatment of acute asthma. the desired effects. Maximum recommended dose is up
Fluticasone propionate: 50-500 meg/day in two divided to 30 pg/kg/min. Side effects: Tachyarrhythmias,
doses. (Mild persistent asthma 50-100 meg/day; moderate hypertension, vasoconstriction, vomiting. Extravasation
persistent 100-200 meg/day; severe persistent 200-500 may cause tissue necrosis.
mcg/d). Adults 100-1000 mcg/day. Digoxin: Digitalizing dose: for premature infants 0.04 mg/
Orciprenaline (Alupent): 0.3-0.5 mg/kg/dose PO with
kg/D, mature neonates 0.06 mg/kg/D, infants (1-12 month)
maximum of 1 mg/kg/D. 0.06-0.08 mg/kg/D, older children 0.04 mg/kg/D PO
(parenteral dose is 2/3rd of this amount). One half of
Ipratropium bromide (Ipravent): As neubliser 250 meg digitalizing dose is given stat followed by 1 /4th dose after
to be diluted in 2-4 ml of saline and given over 10 minutes, 8 hours and l/4th of digitalizing dose after 16 hours. The
every 20 minutes for 3 doses followed by 250 meg maintenance dose is l/4th of digitalizing dose and given
nebulization every 2-4 hours. Ipratropium MDI1-2 puffs once a day. Side effects: Nausea, vomiting, pulsus bigeminy,
thrice daily. extra systoles, partial or complete heart blocks, sinus
Ketotifen: Children >2 yrs 1 mg twice daily for children. arrhythmia, atrial or ventricular tachycardia.
Start at lower dosage at night for 2 to 3 days. Milirinone: 50-75pg/kg loading dose, followed by 0.25-
Montelukast sodium: 2-6 years: 4 mg once a day, 6-14 1.0 pg/kg/min continuous infusion. Inotropic and
years: 5 mg once daily, >14 yr: 10 mg oral once daily in vasodilatory action.
the evening. Indications: exercise induced asthma, alternate Mephentermine (Mephentine): 0.4 mg/kg/dose IV blous
to long acting B 2 agonist. or slow infusion.
Salbutamol (Albuterol, Ventorlin): 0.1-0.4 mg/kg/dose Norepinephrine: 0.05-0.1 pg/kg/min. Titrate dose to
PO every 8 hours. Inhaler 1-2 puffs of 100 pg every 6-8 desired effect (maximum dose 2 pg/kg/min). Used in
hours. Injection 4-6 ug/kg/dose SC, IM or IV q 6-8 h. It is vasodilatory and septic shock.
given effectively through nebulizer with an airflow of 6 Isoproterenol hydrochloride: 0.05-0.5 pg/kg/min IV.
732 Essential Pediatrics
bone fusion occurs. For Turner Syndrome 0.09-0.1 unit/ Clonazepam: 0.03 mg/kg/D PO q 8 h. Gradually increase
kg SC daily can be increased to 0.11-0.14 unit /kg daily. till maximum dose of 0.1-0.3 mg/kg/D is achieved.
Thyroid
Butyrophenones (Haloperidol): 0.25 mg PO q 12 h (for
anxiety). 5-10 mg/D PO q 12 h (for chorea). Side effects:
Carbimazole (Neomercazole): 1-2 mg/kg/D PO divided
Extrapyramidal reactions, dyskinesia.
doses 8 hourly. Side effects: Urticaria, loss of taste, alopecia,
pigmentation, bone marrow depression. Tricyclic antidepressants. (Imipramine): 1.5 mg/kg/D
Liothyronine sodium: 0.5-1.5 |ig/kg/day single dose oral.
PO single or divided doses. For nocturnal enuresis 25 mg
For hypothyroid coma 5-20 jag IV every 12 hours. at bed time. For children over 10 years old, 50 mg may be
given. Duration of treatment 6-8 weeks. Side effects:
Potassium iodide: 1 ml saturated Lugol's iodine solution Anticholinergic effects, dry mouth constipation, urinary
per day q 8 hr oral or potassium iodide 50-150 mg/day q retention, blurred vision, tremors, hypotension.
8 hr oral. Max 0.4 mol/kg/hr; min oral dose 1 mmol/kg
<5 yrs and age >5 yrs 0.5 mmol/kg Chloral hydrate: 5-10 mg/kg/dose for sedation and 20-
Propylthiouracil: 1-4 mg/kg/day. Under 10 years 50-150
75 mg/kg/dose for heavy sedation.
mg/day q 8 hr and >10 years 150-300 mg/day q 8 hr. Chlorpromazine: 2.5-6 mg/kg/day q 6 hr oral. In chorea
Maintenance dose 50 mg twice daily. start with 50 mg/day oral and increase by 25 mg/day till
Thyroxine sodium: 10-15 (ig/kg/day in newborn babies chorea is controlled or maximum dose of 300 mg /day is
and 5 (ig/kg/day in children, single dose oral empty achieved. For neonatal tetanus, 1 to 2 mg/kg per dose 2
stomach in the morning. (By 5 years of age 100 ng per day to 4 hourly.
is reached and by 12 years 200-250 |0,g per day). Fluoxetine hydrochloride: Children >5 yr give 5-10 mg
Pancreas
oral once a day, maximum dose 20 mg per day.
Insulin (Plain): Insulin for diabetic ketoacidosis. Haloperidol: Infantile autism: 0.025-0.05 mg/kg/d,
High dose schedule: Soluble insulin 2 units/kg, half IV psychotic disorder: 0.05-0.15 mg/kg/d q 8-12 hr, non-
and half SC stat. If initial blood glucose is more than 500 psychotic behaviour disorder: 0.05-0.075 mg/kg/d,
mg/dl, administer additional 1 unit/kg IV after one hour, agitation 0.01-0.03 mg/kg/d q 8-12 hr.
followed by 1 unit/kg SC every 2 hours till blood sugar Ketamine: For IV induction 0.5-2 mg/kg at a rate not to
falls below 250mg/dl. exceed 0.5 mg/kg/min; IM, oral, rectal 3-10 mg/kg/dose;
Lozv dose schedule: 0.1 unit/kg IV bolus followed by 0.1 nasal and sublingual 3-5 mg/kg/dose. Minor procedures
unit/kg/hour continuous infusion in normal saline with 0.5-1.0 mg/kg. Sedative dose 2 mg/kg. The concomitant
the help of an infusion pump till blood sugar comes down use of midazolam is beneficial.
to 300 mg/dl. Switch over to N/2 saline in 5% dextrose
and give 0.25 units/kg q 6 hr SC. Midazolam: 0.07-0.2 mg/kg/dose IM or IV for preope
rative sedation or conscious sedation during mechanical
TRACE METALS.................................... ..................... .............. ventilation. IV 0.2 mg/kg bolus followed by 0.4-0.6 (ig/
kg/min as continuous infusion. Oral or rectal 0.5-0 0.75
Magnesium sulphate: 2-3 mEq/kg/D as maintenance mg/kg/dose. Nasal or sublingual 0.2-0.5 mg/kg/dose.
needs in cases of protein energy malnutrition. Magnesium
sulphate 50% solution provides 4 mEq/mL. 20-100 mg/ Triclofos (Tricloryl): 20 mg/kg/dose for sedation.
kg/dose as 1% solution by slow IV infusion not more than
100 mg per minute. 100 mg/kg/dose as 50% solution if VASODILATORS_____ _____
given IM. Captopril: (Venous and arteriolar) Infants: 0.5 -6.0 mg/
Zinc sulphate: For deficiency 0.5 mg/kg/day for infants; kg/day q8 hr oral, children: 12.5 mg ql2 hr oral. Monitor
10 mg/kg/day for older children and 6 mg/kg/d for total leukocyte count and renal functions
acrodermatitis enteropathica. Hydralazine: (Arterial) 0.1-0. 5 mg/kg /dose IV 6 hr, 1-
7.5 mg/kg /day q 6-8 hr.
SEDATIVES, HYPNOTICS AND ANTIDEPRESSANTS
Isosorbide dinitrate (Venous): 0.1 mg/kg/D PO q 6-8 h.
Diazepam: Sedative and anxiolytic in doses of 2-5 mg PO. Side effects: Flushing, headache.
As an anticonvulsant 0.2 mg/kg/dose IV (max 10 mg).
May repeat in 15 minutes. Isoxuprine hydrochloride (Duvadilan): 0.5-1 mg/kg/D
PO IM or IV q 8 h. Side effects: Hypotension.
Lorazepam: Dose 0.1 mg/kg IV. Duration of action is
longer than diazepam. Can repeat after 5 minutes. Oral Nifedipine: (Venous and arteriolar) 0.3 mg/kg/dose oral
dose 0.03-0.05 mg/kg/dose q 8-12 h. q 6hr
734 Essential Pediatrics
Prazosin: (Venous and arteriolar) 5-25 |ig /kg/dose oral Ergocalciferol: Used for renal osteodystrophy in a dose
q 6hr. Side effects: Postural hypotension, dizziness, of 25,000-2,50,000 i.u./D PO, decrease the dose once
faintness, nasal stuffiness, priapism. healing occurs.
Sodium nitroprusside: (Venous and arteriolar) 0.5-8.0 Famotidine: 1-1.2 mg/kg/D, PO q 12 h. Maximum dose
jug /kg/min IV infusion. 50 mg is dissolved in one liter of is 40 mg per day.
5% dextrose to provide concentration of 50 ug/ml. Glycerol: 05-1 g/kg/dose PO 6 hr.
Tolazoline: Used for pulmonary hypertension in Human albumin: 1 g/kg/dose IV over 30-120 minutes
newborns with RDS 1-2 mg/kg IV over 10 min followed for hypoprotinemia.
by 1-2 mg/kg/hour in continuous infusion. Ketamine: 0.5-2.0 mg/kg stat IV 3-7 mg/kg stat
Xanthinol nicotinate (Complamina): 5-10 mg/kg/D IM supplemental dose l/3rd of initial dose. Increases
or IV PO q 8 h. Side effects: Hypotension, flushing. respiratory secretions. Atropine is helpful.
Lactulose: For cases of hepatic coma, <2 yrs 2.5 mL/D
CEREBRAL ACTIVATORS
PO, PR q 12 h (5 mL contains 3.35 g). >2 yrs 5-10 mL PO,
PR ql2h. Side effects: Diarrhea.
Pyritinol (Enecephabol): Improves cerebral metabolism Magnesium sulfate: As cathartic 250 mg/kg/dose PO.
and enhances neurotransmission, used in delayed For hypomagnesemia 100 mg/kg/dose IM 4-6 h (1%
development and sequelae of neurological illnesses. solution contains 10 mg magnesium/mL (0.08 mEq/mL).
For asthma 50-100 mg/kg/dose IV.
Piracetam: Cerebral activator, used in mental subnor
mality. Dose: 150 mg/kg/D PO q 8 h. Mannitol: 0.5-3 g/kg/dose IV single dose. It should be
given over 30-60 min.
Doxapram: Used for neonatal apnea 0.5-2.5 mg/kg/h
continuous infusion. Pancuronium: Neonates 0.05-1.0 mg/kg/dose IV
undiluted over 5 minutes. More than one month 0.04-0.1
Pemoline: Used for minimal brain dysfunction in older mg/kg/dose q 1-4 h. 0.05-0.2 mg/kg/h as continuous
children in a dose of 1 mg/kg/D PO every day single dose. infusion.
Increase weekly by 0.5 mg/kg till a maximum dose of 3
mg/kg/D. Not recommended for children less than 3 Physostigmine: 0.001-0.03 mg/kg/dose IM, SC, IV.
years of age. Repeat q 15-20 min to desired effect or maximum dose of
20 mg.
MISCELLANEOUS _________ _____________ __________ Potassium chloride: 1-2 mEq/kg/D q8 h PO. Maximum
IV dose is 20 mEq/h of infusate.
