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Neonatology
CASE-BASED REVIEW

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Neonatology
CASE-BASED REVIEW

Dara Brodsky, MD Elizabeth G. Doherty, MD


Assistant Professor of Pediatrics Instructor of Pediatrics
Harvard Medical School Harvard Medical School
Beth Israel Deaconess Medical Center Boston Childrens Hospital
Boston, Massachusetts Boston, Massachusetts
Winchester Hospital
Winchester, Massachusetts

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Preface

Pediatric residents in the United States have fewer rotations in the Neonatal Intensive Care Unit
(NICU) than ever before. The recent reduction in resident duty hours has also limited residents
exposure to the NICU. Nonetheless, pediatric residents are still required to have a significant un-
derstanding of neonatology. We created this resource to help residents develop this understanding
through a case-based approach to neonatal diseases. We selected the topics for this book based
on the most recent American Board of Pediatrics Content Specifications recommended for the
Pediatrics certification examination. To make the cases realistic, we incorporated pictures and
radiographs when possible. Although we originally targeted this book to pediatric residents, we
think that it will also be a valuable self-learning tool for medical students and nurse practitioner
students. While students can use this book on their own, they may also benefit from discussing the
cases with neonatologists, neonatology fellows, and pediatricians.

DB and EGD

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Contents

Prefacev Case 7 Differential cyanosis 57


Case 8 Arrhythmias 58
I. MATERNALFETAL MEDICINE
Case 1 Maternal serum screening 2 IV.NEUROLOGY
Case 2 Prenatal ultrasonography 2 Case 1 Head growth 68
Case 3 Invasive prenatal genetic testing 4 Case 2 Brachial plexus injury at birth 69
Case 4 Fetal assessment 5 Case 3 Seizures 69
Case 5 Effects of maternal diabetes mellitus 6 Case 4 Hypoxic-ischemic encephalopathy 70
Case 6 Effects of maternal lupus 7 Case 5 Intracranial hemorrhage 70
Case 7 Maternal medications 8 Case 6 Neonatal encephalopathy 71
Case 8 Maternal substance use 8
Case 9 Delivery room assessment 9 V. MUSCULOSKELETAL system
Case 10 Delivery room resuscitation 10 Case 1 Clubfoot 82
Case 11 Small-for-gestational-age infant 11 Case 2 Developmental dysplasia of the hips 82
Case 12 Initial care of the premature infant 12 Case 3 Torticollis 83
Case 4 Contractures 84
II.Pulmonology Case 5 Osteogenesis imperfecta 85
Case 1 Ventilator management 28 Case 6 Achondroplasia 86
Case 2 Apnea 29 Case 7 Limited neck movements 86
Case 3 Stridor 30
Case 4 Surfactant deficiency 30 VI.GENETICS
Case 5 Pulmonary air leaks 31 Case 1 Postnatal genetic testing 94
Case 6 Meconium aspiration syndrome 33 Case 2 Inheritance patterns 94
Case 7 Patchy lung fields 34 Case 3 Autosomal trisomy syndromes 95
Case 8 Tachypnea 35 Case 4 Turner syndrome 96
Case 9 Cystic lung disease 36 Case 5 Syndromes of tall stature 97
Case 10 Tracheoesophageal abnormalities 37 Case 6 Genetic associations 98
Case 11 Congenital malformations of the lung 38 Case 7 Deletion syndromes 98
Case 8 Treacher Collins syndrome
andPierreRobin sequence 100
III. CARDIOLOGY
Case 1 Congenital heart disease 52
Case 2 Cyanosis 54 VII. INFECTIOUS DISEASES
Case 3 Cardiogenic shock 54 Case 1 Sepsis 112

Case 4 Non-cardiogenic shock 55 Case 2 Group B Streptococcus 113

Case 5 Cyanotic heart disease: Case 3 Herpes simplex virus 114


Diagnosis and management 56 Case 4 Lower respiratory tract infections 115
Case 6 Cyanotic heart disease: Outcomes 57 Case 5 Hepatitis B virus 116

vii

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viiiContents

Case 6 Syphilis 116 Case 7 Thrombocytopenia 182


Case 7 Toxoplasmosis 117 Case 8 Coagulation disorders 183
Case 8 Human immunodeficiency virus 118 Case 9 Hemorrhagic disease of the newborn 184
Case 9 Cytomegalovirus 119
Case 10 Immunizations 119 XII.ENDOCRINOLOGY
Case 1 Hypothyroidism 198
VIII.FLUIDS, ELECTROLYTES, Case 2 Congenital adrenal hyperplasia 199
ANDNUTRITION Case 3 Abnormal male genitalia 200
Case 1 Fluid, caloric, and nutritional Case 4 Female genital findings 201
requirements 134
Case 2 Acidosis and alkalosis 134
XIII.INBORN ERRORS
Case 3 Electrolyte abnormalities 135 OF METABOLISM
Case 4 Mineral deficiencies 136 Case 1 Newborn screening 214
Case 5 Vitamin deficiencies 136 Case 2 Phenylketonuria 214
Case 6 Breast-feeding 137
Case 7 Formula-feeding 138 XIV.Ophthalmology and Audiology
Case 1 Ophthalmologic prophylaxis 220
IX. RENAL system Case 2 Congenital glaucoma and cataracts 220
Case 1 Anuria in a newborn 150 Case 3 Retinoblastoma 221
Case 2 Multicystic dysplastic kidney 150 Case 4 Retinopathy of prematurity 222
Case 3 Autosomal dominant polycystic Case 5 Hearing screening 223
kidney disease 151
Case 4 Autosomal recessive polycystic kidney
XV.DERMATOLOGY
disease 152
Case 1 Pigmentary and vascular lesions 230
Case 5 Renal agenesis 152
Case 2 Benign pustular lesions 231
Case 6 Abnormalities of the collecting
system, kidney, and bladder 153
Case 7 Posterior urethral valves 154 XVI.THERMOREGULATION
Case 1 Temperature control 240
X.GASTROENTEROLOGY
Case 1 Stooling pattern in neonates 164 XVII.PHARMACOLOGY
Case 2 Scaphoid abdomen 164 Case 1 Aminoglycosides 244
Case 3 Necrotizing enterocolitis 165 Case 2 -Lactam antibiotics 245
Case 4 Intestinal obstruction 166 Case 3 Diuretics 246
Case 5 Anterior abdominal wall defects 167
Case 6 Biliary atresia 168 XVIII.ETHICS
Case 1 Maternalfetal conflicts 252
XI.HEMATOLOGY Case 2 Imperiled newborns 253
Case 1 Hematocrit and anemia of
prematurity 178 XIX. DISCHARGE PLANNING
Case 2 Polycythemia 178 Case 1 Newborn discharge from the hospital 258
Case 3 Bilirubin metabolism 179 Case 2 Sudden infant death syndrome
Case 4 Physiologic jaundice 180 prevention 259
Case 5 Nonphysiologic jaundice 181
Case 6 Kernicterus 182 Index263

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S E C T I ON I MaternalFetal
Medicine

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2Section I MaternalFetal Medicine

CASE 1
Maternal serum screening

A pregnant woman undergoes blood testing at 16 weeks The womans test results are shown in the table below:
gestation.

Lab Result
Line A (Multiples of Normal Result
Test Mean, MoM) (MoM)
-Fetoprotein 4.0 0.42.5
-Human
-Fetoprotein

0.8 0.42.5
Line B chorionic
gonadotropin
Inhibin A 1.0 ,2.5
Line C
Unconjugated 0.9 .0.5
estriol
Line D
Her obstetrician meets to discuss possible reasons for these
Week of gestation results.
FIGURE 1.
2. Of the following, the diagnosis that is not consistent with
1. Of the following, the line in Figure 1 that most likely these laboratory findings is:
represents the maternal serum -fetoprotein concentration
A. Gastroschisis
throughout pregnancy is:
B. Neural tube defect
A. Line A C. Line C C. Trisomy 21
B. Line B D. Line D D. Twin gestation

CASE 2
Prenatal ultrasonography

Blood screening results of a 40-year-old G3P2 pregnant


woman were abnormal. Several fetal ultrasounds reveal that
the fetus has multiple anomalies. The woman and her hus-
band meet with a neurologist, a geneticist, a surgeon, and
a cardiologist.
The neurologist meets with this couple to discuss the
14-week ultrasound finding shown in Figure 1. This long-axis
view shows the spine (short arrowheads) and the head (be-
tween the two long arrows).

FIGURE 1. From Eisenberg RL. An Atlas of Differential Diagnosis. 4th ed.


Philadelphia, PA: Lippincott Williams & Wilkins; 2003. Figure 1.01

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Case 2 Prenatal ultrasonography3

1. Of the following, this fetal image most likely is consistent with: 3. Of the following, the potential short-term complication
that can occur after birth is:
A. Anencephaly
B. Holoprosencephaly A. Dehydration
C. Hydrocephalus B. Intestinal perforation
D. Meningomyelocele C. Meconium plug
D. Nonbilious emesis
The family then meets with a cardiologist to discuss the car-
diac findings in the fetus. The fetal ultrasonographic find- The familys high-risk obstetrician is also suspicious of a
ings are shown in Figure 2. The defect is confirmed by fetal genitourinary abnormality because the infants bladder is ex-
echocardiography. tremely large with a thickened wall. The fetal image in Figure 4
shows the markedly dilated bladder (B) and dilated proximal
urethra (U).

FIGURE 2. From Eisenberg RL. An Atlas of Differential Diagnosis. 4th ed. FIGURE 4. From Eisenberg RL. An Atlas of Differential Diagnosis. 4th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2003. Figure 1.35; Philadelphia, PA: Lippincott Williams & Wilkins; 2003. Figure 1.33
f=foramen
4. Of the following, the genitourinary abnormality that this
2. Of the following, the cardiac defect that is most likely in
infant is likely to have is (are):
this infant is:
A. Hydronephrosis
A. Complete atrioventricular canal
B. Pelviectasis
B. Hypoplastic left ventricle syndrome
C. Posterior urethral valves
C. Transposition of the great arteries
D. Renal agenesis
D. Large ventricular septal defect
Because of the multiple anomalies in the fetus, the couple
The fetal ultrasound also demonstrates a gastrointestinal
decides to terminate the pregnancy. Several years later, the
complication (Figure 3). A surgeon meets with the family to
woman becomes pregnant. Her blood screening results are
discuss the diagnosis and possible outcomes.
normal. A fetal ultrasound demonstrates choroid plexus cysts.
The rest of the fetal ultrasound is normal. Given her past his-
tory, the woman is extremely worried that this infant will have
multiple anomalies.

5. Of the following, the diagnosis that is most likely in this


fetus is:

A. Healthy term infant


B. Neurological issues later in life
C. Trisomy 13
D. Trisomy 21

FIGURE 3. From Eisenberg RL. An Atlas of Differential Diagnosis. 4th ed.


Philadelphia, PA: Lippincott Williams & Wilkins; 2003. Figure 1.20

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4Section I MaternalFetal Medicine

CASE 3
Invasive prenatal genetic testing

A pregnant woman at 8 weeks gestation meets with her


obstetrician. She and her husband are both carriers for sickle
cell disease. She asks her obstetrician if she can have prenatal
testing for this disease. Her obstetrician reviews some o
ptions
for prenatal DNA testing.

1. Match the figure with the prenatal invasive testing


approach:

A. Amniocentesis ____
B. Periumbilical blood sampling ____
C. Transabdominal chorionic villus sampling ____
D. Transvaginal chorionic villus sampling ____

FIGURE 3. Modified from Gibbs RS, Karlan BY, Hanley AF, et al.,
eds. Danforths Obstetrics and Gynecology. 10th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2008. Figure 6.15

FIGURE 1. Modified from Gibbs RS, Karlan BY, Hanley AF, et al.,
eds. Danforths Obstetrics and Gynecology. 10th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2008. Figure 6.13

FIGURE 4. Courtesy of LifeART 2014 Lippincott Williams & Wilkins.


All rights reserved

2. Of the following, the prenatal test that is least helpful in the


diagnosis of sickle cell disease is:

A. Amniocentesis
B. Fetal ultrasonography
C. Periumbilical blood sampling
D. Transvaginal chorionic villus sampling

FIGURE 2. Modified from Gibbs RS, Karlan BY, Hanley AF, et al.,
eds. Danforths Obstetrics and Gynecology. 10th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2008. Figure 6.14

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Case 4 Fetal assessment5

Fetal DNA analysis shows that the fetus does not have sickle 3. Of the following, the result that is most consistent with
cell disease. The pregnancy is uncomplicated until the woman mature fetal lungs is a(n):
develops severe sciatica and walking becomes extremely pain-
A. Absence of phosphatidylglycerol
ful. At 36 weeks gestation, she asks her obstetrician to con-
B. Elevated lecithin/sphingomyelin ratio
sider delivering the baby early because she has severe constant
C. Increased amount of phosphatidylinositol
pain. Her obstetrician performs an amniocentesis to deter-
D. Low amount of sphingomyelin
mine fetal lung maturity.