Acetazolamide (Diamox): 30-50 mg/kg/D PO q 6-8h.
Pralidoxime (PAM): 25-50 mg/kg stat repeat for
Allopurinol: 10 mg/kg/D PO q 12 h. organophosphorus poisoning.
Aminocaproic acid: 100 mg/kg/dose 4-6 hourly IV, PO, Probenecid: 20^40 mg/kg/D q 8 h with initial loading
may cause hypercoagulation, nausea, vomiting. dose of 25 mg/kg PO.
_ Bisacodyl (Dulcolax): 5-10 mg to be given 6 hr before the Prostaglandin El: Useful to maintain the patency of
I desired effect. ductus arteriosus prior to surgery in neonates; dose 0.05-
0.4 (ig/kg/min. Usual maintenance dose is 0.01-0.4 jag/
>•1 Calcitriol (1, 25-dihydroxycholecaIciferol): In renal kg/min.
W failure, use 0.01-0.05 |ig/kg/24 hour.
Pulmonary surfactant: Survanta 4 mL/kg/dose intra-
■ Calcium gluconate (Elemental calcium 9%): 1-2 ml/kg tracheally. Exosurf 5 mL/kg/dose. Neosurf 5.0 mL/kg/
of 10% solution. IV infusion is given very slowly under dose.
cardiac monitoring. Ranitidine: 2 mg/kg/D PO, IM or IV q 12 h. Side effects:
Cimetidine: 20-40 mg/kg/D PO, IV q 6 h. Renal impairment.
Dantrolene: 0.5 mg/kg/twice daily. Increase dose till Sodium bicarbonate: 1-2 mEq/kg/dose or calculated on
desired effect is reached in cases of chronic spasticity, for basis of base deficit as follows:
example, cerebral palsy. Intravenously, the drug is used Base deficit x weight in kgs x 0.6 = mEq, or mL of 7.5%
for malignant hyperthermia. solution of sodium bicarbonate required for correction.
29 Integrated Management of Neonatal and
Childhood Illnesses
Child health has remained an essential component of most collaboration with UNICEF and many other agencies in
of the national health programs in India from Expanded mid-1990s, combines improved management of common
Program of Immunization (EPI) in 1974 to the most recent childhood illnesses as well as prevention of diseases and
National Rural Health Mission. Introduction of several promotion of health by dealing with counselling on
new technologies in early 1980's have made it possible to feeding and immunization. This strategy has been adapted
prevent major infectious diseases of childhood through and expanded in India to include neonatal care at
mass immunization campaigns and treatment of diarrheal home as well as in the health facilities and renamed as
dehydration and malaria at low cost. However, the current Integrated Management of Neonatal and Childhood
child health scenario indicates that common childhood Illness (IMNCI).
illnesses like acute respiratory infections, diarrhea,
measles, malaria, and malnutrition continue to result in Essential Components of IMNCI Strategy
high mortality among children less than 5 years of age. The IMNCI strategy includes both preventive and curative
The available trends of under five mortality rate (U5MR) interventions that aim to improve practices in health
suggest that the national goal to reduce U5MR to 42 per facilities, the health system and at home. At the core of
1000 live births by 2015 is not a realistic projection, even the strategy is integrated case management of the most
with the currently available interventions. Even though common neonatal and childhood problems with a focus
effective interventions to manage these conditions are on the most common causes of death in children < 5 years
available, the current child health scenario is not likely to of age.
change significantly unless new strategies are introduced
to reduce child mortality and improve child health and The strategy includes three main components:
development. Integrated Management of Childhood • Improvements in the case-management skills of
Illness (IMCI) strategy optimizes public health approach health staff through use of locally adapted guidelines
for improving children's health through the delivery of • Improvements in the overall health system; and
essential child health interventions. • Improvements in family and community health care
practices.
Why Integrated Management?
This chapter elaborates the clinical guidelines for the
Many well known interventions like universal immuni treatment of sick children in an outpatient or primary care
zation, essential newborn care, exclusive breastfeeding setting.
during first 6 months of life, appropriate complementary
feeding, oral rehydration therapy, and timely and
appropriate use of antibiotics in pneumonia have proven IMNCI Clinical Guidelines
to be effective. While each of these interventions is The IMNCI clinical guidelines target children less than 5
successful, there is evidence to suggest that an integrated years old, the age group that bears the highest burden of
approach is needed to manage sick children. Besides, sick morbidity and mortality. The guidelines represent an
children often present with overlapping signs and evidence-based, syndromic approach to case management
symptoms common to different illnesses and often suffer that includes rational, effective and affordable use of
from more than one illness which may necessitate different drugs. Careful and systematic assessment of common
treatments. Another reason for integrated approach is the symptoms, using well-selected reliable clinical signs, helps
need for incorporating preventive strategies such as to guide rational and effective actions.
immunization and nutrition along with curative care. An evidence-based syndromic approach can be used
to determine: (a) health problem(s) the child may have,
INTEGRATED MANAGEMENT OF NEONATAL AND
(b) severity of the child's condition and (c) actions that
CHILDHOOD ILLNESS (IMNCI) STRATEGY
can be taken to care for the child (e.g. refer the child
Integrated Management of Childhood Illness (IMCI) immediately, manage with available resources, or manage
strategy, developed by World Health Organization in at home). In addition the guidelines suggest the
735
736 Essential Pediatrics
adjustments required to manage with the capacity of child does not have any of the signs in the pink or yellow
health system and active involvement of family members rows, select the classification in the green row. If the young
in health care practices. infant/child has signs from more than one row, the more
severe classifications is selected. However, if the
The Principles of Integrated Care classification table has more than one arm (e.g. possible
Depending on a child's age, various clinical signs and bacterial infection/jaundice, diarrhea in a sick child), one
symptoms differ in their degrees of reliability and may have more than one classification from that box.
diagnostic value and importance. IMNCI clinical IMNCI classifications are not necessarily specific
guidelines focus on children up to 5 years of age. The diagnoses, but they indicate what action needs to be taken.
treatment guidelines have been broadly described under All classifications are colour coded: pink calls for hospital
two age categories: referral or admission, yellow for initiation of treatment,
• Young infants age up to 2 months. and green means that the child can be sent home with
• Children age 2 months up to 5 years. careful advice on when to return.
The IMNCI guidelines are based on the following
principles: Effective Communication with
• All children under 5 years of age must be examined for the Mother/Care Provider
conditions which indicate immediate referral. It is critical to communicate effectively with the infant's
• Children must be routinely assessed for major mother or caretaker. Proper communication helps to
symptoms, nutritional and immunization status, reassure the mother or caretaker that the infant will receive
feeding problems and other problems. appropriate care. In addition, the success of home
• Only a limited number of carefully selected clinical treatment depends on how well the mother or caretaker
signs are used for assessment. knows about giving the treatment and understands its
• Classification - a combination of individual signs is importance.
used to classify the severity of illness which calls for
specific action rather than a 'diagnosis'. Classifications OUTPATIENT MANAGEMENT OF YOUNG
are colour coded and suggest referral (pink), initiation INFANTS AGE UP TO 2 MONTHS
of treatment in health facility (yellow) or management
at home (green). Assess and Classify Sick Young Infants
• IMNCI guidelines address most common, but not all Young infants (infants age <2 months) have special
pediatric problems. characteristics that must be considered when classifying
• IMNCI management protocols use a limited number their illness. They can become sick and die very quickly
of essential drugs. from serious bacterial infections. They frequently have
• Caretakers are actively involved in the treatment of only general signs such as few movements, fever or low
children. body temperature. Mild chest indrawing is normal in
• IMNCI includes counselling of caretakers about home young infants because their chest wall is soft. For these
care including feeding, fluids and when to return to reasons, assessment, classification and treatment of young
health facility. infant is somewhat different from an older infant or young
IMNCI Case Management Process (Fig. 29.1)
child. The assessment procedure for this age group
includes a number of important steps that must be
Steps of case management process are: followed by the health care provider, including: (1) history
Step 1: Assess the young infant/child taking and communicating with the caretaker about the
Step 2: Classify the illness young infant's problem; (2) checking for possible bacterial
Step 3: Identify treatment infection/jaundice; (3) assessing for diarrhea if present;
Step 4: Treat the young infant/child (4) checking for feeding problem or malnutrition; (5)
Step 5: Counsel the mother checking immunization status; and (6) assessing other
Step 6: Follow up care problems.
Classification Tables Checking for Possible Bacterial Infection/Jaundice
IMNCI classification table describes the steps of case In the first step all sick young infants are first examined
management process: Assess, Classify and Identify to assess for signs of possible bacterial infection and
Treatment (See chart). There are separate classification jaundice. The bacterial infection can be serious bacterial
boxes for main symptoms, nutritional status and anemia. infection or a localized infection such as skin infection or
Classification tables are used starting with the pink rows. ear infection.
If the young infant/ child does not have the severe The clinical signs which point to possible serious
classifications, look at the yellow rows. For the classi bacterial infection are : Convulsions (as part of the current
fication tables that have a green row, if the young infant/ illness), fast breathing (the cut-off rate to identify fast
Integrated Management of Neonatal and Childhood Illnesses 737
For all sick children up to 5 years who are bought to a first-level health facility.
ASSESS the child: Check for danger signs (or possible bacterial infection/jaundice). Ask about main symptoms. If a main
symptom is reported, assess further. Check nutrition and immunization status. Check for other problems.
CLASSIFY the child’s illness: Use a colour-coded triage system to classify the child’s main symptoms and his or
her nutrition or feeding status.
REFER THE CHILD: Explain to the child’s COUNSEL THE MOTHER: Assess the child’s
caretaker the need for referral. Calm the feeding, including breastfeeding practices, and
caretaker’s fears and help resolve any problems. solve feeding problems, if present. Advise
Write a referral note. Give instructions and about feeding and fluids during illness and
supplies needed to care for the child on the way about when to return to a health facility.
to the hospital. Counsel the mother about her own health.
FOLLOW-UP care: Give follow-up care when the child returns to the clinic and, if necessary,
reassess the child for new problems.
breathing in young infants is 60 breaths per minute or antibiotics. The mother is advised to continue breast
more; if the count is 60 breaths or more, the count should feeding and to keep the baby warm on the way to hospital.
be repeated, because the breathing rate of a young infant Pus or redness around the umbilicus or presence of <10
is often irregular. If the second count is also 60 breaths or
skin pustules or pus draining from ear is classified as local
more, the young infant has fast breathing); severe chest bacterial infection and treated with oral antibiotics.
indrawing; nasal flaring; grunting; bulgingfontanelle; >10 Jaundice
skinis the visible manifestation of hyperbilirubine
pustules; axillary temperature >37.5°C or <35.5°C; mia. Occurrence of jaundice within first 24 hours of birth
lethargy
or unconsciousness; and less than normal movements. Presence
or after 14 days of age or deep jaundice visible as yellow
of any of these signs indicates possible serious bacterial palms and soles suggests pathological jaundice and is
infection which may be a part of sepsis or pneumonia. A classified as a severe illness necessitating urgent referral to
young infant with possible serious bacterial infection is a hospital for evaluation. (Chart 29.1). An infant age 1-13
referred urgently to hospital after giving first dose of days who has jaundice but palms and soles are not yellow
738 Essential Pediatrics
Chart 29.1
IDENTIFY TREATMENT
CHECK FOR POSSIBLE BACTERIAL SIGNS CLASSIFY AS (Urgent pre-referral treatments are fn bold print.)
unconscious. • Palms and soles not yellow JAUNDICE > Advise mother to give home care for the young infant.
1 Look at the young infant’s movements.
> Advise mother when to return immediately.
Are they less than normal? > Follow up in 2 days.
' Look for jaundice?
Are the palms and soles yellow?
And if the temp, • Temperature between 35.5 - 36.4°C > Warm the young infant using skin to skin contact for
is between LOW BODY one hour and REASSESS.
35.5-36.4°C TEMPERATURE > Treat to prevent low blood sugar.