CASE 4
Fetal assessment

A pregnant woman at 39 weeks gestation has been monitored


with weekly nonstress tests. Her most recent nonstress test
results are shown in Figure 1.

FHR 240bpm FHR 240bpm FHR 240bpm

210 210 210

180 180 180

150 150 150

120 120 120

90 90 90

60 60 60

30 30 30

100 100 100


12 12 12
10 75 10 75 10 75
8 8 8
50 50 50
6 6 6
4 4 4
25 25 25
2 2 2
0 kPa UA0 mm Hg 0 kPa UA0 mm Hg 0 kPa UA0 mm Hg

FIGURE 1. From Pillitteri A. Maternal and Child Nursing. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2003. Figure 8.11

1. Of the following, the result that is most consistent with this Three days later, the woman contacts the obstetrician because
nonstress test is: she feels decreased fetal movements. The obstetrician per-
forms a biophysical profile, which is normal.
A. Normal amniotic fluid volume
B. Normal fetal breathing pattern 3. Of the following, the measurement that is not part of the
C. Normal fetal heart rate response to fetal movement biophysical profile is:
D. Regular, frequent contractions
A. Amount of amniotic fluid
At 40 3/7 weeks gestation, the obstetrician performs a con- B. Blood flow in the umbilical arteries
traction stress test, which is normal. C. Fetal breathing
D. Fetal tone
2. Of the following, the primary purpose of the contraction
stress test is to:

A. Assess the impact of uterine contractions on fetal tone


B. Determine the strength of uterine contractions
C. Evaluate for uteroplacental insufficiency
D. Measure the impact of uterine contractions on fetal
movements

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6Section I MaternalFetal Medicine

CASE5
Effects of maternal diabetes mellitus

A full-term male infant with macrosomia is born by cesarean The infants serum glucose then increases to 61 mg/dL. How-
delivery to a woman with insulin-dependent diabetes mel- ever, the infant is noted to have a right arm oxygen saturation
litus. The mother had extensive prenatal testing (including of 84%. The rest of the infants vital signs, including blood
maternal blood testing, several fetal ultrasonographs, fetal pressure, are normal. With a half liter per minute of 100%
echocardiography) to assess for anomalies in the fetus. All of oxygen, the infants oxygen saturation increases to 98%.
these tests were normal. The infants physical examination at 3 hours of age reveals a
well-appearing, ruddy infant without any respiratory distress
1. Pregnant women with diabetes mellitus are at increased and with a soft I/VI systolic heart murmur heard loudest at
risk of having an infant with congenital anomalies. Of the the left mid to upper sternal border. A chest radiograph is
following, the scenario that is associated with a lower risk of normal.
congenital anomalies is:
4. Of the following, the most likely cause of this infants cya-
A. Diabetes mellitus without evidence of vascular disease
nosis is:
B. Good maternal glucose control before conception
C. Good maternal glucose control during the third A. Cyanotic heart disease
trimester B. Polycythemia
D. A and B C. Respiratory distress syndrome
D. Transient tachypnea of the newborn
Most congenital anomalies found in infants of diabetic women
occur early in gestation. However, there is one anomaly that The baby has the following laboratory findings:
occurs later.
Na = 131 mEq/L
2. Of the following, the anomaly that occurs during the K = 3.1 mEq/L
second half of gestation is: Cl = 95 mEq/L
HCO3 = 16 mEq/L
A. Caudal regression syndrome Ionized calcium = 0.88 mmol/L
B. Meningomyelocele
C. Small left colon syndrome
5. Of the following, the electrolyte abnormality that is often
D. Transposition of the great arteries
found in infants born to women with diabetes mellitus is:
The babys initial breastfeeding attempt was unsuccessful be-
A. Hypocalcemia
cause he did not latch well. Because the babys initial serum
B. Hypochloremia
glucose is 21 mg/dL, he is brought to the Neonatal Intensive
C. Hypokalemia
Care Unit for further care. He is given an intravenous glucose
D. Hyponatremia
bolus and started on a continuous intravenous infusion of
D10W at 60 mL/kg/day. The neonatology fellow meets with
the infants parents to discuss the reason for their babys low
serum glucose and the treatment approach.

3. Of the following, the pathogenesis of this infants hypogly-


cemia is most likely:

A. Diabetes mellitus in the infant


B. Increased insulin production by the infant
C. Intrauterine passage of maternal insulin to the fetus
across the placenta
D. Neonatal liver dysfunction from intrauterine exposure
to maternal insulin

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Case 6 Effects of maternal lupus7

CASE 6
Effects of maternal lupus

A full-term, well-appearing female neonate is noted to have Additional tests are performed on the mother to help identify
a low resting heart rate. The infants mother is in excellent the cause of this infants medical issues.
health without any medical problems. The infants electrocar-
diogram is shown in Figure 1. 2. Of the following, the maternal antibodies that are most
likely associated with this infants clinical findings are:

A. Anti-acetylcholine receptor (AChR) antibodies


B. Antiphospholipid antibodies
C. Anti-Ro/SSA and anti-La/SSB antibodies
D. Thyroid-stimulating hormone receptorblocking
antibodies

Testing of the infants mother confirms that she has these se-
rum antibodies.

3. Of the following, the percentage of affected infants with


this disease who are born to an undiagnosed, healthy
FIGURE 1. From Miles MM, Klein LS. Sinus nodal dysfunction and woman is:
atrioventricular conduction disturbances. In: Naccarelli GV, ed.
Cardiac Arrhythmias: A Practical Approach. Mount Kisco, NY: Futura; A. <2%
1991:269 B. 25%
C. 50%
1. Of the following, the electrocardiographic diagnosis of this D. 90%
infant is:
The infant in this vignette has additional testing.
A. Complete heart block
B. First-degree heart block 4. Of the following, the laboratory finding that is most likely
C. Sinus bradycardia to be found in this infant is:
D. Wenckebach second-degree heart block
A. Hypocalcemia
Soon after birth, the infant is noted to have a rash involving B. Indirect hyperbilirubinemia
the face and trunk. C. Polycythemia
D. Thrombocytopenia

FIGURE 2. From Goodheart HP. Goodhearts Photoguide of Common Skin


Disorders. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins;
2003. Figure 25.33

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8Section I MaternalFetal Medicine

CASE7
Maternal medications

A 39-year-old woman with a seizure disorder and a clotting ab- Aneonatologist examines the infant after birth and observes
normality finds out that she is 13 weeks pregnant. Although that the infant also has digit and nail hypoplasia in addition
she had not been taking any anticoagulant medication, she to a cleft palate.
has been taking her antiseizure medication regularly. Her ob- Postdelivery, the woman develops a deep vein thrombosis
stetrician discusses the potential impact of anticonvulsant use and is placed on warfarin.
during pregnancy. A few years later, the woman meets with her obstetrician in
anticipation of expanding her family. Her obstetrician changes
1. Of the following, the statement that is most accurate is: her anticoagulant therapy from warfarin to heparin and, in
A. All anticonvulsants marketed prior to 1976 have been consultation with a neurologist, discontinues her antiseizure
shown to have teratogenic effects. medication.
B. Although intrauterine anticonvulsant exposure can lead
3. Of the following, potential effects of warfarin exposure
to dysmorphic features, neurological outcomes are not
during the first trimester are:
altered in exposed children.
C. Fetal risk of anticonvulsant exposure is greatest if the ex- A. Ebstein anomaly
posure occurs during the third trimester. B. Microtia, cerebellar hypoplasia, and transposition of the
D. Major malformations associated with intrauterine an- great arteries
ticonvulsant exposure occur in more than 50% of ex- C. Nasal hypoplasia and stippled bone epiphyses
posed fetuses. D. Yellow-brown discoloration of deciduous teeth
Ultrasonography at 14 weeks gestation reveals that the fetus During this pregnancy, the fetal imaging is normal and there
has a cleft palate. are no medical concerns in either the woman or the fetus.
However, at 30 weeks gestation, the woman is admitted to the
2. Match the morphogenesis problem with the resulting fetal hospital in preterm labor. Because of the teratogenic effects of
abnormality: her antiseizure medications in her first child, she is extremely
concerned about potential effects of tocolytic medications.
A. Deformation 1. Amniotic bands Her obstetrician discusses the risks and benefits of several pos-
B. Disruption 2. Arthrogryposis caused by sible tocolytic agents.
intrauterine constraints
4. Of the following, the tocolytic medication that has been as-
C. Dysplasia 3. Cleft palate
sociated with pulmonary hypertension in the newborn is:
D. Malformation 4. Hemangioma
A. Indomethacin
B. Magnesium sulfate
Delivery is induced at 34 weeks gestation because of con- C. Nifedipine
cerns about significant intrauterine growth restriction. D. Terbutaline

CASE8
Maternal substance use

A woman and her husband have tried for several years to pediatrician to review the infants medical history. Upon
have a baby. Because they have been unsuccessful, they meet review of the medical records, the pediatrician notes that

with an adoption agency. The agency offers them an option the baby was born by emergent cesarean section because of
to adopt a 6-month-old boy. The couple then meets with a placental abruption.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 9 Delivery room assessment9

1. Of the following, the maternal drug that has been associ- The pediatrician then looks at a picture of the infant and tells
ated with placental abruption is: the couple that the infant likely has fetal alcohol syndrome.
A. Cocaine 4. Of the following, a common physical finding in infants
B. Heroin with fetal alcohol syndrome is (a):
C. Methadone
D. Morphine A. Long nose
B. Long palpebral fissures
During the newborn period, the infant had the following C. Macrocephaly
symptoms after birth: D. Thin upper lip
Irritability The parents are not concerned about the infants physical fea-
Shrill, high-pitched cry tures but want to know about the babys long-term neurologi-
Tremors cal prognosis.
Hyperreflexia
Hypertonia 5. Of the following, the least likely neurological outcome in
Nasal stuffiness this infant is:
Tachypnea
A. Behavioral issues
Frequent sneezing
B. Cognitive deficits
Poor feeding
C. Macrocephaly
Loose, watery stools
D. Structural brain abnormalities
Vomiting
Given the potential of significant medical issues in this baby, the
2. Of the following, the maternal drug that is least likely to family decides not to pursue the adoption. A few weeks later, the
lead to neonatal withdrawal symptoms is: adoption agency contacts the couple again about a 7-month-old
infant girl. The infants medical records reveal that the mother
A. Codeine
smoked one pack per day throughout the pregnancy. She had
B. Heroin
monthly drug testing that was negative except for one positive
C. Methamphetamine
test for marijuana. The infant was born at term gestation with
D. Methadone
a normal birth weight and did not have any medical problems
These withdrawal symptoms resolved with treatment, and by a after birth. She has been developing appropriately without any
few weeks of age, the infant was symptom-free and not receiv- medical concerns. The couple again meets with the pediatrician
ing any medications. to discuss the potential effects of smoking on the baby.

3. Of the following, potential drugs that can be used to treat 6. Of the following, a potential effect of prenatal exposure to
neonatal withdrawal are: tobacco is:

A. Methadone A. Intestinal atresia


B. Morphine sulfate B. Macrosomia
C. Phenobarbital C. Postterm delivery
D. All of the above D. Sudden infant death syndrome

CASE 9
Delivery room assessment

Fetal heart rate monitoring of a fetus at 40 weeks gestation neonatology fellow, pediatric resident, and neonatal nurse,
reveals decreased fetal heart rate variability and a prolonged evaluates the infant. The team begins to dry the baby and
late deceleration. The obstetrician asks the neonatology team provide stimulation. Because the infant does not have any
to be present for an emergent cesarean delivery. respiratory effort, the pediatric resident provides bag-mask
After delivery, the infant is brought over to a radiant ventilation and the nurse places a pulse oximeter on the in-
warmer. The neonatology team, consisting of a neonatologist, fants right wrist. The nurse reports that the infants heart rate

(c) 2015 Wolters Kluwer. All Rights Reserved.


10Section I MaternalFetal Medicine

is 80beats per minute. The resident continues to provide pos- The Apgar score at 5 minutes of age is 8. The father asks the
itive-pressure ventilation. At 1 minute of age, the team notes neonatologist about the significance of his infants low Apgar
that the infant has: score at 1 minute of age.
A heart rate of 78 beats per minute 3. Of the following, the statement that the neonatologist is
An oxygen saturation of 65% most likely to say to the father is:
No respiratory effort
No spontaneous movements A. An amplitude electroencephalogram can help assess if
No tone the infants status at 1 minute of age has impacted the
Poor perfusion infants brain activity.
B. The infants Apgar score < 3 at 1 minute of age corre-
1. Of the following, the clinical finding that is not used when lates with a 1% risk of cerebral palsy.
calculating an infants Apgar score is: C. The infants Apgar score is a poor indicator of neurologi-
cal outcome.
A. Activity D. The infant is at increased risk for seizure activity in the
B. Color first 24 hours of age.
C. Perfusion
D. Respiratory rate The next morning, the pediatrician and a third-year medical
student examine the full-term infant in the newborn nursery.
2. Of the following, the number that corresponds to this The pediatrician discusses the physical examination findings
infants Apgar score at 1 minute is: in a full-term infant compared with those of a preterm and
postterm infant.
A. 0
B. 1 4. Of the following, the physical finding often found in a pre-
C. 2 term infant is (are):
D. 3
A. Cracked, wrinkled skin
The team continues to provide positive-pressure ventilation B. Excessive plantar creases
and the infants heart rate increases to 150 by 2 minutes of age. C. Instant recoil of ear pinna
The infant starts to breathe spontaneously and becomes active. D. Minimal flexion of arms and legs at rest

CASE 10
Delivery room resuscitation

A group of medical students attend a simulation course about Using a newborn mannequin, the instructor then demon-
neonatal resuscitation. The instructor begins the class by strates appropriate bag-mask ventilation and chest compres-
showing a video of a resuscitation using a high-fidelity new- sions. The students review the details of these techniques and
born simulator. The instructor asks the students to identify the then practice on the mannequin.
resuscitative actions that were appropriate.
2. Of the following, the most appropriate technique to pro-
1. Of the following, the action that is most appropriate in the vide effective chest compressions in a newborn is:
resuscitation of a newborn is:
A. Apply compressions over the upper third of the new-
A. Continued stimulation of a newborn with a slow heart borns sternum
rate and apnea B. Compress to a depth one-third the anteriorposterior
B. Establishment of a patent airway before applying posi- diameter of the chest
tive-pressure ventilation C. Provide chest compressions and bag-mask breaths in a
C. Placement of a pulse oximeter probe on the new- ratio of 2:1
borns right wrist after 5 minutes of positive-pressure D. Use the two-finger technique instead of the two-thumb-
ventilation encircling-hands approach
D. Technique of applying low peak inspiratory pressure by
bag-mask ventilation for the first few assisted breaths

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 11 Small-for-gestational-age infant11

3. Of the following, an indication for beginning chest com- gestation with severe respiratory distress. Thin meconium was
pressions in a newborn is: noted when the membranes ruptured prior to delivery and
there were no sepsis risk factors.
A. If the heart rate does not increase above 60 beats per min-
ute despite effective ventilation with oxygen for 30 seconds 4. Of the following, the approach that might have decreased
B. If the heart rate is less than 30 beats per minute imme- the severity of this newborns respiratory disease is:
diately after birth
C. If the newborn remains cyanotic despite appropriate A. Administration of maternal steroids prior to delivery
bag-mask ventilation B. Initiation of continuous positive airway pressure soon
D. If the newborns perfusion is extremely poor after after birth
30seconds of bag-mask ventilation C. Intubation and suctioning the infants trachea if the
infant was not vigorous immediately after birth
The instructor then shows the students a chest radiograph D. Minimal use of oxygen supplementation in the delivery
(Figure 1) of a 30-minute-old newborn born at 36 weeks room

FIGURE 1. From MacDonald G, Seshia MK, et al. Averys Neonatology:


Pathophysiology & Management of the Newborn. 6th ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 2005. Figure 29.9

CASE 11
Small-for-gestational-age infant

Figure 1 shows three fetal growth curves. 2. Of the following, the most likely cause of the fetal growth
pattern in Curve 3 is:
Curve 1 A. Familial short stature
B. Maternal gestational diabetes
Growth
Curve 2 C. Pregnancy-induced hypertension
curves
Curve 3
D. Twin gestation
90%
A high-risk obstetrician is closely monitoring a pregnant
50%
woman with pregnancy-induced hypertension because of fe-
10% tal growth restriction. After a poor fetal biophysical profile at
34 40 36 weeks gestation, the obstetrician decides to induce labor.
Gestational age (weeks) Because the fetal heart rate patterns show late decelerations
FIGURE 1. with each contraction, the obstetrician delivers the baby by
1. Of the following, the graph(s) (Figure 1) that represents a cesarean.
fetus with intrauterine growth restriction (IUGR) is (are):

A. Curve 1 C. Curve 3
B. Curve 2 D. Curves 1 and 2

(c) 2015 Wolters Kluwer. All Rights Reserved.


12Section I MaternalFetal Medicine

The neonatal team attends the delivery and needs to ad- 3. Of the following, the morbidity that is most likely in this
minister bag-mask ventilation because the infant emerges infant is:
apneic. After 1 minute of assisted ventilation, the infant is
A. Anemia
breathing spontaneously and well-appearing. The babys birth
B. Hypercalcemia
weight is 2,000 g, which is 6th percentile for a baby born at 36
C. Hyperthermia
weeks gestation.
D. Hypoglycemia

CASE 12
Initial care of the premature infant

A pregnant woman presents to the hospital with s pontaneous The baby is then brought to the Neonatal Intensive Care Unit
rupture of membranes and contractions. Her obstetrician for further care. The neonatal nurse places the infant on a radi-
orders antenatal steroids and antibiotics. Although tocolysis ant warmer and assesses the infants vital signs. The pediatric
is attempted, her labor progresses and she delivers a preterm resident orders laboratory studies, a chest radiograph, and an
infant at 28 weeks gestation with a birth weight of 1,200 g intravenous solution containing total parenteral nutrition.
(70%). The pediatric resident meets with the family to discuss the re-
sults of these studies and the management plan.
1. Of the following, the term that best describes this infant is:
3. Of the following, the current issue that is least likely to be
A. Low-birth-weight (LBW) infant
present in this 1-hour-old infant is:
B. Very low-birth-weight (VLBW) infant
C. Extremely low-birth-weight (ELBW) infant A. Anemia of prematurity
D. Micropremie B. Hypoglycemia
C. Hypothermia
The neonatology team cares for the infant immediately af-
D. Hypoxemia
ter delivery. At 5 minutes of age, the infant is receiving facial
continuous positive airway pressure because of respiratory
distress and appears hypotonic with decreased reflex irritabil- 4. Of the following, the laboratory studies that were most
ity. The infants Apgar score is 5 and 6 at 1 and 5 minutes, likely sent on this infant are:
respectively. A. Blood urea nitrogen and serum creatinine
The neonatology fellow updates the parents in the delivery B. Complete blood cell count and blood culture
room. The parents express concern that the babys Apgar score C. Serum electrolytes
is lower than their older childs score; the parents relate that D. Serum transaminases
the infants sibling was born at 39 weeks gestation and had
an Apgar score of 8 at 1 minute of age and 9 at 5 minutes of
age. The fellow is reassures the parents and discusses that a
premature infant often cannot achieve as high an Apgar score
as does a full-term infant.

2. Of the following, the physiologic reason why premature


infants often cannot achieve an Apgar score above 6 is:

A. A low resting heart rate


B. Neurologic immaturity
C. Persistence of fetal circulation
D. Poor perfusion

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 2 Prenatal ultrasonography13

secti on I
Answers

maternal serum -fetoprotein elevation can result from the


CASE 1 ANSWERS
following:
1. C. Line C Neural tube defect
-Fetoprotein is a protein that is produced by the fetal yolk Omphalocele or gastroschisis
sac during early gestation. After peak production by the fetus Sacrococcygeal teratoma
at 13 weeks gestation, the fetal -fetoprotein concentrations Cloacal exstrophy
decrease. The fetal serum -fetoprotein is then excreted into Multiple gestation
fetal urine and enters the amniotic fluid. Thus, the amniotic Underestimation of gestational age (i.e., pregnancy is fur-
fluid -fetoprotein curve corresponds directly with the fetal ther along than previously thought)
serum -fetoprotein curve. -Fetoprotein can diffuse across
the placenta into the maternal circulation. The peak maternal A low maternal serum -fetoprotein concentration may be
-fetoprotein concentration typically occurs at approximately found in infants with trisomy 21 or trisomy 18.
32 weeks gestation. These three -fetoprotein curves are rep- Because maternal serum -fetoprotein test results have a
resented in Figure 2. high false-positive rate, further testing, such as fetal ultraso-
Fetal serum
nography and amniocentesis, is necessary to determine if there
is any significance to an abnormal value.
1000

100 AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATIONS
Afp (g/ml

10 Know the significance of abnormal maternal serum


-fetoprotein concentrations
Amniotic
1 Know that the measurement of maternal serum
fluid
-fetoprotein concentration is a useful screening test for
the diagnosis of open neural tube defects in a fetus
0.1

Maternal serum
0.02
12 16 20 24 28 32 36 40
SUGGESTED READINGS
Week of gestation Blumenfeld Y. First trimester screening for fetal aneuploidy. NeoReviews.
FIGURE 2. From Seppala M, ed. Amniotic Fluid. 2nd ed. New York, NY: 2012;13:e4e8.
Excerpta Medica; 1978, with permission Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
Cunningham FG, Leveno KJ, Bloom SL, et al., eds. Williams Obstetrics.
2. C. Trisomy 21 23rd ed. New York, NY: McGraw-Hill; 2009.
The combination of maternal serum -fetoprotein, unconju-
gated estriol, -human chorionic gonadotropin, and inhibin
A testing is known as a quadruple screen. It is typically mea- CASE 2 ANSWERS
sured between 14 and 20 weeks gestation, with 16 weeks
gestation being the optimal time. Assessment of these results 1. A. Anencephaly
can help determine the risk of fetal chromosomal anomalies, This ultrasonographic image demonstrates a poorly developed,
particularly trisomy 21 and trisomy 18. If this second trimester small head that is most consistent with anencephaly. Anenceph-
testing is combined with first trimester maternal pregnancy- aly is caused by a failure of the anterior tube to close, leading to
associated plasma protein A (PAPP-A) levels and first trimester degeneration of the forebrain within the first month of gesta-
nuchal translucency measurements, the detection rate of tri- tion. This results in absence of most of the brain tissue, skull,
somy 21 approaches 90% to 95%. and scalp; an affected fetus may have sparing of the brainstem
In this vignette, the pregnant womans quadruple screen and cerebellum. The maternal serum -fetoprotein is often el-
is normal except for an elevated -fetoprotein. An isolated evated. Ultrasonographic findings are typically apparent by 15

(c) 2015 Wolters Kluwer. All Rights Reserved.