# If referral is not possible, see the section Where Referral Is Not
Possible in the module Treat the Young Infant and Counsel the
Mother.
THEN ASK:
Does the young infant have diarrhoea?*
for
DEHYDRATION
IF YES, ASK: LOOK AND FEEL:
and if
diarrhoea
14 days or
* What is diarrhoea in a young infant?
If the stools have changed from usual pattern and are many and watery
(more water than fecal matter). The normally frequent or loose stools of
a breastfed baby are not diarrhoea.
and if blood
# If referral is not possible, see the section Where Referral Is Not in stool
Possible in the module Treat the Young Infant and Counsel the
Mother.
Two of the > Give first dose of intramuscular ampicillin and gentamicin.
following signs: > If infant also has low weight or another severe
SEVERE
classification:
• Lethargic or DEHYDRATION - Refer URGENTLY to hospital with mother giving frequent
unconscious.
sips of ORS on the way.
• Sunken eyes.
- Advise mother to continue breastfeeding.
- Advise mother how to keep the young infant warm on the
• Skin pinch goes
way to the hospital.
back very slowly.
OR
> If infant does not have low weight or any other severe
classification:
- Give fluid for severe dehydration (Plan C) and then refer to
hospital after rehydration.
Two of the > If infant also has low weight or another severe classification
following signs: — Give first dose of intramuscular ampicillin and gentamicin
SOME — Refer URGENTLY to hospital with mother giving frequent
• Restless, irritable. DEHYDRATION sips of ORS on the way.
• Sunken eyes. — Advise mother to continue breastfeeding.
• Skin pinch goes — Advise mother how to keep the young infant warm on the
back slowly. way to the hospital.
> If infant does not have low weight or another severe classification:
— Give fluids for some dehydration (Plan B).
— Advise mother when to return immediately.
— Follow up in 2 days.
1 Not enough signs > Give fluids to treat diarrhoea at home (Plan A).
»Does the mother have pain If yes, look and feel for:
while breastfeeding? • Flat or inverted nipples, or sore nipples
• Engorged breasts or breast abscess
# If referral is not possible, see the section Where Referral Is Not Possible in the module Treat the Young Infant and Counsel the Mother.
Integrated Management of Neonatal and Childhood illnesses 741
is advised home care but should be advised to come for for age identifies children whose weight is -2 standard
follow up after 2 days and advised when to return deviations below the mean weight of infants in the
immediately. reference population (Z score <-2). Infants who are very
In addition to possible bacterial infection and jaundice, low weight for age are given pink classification and should
sick young infants with temperature between 35.5°-36.5°C be referred to a hospital. Infants who are low weight for
are classified as low body temperature. This may be due age need special attention to how they are fed and on
to environmental factors or can be due to infection. Such keeping them warm.
infants are warmed using skin to skin contact and To assess the young infant for feeding problems the
reassessed after 1 hour. If the temperature becomes normal mother is asked specific questions about infant feeding to
and the infant has no other pink classification he can be determine if the feeding practices are optimal. The weight
sent home after advising the mother on how to keep the of the child and feeding history is taken in to consideration
baby warm. If the temperature is still below 36.5°C the to determine if breast feeding technique needs to be
infant should be referred to the hospital. checked. Thus an exclusively breast fed infant who is not
Assessing for Diarrhea
low weight for age does not require any intervention and
is therefore not observed for breast feeding. If the mother
Diarrhea is a main symptom, which is assessed if the gives history of feeding problem or the infant is low weight
mother says it is present. Exclusively breastfed infants for age and has no indication for referral the mother is
normally pass frequent soft stools. This should not be observed for breast feeding. Breast feeding is observed to
confused with diarrhea. A young infant is said to have see the signs of attachment and whether the infant is
diarrhea if the stools have changed from usual pattern suckling effectively. Mothers of infants with problem in
and the child is passing many and watery stools (more feeding are counselled appropriately. Infants who are not
water than fecal matter). low weight for age and have no feeding problem are
Clinical Assessment and Classification classified as "no feeding problem" and counselled about
home care of young infant.
All infants with diarrhea should be assessed for presence
of dehydration. A number of clinical signs are used to Checking Immunization Status
determine the level of dehydration: infant's general Immunization status should be checked in all sick young
condition (lethargic or unconscious or restless /irritable); infants. A young infant who is not sick enough to be
sunken eyes and elasticity of skin (skin pinch goes back very referred to a hospital should be given the necessary
slowly, slowly or immediately). In addition the infant is immunizations before s/he is sent home.
assessed for persistent diarrhea and dysentery.
Persistent diarrhea is an episode of diarrhea, with or Assessing Other Problems
without blood, which begins acutely and lasts at least 14 All sick young infants need to be assessed for other
days. Persistent diarrhea is usually associated with weight
loss and often with serious non-intestinal infections. potential problems mentioned by the mother or observed
Persistent diarrhea in a young infant is considered as during the examination. If a potentially serious problem
severe illness and requires urgent referral. Similarly visible is found or there are no means in the clinic to help the
blood in stool in a young infant is classified as severe infant, s/he should be referred to hospital.
dysentery and the infant should be referred to hospital. Identify Treatment and Treat
All young infants with diarrhea are classified for degree
of dehydration and in addition may be classified if they The next step is to identify treatment required for the
have persistent diarrhea and /or dysentery. Young infants young infant according to the classification. All the
with severe dehydration will need IV fluids while those treatments required are listed in the "Identify Treatment"
with some dehydration are treated as plan B with oral rehy column of the ASSESS and CLASSIFY THE SICK YOUNG
dration. Young infants with no dehydration will require INFANT, Chart 29.1. If a sick young infant has more than
more fluid to prevent dehydration (see chapter on one classification, treatment required for all the classifi
diarrhea). cations must be identified. The first step is to determine if
there is need to refer the child to hospital.
Checking for Feeding Problems or Malnutrition All infants and children ivith a severe classification
All sick young infants seen in outpatient health facilities as soon as assessment is
(pink) are referred to a hospital
should be routinely evaluated for adequate feeding and completed and necessary pre-referral treatment is
have their weight checked. Weight for age compares the administered. Successful referral of severely ill infants to
young infant's weight with the infants of the same age in the hospital depends on effective counselling of the
the reference population (WHO-NCHS reference). The caretaker. The first step is to give urgent pre-referral
very low weight for age identifies children whose weight is treatment (written in bold font in identify treatment
-3 standard deviations below the mean weight of infants section of chart). This may be:
in the reference population (Z score <-3). The low weight • Administering first dose of antibiotic.
742 Essential Pediatrics
}
For how long? ► Count the breaths in one
CHILD DIFFICULT
minute. > Give Cotrimoxazole for 5 days.
* Look for chest indrawing. MUST BE BREATHING > Soothe the throat and relieve the cough with
» Look and listen for stridor. CALM a safe remedy if child is 6 months or older.
• Fast breathing. PNEUMONIA
> Advise mother when to return immediately.
> Follow-up in 2 days.
If the child is: Fast breathing is: >lf coughing more than 30 days, refer to assessment.
>Soothe the throat and relieve the cough with a safe
2 months up 50 breaths per • No signs of pneumonia NO PNEUMONIA: home remedy if child is 6 months or older.
to 12 months minute or more or very severe disease. COUGH OR COLD > Advise mother when to return immediately.
12 months up 40 breaths per >Follow-up in 5 days if not improving.
to 5 years minute or more
# If referral is not possible, see the section Where Referral Is Not Possible in the module Treat the Child.
744 Essential Pediatrics
Does the child have diarrhoea?
Two of the following signs: > If child has no other severe classification:
IF YES, ASK: LOOK AND FEEL: for - Give fluid for severe dehydration (Plan C).
DEHYDRATION • Lethargic or unconscious
For how long? » Look at the child's general • Sunken eyes >■ If child also has another severe classification :
SEVERE
condition. • Not able to drink or Refer URGENTLY to hospital' with mother giving frequent
DEHYDRATION
Is there blood in drinking poorly sips of ORS on the way. Advise the mother to continue
the stool? • Skin pinch goes back very breastfeeding.
- Lethargic or unconscious?
- Restless and irritable? slowly.
> If child is 2 years or older and there is cholera in your area,
* Look for sunken eyes. give doxycycline for cholera.
- Very slowly (longer than 2 Not enough signs to NO > Give fluid and food to treat diarrhoea at home (Plan A).
seconds)? classify as some or severe DEHYDRATION > Advise mother when to return immediately.
- Slowly? dehydration. > Follow-up in 5 days if not improving.
and if diarrhoea • Dehydration present. SEVERE > Treat dehydration before referral unless the child has another
14 days or more PERSISTENT severe classification.
DIARRHOEA > Refer to hospital.#
• No dehydration. PERSISTENT > Advise the mother on feeding a child who has PERSISTENT
DIARRHOEA DIARRHOEA.
> Give single dose of vitamin A.
> Give zinc sulphate 20 mg daily for 14 days.
> Follow-up in 5 days.
and if blood • Blood in the stool. DYSENTERY > Treat for 5 days with cotrimoxazole.
in stool > Follow-up in 2 days.
# If referral is not possible, see the section Where Referral Is Not Possible in the module Treat the Child.
HIGH MALARIA RISK
• Any general danger >Give first dose of IM quinine after making a blood smear.
Does the child have fever? High
sign or VERY SEVERE > Give first dose of IV or IM chloramphenicol (If not possible, give oral
amoxycillin).
(by history or feels hot or temperature 37.5°C* or above) • Stiff neck or FEBRILE
Malaria Risk • Bulging DISEASE > Treat the child to prevent low blood sugar.
fontanelle. rGive one dose of paracetamol in clinic for high fever (temp. 38.5°C or above).
> Refer URGENTLY to hospital’.
IF YES: •Fever (by history or > Give oral antimalarials for HIGH malaria risk area after making a blood smear.
Decide Malaria Risk: High or Low feels hot or > Give one dose of paracetamol in clinic for high fever (temp. 38.5°C or above)
temperature 37.5°C MALARIA >• Advise mother when to return immediately.
THEN ASK: LOOK AND FEEL: Classify or above). >Follow-up in 2 days if fever persists.
> If fever is present every day for more than 7 days, refer for assessment.
• Fever for how long? • Look or feel for stiff neck. FEVER
• If more than 7 days, has fever • Look and feel for bulging
been present every day? fontanelle. LOW MALARIA RISK
• Has the child had measles • Look for runny nose. • Any general danger > Give first dose of IM quinine after making a blood smear.
within the last 3 months? sign or VERY SEVERE > Give first dose of IV or IM chloramphenicol (If not possible, give oral
Look for signs of MEASLES amoxycillin).
• Stiff neck or FEBRILE
• Bulging DISEASE > Treat the child to prevent low blood sugar.
• Generalized rash and
fontanelle. > Give one dose of paracetamol in clinic for high fever (temp. 38.5°C or above).
• One of these: cough, runny nose, > Refer URGENTLY to hospital*
or red eyes.
• NO runny nose and > Give oral antimalarials for LOW malaria risk area after making a blood smear.
If the child has measles » Look for mouth ulcers. NO measles > Give one dose of paracetamol in clinic for high fever (temp. 38.5°C or above).
• Pus draining from MEASLES WITH > Give first dose of Vitamin A.
the eye or EYE OR MOUTH > If pus draining from the eye, treat eye infection with tetracycline eye
• Mouth ulcers. COMPLICATIONS* ointment.
> If mouth ulcers, treat with gentian violet.
> Follow-up in 2 days.
* This cutoff is for axillary temperatures; rectal temperature cutoff is approximately 0.5°C higher.
** Other causes of fever include cough or cold, pneumonia, diarrhoea, dysentery and skin infections.
# * If referral is not possible, see the section Where Referral Is Not Possible in the module
* Other important complications of measles - pneumonia, stridor, diarrhoea, ear infection, and malnutrition - are classified in other tables.
Treat the Child.