14Section I MaternalFetal Medicine

weeks gestation. This abnormality needs to be distinguished of the herniated mass. The liver is often within the covered sac
from a ruptured encephalocele or amniotic bands involving the (designated as L in Figure 5). An infant with an omphalocele
scalp. Although holoprosencephaly, hydrocephalus, and me- has a much higher risk of additional anomalies (45%80%)
ningomyelocele can all be diagnosed by fetal ultrasonography, compared with an infant who has a gastroschisis.
these findings are not apparent on this radiographic image.
4. C. Posterior urethral valves
2. D. Large Ventricular septal defect The image shown in this vignette is most consistent with
The fetal ultrasound imaging shows two ventricular chambers posterior urethral valves. This diagnosis is suggested by fe-
that are not separated by a septum (white dots). Thus, the fe- tal ultrasonography if there is bilateral hydronephrosis, a hy-
tus in this vignette also has a large ventricular septal defect. droureter, a thick-walled large bladder, and dilation of the
Transabdominal echocardiography can be helpful to further proximal urethra. The diagnosis can be confirmed postnatally
delineate cardiac defects. The optimal timing of perform- by a voiding cystourethrogram that demonstrates the valve
ing transabdominal echocardiography is between 18 and leaflets.
32weeks gestation; however, this procedure can be performed
as early as 14 weeks gestation. A transvaginal approach can be 5. A. Healthy term infant
performed as early as 10 weeks gestation, but the quality of the Choroid plexus cysts are thought to be caused by fluid- and
images are dependent on the position and activity of the fetus. debris-filled neuroepithelial folds. This finding is usually iso-
Most cardiac defects are apparent by routine fetal ultraso- lated and seen in 0.5% of normal fetuses. If the fetus has
nography between 18 and 22 weeks gestation. If a defect is other anomalies, the finding of these cysts raises the possibil-
observed, it can be further delineated by fetal echocardiogra- ity that the fetus has trisomy 18.
phy. The following cardiac defects may not always be identified
by fetal echocardiography:
AMERICAN BOARD OF PEDIATRICS
Small ventricular or atrial septal defect, CONTENT SPECIFICATIONS
Coarctation of the aorta, and
Minor valve abnormalities. Recognize that prenatal ultrasonography can detect ma-
jor fetal anomalies (e.g., hydrocephalus or anencephaly,
3. A. Dehydration myelomeningocele, congenital heart defects, gastro-
This fetal ultrasound demonstrates loops of bowel without a intestinal or genitourinary abnormalities) as early as
covering sac outside the abdominal cavity; this abnormality 16weeks gestation
is consistent with a gastroschisis. In this lesion, the abdomi-
nal wall defect is located to the right of an intact umbilical
cord. The diagnosis is typically made in the second trimester.
SUGGESTED READINGS
An infant with gastroschisis has a 10% to 20% risk of addi-
tional anomalies. Because bowel is exposed, infants with gas- Bianchi D, Crombleholme T, DAlton M, et al. Fetology: Diagnosis and
troschisis are at increased risk for dehydration and infection Management of the Fetal Patient. 2nd ed. New York, NY: McGraw-
after birth. If an intestinal atresia is present (16% of affected Hill; 2010.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
infants), infants may have bilious emesis. 2010.
In contrast to gastroschisis, an omphalocele is an abdomi-
nal wall defect that has a covering membrane (large white a rrow
in Figure 5) with an umbilical vein (uv in image) that is part CASE 3 ANSWERS

1. A 5 4, amniocentesis; B 5 3, periumbilical blood sam-


pling; C 5 2, transabdominal chorionic villus sampling;
D 5 1, transvaginal chorionic villus sampling
There are several prenatal methods for fetal DNA analysis. An
amniocentesis is performed by placing a needle into the am-
niotic cavity with guidance from real-time ultrasonography.
Possible indications for performing an amniocentesis include:

Increased risk for fetal chromosomal abnormalities


Increased risk for genetic or biochemical abnormalities
Increased risk for open neural tube defects
Assessment of fetal lung maturity

FIGURE 5. From Eisenberg RL. An Atlas of Differential Diagnosis. 4th ed. In periumbilical blood sampling, also known as cordocente-
Philadelphia, PA: Lippincott Williams & Wilkins; 2003. Figure 1.21 sis, a needle is placed through the pregnant womans abdomen

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 4 Fetal assessment15

into the umbilical cord using real-time ultrasonography. The 3. B. Elevated lecithin/sphingomyelin ratio
most common indications for performing this procedure During the end of the third trimester, the fetal lung begins
include: to mature. An amniocentesis can measure specific surfac-
tant components to assess for fetal lung maturity. Phospha-
Need for rapid chromosomal analysis
tidylglycerol typically increases after 34 weeks gestation and
Assessment for fetal anemia in red cell isoimmunization
correlates with lung maturation. Similarly, lecithin content
Evaluation for fetal infection
increases with advancing gestational age and increasing lung
Evaluation of nonimmune hydrops
maturity. Because sphingomyelin is a lipid within amniotic
Assessment for fetal thrombocytopenia in alloimmune
fluid that is not related to fetal lung maturation, it can be used
thrombocytopenia
to standardize amniotic fluid volume changes. Thus, the ratio
Chorionic villus sampling allows for reliable testing for of lecithin to sphingomyelin correlates with lung maturation
DNA analysis, karyotype, and biochemical abnormalities and normalizes amniotic fluid volume. Phosphatidylinositol
early in pregnancy. In the transvaginal (also known as trans is present in fetal lung fluid in the beginning of the third tri-
cervical) approach, a catheter is placed through the cervix mester, and its levels decrease as the lung matures. Thus, the
into the placental tissue using real-time ultrasonography. following are consistent with mature fetal lungs:
A syringe containing nutrient medium is then attached to Presence of phosphatidylglycerol (10%)
the catheter and pulled back until villi are visible in the sy- Elevated lecithin/sphingomyelin ratio (ideal if >2)
ringe. In the transabdominal approach, a needle is placed Low amounts of phosphatidylinositol (2%)
across the pregnant womans abdomen into the placenta
using real-time ultrasonography and villi are aspirated into This diagnostic approach to fetal lung maturity assessment is
the syringe. Chorionic villus sampling is usually performed no longer commonly performed. This is partly because obstetri-
by a transvaginal approach; however, a transabdominal ap- cians are performing elective preterm deliveries only for signifi-
proach can be used if karyotype analysis is needed late in cant maternal or fetal indications and the fetal lung maturity
pregnancy. results would not impact their decision to deliver an infant.

2. B. Fetal ultrasonography
DNA testing can be performed using amniotic fluid ob- AMERICAN BOARD OF PEDIATRICS
tained by an amniocentesis, fetal blood obtained by peri- CONTENT SPECIFICATIONS
umbilical blood sampling, and placental cells obtained
Chorionic villus sampling
from chorionic villus sampling. If a specific DNA abnor-
Know that sickle cell disease can be diagnosed prenatally
mality is of concern, chorionic villus sampling is the pre-
(e.g., chorionic villus sampling, amniocentesis, fetal
ferred method because this procedure obtains the largest
erythrocytes)
amount of tissue for testing. At present, some of the most
common diseases that can be prenatally diagnosed using Amniocentesis
DNA analysis include: Know the appropriate tests for predicting the absence of
neonatal respiratory distress syndrome
1-Antitrypsin deficiency
Congenital adrenal hyperplasia
Cystic fibrosis SUGGESTED READINGS
DiGeorge syndrome
Bianchi D, Crombleholme T, DAlton M, et al. Fetology: Diagnosis and
Fragile X syndrome Management of the Fetal Patient. 2nd ed. New York, NY: McGraw-
Muscular and myotonic dystrophy Hill; 2010.
Ornithine transcarbamylase deficiency Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
Phenylketonuria Martin RJ, Fanaroff AA, Walsh MC. Fanaroff and Martins Neonatal
Retinoblastoma Perinatal Medicine: Diseases of the Fetus and Infant. 9th ed. Philadel-
Sickle cell disease phia, PA: Mosby; 2010.
Spinal muscular atrophy
Thalassemia
TaySachs disease CASE 4 ANSWERS
WiskottAldrich syndrome
1. C. Normal fetal heart rate response to fetal movement
Cell-free DNA obtained from the maternal circulation is an The nonstress test assesses the fetal heart rate in response to
exciting new method of fetal genetic testing. Currently, ma- fetal movements. The upper strip of the nonstress test, shown
ternal blood can be analyzed to determine fetal gender, fetal in the question, represents the fetal heart rate pattern and the
Rh (D) genotype, some aneuploidies, and some single gene lower strip corresponds with uterine activity. Arrows on the
disorders. bottom of the upper strip indicate fetal movement.

(c) 2015 Wolters Kluwer. All Rights Reserved.


16Section I MaternalFetal Medicine

If a fetus has two accelerations in heart rate that are asso- Fetal breathing
ciated with fetal movements within a 20-minute period, the Fetal muscle tone
nonstress test is reactive. A nonreactive nonstress test result Amniotic fluid volume
occurs if there are fewer than two accelerations in heart rate
Each of these parameters receives a score of 2 if normal or
during a period of 20 minutes. In this scenario, the test is then
0 if abnormal. The highest score is 10, suggesting a well fetus
repeated 20 minutes later. While a reactive nonstress result
who does not require any intervention. If the biophysical score
is predictive of intrauterine survival for 7 days, a nonreactive
is 0 or 2, the obstetrician is likely to deliver the fetus because of
nonstress test may suggest a compromised fetus. Because a
the possibility of fetal asphyxia.
nonreactive result is not specific for poor fetal well-being, fur-
Blood flow within the umbilical arteries moves from the
ther testing (e.g., biophysical profile) is required.
fetal to placental circulation. Doppler studies can assess the
This fetal strip demonstrates a reactive nonstress test be-
blood flow in the umbilical arteries during diastole to evaluate
cause the fetus has four accelerations following four fetal
placental insufficiency. If the placenta is not functioning well,
movements. The strip also shows that the fetus has good heart
the placental vascular resistance will increase. If this happens,
rate variability throughout the monitored period. While a
the flow through the umbilical arteries will be decreased or,
nonstress test also demonstrates uterine activity, regular and
if the placental vascular resistance is extremely high, the flow
frequent contractions are not seen on this fetal strip. A non-
in the umbilical arteries will be reversed. Possible umbilical
stress test does not measure the fetal breathing pattern or am-
artery Doppler study results are:
niotic fluid volume.
An example of a nonreactive nonstress test is shown in Normal umbilical artery blood velocity
Figure2B. While the upper panel (A) shows that the fetal heart Increased resistance but blood flow is still present during
rate increases in response to two fetal movements, the lower diastole
panel (B) shows that the fetal heart rate does not change after Absence of umbilical arterial blood flow during dias-
a fetal movement. tole (leads to decreased blood flow from the fetus to the
placenta)
Reversal of umbilical arterial blood flow during diastole
Doppler flow studies of the umbilical arteries are not part of
the biophysical profile fetal assessment.

Reactive NST
AMERICAN BOARD OF PEDIATRICS
CONTENT SPECIFICATIONS
Nonstress test: Know that the nonstress test monitors fe-
tal heart rate reactivity in response to fetal activity
Stress test: Recognize that the stress test is used to evalu-
Nonreactive NST ate uteroplacental insufficiency
FIGURE 2. From Beckmann CRB, Ling FW, et al. Obstetrics and Biophysical profile: Know the factors used by obstetri-
Gynecology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; cians in evaluating fetal well-being
2006. Figure 5.02

2. C. Evaluate for uteroplacental insufficiency SUGGESTED READINGS


A contraction stress test assesses the fetal heart rate in response
to contractions. If the fetus has a late deceleration (decrease Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
in fetal heart rate 1030 seconds after the beginning of a con- 2010.
Cunningham FG, Leveno KJ, Bloom SL, et al., eds. Williams Obstetrics.
traction) associated with half of the contractions, prompt in- 23rd ed. New York, NY: McGraw-Hill; 2009.
tervention is required. A positive (i.e., abnormal) test result
suggests uteroplacental insufficiency that may be associated
with an increased risk for intrauterine fetal demise, intolerance CASE 5 ANSWERS
of labor, and perinatal depression.
1. D. Diabetes mellitus without evidence of vascu-
3. B. Blood flow in the umbilical arteries
lar disease and good maternal glucose control before
The biophysical profile assesses fetal well-being by combining
conception
the results of a fetal ultrasound and a nonstress test. It mea-
Congenital anomalies are more frequent among infants of dia-
sures five discrete variables:
betic mothers than among healthy control infants. This risk of
Nonstress test anomalies is greatest in women who have severe diabetes mel-
Fetal body movement litus. For example, a woman with insulin-dependent diabetes

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 5 Effects of maternal diabetes mellitus 17

who does not have any vascular disease has an 9% risk of viscosity, which results in poor blood flow and decreased
having an infant with congenital anomalies. In contrast, if the tissue oxygenation. Similar to the infant in this case, babies
woman has nephropathy or retinopathy, this risk increases to with polycythemia often appear ruddy and have an oxygen
22%. Recent studies have found that the risk of congenital requirement.
anomalies correlates with the degree of uncontrolled diabe- The infant in this vignette is unlikely to have cyanotic heart
tes prior to conception. If a woman achieves glycemic control disease because his oxygen saturation increased to normal
prior to conception, the risk of congenital anomalies is 2.5% with supplemental oxygen. While the infant is likely to have a
compared with 7.8% in women who attain glycemic con- patent ductus arteriosus at 3 hours of age, it is unlikely to be
trol after becoming pregnant. Glycemic control in pregnant causing the cyanosis. If the cause of this infants cyanosis is
women can be assessed by measuring the hemoglobin A1C from significant right-to-left shunting across a patent ductus
values, with lower hemoglobin A1C values correlating with arteriosus, one would expect the infant to have radiographic
better glucose control. evidence of decreased pulmonary blood flow and the cyanosis
should be more significant. If the infant had significant left-
2. C. Small left colon syndrome
to-right shunting across a patent ductus arteriosus, one would
The fetal structural anomalies associated with women with
expect the infant to have radiographic evidence of increased
diabetes mellitus typically occur prior to 2 months gestation,
pulmonary blood flow. An infant with retained fetal lung fluid
at the time of organogenesis. Most of these anomalies involve
leading to transient tachypnea of the newborn may have a
the cardiac and neurological systems and include:
small oxygen requirement but also should have an increased
Cardiac: transposition of the great arteries, ventricular respiratory rate and radiographic evidence of increased fetal
septal defect, atrial septal defect, hypoplastic left heart lung fluid. Infants of diabetic women are at increased risk for
syndrome, aortic stenosis, coarctation of the aorta surfactant deficiency even if they are born at term gestational
Neurologic: meningomyelocele, encephalocele, anencephaly age; however, this is unlikely in this case because the infant
does not have any respiratory distress.
Infants are also at risk for caudal regression syndrome, which
consists of spinal abnormalities and syringomyelia. Renal 5. A. Hypocalcemia
anomalies (hydronephrosis, renal agenesis, cystic kidneys) Infants born to women with diabetes mellitus are at increased
and intestinal atresias can also occur. risk for hypocalcemia. This most likely results from a delay
Small left colon syndrome usually occurs during the second in the appropriate parathyroid hormone response after birth.
half of gestation, after organogenesis is complete. In this syn- Infants born to women with diabetes are also at risk for hypo-
drome, the diameter of the descending colon, sigmoid colon, magnesemia as a result of the decreased postnatal parathyroid
and rectum are smaller than normal. The cause is thought to hormone response and maternal hypomagnesemia from renal
be related to large changes in maternal and fetal serum glucose losses leading to decreased placental transfer of magnesium
concentrations. Affected infants often present with signs of during gestation. Hypocalcemia and hypomagnesemia usually
intestinal obstruction, such as bilious emesis and abdominal occur within the first few days of life, especially if the infant
distention. has respiratory distress.

3. B. Increased insulin production by the infant


If pregnant women with insulin-dependent diabetes mellitus AMERICAN BOARD OF PEDIATRICS
have increased serum glucose concentrations, then glucose CONTENT SPECIFICATIONS
will cross the placenta into the fetal circulation. The fetus re-
sponds appropriately to this increased glucose by increasing Recognize that congenital anomalies are more frequent
pancreatic insulin production. After birth, the infant continues among infants of diabetic mothers than among normal
to produce insulin even though the glucose supply from the control infants
mother has now stopped. As a result, hypoglycemia can oc- Understand the pathogenesis of hypoglycemia in an
cur soon after birth. Over time, the infants pancreatic produc- infant of a diabetic mother
tion of insulin decreases and the infant can be weaned from Recognize that an infant of a diabetic mother is at risk for
supplemental glucose. Thus, the cause of the hypoglycemia in hypoglycemia, hypocalcemia, polycythemia, and small
the infant in this case is most likely from increased insulin left colon syndrome
production by the infant.

4. B. Polycythemia
Infants born to women with insulin-dependent diabetes
SUGGESTED READINGS
are at increased risk of having polycythemia. This associa- Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
tion is likely a result from increased oxygen consumption in 2010.
utero, prompting the fetal bone marrow to produce more red Nold JL, Georgieff MK. Infants of diabetic mothers. Pediatr Clin N Am.
2004;619637.
blood cells to increase oxygen-carrying capacity. After birth, White BA and Porterfield SP. Endocrine and Reproductive Physiology. 4th
cyanosis may then occur because of an increase in blood ed. St Louis, MO: Mosby; 2012.

(c) 2015 Wolters Kluwer. All Rights Reserved.


18Section I MaternalFetal Medicine

Hematologic (35%)
CASE 6 ANSWERS
Hepatobiliary (9%25%)
1. A. Complete heart block Hematologic complications include anemia, thrombocyto-
This infants electrocardiogram shows complete heart block penia, and neutropenia. These manifestations typically occur
because there is no association between the depolarization of during the second week of life and resolve by 3 months of
the atria and the ventricles. In first-degree heart block, the PR age. If hematologic manifestations are severe and persistent,
interval is consistently prolonged but is followed by a QRS treatment with intravenous immunoglobulin and/or cortico-
complex. Infants with sinus bradycardia will have a slow heart steroids may be indicated. Hepatobiliary findings typically
rate with a normal sinus rhythm evident by a QRS complex include transiently elevated transaminases and conjugated
appropriately following every P wave. In a Wenckebach pattern hyperbilirubinemia, first occurring at a few weeks of age. In
of second-degree atrioventricular heart block (also known as addition to these complications, recent data suggest that af-
Mobitz type I), electrocardiographic findings will demonstrate fected infants are also at risk for central nervous system injury.
increasing PR intervals followed by QRS complexes until the Thus, affected neonates require close neurological follow-up.
PR interval becomes so prolonged that an atrial impulse is not Based on these clinical manifestations, if an infant is
conducted and the QRS complex is absent. diagnosed with neonatal lupus, the following tests are
2. C. Anti-Ro/SSA and anti-La/SSB antibodies recommended:
The infant described in this vignette has complete heart block Electrocardiogram
and annular erythematous plaques on the face and trunk. These Complete blood count
two findings are found in infants with neonatal lupus erythe- Transaminases
matosus. Neonatal lupus is a rare autoimmune disease that is Direct bilirubin
usually benign and self-limited. It is caused by maternal anti-
Ro/SSA and/or anti-La/SSB antibodies that cross the placenta. In addition, head imaging should be considered, particularly
A rash is the most common clinical manifestation of if an infant has neurological symptoms. If an affected infant
neonates with lupus. This rash usually appears during the has hematuria or proteinuria, an evaluation for nephritis
first weeks of life and is characterized by round or elliptical should be considered.
erythematous lesions with a central clearing (i.e., annular er-
ythema). These findings are typically found on the face and
scalp but can also be observed on an infants neck, trunk, and AMERICAN BOARD OF PEDIATRICS
extremities. The classic malar rash found in adults with lupus CONTENT SPECIFICATIONS
is uncommon in infants with lupus. The rash typically resolves
Identify the clinical picture of neonatal lupus, including
spontaneously by 8 months of age when the maternal autoan-
heart block
tibodies have been completely cleared from the infants body.
Know which tests are useful in evaluating neonatal lupus
Sometimes, residual skin abnormalities such as dyspigmenta-
tion, telangiectasias, or skin atrophy may occur.
Infants with neonatal lupus can have first-, second-, or
third-degree (i.e., complete) heart block caused by antibody- SUGGESTED READINGS
mediated injury to the fetal and neonatal cardiac conduction
tissues. Neonatal lupus is responsible for 85% of cases of Frankovich J, Sandborg C, Barnes P, et al. Neonatal lupus and related
autoimmune disorders of infants. NeoReviews. 2008;9:e206e217.
complete heart block. However, the incidence of complete White BA and Porterfield SP. Endocrine and Reproductive Physiology. 4th
heart block in infants born to mothers with anti-Ro/SSA or ed. St Louis, MO: Mosby; 2012.
anti-La/SSB antibodies is low, only 1% to 2%. If a woman with
lupus has a child with neonatal lupus and heart block, the risk
of heart block increases dramatically to 16% to 18% in sub- CASE 7 ANSWERS
sequent pregnancies. Complete heart block can be associated
with significant morbidity and mortality. 1. A. All anticonvulsants marketed prior to 1976 have
been shown to have teratogenic effects
3. C. 50% All antiseizure medications marketed prior to 1976, includ-
Approximately half of the infants affected with lupus are ing carbamazepine, hydantoin, phenobarbital, and valproate,
born to undiagnosed, healthy mothers. These asymptomatic have been shown to have teratogenic effects when exposure
women are often diagnosed after delivery, when their infant occurs during the first trimester. These effects have varying clin-
presents with symptoms of neonatal lupus. ical manifestations and degrees of severity. The most common
4. D. Thrombocytopenia manifestations observed in infants are:
Infants with neonatal lupus are at risk of the following clinical
Digit hypoplasia,
manifestations:
Growth restriction,
Cutaneous (70%) Midface hypoplasia, and
Cardiac (65%) Microcephaly.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 7 Maternal medications19

Intrauterine exposure to carbamazepine and valproate also in- A dysplasia is an abnormal organization of cells within tissues
creases the risk for meningomyelocele. Fortunately, the associ- caused by a deregulation. A hemangioma and ectodermal dys-
ated major malformations are relatively uncommon. Indeed, plasia are examples of dysplasias.
most of the major malformations found in infants exposed to
3. C. Nasal hypoplasia and stippled bone epiphyses
intrauterine anticonvulsants are also common in unexposed
First-trimester exposure to warfarin can lead to a syndrome
children. Older children exposed to anticonvulsants in utero
of nasal hypoplasia and stippled epiphyses. Approximately
are at increased risk for cognitive disabilities.
one-third of exposed fetuses have these findings. Affected
The infant described in this vignette has some clinical fea-
infants often present with upper airway obstruction that
tures that are consistent with intrauterine hydantoin exposure.
is improved with an oral airway. Because heparin does not
The fetal hydantoin syndrome consists of:
cross the placenta, heparin has not been associated with
Digit and nail hypoplasia teratogenic effects and is often used as a substitute for
Craniofacial features, such as wide anterior fontanel; me- warfarin.
topic ridging; ocular hypertelorism; broad, depressed na- Previous data has identified an association between intra-
sal bridge; short nose; cleft lip and palate uterine exposure to lithium and Ebstein anomaly. However,
Growth deficiency, usually of prenatal onset recent studies question this association.
Mental deficiency, usually mild First-trimester exposure to retinoic acid can lead to abnor-
mal findings, such as central nervous system abnormalities,
2.
A. Deformation 2. Arthrogryposis caused by microtia, and cardiac defects. The possible central nervous
intrauterine constraints system findings include hydrocephalus, microcephaly, abnor-
B. Disruption 1. Amniotic bands malities in neuronal migration, and posterior fossa structural
abnormalities.
C. Dysplasia 4. Hemangioma
Maternal tetracycline intake during pregnancy has been as-
D. Malformation 3. Cleft palate sociated with a yellow-brown discoloration of deciduous teeth
and impaired bone growth in the exposed child.
There are four types of problems in morphogenesis: mal-
4. A. Indomethacin
formation, deformation, disruption, and dysplasia. A mal-
Prolonged use of indomethacin, a prostaglandin synthase in-
formation is caused by an abnormality in tissue formation
hibitor, is associated with risks, including oligohydramnios,
associated with an environmental exposure, a genetic abnor-
premature closure of the ductus arteriosus, renal insufficiency,
mality, or an unknown cause. These problems typically impact
pulmonary hypertension, ileal perforation, and necrotizing
the fetus during the first trimester and can lead to minor or
enterocolitis.
major malformations. Some examples of malformations are:
Magnesium sulfate decreases uterine contractility by inhib-
Anencephaly iting acetylcholine release from the neuromuscular junction
Bladder exstrophy and functioning as a calcium antagonist. Postnatal effects of
Branchial sinus or cyst intrauterine exposure to magnesium sulfate include decreased
Cleft lip or palate peristalsis, hypotension, hypotonia, and apnea.
Diaphragmatic hernia Nifedipine is a calcium-channel blocking agent that de-
Hypospadius creases uterine contractility. Prolonged use of nifedipine dur-
Intestinal atresias ing pregnancy can lead to uteroplacental insufficiency.
Meningomyelocele Terbutaline is a 2-agonist that leads to decreased intracel-
Omphalocele lular calcium, inhibiting uterine contractility. Use of terbuta-
Transposition of the great arteries line during pregnancy can lead to fetal tachycardia.
The recurrence risk typically ranges between 1% and 5%. A
syndrome occurs when a fetus has many primary malforma-
tions caused by one etiology. AMERICAN BOARD OF PEDIATRICS
A deformation occurs when there are mechanical forces CONTENT SPECIFICATIONS
that alter normal tissue formation. Some examples of defor-
mations are arthrogryposis caused by intrauterine constraints Recognize that the use of some anticonvulsants during
and breech deformation sequence. Most deformations have a pregnancy is associated with an increased risk of fetal
good prognosis and the risk for recurrence is very low, unless anomalies
there is a persistent issue, such as a bicornate uterus. Know the effect on a fetus of lithium use during pregnancy
A disruption occurs when there is a breakdown of normal Know that isotretinoin is a potent teratogen
tissue. Some examples of disruptions are: Know the effect on a fetus of warfarin use during pregnancy
Understand the effects of drugs given to the mother dur-
Amniotic bands ing labor (e.g., opiates, -adrenergic tocolytic agents) on
Limb reduction defects as a result of vascular anomalies the fetus/neonate
Porencephaly

(c) 2015 Wolters Kluwer. All Rights Reserved.