Does the child have an ear problem?
• Tender swelling behind the ear. > Give first dose of injectable
MASTOIDITIS chloramphenicol (If not possible
give oral amoxycillin).
IF YES, ASK: LOOK AND FEEL: > Give first dose of paracetamol for
Classify pain.
Is there ear pain? Look for pus draining from the ear. EAR PROBLEM > Refer URGENTLY to hospital*.
Is there ear discharge? Feel for tender swelling behind the ear.
If yes, for how long? • Pus is seen draining from the >Give cotrimoxazole for 5 days.
ear and discharge is reported ACUTE EAR > Give paracetamol for pain.
for less than 14 days, or INFECTION > Dry the ear by wicking.
• Ear pain. > Follow-up in 5 days.
# If referral is not possible, see the section Where Referral Is Not Possible in the
module Treat the Child.
SEVERE
THEN CHECK FOR MALNUTRITION • Visible severe wasting or
• Oedema of both feet. MALNUTRITION
>Give single dose of Vitamin A.
>Prevent low blood sugar.
> Refer URGENTLY to hospital.
Classify > While referral is being organized, warm the child.
LOOK AND FEEL: NUTRITIONAL \ >Keep the child warm on the way to hospital.
O //A / U O y/
• Very low weight for age. VERY > Assess and counsel for feeding.
• Look for visible severe wasting.
LOW WEIGHT >Advise mother when to return immediately.
> Follow-up in 30 days.
• Look for oedema of both feet.
• Determine weight for age. • Not very low weight for age NOT VERY >lf child is less than 2 years old, assess the child's feeding
and no other signs of LOW WEIGHT and counsel the mother on feeding according to the FOOD
malnutrition. box on the COUNSEL THE MOTHER chart.
- If feeding problem, follow-up in 5 days.
>Advise mother when to return immediately.
• No palmar pallor NO ANAEMIA >Give prophylactic iron folic acid if child 6 months or older.
THEN CHECK THE CHILD’S IMMUNIZATION *, PROPHYLACTIC VITAMIN A & IRON-FOLIC ACID SUPPLEMENTATION STATUS
AGE VACCINE PROPHYLACTIC VITAMIN A PROPHYLACTIC IFA
Birth BCG + OPV-O Give a single dose of vitamin A:
6 weeks DPT-1 + OPV-1 (+ HepB-1**) 100.000 IU at 9 months with measles immunization Give 20 mg elemental iron +100 meg folic acid (one tablet of Pediatric
IMMUNIZATION 10 weeks DPT-2 + OPV-2 (+ HepB-2**) 200.000 IU at 16-18 months with DPT Booster IFA or 5 ml of IFA syrup or 1 ml of IFA drops) for a total of 100 days in a
14 weeks DPT-3 + OPV-3 (+ HepB-3**) 200.000 IU at 24 months year after the child has recovered from acute illness if:
SCHEDULE:
9 months Measles + Vitamin A 200.000 IU at 30 months >The child 6 months of age or older, and
16-18 months DPT Booster + OPV + Vitamin A 200.000 IU at 36 months >Has not received Pediatric IFA tablet/syrup/drops for 100 days in last
60 months DT one year.
* A child who needs to be immunized should be advised to go for immunization the day vaccines are available at AW/SC/PHC
** Hepatitis B to be given wherever included in the immunization schedule
Many children are brought to the clinic with less serious addition a child with diarrhea should be asked how
respiratory infections. Most children with cough or long the child has had diarrhea and if there is blood in
difficult breathing have only a mild infection. They do the stool. This will allow identification of children with
not need treatment with antibiotics. Their families can persistent diarrhea and dysentery.
manage them at home. Very sick children with cough Children with severe dehydration require immediate
or difficult breathing need to be identified as they IV infusion according to WHO treatment guidelines
require antibiotic therapy. Fortunately, one can identify described in plan C. Children with some dehydration
almost all cases of pneumonia by checking for these require active oral treatment with ORS as per plan B.
two clinical signs: fast breathing and chest indrawing. Patients with diarrhea and no dehydration are advised
Chest indrawing is a sign of severe pneumonia. to give more fluid than usual to prevent dehydration
Clinical assessment and classification: A child presenting according to WHO treatment plan A.
with cough or difficult breathing should first be assessed All children with persistent diarrhea are classified
for general danger signs. This child may have pneu based on presence or absence of dehydration. Children
monia or another severe respiratory infection. Three key with persistent diarrhea and dehydration are classified
clinical signs are used to assess a sick child with cough as severe persistent diarrhea and need to be referred to
or difficult breathing: fast breathing (cut-off respiratory hospital after treatment of dehydration. Children with
rate for fast breathing is 50 breaths per minute or more persistent diarrhea and no dehydration can be safely
for a child 2 months up to 12 months, and 40 breaths per managed on outpatient basis with appropriate feeding.
minute or more for 12 months up to 5 years); lower chest Children with dysentery are given effective antibiotics
wall indrawing and stridor in a calm child. Based on a for shigellosis.
combination of the above clinical signs, children pre c. Fever: Fever is a very common condition and is often
senting with cough or difficult breathing can be classi the main reason for bringing children to the health
fied into one of the three categories. A child with general center. It may be caused by minor infections, but may
danger sign or chest indrawing or stridor is classified as
severe pneumonia or very severe disease and merits also be the most obvious sign of a life-threatening ill
urgent referral to the hospital. A sick child with cough ness, e.g. P. falciparum malaria or meningitis. When
who has fast breathing is classified as pneumonia and diagnostic capacity is limited, it is important first to
his treatment initiated in clinic with oral antimicrobials. identify those children who need urgent referral with
A child with cough with none of these signs is classified appropriate pre-referral treatment (antimalarial or
as cough and cold and given home remedies to soothe antibacterial). All sick children should be assessed for
throat and counselled for home care. fever if it is reported by mother or fever is present on
A child with cough or cold normally improves in one examination.
or two weeks. However, a child with chronic cough Clinical assessment and classification: In endemic areas
(more than 30 days) needs to be further assessed (and, the risk of malaria transmission is defined by areas of
if needed, referred) to exclude tuberculosis, asthma, high and low malaria risk in the country. National Anti-
whooping cough or any other problem). Malaria Program (NAMP) has defined areas depending
b. Diarrhea: A child with diarrhea passes stools with more on malaria risk. A child presenting with fever is
water than normal. A child with diarrhea may have (1) assessed and classified depending on risk of malaria.
acute watery diarrhea (including cholera); (2) dysentery History of duration of fever is important in evaluating
(bloody diarrhea); or (3) persistent diarrhea (diarrhea fever. If fever has persisted daily for more than seven
that lasts 14 days or more). days the child needs to be referred to hospital for
Most diarrheal episodes are caused by agents for assessment and diagnostic tests. The other signs looked
which antimicrobials are not effective and therefore for in a child with fever include general danger signs
antibiotics should not be used routinely for treatment (assessed earlier) and signs of meningitis, e.g. bulging
of diarrhea. Anti-diarrheal drugs do not provide fontanelle and stiff neck. Besides these, signs of measles
practical benefits for children with acute diarrhea, and and runny nose are also looked for.
some may have dangerous side effects. Therefore these If the child has measles currently or within the last three
drugs should never be given to children. months, he should be assessed for possible complica
tions. Some complications of measles are assessed as
Clinical assessment and classification: All children withmain symptoms, e.g. cough/difficult breathing, diar
diarrhea should be assessed for dehydration based on rhea and ear infections. Clouding of cornea and mouth
the following clinical signs: child's general condition ulcers are assessed along with measles. Clouding of cor
(lethargic or unconscious or restless/irritable); sunken nea is a dangerous eye complication. If not treated, cor
eyes; child's reaction when offered to drink ( not able tonea can ulcerate and cause blindness. An infant with cor
drink or drinking poorly or drinking eagerly/ thirsty neal clouding needs urgent treatment with vitamin A.
or drinking normally) and elasticity of skin (skin pinch Before classifying fever, one should check for other
goes back very slowly, slowly or immediately). In obvious causes of fever.
Integrated Management of Neonatal and Childhood Illnesses 749
Children with fever are classified based on the presence Edema of both feet: The presence of oedema in both feet
of any of the general danger signs, stiff neck, level of may signal kwashiorkor.
malaria risk in the area and presence/absence of Weight for age: Plotting weight for age in the growth chart,
symptoms like runny nose, measles or clinical signs of based on reference population, helps to identify children
other possible infection. In high malaria risk area all with lozv (Z score less than -2) or ven/ low (Z score less
children with fever need to get antimalarial treatment than -3) weight for age, those who are at increased risk of
as per NAMP guidelines. In areas with low malaria risk infection and poor growth and development.
children with fever with no other obvious cause are
classified as malaria and should be evaluated with Classification of nutritional status: Using a combination of
blood smear and treated with oral antimalarial drugs the simple clinical signs above, children can be classified
(chloroquine). In low malaria risk area children with as severe malnutrition (visible wasting with or without
fever with another cause of fever (e.g. cough and cold edema), very low weight or not very low weight.
or ear infection or diarrhea) are classified as fever,
malaria unlikely and given symptomatic treatment for Checking for Anemia
fever. Since the malaria risk may change with time All children should also be assessed for anemia. The most
malaria is treated as per national guidelines. common cause of anemia in young children in developing
d. Ear problems: A child with an ear problem may have countries is nutritional or because of parasitic or
otitis. It may be acute or chronic infection. If the infection helminthic infections.
is not treated, the ear drum may perforate. Ear infections Clinical assessment and classification: Palmar pallor can help
are the main cause of deafness in low-income areas,
which in turn leads to learning problems. The middle ear to identify sick children with severe anemia. Wherever
feasible, diagnosis of anemia can be supported by using a
infection can also spread from the ear and cause simple laboratory
mastoiditis and /or meningitis. The sick child is assessed clinical assessment oftestanemia
for hemoglobin estimation. For
the color of the child's palm
for ear infection if any ear problem is reported. is compared with examiner's own palm. If the skin of the
Clinical assessment and classification: The mother ischild's asked palm is pale, the child has somepalmarpallor. If the
about history of ear pain and ear discharge or pus. The skin of the palm is very pale or so pale that it looks white,
child is examined for tender swelling behind the ear. the child has severe palmar pallor. Based on palmar pallor
Based on these clinical findings a child can be classified it is classified as severe anemia, anemia or no anemia.
as mastoiditis, acute ear infection, chronic ear infection
or no ear infection. Children with mastoiditis are Assessing the Child's Feeding
classified as severe illness and referred urgently to
hospital. Children with acute ear infection are given All children less than 2 years old and all children classified
oral antibiotics and those with chronic ear infection are as anemia or very low weight need to be assessed for
advised to keep the ear dry by wicking. feeding even if they have a normal Z-score. Feeding
assessment includes questioning the mother or caretaker
Checking for Malnutrition about feeding history. The mother or caretaker should be
After assessing for general danger signs and the four main given appropriate advice to help overcome any feeding
symptoms, all children should be assessed for mal problems found.
nutrition. There are two main reasons for routine assess To assess feeding, ask the mother: does she breastfeed
ment of nutritional status in sick children: (1) to identify her child (how many times during the day and night), does
children with severe malnutrition who are at increased risk the child take any other food or fluids (what food or fluids,
of mortality and need urgent referral to provide active how many times a day, how the child is fed, how large
treatment; and (2) to identify children with sub-optimal are the servings, does the child receive his own serving,
nutritional status resulting from ongoing deficits in dietary who feeds the child) and during the illness, has the child's
intake plus repeated episodes of infection and who may feeding changed, (if yes, how?).
benefit from nutritional counseling.
Identify feeding problems: When counselling a mother about
Clinical Assessment and Classification feeding, one should use good communication skills. It is
Visible severe zuasting : This is defined as severe wasting ofimportant to complete the assessment of feeding by
the shoulders, arms, buttocks, and legs, with ribs easily referring to age appropriate feeding recommendations
seen, and indicates presence of marasmus. When wasting and identify all the feeding problems before giving advice.
is extreme, there are many folds of skin on the buttocks In addition to differences from the feeding recommen
and thigh. It looks as if the child is wearing baggy pants. dations, some other problems may become apparent from
The face of a child with visible severe wasting may still the mother's answers. Other common feeding problems
look normal. The child's abdomen may be large or are: Difficulty breastfeeding, use of feeding bottle, lack of active
distended. feeding and not feeding well during illness. IMNCI guidelines
750 Essential Pediatrics
recommend locally acceptable, available and affordable • Prevention of hypoglycemia with breast milk or sugar
foods for feeding a child during sickness and health. A water.
sample of such recommendations is given in the IMNCI • Oral antimalarials as per guidelines.
chart which needs to be adapted to local conditions. • Paracetamol for high fever (38.5°C or above) or pain.
• Tetracycline eye ointment (if clouding of the cornea or
Checking Immunization, Vitamin A and pus draining from eye).
Folic Acid Supplementation Status • Frequent sips of ORS solution on the way to the hospital
The immunization status of every sick child brought to a in sick children with diarrhea.
health facility should be checked. Children who are well If a child does not need urgent referral, check to see if
enough to be sent home can be immunized. the child needs non-urgent referral for further assessment;
After checking immunization status, determine if the for example, for a cough that has lasted more than 30 days,
child needs vitamin A supplementation and/or pro or for fever that has lasted seven days or more. These
phylactic iron folic acid supplementation. referrals are not as urgent, and other necessary treatments
may be done before transporting for referral.
Assessing Other Problems Treatment in Outpatient Clinics and at Home
The IMNCI clinical guidelines focus on five main symp Identify the treatment associated with each non-referral
toms. In addition, the assessment steps within each main classification (yelloiv and green) in the IMNCI chart.
symptom take into account several other common Treatment uses a minimum of affordable essential drugs.
problems. For example, conditions such as meningitis, Following guidelines for treatment need to be followed:
sepsis, tuberculosis, conjunctivitis, and different causes • Counselling a mother/caretaker for looking after the
of fever such as ear infection and sore throat are routinely child at home is very important. Good communication
assessed within the IMNCI case management process. If skills based on principles of APAC are helpful for
the guidelines are correctly applied, children with these effective counselling.
conditions will receive presumptive treatment or urgent • Give appropriate treatment and advice for 'yellow' and
referral. Nevertheless, health care providers still need to 'green' classifications as detailed in Table 29.2.
consider other causes of severe or acute illness.
Counseling A Mother or Caretaker
Identify Treatment and Treat A child who is seen at the clinic needs to continue
All the treatments required are listed in the "Identify treatment, feeding and fluids at home. The child's mother
Treatment" column of the ASSESS and CLASSIFY THE or caretaker also needs to recognize when the child is not
SICK CHILD AGE 2 MONTHS UP TO 5 YEARS (Chart improving, or is becoming sicker. The success of home
29.2). All sick children with a severe classification (pink) treatment depends on how well the mother or caretaker
are referred to a hospital as soon as assessment is knows how to give treatment, understands its importance
completed and necessary pre-referral treatment is and knows when to return to a health care provider. Some
administered. If a child only has severe dehydration and advice is simple; other advice requires teaching the mother
no other severe classification, and IV infusion is available or caretaker how to do a task. When you teach a mother
in the outpatient clinic, an attempt should be made to how to treat a child, use three basic teaching steps: give
rehydrate the sick child. The principles of referral of a information; show an example; let her practice.
sick child are similar to those described for a sick young • Advise to continue feeding and increase fluids during
infant. illness;
• Teach how to give oral drugs or to treat local infection;
Referral of Children Age 2 Months up to 5 Years • Counsel to solve feeding problems (if any);
Possible pre-referral treatment (s) includes: • Advise when to return (Table 29.3). Every mother or
^ • For convulsions diazepam IV or rectally. If convulsions caretaker who is taking a sick child home needs to be
continue after 10 minutes give a second dose. advised about when to return to a health facility. The
I] • First dose of appropriate intramuscular antibiotic— health care provider should (a) teach signs that mean
Chloramphenicol or ampicillin + gentamicin or to return immediately for further care, (b) advise when
ceftriaxone (for severe pneumonia or severe disease; to return for a follow-up visit and (c) schedule the next
" very severe febrile disease; severe complicated well-child or immunization visit.
measles; mastoiditis). Give oral antibiotic if injectable
antibiotics are not available.
• First dose of quinine (for severe malaria ) as per national REVISION IN IMNCI CLINICAL AND
guidelines. MANAGEMENT GUIDELINES__________________________
• Vitamin A (persistent diarrhea, measles, severe IMNCI strategy recommends adaptation of clinical and
malnutrition). management guidelines based on the local epidemiologic
Integrated Management of Neonatal and Childhood Illnesses 751
Tabic 29.2: Treatment guidelines for managing sick child in Table 29.3: Counsel mother when to return
outpatients and at home
• Pneumonia, acute ear infection: Give the first dose of the Mother should report immediately if she notices
antibiotics in the clinic and teach the mother how to give following symptoms :
oral drugs, cotrimoxazole (first line) or amoxicillin (second Young infant Sick child
line)*. (age 0-2 months) (2 months-5 yrs)
• Dysentery: Give the first dose of the antibiotics in the clinic • Breastfeeding or drinking Any child
and teach the mother how to give oral drugs, cotrimoxazole poorly -Not able to drink or
(first line) or nalidixic acid (second line)*. • Becomes sicker breastfeed
• Cholera: In areas where cholera can not be excluded, children • Develops fever or cold - becomes sicker
more than 2 years old with severe dehydration should be to touch -develops fever
given a single dose of doxycycline. • Fast/difficult breathing Child with cough and
• Blood in stools (if infant cold
• Dehydration and persistent diarrhea: Treat 'some' and 'no'
dehydration and persistent diarrhoea as per standard WHO has diarrhea) -develop fast/difficult
• Yellow palms and soles breathing
Guidelines. (if jaundiced) Child with diarrhoea
• Persistent diarrhea: Give zinc (20 mg elemental zinc) daily - has blood in stool
for 14 days and a single dose of vitamin A. -drinking poorly
• Malaria: Treat as per recommendations • Mother shoidd bring infant for follow up visit *
• Mother should come for scheduled immunization visit
• Anemia: Give iron folic acid for 14 days. • See section on identify treatment
• Cough and cold: If the child is 6 months or older use safe
home remedies (continue breastfeeding, use honey, tulsi,
ginger and other safe local home remedies). ages and supplementation of elemental zinc (20 mg in
• Local infection: Teach the mother or caretaker how to treat children older than 6 months and 10 mg per day in
the infection at home. Instructions may be given about how infants less than 6 months) to be started as soon as
to: Treat eye infection with tetracycline eye ointment; dry diarrhea starts and continued for a total period of 14
the ear by wicking to treat ear infection; treat mouth ulcers days. Reduced osmolarity ORS has been introduced in
with gentian violet. the National Health Programme in 2002 and a policy
* Give a second-line drug only if first-line drug is not available decision has been taken for including zinc in the RCH/
or if the child has not responded to first-line drug National Rural Health Mission by the Government of
India.
scenario and management guidelines, which are evidence- • Management of dysentery: In view of wide spread
based, pertain to majority of common childhood illnesses, resistance to cotrimoxazole, the Indian Academy of
are locally relevant and feasible. Evaluation and providing Pediatrics Task Force recommends ciprofloxacin as first
justification for revision of these guidelines is a continuous line drug in areas where resistance rates to cotri
process. With the availability of more epidemiological data moxazole exceeds 30%.
on common childhood illnesses in India, there is a possi
bility of future inclusion of conditions like HIV/AIDS, Suggested reading
dengue fever and asthma at national or state level revision 1. Murray QL, Lopez AD. The global burden of disease: A compre
of IMNCI guidelines. hensive assessment of mortality and disability from diseases, inju
During the last decade, there has been a significant ries and risk factors in 1990 and projected to 2020. In: Global Bur
breakthrough in introducing newer concepts and den of Disease and Injury Series (vol. I), Cambridge, MA, Harvard
School of Public Health, 1996.
recommendations pertaining to management of childhood 2. Gove S. For the WHO Working Group on Guidelines for Integrated
illnesses. With the availability of more evidence based Management of the Sick Child. Bull WHO 1997, 75: 7-24.
information, some of these guidelines have already been 3. World Health Organization. Integrated Management of the Sick
revised by World Health Organization and incorporated Child. Bull WHO 1995; 73:735-740.
in national health programs. Future adaptation of IMNCI 4. World Health Organization. Management of the Child with a
Serious Infection or Severe Malnutrition: Guidelines for care at the
guidelines is likely to have following revisions: first-referral level in developing countries. WHO, Geneva, 2000.
• Management af diarrhea! WHO recommends use of 5. World Health Organization. Integrated Management of Childhood
The Constitution of India guarantees equality before the (i) tracking in relation to health, nutrition and education;
law to all citizens, and pledges special protections for chil (ii) universal immunization against vaccine-preventable
dren. In 1974, India adopted a National Policy for Children diseases; (iii) early identification for special health needs
and declared it a supreme national asset. In 1992, India and appropriate referrals; (iv) promotion of breastfeeding;
accepted the obligations of the UN Convention on the (v) control of common infectious diseases; and (vi) that
Rights of the Child. The National Commission for Pro services are of good quality, affordable and accessible for
tection of Child Rights has been set up as a statutary body all.
under the Commission for Protection of Child Rights Act,
2005 to protect, promote and defend child rights in the Provide better public health services: (i) Ensure safe drinking
country. water, sanitation, and environmental protection, giving
Physicians should have a knowledge of child rights and the most disadvantaged communities access to common
advocate them in their daily practice. This chapter dis resources; (ii) Combat hunger and malnutrition by ensur
cusses major concerns and strategies of rights of every ing food security to families and nutrition security to child
child in the area of child survival, identity, development, ren; supplementary nutrition and provision of midday
protection and participation. meals; (iii) Universalize ICDS services to all 0-3-year-old;
ensure survival support and childhood care.
Child Survival: Major Concerns
Child Identity
High infant and newborn mortality: The infant mortality rate
Birth registration and identity is a child's first civil right.
has declined to 57 (National Family Health Survey 2005), International standards recognize all people up to 18-year-
mainly due to survival of post-neonatal infants (between old as children. India has acknowledged this basic princi
29 days and 1 year). The current neonatal mortality rate ple in 1992, but this is not reflected in the laws. India must
(39 per 1000 live births) accounts for two-thirds of all infant recognize all persons up to the age of 18-years as children,
deaths and half of under-5 child mortality. One-fourth of and reflect this uniformly in all its laws and practices.
all neonates are low birth weight (birth weight <2.5 kg);
they have a 15-fold higher risk of dying during the new Child Development
born period.
Education: About half of India's children of school-going
Nutrition security is a basic right: Millions of children lackage are not in school. At present, the 86th Constitutional
protection against hunger. Based on data from the Third Amendment pledging free and compulsory education as
National Family Health Survey, 46% of children less than a fundamental right serves only the 6-14 yr age group,
3-year are stunted and 75% young children are anemic. denying learning rights to children below 6-yr and leaving
Infectious diseases: Diarrhea and respiratory tract infections,out children above 14-yr.
rising rates of tuberculosis, infection with HIV and per Health care, nutrition, shelter and security should be
sistence of malaria pose serious threats to child survival. provided for the underserved children. Children with
Gender inequality: Girls are denied equal right to life. The disabilities or special needs are seriously underserved.
birth of girls is being prevented and girl infants are dying. Only 5% of children with disability are reached by any
Female feticide is increasing despite being banned. Pre kind of services; only 2% can access schooling. Children
birth sex selection is on the rise. The 2001 Census reveals on the street or those not accessible through family chan
that the 0-6 sex ratio is now 927 girls to 1,000 boys. This is nels cannot avail of development opportunities. The
a serious threat to India's population balance. budget allocation for children is 2.3% of total budget.