20Section I MaternalFetal Medicine

SUGGESTED READINGS Buprenorphine


Methadone
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; Morphine sulfate
2010. Phenobarbital
Cunningham FG, Leveno KJ, Bloom SL, et al., eds. Williams Obstetrics.
23rd ed. New York, NY: McGraw-Hill; 2009. Once an infant has low scores, the medication is slowly de-
Jones KL. Smiths Recognizable Patterns of Human Malformations. 6th ed.
Philadelphia, PA: WB Saunders; 2005. creased. The length of treatment can vary from weeks to months.
Holmes LB. The teratogenicity of anticonvulsant drugs: a progress re-
port. J Med Genet. 2002;39:245247. 4. D. Thin upper lip
First-trimester alcohol exposure can lead to teratogenic effects
in the fetus. Infants with fetal alcohol syndrome have distinc-
CASE 8 ANSWERS tive facial features. The three most common facial findings in
this syndrome are:
1. A. Cocaine
A smooth philtrum
Cocaine use during pregnancy is associated with spontaneous
Thin upper lip
abortions, preterm delivery, stillbirth, and placental abruption.
Short palpebral fissures
Exposed infants are at increased risk for skull abnormalities,
cutis aplasia, porencephaly, ileal atresia, cardiac abnormalities, Additional facial findings include a flat midface, microgna-
intestinal ischemia, and urinary tract abnormalities. Intrauter- thia, minor ear anomalies, low nasal bridge, and epicanthal
ine exposure also increases the risk for long-term neurodevelop- folds (Figure 1). Fetal alcohol syndrome is also associated with
ment impairments, although it is uncertain if these effects are other abnormalities, including intrauterine growth restriction,
related to pregnancy exposure or postnatal environment. cardiac defects, and neurological effects.
Heroin use during pregnancy is not associated with terato-
genic effects but has been linked to intrauterine growth restric-
Facies in fetal alcohol syndrome
tion, preterm delivery, and stillbirth.
Use of morphine and methadone during pregnancy has Discriminating Associated
minimal teratogenic effects. Features features

2. C. Methamphetamine Epicanthal folds


Signs of neonatal withdrawal are nonspecific, as evident in the Short palpebral
Low nasal bridge
infant described in this vignette. If a pregnant woman takes the fissures
Flat midface
stimulant methamphetamine, withdrawal signs are observed
Short nose Minor ear
in only a small number of exposed infants (4%). These signs anomalies
are usually less severe than with methadone or heroin expo- Indistinct philtrum
sure and often demonstrate the impact of the amphetamine Thin upper lip Micrognathia
rather than withdrawal from its effects.
Narcotics, such as buprenorphine, codeine, heroin, metha- A In the young child
done, morphine, and oxycodone, are the most common causes FIGURE 1. Characteristic features of a child with fetal alcohol syndrome.
Modified from Sadler T. Langmans Medical Embryology. 9th ed. Image
of neonatal withdrawal syndrome.
Bank. Baltimore, MD: Lippincott Williams & Wilkins; 2003
Infants exposed to intrauterine alcohol can also have etha-
nol withdrawal, although the symptoms are less severe than in
infants withdrawing from opiates. 5. C. Macrocephaly
Fetal alcohol syndrome is the most common cause of mental re-
3. D. All of the above
tardation in developed countries. In the United States, this syn-
Nonpharmacologic approaches to infants with neonatal absti-
drome is estimated to occur in 1 to 3 per 1,000 live births, with a
nence syndrome include:
higher occurrence in certain populations, such as Native Ameri-
Demand feeding cans. Infants with prenatal exposure to alcohol are at risk for
Gentle handling neurobehavioral issues, such as attention deficit/hyperactivity
Minimize noise disorder, poor impulse control, problems with memory or
Swaddling attention, problems in social perception, and autism.
Affected infants may also have structural central nervous
Pharmacologic treatment is determined by the specific clini-
system abnormalities such as:
cal symptoms in the infant and the type of exposed drug.
Hospitals use an abstinence scoring system that helps deter- Decreased size of cerebrum, cerebellum, basal ganglia
mine the severity of symptoms. If the score reaches a certain DandyWalker malformation
level, the infant is started on medications to minimize exces- Heterotopia
sive excitation and decrease the risk for seizures. Medications Holoprosencephaly
include: Microcephaly (small head size)

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 9 Delivery room assessment21

Microencephaly (small brain size) SUGGESTED READINGS


Partial or complete agenesis of the corpus callosum
Ventricular enlargement Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
The adverse effects on brain development caused by intrauter- Burgos AE, Burke Bl. Neonatal abstinence syndrome. NeoReviews.
ine alcohol exposure are believed to be most impacted by peak 2009;10:e222e229.
Gleason CA. Fetal alcohol exposure: effects on the developing brain.
blood-alcohol concentration. Structural central nervous system NeoReviews. 2001;2:e231e236.
abnormalities and craniofacial abnormalities are strongly associ-
ated with heavy alcohol consumption during the first trimester.
In contrast, the development of microcephaly is thought to cor-
respond to the amount of alcohol exposure during late gestation. CASE 9 ANSWERS

6. D. Sudden infant death syndrome 1. C. Perfusion


Intrauterine tobacco exposure has been associated with the In 1953, Virginia Apgar published a method to evaluate the
following: physical condition of a newborn soon after birth. This assess-
ment evaluates five clinical signs:
Placental abruption
Placenta previa Appearance (i.e., color)
Premature rupture of membranes Pulse (i.e., heart rate)
Premature delivery Grimace (i.e., reflex irritability)
Low-birth-weight infant Activity (i.e., muscle tone)
Neurobehavioral issues Respirations (i.e., respiratory effort)

Prenatal exposure to smoke places infants at increased risk for To recall the specific components of the Apgar score, it may
sudden infant death syndrome. be helpful to remember that the first letter of each sign spells
The effects of marijuana use during pregnancy are not clear. the word Apgar. The perfusion of an infant is not part of the
Some studies have demonstrated long-term cognitive deficits Apgar score.
and neurobehavioral concerns, but this has not been consis-
2. B. 1
tently found.
After birth, the medical team reports an infants Apgar score
by assessing the infants color, heart rate, reflex irritability,
tone, and respiratory effort. This assessment occurs at 1 and
AMERICAN BOARD OF PEDIATRICS
5 minutes of age; if the Apgar score is less than 7 at 5 min-
CONTENT SPECIFICATIONS
utes of age, the scoring is continued every 5 minutes until the
Neonatal abstinence syndrome score is 7 or greater for up to 20 minutes. The team provides a
Know the association between the maternal use of co- score of 0, 1, or 2 for each of the five clinical signs, as shown
caine and neonatal withdrawal syndrome in Figure 1.
Know the association between the maternal use of barbi-
turates and neonatal withdrawal syndrome
Know the association between the maternal use of opi-
Apgar Scoring Chart
ates and neonatal withdrawal syndrome
Know the association between the maternal use of am- Score
phetamines and neonatal withdrawal syndrome Sign 0 1 2
Know the management of neonatal abstinence syndrome Heart rate Absent Slow (<100) >100
Respiratory Absent Slow, irregular; Good; strong
Fetal alcohol exposure effort weak cry cry
Recognize the physical features of fetal alcohol Muscle tone Flaccid Some flexion Well flexed
syndrome of extremities
Reflex
Know that fetal alcohol syndrome is a frequently docu- irritability
mented cause of mental retardation Response No Grimace Cough or
to catheter response sneeze
Know the association between the maternal use of alco- in nostril
hol and neonatal withdrawal syndrome or
slap of sole No Grimace Cry and with-
Maternal marijuana and smoking of foot response drawal of foot
Know the association between the maternal use of mari-
juana and any fetal abnormalities Color Blue, pale Body pink, Completely
extremities blue pink
Know the association between the maternal use of
tobacco and any fetal abnormalities FIGURE 1. Courtesy of Artesia Assets 2014 Lippincott W
illiams &
Wilkins. All rights reserved

(c) 2015 Wolters Kluwer. All Rights Reserved.


22Section I MaternalFetal Medicine

The infant in this vignette has a heart rate, but it is less than 0 1 2 3 4 5

100 beats per minute. This corresponds to a score of 1. Because Skin Gelatinous
red, trans-
Smooth,
pink,
Superficial,
peeling
Cracking,
pale area,
Parchment, Leathery,
deep cracked,
the infant is cyanotic without any respiratory effort, tone, or parent visible
veins
&/or rash,
few veins
rare veins cracking,
no vessels
wrinkled

reflex irritability, the other signs have a score of 0 and the in- Lanugo None Abundant Thinning Bald Mostly
fants total score is 1. areas bald

3. C. The infants Apgar score is a poor indicator of neu-


Plantar No Faint Anterior Creases Creases
rological outcome Creases crease red marks transverse ant. cover
crease 2/3 entire
The Apgar score was created to describe an infants clinical only sole

condition after birth and was not intended to predict neuro- Breast Barely Flat Stippled Raised Full
percept. areola, areola, areola, areola,
logical outcome. While a low Apgar score at 1 minute of age no bud 12 mm 34 mm 510 mm
bud bud bud
shows that an infant needs medical assistance, it does not in-
Ear Pinna Sl. curved Well-curv. Formed & Thick
dicate long-term problems, especially if the 5-minute score is flat, pinna, soft pinna, firm with cartilage,
stays with slow soft but instant ear stiff
high. Thus, the neonatologist is most likely to tell the infants folded recoil ready recoil recoil
father that the Apgar score is a poor indicator of neurological Genitals Scrotum Testes Testes Testes
outcome. Male
empty,
no rugae
descend-
ing, few
down,
good
pendulous,
deep
An amplitude electroencephalogram is used to assess an in- rugae rugae rugae

Genitals Prominent Majora Majora Clitoris


fants cerebral activity to determine whether a newborn meets clitoris & & minora large, & minora
Female
criteria for therapeutic hypothermia. Eligible neonates have labia
minora
equally
prominent
minora
small
completely
covered
evidence of fetal distress, neonatal distress, physical examina-
tion findings consistent with neonatal encephalopathy, and an A
abnormal cerebral function monitor recording.
0 1 2 3 4 5
The majority of full-term infants who develop cerebral Posture
palsy have a normal Apgar score. However, if an infants Apgar
score is extremely low (<3) at 10 or 20 minutes of age, there is Score Wks
Square
a small but increased risk of cerebral palsy. Window
5 26
(Wrist)
Infants with hypoxic-ischemic encephalopathy are at in- 90 60 45 30 0
10 28
creased risk for seizure activity after birth. Infants with an Arm
Recoil 15 30
abnormal neurological examination (lethargy, mild hypo- 180 100-180 90-100 <90 20 32
tonia, overactive reflexes, myoclonus, weak suck, and weak Popliteal
Angle 25 34
Moro reflexes) and low-voltage activity by an electroen-
180 160 130 110 90 <90
cephalogram are at particular risk for seizures. The infant 30 36

Scarf
in this vignette is not at increased risk for seizure activity Sign 35 38

because the baby is well-appearing and without any signs of 40 40

encephalopathy. Heel
to
45 42
Ear
50 44
4. D. Minimal flexion of arms and legs at rest
Infants born preterm, full-term, and postterm have specific B C
physical findings. A preterm infants examination may have FIGURE 2. From Ballard JL. New Ballard score expanded to include
the following characteristics: extremely premature infants. J Pediatr. 1991;119: 417423

Decreased or absent plantar creases


Lack of recoil of ear pinna AMERICAN BOARD OF PEDIATRICS
Lanugo CONTENT SPECIFICATIONS
Minimal flexion of arms and legs at rest
Prominent labia minora in females Know the components of the Apgar score
Small or absent areola and breastbud Understand the significance of the one- and five-minute
Undescended testes and decreased/absent scrotal rugae in Apgar scores
males Know the physical characteristics of preterm, full-term,
and postterm infants
Postterm infants may have leathery, cracked, and wrinkled
skin.
To calculate an infants gestational age, a clinician can use SUGGESTED READINGS
the Ballard assessment scale (shown in the next column). A
clinician provides a specific score to each physical and neuro- American Academy of Pediatrics and American Heart Association.
Textbook of Neonatal Resuscitation. 6th ed. American Academy of
muscular assessment and then tallies the total. This point total Pediatrics; 2011.
corresponds with a specific gestational age (in Figure 2C). Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 10 Delivery room resuscitation23