Strategies for Child Survival Strategies Enabling Child Development
Invest in child survival: Children should have access to Every child should receive services that support early
preventive, protective and curative services, ensuring childhood care and development. Pediatricians can
752
Rights of Children 753
advocate, supervise or assist the government agencies to appropriate and supportive environment, including acts
develop and operate a network of child care and deve that have an adverse effect on the emotional health and
lopment services including ICDS, creches and preschools development, (iv) neglect - failure of a parent/guardian
for young children. Pediatricians can advocate, supervise to provide for the development of the child, where the
or assist the government agencies to increase investment parent is in a position to do so, in one or more of the
in primary education. Quality standards for education, following areas: health, education, emotional develop
teaching content and methods, and curriculum reforms ment, nutrition, shelter and safe living conditions. Neglect
should be ensured. Other strategies include ensuring food is thus distinguished from circumstances of poverty in
and nutrition security, especially for the poor and most that neglect can occur only in cases where reasonable
disadvantaged, providing basic health care and resources are available to the family or caregiver.
immunization.
Extent of the Problem in India
Child Protection The recent study on child abuse in India (2007) by Ministry
Children have the right to be protected against all forms of Women and Child Development highlights the high
of abuse (physical, sexual or emotional), neglect, exploi prevalence of all forms of child abuse in our country. The
tation and corporal punishment. All forms of child labor term child abuse has different connotations in different
are an abuse of basic child rights. Lack of family or adult cultural milieu and socioeconomic situations. In the Indian
support results in denial of basic services; such children context, it is important to include children being deprived
deserve special protection and assistance. Children are of education, early development, basic health care and
targeted in communal violence as never before. They also nutrition. Child labor is the worst kind of child abuse and
suffer discrimination and denial in post-riot situations. neglect.
Children of indigenous and tribal communities suffer Manifestations of Child Abuse and Neglect
neglect, discrimination and alienation and are affected by
armed conflict and other civil violence. Injuries inflicted by a caregiver on a child can take many
Children have the right to special protection against forms. Death in abused children is most often the
trafficking, communal and political violence, armed consequence of a head injury or injury to the internal
conflict, terrorist activities and migrant situations. Every organs. Abuse is suggested by patterns of injury to the
child has the right to adequate housing and shelter, skin and skeletal manifestations including multiple frac
including in urban and tribal settings. The State needs tures at different stages of healing. There is evidence that
effective legislation to punish and deter abuse, sexual abuse about one-third of severely shaken infants die and that
and trafficking in children as well as prenatal sex determi the majority of the survivors suffer long-term conse
nation, feticide and infanticide. Street children should be quences such as mental retardation, cerebral palsy or
provided with safe shelter services and opportunities for blindness. Children who have been sexually abused
relevant education and vocational training. Children exhibit symptoms of infection, genital injury, abdominal
should have access to contact services to help them in case pain, constipation, chronic or recurrent urinary tract
of emergency or distress. The emergency toll-free phone infections or behavioral problems. To be able to detect
service for children in distress (Child Line 1098) should be child sexual abuse requires a high index of suspicion and
expanded and awareness generated about such help lines. familiarity with the verbal, behavioral and physical
Orphanages and shelter homes are required to assist indicators of abuse. Many children will disclose abuse to
children without families. Adoption should give first caregivers or others spontaneously, though there may also
priority to the best interests of the child concerned. be indirect physical or behavioral signs. Emotional and
psychological abuse has received less attention globally
CHILD ABUSE AND NEGLECT_________________________ due to cultural variations in different countries. However,
corporal punishment of children, e.g. slapping, punching,
Definition kicking or beating, is a significant phenomenon in schools
The WHO defines child abuse as forms of physical and/ and other institutions. Child neglect can manifest as failure
or emotional ill-treatment, sexual abuse, neglect or to thrive, failure to seek basic health care and immuni
negligent treatment, commercial or other exploitation, zation, deprivation of education and basic nutrition needs.
resulting in actual or potential harm to the child's health, A neglected child may be exposed to environmental
survival, development or dignity in the context of a hazards, substance abuse, inadequate supervision, poor
relationship of responsibility, trust or power. Major types hygiene and abandonment.
of child abuse by caregiver or other adults include: (i)
physical abuse - acts of commission that cause actual Strategies to Reduce Child Abuse and Neglect
physical harm or have the potential for harm; (ii) sexual In India, the problems of socially marginalized and
abuse - caregiver uses a child for sexual gratification; (iii) economically backward groups are immense, particularly
emotional abuse-failure of a caregiver to provide an amongst children in urban slums, street and working
754 Essential Pediatrics
children, children of construction workers, etc. Although practitioners and pediatricians play a vital role in
child labor cannot be abolished in presence of poverty, it influencing health and social decisions of their adoptive
is necessary to ensure that working children are not patients and need to work closely with counselors and
exploited. They must get time for education and must allied health professionals.
receive health care. Laws for protection of children against 'Right to a family' is proposed as a fundamental right
all forms of abuse and exploitation should be enforced. by the United Nations. Adoption agencies need to ensure
Child protection services should reach the rural areas, that these rights are protected.
where a large proportion of the population resides. A
comprehensive approach to child protection in these areas Legal Aspects
must involve the Panchayati Raj institution. The panchayat In India, only agencies recognized by the Government can
officials should be given the responsibility to ensure that deal with adoption placement. Direct adoption placement
basic education, nutrition, health care and sanitation by hospitals, maternity and nursing homes is not per
available for proper development of every child in their mitted. Prior to 2000, adoption was allowed to Hindus
village. The panchayat should be duty bound to ensure under the Hindu Adoption and Maintenance Act; other
that every child is in school and thus protected from religious groups were governed by the Guardianship and
agrarian and allied rural occupations as a part of family Wards Act. The Juvenile Justice (Care and Protection of
or individual child labor. Children) Act, passed by the Parliament in 2000, enables
Pediatricians are the best advocates for children and citizens of all religions the freedom to adopt a minor child,
for protection of their rights. They can contribute by recog irrespective whether he/she is a single parent and /or such
nizing, responding to and reporting child abuse. Physi adoptive parent/s adopt a child of the same sex, irres
cians in developed countries are required by law to report pective of the number of living biological sons or
cases of child abuse and neglect. They are protected in daughters.
cases of erroneous reporting, as long as it is done in good
faith to protect a child. A similar legislation that makes Adoption Procedures
child abuse reporting mandatory for pediatricians and cer
tain professional groups is welcome. In addition, pedia A child, who has been relinquished by his/her biological
tricians can work with the community, NGOs and admini parents or found abandoned, must first be presented to
strators in government and reach out to the neglected, the Child Welfare Committee. This committee has the sole
deprived and abused children for their comprehensive authority to declare the child free for adoption under the
needs that include education, health aspects, protection current law. In case of an abandoned child, the committee,
and rehabilitation. after due investigations, declares the child as destitute and
The Constitution of India guarantees many funda free for adoption. In case the biological parents want to
mental rights to children, however, the approach to fulfil relinquish a child, they have to execute a document in
these rights has been needs based rather than rights based. favor of the adoption agency, duly witnessed by any
Child abuse is a basic violation of the child's rights. The authority of the hospital and a relative. A waiting period
adoption of rights based approach is needed to provide of 2 months is given to the biological parents to reconsider
care and protection to the large numbers of children in the decision, following which the child is free for adoption.
our country. There is an urgent need for the State to create
an enabling environment through legislation, schemes and Prospective Adoptive Parents
enhanced budget to address the problem of child abuse A child can be adopted by a married couple having inferti
and neglect in our country. lity or voluntarily opting for adoption. Even single persons
are eligible to adopt. Couples who have taken a decision to
Suggested reading adopt should go to a registered agency, which is licensed
1. National Family Health Survey, India, 2006. http:// to process adoption by both state government and the
www.nfhsindia.org/nfhs3.html Central Adoption Resource Authority (an autonomous
2. UNICEF. Convention on the Rights of the Child, 2004. http://
body under the Ministry of Women and Child Develop
3.
www.kidzee.com/images/unicef.pdf
Study on Child Abuse. Ministry of Women and Child
ment, Government of India). Recognized placement
Development, Government of India, 2007 agencies alone can process the application of abandoned
4. International Society for Prevention of Child Abuse and Neglect. children for in country and inter-country adoptions of
World perspective on child abuse, 6th edn, 2006. http:// Indian children. Applications for inter-country adoption,
www.ispcan.org
of a child born in India, should be forwarded by an accre
dited agency of the country of the adoptive parents, to a
ADOPTION ___ recognized placement agency in India along with all
Adoption is an important alternative for the rehabilitation documents to Central Adoption Resource Authority.
of children who are destitute and abandoned or for social A social worker from the adoption agency provides
reasons cannot be brought up by their parents. Medical guidelines and support to preadoptive parents, and helps
Rights of Children 755
them make informed decisions (pre-adoption counseling). • They can counsel and teach the public about the process
A home study is conducted by the professional social of adoption.
worker. Additionally, parents are required to submit • Parents who wish to relinquish their children due to
documents regarding their health, financial status, etc. any reason must be told about correct procedure;
Once their application is approved, a suitable child is leaving young children in public places or in unhealthy
shown to them. After they accept the child, placement is surroundings is unsafe and traumatizing.
legalized. The placement is followed up to a period of 3 • Doctors should discourage private adoptions, since
years or such time until legal adoption is complete. The these are illegal.
adoptive parents are assured confidentiality and provided • Babies in placement agencies are usually taken for a
support as needed. second opinion to a pediatrician, where the child should
be examined carefully and a realistic diagnosis and
Role of a Pediatrician prognosis should be explained to the adoptive parents.
Pediatricians are in the position where families take them • A supporting and understanding attitude encourages
into confidence and seek their advice in many situations. adoptive parents to overcome their fears.
• All essential tests (HIV, hepatitis B) which have a
window period may be repeated at 3 and 6 months, Suggested reading
before placement. Central Adoption Resource Agency; www.adoptionindia.nic.in
Index
757
758 Essential Pediatrics
Cardiopulmonary resuscitation 689, 694 management 464 Constrictive pericarditis 425, 426
drugs used during 694 pathophysiology 464 chronic 425
Cardiotonics 731 stages of 463 Convulsions 523
Carey Coombs' murmur 381 Chronic liver disease (CLD) 281, 282 approach to a child with 523
Carotenemia 80 clinical features 282 causes of 523
Carotenoids 79 diagnosis 283 role of investigations 524
Cataract 649 etiology 282 Copper 93
Catch-up diets 74 grading and staging 282 Corrected transposition of great vessels 413
Categorization of vaccines by the Indian Chronic myeloid leukemia (CML) 586 Cough 346
Academy of Pediatrics 178 juvenile 586 causes of acute 346
Cat-Scratch disease 342 Chronic suppurative otitis media (CSOM) 330 causes of chronic or recurrent 346
CD55 312 etiology 331 CPR/BLS 689
CD59 312 diagnosis 331 sequence of 689
Celiac disease 272 treatment 331 Craniopharyngioma 546
clinical presentation 272 Chvostek sign 486 Craniotabes 82
diagnosis 273 Chvostek 83 Creatinine clearance 443
management 273 Classification 64 Crescentic glomerulonephritis 448
Central nervous system 519 Gomez 64 Crisis 311
Central venous cannulation 715 IAP 64 acute chest syndrome 311
Cephalohematoma 112 Waterlow 64 aplastic 311
Cerebral edema 287, 516 Cleft lip and cleft palate 152 assessment 311
Cerebral palsy 559 Cleft palate 337 laboratory studies 311
cerebellar 560 CML (ACML) 586 management 311
extrapyramidal 560 adult variety of 586 sequestration 311
hypotonic (atonic) 559 Coagulation cascade 318 vaso-occlusive 311
mixed 560 Coagulation defects 317 Critical care 686
spastic 559 Coagulation disorder 318 Crohn's disease 277
Cerebral salt wasting 51 Coarctation of the aorta 419 Croup (laryngotracheobronchitis) 339
Cervical lymphadenopathy 342 Cobalamin (vitamin B12) 89 Croup 351
Cestodes 247 cyanocobalamin 89 differential diagnosis of 351
Charcot-Marie-tooth disease 576 methylcobalamin 89 management of 351
CHARGE 337 Cochlear implantation 334 spasmodic 351
Coenzymes 78 Cryoprecipitate 324
Chart 1 738
assess and classify sick 742 Cold chain 166 Cryptorchidism (undescended testes) 508
clinical assessment and classification 741 Cold stress 116 approach to 508
identify treatment 741 response to 116 CSOM 330
treatment guidelines for managing sick young Collodion baby 656 Cupping 82
Colostrum 125 Cushing syndrome 489, 490
infant 742
Coma 533, 534 etiology of 489
Chart 2 743
approach to diagnosis of 534 laboratory findings of common causes of 490
identify treatment and treat 750
causes of 533, 534 screening tests for 490
treatment guidelines for managing sick
grades of 534 Cutaneous tuberculosis 660
child 751
investigations 535 Cyanosis with increased pulmonary blood
Chediak Higashi syndrome 327
pathophysiology 533 flow 415
Chest circumference 5
treatment 535 Cyanotic congenital heart disease with
Chest compressions 101
Combination vaccines 178 pulmonary arterial hypertension 416
Chikungunya 201
Common cold 335, 349 Cystic fibrosis 274, 369
Child abuse 754 Common variable immunodeficiency 162
emotional 754 clinical manifestations 369
Community-based therapeutic care diagnosis 369
neglect 754 (CTC) 75
physical 754 genetics 369
Composition of fluid 54 management 369
sexual 754 Conditioning 315
Child vaccine initiative (CVI) 164 Cystic hygromas 342
Congenital adrenal hyperplasia 492 Cysticercosis 247
Chipmunk facies 310 21-hydroxylase deficiency 492
Choanal atresia 336, 337 Cystinuria 469, 631
Congenital heart disease 372, 395, 401 Cytopenias 313
unilateral 337 assessment for presence of heart disease 399
Cholera 267 single lineage 313
classification of 401
treatment of 267 etiology 396
Cholesteatoma 331 incidence 396 Decay accelerating factor 312
Cholesterol 60 Congenital hypertrophic pyloric stenosis 252 Defibrillation 695
Chromium 93 Congestive cardiac failure 372, 373, 375 Definitive tests 34
Chromosomal disorders 611 causes of 372 Degenerative brain disorders 561
Chronic and recurrent abdominal pain 258 due to diastolic dysfunction 372 Dehydration 264, 266
causes of 258 etiopathogenesis 372 assessment of severity of 264
Chronic cough 370 in infants 375 assessment of 264
diagnostic approach to 370 prognosis 379 drug therapy in acute 267
Chronic glomerulonephritis 455 signs of 375 intravenous fluid therapy in severe 266
Chronic granulomatous disease 327 stepwise management of 378 no 264
Chronic hepatitis 283 time of onset of 373 nutritional management of 266
chronic hepatitis B 283 treatment of 375 severe 264
investigations 283 Congestive failure 373, 378 some 264
management 284 Constipation 255 treatment plan A 264
prognosis 284 causes of 255 treatment plan B 265
chronic hepatitis C 284 evaluation 255 treatment plan C 265
Chronic kidney disease 463, 464 management 255 Deletion 612
clinical features 464 Constitutional delay 20 Dengue fever 196, 199
common causes of 464 comparison of 20 diagnostic tests for 199
investigations 464 growth delay 19 manifestations of 198
760 Essential Pediatrics
Dengue hemorrhagic fever (DHF) 196, 198 Diarrheal dehydration 54 Ehlers-Danlos syndrome 576
grading of 198 deficit replenishment 54 Eicosapentanoic acid (EPA) 59
intravenous fluid therapy in 200 maintenance fluids 54 Electroencephalogram (EEG) 520
Dengue shock syndrome 196 ongoing losses 54 Electromyography 522
treatment of patients with 201 Diet 60 Emery Dreifuss muscular dystrophy
Denys-Drash 471 balanced 60 (EDMD) 569
Dermatophytoses (ringworm) 663 normal 60 Empyema thoracis 371
Development 1, 22, 23, 27, 31, 33 DiGeorge anomaly 161 Enamel spots 67
abnormal 22 Dilated cardiomyopathy (DCM) 373 Encephalitis like syndromes 76
advantages of screening 33 Diphtheria vaccine 168 Encephalitis 542
assessment 31 Diphtheria 219 clinical manifestations 542
delay 31 antitoxin 220 diagnosis 542
evaluation of 31 faucial 220 etiology of 542
factors affecting 22 laryngotracheal 220 management 542
fine motor 23 nasal 220 prognosis 542
gross motor 23 Directly observed treatment short course Encephalopathies 542
language 23 (DOTS) 217 clinical manifestations 542
limitations of screening 33 Disaccharide malabsorption 273 diagnosis 542
normal 22, 23 causes of 273 etiopathology 542
personal and social 23 diagnosis 274 management 543
quotient (DQ) 32 treatment 274 prognosis 542
rules of 22 Disorders of communication 39 Endemic cretinism 485
screening 33 Disorders of sexual differentiation Endemic goiter 484
vision and hearing 23 (DSD) 505, 507 Endocardial fibroelastosis 423
Developmental dysplasia of hips classification 506 Endoscopic sinus surgery (ESS) 336
(DDH) 114 evaluation 506 Endotracheal intubation 692
Developmental milestones 27, 28 management 507 Energy density 61
fine motor 27 pointers to etiology of 507 Energy 60
key fine motor 28 Disorders of urea cycle 633 Enteric fever 222
key gross motor 27 Disseminated intravascular coagulopathy 322, carrier state 223
key language 30 323
clinical features 222
key social and adaptive 30 clinical evaluation 320
complications 222
red flags signs in 33 laboratory evaluation 320
diagnosis 223
Dhatura (belladona) poisoning 681 management 320
empirical therapy 224
Diabetes insipidus 468, 477, 478 pathogenesis 320
etiopathogenesis 222
nephrogenic 468 Dissociation 32
prevention 224
Diabetes mellitus 509, 514 Distal 571
relapse 222
classification 509 Diuretics 732
treatment 223
clinical features 511 Docosahexanoic acid (DHA) 59
Enuresis 35
complications of 515 Double malleoli 82
classification 35
criteria for the diagnosis of 510 Double outlet right ventricle 413
Down syndrome 613 definition 35
diagnosis 510 diurnal 35
distinguishing features of type 1 and characteristic features of 613
clinical features 613 nocturnal 35
type 2 514 primary nocturnal enuresis (PNE) 36
gestational 509 diagnostic considerations 613
Draining ear 330 primary 35
insulin therapy 512 secondary 35
Drawing skills 28
medical nutrition therapy (MNT) 513 treatment 36
Drooling 344
pathogenesis 510 Eosinophilia 327
Drowning 684
treatment 511 common causes of 327
Drug eruptions 666
type 1 509 Epidermal growth factor 1
Dry powder inhaler (DPI) 364
type 2 509 Epidermolysis bullosa (EB) 655, 657
Duchenne muscular dystrophy (DMD) 566
Diabetic ketoacidosis 515, 517 Epidural abscess 332
clinical features 566
practical guide for assessment and Epiglottitis 340, 351
course 567
management of 517 acute 340
diagnosis 568
screening for chronic complications in type 1 Epilepsies 531
differential diagnosis 568
518 myoclonic 531
genetics 566
Dialysis 462 management 568 Epilepsy 529, 531, 532
Diamond-Blackfan (PRCA) 313 classification 529
Dural venous (sigmoid sinus) thrombosis 332
Diaper dermatitis 670 Dwarfism 2 clinical features of 529
Diaper rash 106 Dyselectrolytemias 51 common errors in diagnosing 531
ammoniacal 106 Dysentery 267 duration of therapy 533
candidal 106 management of 267 generalized 529
Diaphragmatic hernia 153 Dyskeratosis congenita 313 localized 529
Diarrhea 260,262 Dyslexia 39 management of 531
acute bloody 260 clinical manifestations 39 medications used in 532
acute watery 260 diagnosis 39 prognosis 533
assessment of child with 262 etiology 39 surgical treatment 533
chronic 271, 272 management 39 syndromes 529
due to fermentation 272 Dyspnea 348 undetermined syndromes 529
due to impaired intraluminal causes of 348 Epistaxis 336
digestion 272 Epstein Barr virus 187
due to intestinal malabsorption 272 Ear discharge 331 Erythema toxicum 105
clinical approach 262 Early stimulation 34 Esophageal atresia 151
laboratory investigations 262 Ebstein anomaly 411 Essential fatty acids (EFA) 59
persistent (PD) 260, 269 Echinococcosis 249 Evoked potential response 521
physiological basis for management 262 Eczematous dermatitis 668 Ewing's sarcoma 593
prevention of 268 atopic 668 Expanded program of immunization 164
with severe malnutrition 260 diaper 670 Expectoration 346
Oral rehydration therapy (ORT) 263 seborrheic 670 Extrahepatic biliary atresia 293
Index 761
Hemolytic uremic syndrome 449 Hydrocephalus 548, 549 comparison of different forms of primary
D- or atypical 449 causes of 549 congenital 481, 482
D+ or typical 449 differential diagnosis of large head 549 correction of deficiency 94
Hemophilia 320 treatment 549 endemic cretinism 94
Hemophilus influenza B vaccine 175 Hymenolepiasis 249 etiology of 480, 485
Hemoptysis 346 Hyper IgE syndrome 163 goiter 94
Hyper IgM syndrome 162 iodine deficiency disorders, IDD 94
Henderson-Hasselbach equation 49
Hyperaldosteronism 491 neonatal 94
Henoch-Schonlein purpura 449, 607 etiology of 491 peripheral 480
classification criteria for 607 primary 491 primary 480
Hepatic encephalopathy 287, 288 secondary 491 screening for congenital 483
staging of 287 Hypercalcemia 488 Hypotonic cerebral palsy 575
Hepatitis A vaccine 174 Hyperkalemia 53 Hypoxic ischemic encephalopathy 96, 140
Hepatitis A 191 causes 53 Sarnat and Sarnat stages of 141
Hepatitis B immunoglobulin (HBIG) 193 clinical features 53
Hepatitis B vaccine 171 management 53 Ichthyosis 655, 656
Hepatitis B 192 mild 53 clinical features of 656
moderate 53 vulgaris 656
Hepatitis C 194
severe 53 Idiopathic hypercalcemia 81
Hepatitis D 193
Hyperleukocytosis 597 Idiopathic hypercalciuria 446
Hepatitis E 195 Hypernatremia 52 Idiopathic thrombocytopenic purpura 319
Hepatomegaly 279 causes 52 clinical evaluation 320
causes of 279 clinical features 52 laboratory evaluation 320
Hepatorenal syndrome 288 management 52 management 320
specific treatment of acute 288 Hyperparathyroidism 488 pathogenesis 320
Herd effect 165 Hypersensitivity pneumonitis 347 IEM 624
Hereditary hemorrhagic telangiectasia Hypertension 431 approach to a newborn infant with
(HHT) 336 causes of persistent 434 suspected 626