4. C. Intubation and suctioning the infants trachea if the


CASE 10 ANSWERS
infant was not vigorous immediately after birth
1. B. Establishment of a patent airway before applying This infants chest radiograph demonstrates bilateral, diffuse,
positive-pressure ventilation patchy densities with overexpanded lungs. Areas of overdisten-
If an infant is not breathing after birth, a neonatal team needs sion result from air trapping because of airway obstruction.
to provide warmth, ensure airway patency, and stimulate the These radiographic findings are most consistent with meco-
baby. If the baby, despite these measures, has a heart rate nium aspiration pneumonia. Current neonatal resuscitation
less than 100 beats per minute, has apnea, or is gasping, the guidelines recommend that newborns with a history of intra-
neonatal team needs to begin positive-pressure ventilation. uterine passage of meconium who emerge apneic, limp, and
Continued stimulation is not appropriate because it will not inactive should undergo endotracheal intubation to suction
induce breathing if the newborn has irreversible secondary ap- the trachea for meconium and try to decrease the risk for aspi-
nea. For the first few assisted breaths, a higher pressure may be ration. This recommendation is independent of the thickness
required to effectively inflate the neonates lungs. Once a neo- of the meconium.
nate is receiving respiratory support, the team needs to place a Classic radiographic findings of surfactant deficiency in-
pulse oximeter probe on the newborns right wrist to measure clude the following:
a preductal oxygen saturation. Air bronchograms
Diffuse reticulogranular pattern or ground-glass appearance
2. B. Compress to a depth one-third the anteriorposterior
Low lung volumes
diameter of the chest
The current neonatal resuscitation guidelines for chest com- Some options that might decrease the severity of surfactant
pressions include the following: deficiency include:

Apply compressions over the lower third of the newborns Administration of maternal steroids prior to delivery
sternum Initiation of continuous airway pressure soon after
Compress to a depth one-third the anteriorposterior di- birth
ameter of the chest Intratracheal administration of surfactant soon after
Provide chest compressions and bag-mask breaths in a birth
ratio of 3:1 Although oxygen supplementation does lead to pulmonary
Use the two-thumb-encircling-hands approach instead of inflammation, minimizing the use of supplemental oxy-
the two-finger technique when possible gen would not have decreased the severity of this infants
disease.
The two-thumb-encircling technique is preferred because of
the likelihood that it generates greater coronary perfusion.
However, if a neonate requires an umbilical line placement,
the two-finger technique may need to be used to allow access
to the umbilicus. AMERICAN BOARD OF PEDIATRICS
CONTENT SPECIFICATIONS
3. A. If the heart rate does not increase above 60 beats
per minute despite effective ventilation with oxygen for Ventilation
30seconds Recognize the need to establish a patent airway before
It is really important that assisted ventilation is being deliv- applying positive-pressure ventilation
ered effectively before starting chest compressions. If a new- Recognize that a newborn who has a slow heart rate and
borns heart rate does not increase above 60 beats per minute impaired ventilatory effort requires immediate positive-
despite effective ventilation with oxygen for 30 seconds, chest pressure ventilation
compressions should be initiated. Know that the initial lung inflation may require in-
If a newborn has a heart rate less than 30 beats per minute creased pressure for the first breath
immediately after birth, the team should provide bag-mask Perfusion
ventilation. Know the proper technique for external cardiac massage
If a newborn remains cyanotic despite appropriate bag- in a newborn
mask ventilation, a team member should intubate the baby. Recognize the indications for external cardiac massage of
Decreased perfusion is not an indication for chest compres- a newborn during resuscitation
sions in a newborn. If a newborns perfusion is extremely poor Suctioning
with pale skin color and weak pulses, volume expansion is in- Recognize a newborns larynx needs to be visualized and
dicated if the heart rate has not responded to other resuscita- the trachea suctioned if meconium is present in the am-
tive approaches. Poor perfusion is not a specific indicator to niotic fluid and the infant is not vigorous
start chest compressions.

(c) 2015 Wolters Kluwer. All Rights Reserved.


24Section I MaternalFetal Medicine

SUGGESTED READINGS These fetuses may have a growth curve similar to Curve 1 or
Curve 2.
American Academy of Pediatrics and American Heart Association. A woman with pregnancy-induced hypertension may have
Textbook of Neonatal Resuscitation. 6th ed. American Academy of associated placental insufficiency, which leads to a decrease in
Pediatrics; 2011.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; fetal growth. Although this decrease in fetal growth may occur
2010. in the second or third trimester, it most commonly occurs in
the third trimester, similar to the pattern of growth shown in
Curve 1 or Curve 2.
CASE 11 ANSWERS Multiple gestation will also lead to a decrease in fetal
growth over time, partly because growth is limited by the
1. D. Curves 1 and 2
size of the uterus. Examples of typical fetal growth curves
Although the terms intrauterine growth restriction or IUGR and
for a twin, triplet, and quadruplet gestation are shown in
small for gestational age or SGA are often used interchangeably,
Figure 2.
they are actually distinct. A fetus or infant has growth restric-
tion if the intrauterine rate of growth is less than the prede-
termined growth potential of the fetus. Curve 1 corresponds 8
with a growth-restricted infant because the initial intrauterine Singletons
growth along the 75th percentile was disrupted, preventing the
infant from achieving his/her growth potential. At birth, the
6 Twins
infant had a normal birth weight percentile of 40%, which is
appropriate for gestational age.
Triplets
A neonate is described as being SGA if the babys birth Mean weight
weight is lower than that of the standard population, typically 4
lower than the 10th percentile of population-based weight Quads
data. Curve 3 represents an infant who is SGA because the
birth weight percentile is below the 10th percentile. Because 2
the fetal growth pattern was less than the 10th percentile
throughout gestation, there was no interruption of intrauter-
ine growth; thus, Curve 3 corresponds to an infant who is SGA
but not growth-restricted. 0
24 28 32 36 4042 and 43
An infant can have IUGR and be SGA if the intrauterine
Week of gestation
growth curve was disrupted and the infants birth weight
FIGURE 2. Adapted from McKeown T Record RG. Observation on
percentile is less than the 10th percentile. Curve 2 shows a foetal growth in multiple pregnancy in man. J Endocrinol 1952;8:386,
growth-restricted infant because the infants growth potential with permission
was never reached. The infant is also SGA because the birth
weight percentile is less than the 10th percentile.
Other causes of IUGR include maternal smoking, maternal
2. A. Familial short stature undernutrition, and intrauterine infection.
The intrauterine growth curve of a fetus with familial short
3. D. Hypoglycemia
stature may appear similar to Curve 3 with a low growth per-
Similar to the fetus in this vignette, growth-restricted fetuses
centile throughout the pregnancy. Fetuses with a genetic ab-
are at increased risk for intolerance of labor because uterine
normality may have a similar growth curve because of their
contractions cause additional stress to the fetus. This leads to
small size throughout gestation. However, some genetic ab-
a greater risk for cesarean delivery, need for neonatal resuscita-
normalities will cause IUGR, leading to an infant who is either
tion, and/or perinatal asphyxia.
SGA or an appropriate size for gestational age.
The infant in this vignette had a decline in intrauterine
Maternal gestational diabetes may impact fetal growth by
growth, which led to a low birth weight (less than 10th per-
leading to a large-for-gestational-age infant (i.e., above the
centile), characterizing the infant as IUGR and SGA. In gen-
90th percentile). This mechanism is caused by high maternal
eral, SGA infants have a higher mortality and a greater risk
serum glucose concentrations that cross into the fetal circula-
for morbidities compared with appropriate-for-gestational-
tion. The fetal pancreas responds by increasing insulin pro-
age infants. The two most common morbidities found in SGA
duction. Because insulin is an important intrauterine growth
infants include:
hormone, infants born to women with gestational diabetes
often have macrosomia. If a woman has severe type I diabetes Hypoglycemia because of decreased glycogen stores,
mellitus with significant small vessel disease, the fetal growth decreased gluconeogenesis, and increased sensitivity to
pattern may be inhibited because of placental insufficiency. insulin

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 12 Initial care of the premature infant 25

Hypothermia because of decreased subcutaneous fat and While term infants may have a low resting heart rate, this
a large surface area to body-weight ratio finding is uncommon in premature infants.
Premature infants, especially those born less than 34 weeks
Because of these risks, clinicians will typically monitor the ini-
gestation, often have respiratory distress and cyanosis in the
tial serum glucose concentrations and temperatures of a SGA
delivery room as a result of surfactant deficiency. However,
infant.
these symptoms are unlikely to result from persistence of the
SGA infants are also at risk for polycythemia because of
fetal circulation because a preterm infants pulmonary vessel
chronic intrauterine hypoxemia. Finally, SGA infants may
musculature is inadequately developed.
have hypocalcemia because of decreased amount of calcium
Both term and preterm infants may have poor perfusion
acquired in utero.
soon after birth, but this finding will not alter an infants
Apgar score.

AMERICAN BOARD OF PEDIATRICS 3. A. Anemia of prematurity


CONTENT SPECIFICATIONS Anemia of prematurity is a common complication found in
many premature infants. Numerous factors contribute to this
Distinguish between small for gestational age (SGA) and finding in preterm infants, including:
intrauterine growth restriction (IUGR)
Know that SGA fetuses are seen in women with chronic Exposure to a relatively postnatal hyperoxic environment
systemic illnesses that leads to a decrease in erythropoietin production
Know that perinatal asphyxia is a frequent complication Need for multiple blood draws
of IUGR Shorter life span of red blood cells
Recognize that SGA infants have a higher neonatal
Preterm infants usually develop anemia of prematurity at 1
mortality rate than appropriate-for-gestational-age
to 2 months of age. This finding is not apparent soon after
infants
birth.
Know that SGA infants are prone to fasting hypoglyce-
Preterm infants have decreased glycogen and fat stores,
mia, polycythemia, and temperature instability
increasing their risk for hypoglycemia. Thus, soon after
birth, a neonatal nurse will measure a preterm infants
serum glucose concentration and start a continuous intra-
SUGGESTED READINGS venous glucose infusion. To maximize the infants nutri-
tion, this intravenous fluid often contains total parenteral
Brodsky D, Christou H. Current concepts in intrauterine growth re-
striction. J Intensive Care Med. 2004;19:307319. nutrition.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; Preterm infants are at increased risk for hypothermia be-
2010. cause of a(n):

Decreased skin thickness


CASE 12 ANSWERS Low amount of subcutaneous fat
Immature nervous system
1. B. Very low-birth-weight (VLBW) infant Increased surface area to body weight ratio
Premature birth (infant born less than 37 weeks gestation)
accounts for 12% of all births in the United States. Indepen- Thus, premature infants require external heat and frequent
dent of gestational age, infants can be categorized by birth monitoring of their temperature.
weight: Premature infants are at increased risk for surfactant de-
ficiency. Thus, it is important to monitor a preterm infants
LBW infant = infant <2,500 g at birth respiratory status, including arterial oxygen and carbon diox-
VLBW infant = infant <1,500 g at birth ide concentrations, soon after birth. An infant with a signifi-
ELBW infant = infant <1,000 g at birth cant respiratory acidosis may require additional respiratory
Micropremie = infant <750 g at birth assistance, such as endotracheal intubation and surfactant
The infant in this vignette is characterized as a VLBW infant administration.
because the birth weight is less than 1,500 g.
4. B. Complete blood cell count and blood culture
2. B. Neurologic immaturity The reason for a spontaneous preterm birth is often unknown.
Premature infants often cannot achieve an Apgar score greater However, because chorioamnionitis is a common known
than 6 because they are neurologically immature with a cause of preterm labor, neonatal providers will usually eval-
greater likelihood of hypotonia and poor reflex irritability uate a preterm infant for infection by obtaining a complete
soon after birth. blood cell count and blood culture. Preterm infants with

(c) 2015 Wolters Kluwer. All Rights Reserved.


26Section I MaternalFetal Medicine

hypoglycemia, hypothermia, or respiratory distress usually are


treated with antibiotics because of the possibility of a bacterial AMERICAN BOARD OF PEDIATRICS
infection. CONTENT SPECIFICATIONS
Serum electrolytes, blood urea nitrogen, and serum cre-
Recognize that premature infants often cannot achieve
atinine concentrations are not usually tested soon after birth
an Apgar score greater than 6 because they are neuro-
because the values at this early age of life reflect maternal
logically immature (e.g., hypotonic, blunted response to
concentrations. These test results reliably correspond to a
noxious stimuli)
newborns values by 24 hours of age. Because extremely pre-
Plan the initial care of a premature infant (e.g., monitoring
mature infants have an increased risk for excessive fluid losses,
of blood glucose, administration of a parenteral glucose
the neonatal team often tests the newborns concentration of
solution, maintenance of a thermoneutral environment,
serum electrolytes within 6 hours of age and then follows the
and monitoring of arterial oxygen concentrations)
electrolyte trend every 4 to 12 hours.
Recognize that initial care of the premature infant
If neonatal providers are concerned that an infant might
includes evaluation for sepsis, if appropriate
have hepatic injury because of perinatal depression or an in-
fection, they may measure the newborns serum transaminase
concentration soon after birth. SUGGESTED READING
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010.