Hereditary motor and sensory neuropathies causes of transient 434 clinical syndromes 625
(HMSN) 576 clinical features 433 four basic tests for 628
Hereditary nephropathies 471 diagnosis 434 investigations for acutely presenting 627
Hereditary sensory and autonomic neuropathies diagnostic tests for sustained 434 laboratory work-up 627
(HSAN) 576 etiology 432 management 628
Hereditary spherocytosis 305 management 435 when to suspect 624
Herpes zoster 186 measuring blood pressure 431 IgA deficiency 162
Hirschsprung disease 256 physical examination and differential IgA nephropathy 446
Histiocytoses 595 diagnosis 434 IgG subclass deficiency 162
class 1595 screening investigations for patients Immune system 160
class II 595 with 434 adaptive 160
class III 595, 596 Hypertensive emergencies 435 innate 160
HIV 208 drugs for 435 Immunity 160
HIV/AIDS 204, 208 Hyperthermia 116, 117, 129 Immunization 160, 164-166, 178
WHO clinical staging of 204 Hypertrophic cardiomyopathy (HCM) 424 basic principles of 166
HIV-1 202 Hypertrophic pyloric stenosis 253 principles of 165
HIV-2 202 Hypervitaminosis A 79 Recommendations of the Indian Academy of
Hoarseness 341 Hypervitaminosis D 81 Pediatrics Committee on 178
Hodgkin lymphoma 588-590 Hypervitaminosis K 86 Immunodeficiency 161, 162
ABVD and COPP chemotherapy protocol Hypnotics 733 cellular and/or combined 161
for 590 Hypocalcemia 53, 155, 486, 487, 488 cellular 162
Ann Arbor staging classification for 589 causes 53 disorders 163
clinical features 588 clinical features 53, 486 treatment of primary 163
diagnostic evaluation for children with 589 etiology of 486, 487 humoral 162
diagnostic work up 589 evaluation 487 investigations for suspected 161
epidemiology 588 evaluation of a child with 488 primary
pathology 588 laboratory features of common causes screening investigations 161
staging 589 of 488 secondary
treatment 589 management 53, 487 secondary causes of 161
Homocystinuria 630 Hypoglycemia 155, 516 specific investigations 161
Hormone 473 Hypogonadism 502 Immunoglobulins 730
comparison of intracellular and extracellular hypergonadotropic 50, 502 Immunonutrition 704
receptors 473 Hypokalemia 52 IMNCI food box 61
Hormones 472 causes 52 IMNCI 735, 736, 737
comparison of peptide and steroid 472 clinical features 52 assess and classify 736
peptide 472 management 52 case management process 736, 737
steroid 472 Hyponatremia 51, 52 chart 736
HSCT 314 acute 52 classification tables 736
Human genome project 610 causes 51 clinical guidelines 735
Human immunodeficiency virus (HIV) chronic 52 essential components of 735
infection 202 Hypoparathyroidism 486, 487 principles of 736
diagnosis in children below the age of 18 autoimmune 486 Impetigo 659
months 208 Hypothermia 115, 116 bullous 659
classification of severity of immune moderate 116 contagiosa 659
suppression 205 severe 116 Inactivated polio vaccine (IPV) 168
Human papilloma virus (HPV) vaccine 177 Hypothyroidism 480^483, 485 Inborn errors of metabolism (IEM) 624
Human rabies immunoglobulin (HRIG) 173 acquired 482 Increased intracranial tension (ICT) 544
Hyaline membrane disease (HMD) 143 approach to a child with congenital 482 Index 64
Hydatid disease 249 central 480 Dugdale's 64
Hydrocarbon poisoning 681 clinical features of 481 Kanawati 64
Index 763
Neurological 519, 520 Oral polio vaccine (OPV) 167 Asperger syndrome 40
approach to diagnosis 519 Oral rehydration salt (ORS) 263 autistic disorder 40
investigations for diseases 520 Orbital cellulitis 646 childhood disintegrative disorder 40
Neuromuscular blocking drugs 705 Organic acidemias 624 not otherwise specified 40
Neuromuscular disorders 624 Organic acidurias 632, 633 Rett syndrome 40
clinical classification of 624 clinical pointers to specific 633 Pesticides 680
Neuropathies 576, 577 ORS 263 organophosphorous 680
hereditary 576 low osmolarity 263 pH 49
metabolic 577 WHO 263 Pharyngeal injury 338
toxic 577 Osmolality 441 Pharyngitis 338
Neuropathy 577 Osmolarity 47 Pharyngotonsillitis 338
drug-induced 577 Osteogenic sarcoma 593 acute bacterial 338
Neutropenia 327 Osteoporosis 81 Phenylketonuria 628
common causes of 327 Otitic hydrocephalus 332 Pheochromocytoma 491
Neutrophilia 326 Otitis externa 332 PHEX gene 83
common causes of 326 acute diffuse 332 Phlyctenular conjunctivitis 647
Nevi 666 eczematous or psoriatic 333 Phototherapy 149
Newborn 96, 106 etiology of 332 Pica 34
anthropometry 109 fungal 333 PICU 686
evaluation of 106 localized 332 indications for admission into 686
Niacin (vitamin B3) 88 Otitis media 329 Pierre Robin sequence 337
Niacin equivalents 88 Otoacoustic emissions (OAE) 333, 521 Pituitary gland 473
Nicotinamide 88 Otomycosis 333 disorders of 473
Nicotinic acid 88 Otorrhea 332 Pityriasis versicolor 665
Niemann Pick disease 639 Overlap syndromes 605 Pivot 25
Non-alcoholic fatty liver disease 281 Oxytocin reflex 124, 125 Plasmodium 227
etiology 281 Platelet disorder 318
diagnosis 281 Pancytopenia 313, 314 Platelet dysfunction 317
management 281 evaluation of 314 classification of 317
Nondisjunction 612 syndromes associated with 313 Platelet factors 317
Non-Hodgkin lymphoma 587 Pantothenic acid 90 Pneumatic otoscopy 329
clinical presentation 587 Paralysis 704 Pneumococcal vaccine 175
diagnosis 587 Paraplegia 553 Pneumonia 145, 352, 353, 354, 355
epidemiology 587 causes of 553 atypical 352
evaluation of patient with 587 flaccid 553 bacterial 352
management 588 pseudoparalysis 553 clinical features 352
staging system for 587 spastic 553 due to gram-negative organisms 355
Nonketotic hyperosmolar state 516 Parasite rate 228 etiology 352
Non-nucleoside reverse transcriptase Parotitis 343 hemophilus 354
inhibitors 209 viral 343 hydrocarbon 355
Non-shivering thermogenesis 115 Paroxysmal nocturnal hemoglobinuria 312 Loeffler's syndrome 355
Non-specific immunity 162 Patent ductus arteriosus 405 pneumococcal 352
disorders of 162 Pediatric advanced life support (PALS) 692 pneumocystis carinii 352
Normal blood gas measurements 50 components of 692 primary atypical 354
Normocytic anemia 299 endotracheal intubation 692 staphylococcal 353
approach to 299 fluid therapy 694 streptococcal 354
Nosocomial infections 706 vascular access 693 viral 352, 355
Nucleoside reverse transcriptase inhibitors 209 Pediculosis 665 Pneumothorax 146
Nutrition 57, 703 Pedigree 617 Poisoning 676, 680
Nutritional recovery syndrome 76 abbreviations 617 clinical clues to nature of 677
common symbols 617 clinical features suggesting 676
Obesity 494, 495, 496, 497 definitions 617 diagnosis of 676
approach to management of 497 Pellagra 88 indications of dialysis in a patient with
comparison of constitutional and treatment of 88 suspected 680
pathological 495 Pendred syndrome 333 management of 677
complications 496 Percentiles 8 presenting features of 676
constitutional 494 Pericardial diseases 425 acetaminophen (paracetamol) 680
criteria for 494 etiology of 425 dhatura (belladona) 681
etiology 494 Pericarditis 425 hydrocarbon 681
evaluation 495 acute 425 iron 681
features of pathological 496 Perinatal 96 Poliomyelitis 188, 189, 555, 556
hypothalamic 495 period 96 abortive 189
management 496 Peripheral blood smear examination 232 bulbar 189
monogenic 495 Peripheral neuropathies 576 bulbospinal 189
pointers to diagnosis of 495 Peripheral smear 231 clinical features 189
Obstructive lesions 373, 417 Peritoneal dialysis (PD) 466 differential diagnosis 190
Obstructive sleep apnea (OSA) 338 Peritonsillar abscess 338 encephalitis 189
diagnosis 338 Peroxisomal disorders 624, 640 eradication of 190
treatment 339 Persistent diarrhea (PD) 269 paralytic 189
Oliguria 442, 445 dietary algorithm for the treatment pathogenesis 188
OME 329 of 269 spinal paralytic 189
Omphalitis 105 Persistent pulmonary hypertension treatment 190
Oncologic emergencies 596 (PPHN) 145 vaccines 190
OptiMAL 231, 232 Pertussis (whooping cough) 221 Polyarteritis nodosa (PAN) 606, 607
Oral candidiasis (thrush) 337 catarrhal 221 classification criteria for childhood 607
Oral cavity 337 convalescent 221 Polygenic inheritance 620
congenital disorders 337 paroxysmal 221 Polysomnography 339
inflammatory disorders 337 Pertussis vaccine 169 Polyuria 477, 478
systemic processes 337 Pervasive developmental disorders 40 causes of 478
766 Essential Pediatrics
S and science of pediatrics in India and beyond. It has come out when there is unprecedented focus and
investment on child survival and health, child health education and training at the national level, coupled with a
global endeavour for improving child health and care. It also underlines the transition of pediatrics from the
existing priorities such as nutrition and infectious diseases to the emerging areas such as genetics, adolescence,
intensive care and care of children with chronic systemic diseases.
This edition highlights extensive revision in most chapters to effectively meet the contemporary needs of the
undergraduate and postgraduate medical and nursing students, and practising pediatricians as well. Chapters
on growth and development have been rewritten with inclusion of fresh illustrations and WHO growth norms;
chapters on nutrition and neonatology have been completely revised with emphasis on practical and evidence-
based management of common conditions; chapter on infections has also been rewritten keeping in view their
relevance in practice; and chapters on hematology, endocrines, nervous system and renal disorders have been
thoroughly updated and reorganised.
New chapter-sections on hypertension, interventional cardiology, newer vaccines, poisonings and accidents,
national and WHO guidelines on management of common conditions and IMNCI have been incorporated. The
multiple diagnostic and therapeutic algorithms are expected to serve as a useful educational resource. Fresh
chapters on skin and ocular disorders, practical procedures and the rights of children provide a comprehensive
review on issues pertaining to the care of children.
Some of the best-known academics, with a remarkable understanding of the learning needs of the students,
have contributed to this edition and the text reflects the essence of their knowledge and experience.
OP Ghai md, fiap, faap was Professor and Head, Department of Pediatrics, and Dean, All India Institute of Medical Sciences
(AIIMS), New Delhi. A distinguished academician, he was President of the Indian Academy of Pediatrics (1978) and President of
International College of Pediatrics (1987-1990). An honorary fellow of the American Academy of Pediatrics, he was bestowed
upon various prestigious awards by the Indian Council of Medical Research and many other institutions. As the founder editor of
Essential Pediatrics, he brought out the first edition in 1982 and nurtured its subsequent editions till 2008 when the ‘visionary and
doyen of pediatrics’ suddenly passed away.
Vinod K Paul MD, PhD, fams, fiap is Professor and Head, Department of Pediatrics, AIIMS, New Delhi. An internationally
recognised expert on newborn and child health, he is also head of the WHO Collaborating Centre for Training and Research in
Newborn Care, and has been coordinator of the Centre for Medical Education and Technology at AIIMS. He is fellow of the
National Academy of Medical Sciences, the Indian Academy of Pediatrics and the National Neonatology Forum.
Arvind Bagga MD, fiap, fams is Professor, Department of Pediatrics, and incharge of Pediatric Nephrology, AIIMS, New Delhi.
He has been the councillor of the International Pediatric Nephrology Association and is the founder member of the Indian
Society of Pediatric Nephrology. He is fellow of the National Academy of Medical Sciences and the Indian Academy of
Pediatrics. He has coordinated formulation of the standard treatment guidelines for common childhood renal disorders.
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