(c) 2015 Wolters Kluwer. All Rights Reserved.


S E C T I ON II Pulmonology

(c) 2015 Wolters Kluwer. All Rights Reserved.


28Section II Pulmonology

CASE 1
Ventilator management

A neonatology team was called to evaluate a full-term male Even though the team increases the Fio2 to 100% and increases
infant with severe respiratory distress and cyanosis at a few the PEEP to 7 cm H2O, the infant remains cyanotic and has
minutes of age. The infant had been born by vaginal delivery persistent respiratory distress. The infant is then intubated and
after his mother presented in spontaneous labor. Labor was placed on spontaneous intermittent mechanical ventilation
complicated by maternal fever. with the following settings:
Upon arrival, the pediatric resident initiates continuous
Peak inspiratory pressure (PIP) of 26 cm H2O
positive airway pressure (CPAP) with 21% Fio2 using a bag-
PEEP = 6 cm H2O
mask. The infants work of breathing decreases and the baby
Rate = 25 breaths per minute
appears pink with a right-arm pulse oximetry reading of 94%.
Fio2 = 100%
The infants physical examination reveals decreased aeration
bilaterally. The infant is then admitted to the Neonatal Inten- A chest radiograph shows that the endotracheal tube is
sive Care Unit for further care. appropriately positioned and the lung fields reveal bilat-
In the intensive care unit, the baby is placed on a cardiovas- eral pneumonia. There is no evidence of a pneumothorax
cular monitor. The infants vital signs are: or pleural effusions. An echocardiograph reveals a structur-
ally normal heart with normal function and a patent duc-
HR = 160 beats per minute tus arteriosus with left-to-right (aorta to pulmonary artery)
RR = 84 breaths per minute shunting.
BP = 60/40 mm Hg A repeat arterial blood gas is obtained and the results are:
T = 100.9F (38.3C)
pH = 7.08, Paco2 = 95 mm Hg, Pao2 = 38 mm Hg, HCO3=
The nurse sends a complete blood count, blood culture, and 27 mEq/L, base excess = 1.8 mEq/L
an arterial blood gas. She also places an IV and administers The infants complete blood count results are:
intravenous ampicillin and gentamicin.
White blood cell count = 3 103/l (neutrophils 20%,
1. Of the following (noted in the table below), the normal bands 20%, lymphocytes 60%)
arterial blood gas results in a newborn in room air are: Hemoglobin = 11g/dL (mmol/L)
Hematocrit = 33% (0.33)
Option pH Paco2 (mm Hg) Pao2 (mm Hg) Platelet count = 150 103/l (150 109/L)

A 7.37 40 30 3. Of the following, the most effective next step to improve


B 7.39 44 70 this infants oxygenation is to:

C 7.40 30 90 A. Increase the inspiratory time


D 7.42 42 140 B. Increase the PEEP
C. Increase the PIP
D. Increase the rate
The infants arterial blood gas results while receiving CPAP
with a positive end-expiratory pressure (PEEP) of 5 cm H2O 4. Of the following, the most effective next step to decrease
and 21% Fio2 are shown below: this infants carbon dioxide concentration is to:
pH = 7.17, Paco2 = 75 mm Hg, Pao2 = 32 mm Hg, HCO3=
26 mEq/L, base excess = 1.3 mEq/L A. Decrease the flow
B. Decrease the PIP
2. Of the following, the most likely interpretation of this C. Increase the PEEP
infants arterial blood is a: D. Increase the rate

A. Metabolic acidosis In the setting of respiratory failure, the team attempts multiple
B. Metabolic alkalosis strategies to improve this infants oxygenation, including:
C. Respiratory acidosis
Ventilator change to a high-frequency oscillator
D. Respiratory alkalosis
Frequent endotracheal suctioning
The infants clinical examination worsens, and the infant has Packed red blood cell transfusion to increase the infants
severe respiratory distress and decreasing oxygen saturations. oxygen-carrying capacity

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 2 Apnea29

Sedation to prevent the infant from breathing against the 5. Of the following, the type of ECMO that is most indicated
ventilator in this infant is:
Placement of an arterial line for frequent arterial gas
A. Arterio-arterial (AA)
monitoring
B. Arteriovenous (AV)
Because this infant has severe respiratory failure with persis- C. Venoarterial (VA)
tent hypoxemia that has not responded to any medical inter- D. Veno-venous (VV)
ventions, the neonatal team consults the pediatric surgeon
The infant is placed on ECMO for 5 days, and with resolution
to place the infant on extracorporeal membrane oxygenation
of the pneumonia, the baby is able to be decannulated with-
(ECMO).
out difficulty. The infant is discharged home at 3 weeks of age
with close neurologic follow-up.

CASE 2
Apnea

A male infant is born at 30 weeks gestation. He initially has On the fifth day of life, he has five pauses in breathing, each
some respiratory distress, which requires treatment with con- lasting 15 seconds, and followed by cyanosis and bradycardia.
tinuous positive airway pressure (CPAP) for 12 hours. He These apneic events occur over a period of 1 hour. The neona-
starts nasogastric feedings at 24 hours of age and feedings are tology fellow meets with the babys mother to discuss possible
advanced slowly. At 48 hours of age, he has several episodes causes for this infants breathing pattern.
of periodic breathing.
3. Of the following, the least likely etiology for this infants
1. Of the following, the description that best describes peri- apnea is:
odic breathing is a:
A. Anemia
A. Pause in breathing associated with an inward movement B. Infection
of both the rib cage and the abdomen during inspiration C. Prematurity
B. Pause in breathing for longer than 20 seconds D. Reflux
C. Pause in breathing that is usually associated with either
After a complete evaluation and several interventions includ-
cyanosis or a decrease in heart rate
ing caffeine therapy, the infants apnea decreases to 1 to 4 epi-
D. Pause in breathing that is less than 20 seconds followed
sodes per day.
by several rapid shallow breaths

During the infants third and fourth day of life, he has three 4. Of the following, the least likely mechanism of caffeine
apneic events over a period of 24 hours. therapy is a(n):

A. Decrease in hypoxia-associated breathing depression


2. Match the type of breathing pattern with the corresponding
B. Decrease in minute ventilation
physiology:
C. Increase in diaphragmatic activity
A. Central apnea 1. Absent nasal airflow and D. Improvement in CO2 sensitivity
absent breathing efforts
At 35 weeks postmenstrual age, the caffeine therapy is discon-
B. Mixed apnea 2. Absent nasal airflow while tinued. The infant continues to have 1 to 2 apneic episodes per
breathing efforts continue day that are associated with mild desaturations. By 38 weeks
C. Obstructive 3. Absent nasal airflow and absent postmenstrual age, the apneic events resolve and the infant is
apnea breathing efforts followed by discharged to home 1 week later when his feeding ability is
absent nasal airflow while mature.
breathing efforts continued
D. Respiratory 4. Nasal airflow with increased
distress work of breathing

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30Section II Pulmonology

CASE 3
Stridor

A nurse pages a pediatric resident to evaluate a 1-hour-old full- 2. Match the type of stridor with the most likely location of
term infant who is making a loud breathing noise. The resi- the obstruction:
dent assesses the baby and finds the following:
A. Biphasic stridor 1. Intrathoracic obstruction
A high-pitched upper airway sound that occurs during in- B. Expiratory stridor 2. Laryngeal obstruction
spiration and expiration
C. Inspiratory stridor 3. Supraglottic obstruction
An upper airway noise that worsens with crying and im-
proves when the infant is prone A few weeks later, the same pediatric resident is rotating in the
No respiratory distress Neonatal Intensive Care Unit. A neonatal intensive care nurse
No difficulty with feeding calls him to the bedside to evaluate an infant with respiratory
distress. The nurse reports that the female infant had been
1. Of the following, the most likely diagnosis in this infant is:
born at 25 weeks gestation. Her clinical course had been com-
A. Choanal atresia plicated by severe lung disease requiring prolonged intuba-
B. Laryngomalacia tion. The infant had self-extubated a few minutes prior to the
C. Macroglossia residents arrival. Upon examination, the resident notices that
D. Tracheomalacia the infant has biphasic stridor and respiratory distress. The
resident asks the nurse to page the neonatologist. The neona-
The resident consults an otolaryngologist to help determine
tologist then intubates the infant after the second attempt, and
the cause of this infants breathing. The specialist discusses
an otolaryngologist evaluates the infant.
that the infants clinical findings often correspond to the lo-
cation of the obstruction. The otolaryngologist speaks with 3. Of the following, the most likely cause of this infants stri-
the infants parents and is optimistic about their infants long- dor is:
term prognosis.
A. Bronchospasm
B. Pulmonary edema
C. Retropharyngeal abscess
D. Subglottic stenosis

CASE 4
Surfactant deficiency

A pregnant woman presents at 32 weeks gestation with pre- 1. Of the following, the typical clinical course found in most
mature rupture of membranes. The obstetrician orders to- infants with surfactant deficiency is:
colytics, antibiotics, and dexamethasone. Despite tocolytic
A. Delayed respiratory symptoms in infants exposed pre-
therapy, the labor progresses and she delivers later that day.
natally to steroids
After birth, the infant has severe respiratory distress and cya-
B. Peak severity of illness usually occurs at 12 to 24 hours
nosis, requiring intubation. The neonatology fellow meets
of age
with the infants parents to discuss the infants expected clini-
C. Recovery begins at ~72 hours of age
cal course.
D. Respiratory symptoms are initially observed at 2 to
4hours of age

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Case 5 Pulmonary air leaks31

A respiratory therapist administers surfactant through the 3. Of the following, the radiographic finding that is most con-
infants endotracheal tube. sistent with surfactant deficiency is (are):

2. Of the following, the most likely effect of synthetic surfac- A. Air bronchograms
tant administration is to: B. Enlarged heart size
C. Heterogeneous lung disease
A. Decrease alveolar surface tension
D. Hyperinflated lung fields
B. Increase the pressure needed to keep alveoli open
C. Maintain bronchiolar patency After surfactant therapy, the infants ventilator support de-
D. Preferentially improve the surface tension of collapsed creases significantly and the infant is extubated to continuous
alveoli positive airway pressure (CPAP) at 8 hours of age.

The infants chest radiograph at 15 minutes of age is shown 4. Of the following, the least likely strategy to decrease the se-
in Figure 1. verity of respiratory distress syndrome in preterm infants is:

A. Antenatal steroid administration


B. Avoidance of supplemental oxygen in the delivery room
C. Early CPAP
D. Tocolysis to delay preterm birth

FIGURE 1. From MacDonald G, Seshia MK, et al. Averys Neonatology:


Pathophysiology & Management of the Newborn. 6th ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 2005

CASE 5
Pulmonary air leaks

A pediatric resident is asked to evaluate a full-term infant who 1. Of the following, the most likely diagnosis in this infant is:
developed respiratory distress soon after birth. The resident ex-
A. Bilateral pneumothoraces
amines the infant and finds the following:
B. Left pneumothorax
RR = 70, HR = 160s, BP = 60/46, T = 98.6F (37C) C. Pneumomediastinum
Oxygen saturation = 88% in room air D. Right pneumothorax
Mild intercostal retractions
The infant has an oxygen saturation of 96% after being placed
Slightly decreased breath sounds on the left
in an oxygen hood with 100% Fio2. The neonatal nurse places
Slightly increased anteriorposterior diameter of the left
an IV and starts D10W at 60 ml/kg/day. The resident is unable
chest
to identify an air leak by transillumination and orders a chest
The resident suspects an air leak and brings the infant to the radiograph. While waiting for the results, the resident teaches
Neonatal Intensive Care Unit. the medical student about the radiographic findings found in
infants with air leaks.

(c) 2015 Wolters Kluwer. All Rights Reserved.


32Section II Pulmonology

2. Match the chest radiograph (Figs. 14) with the corre-


sponding diagnosis:

A. Bilateral pneumothoraces
B. Left pneumothorax
C. Pneumomediastinum
D. Right pneumothorax

FIGURE 4. Courtesy of Brodsky D

The medical student asks the pediatric resident to review the


possible causes of a pneumothorax in a newborn.

3. Of the following, the least likely cause of a pneumothorax


in a newborn is:

A. Esophageal atresia
B. Excessive bag-mask ventilation
FIGURE 1. From Eisenberg L. Clinical Imaging: An Atlas of Differential C. Severe lung disease requiring high ventilator pressures
Diagnosis. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins;
D. Spontaneous occurrence
2003. Figure 29.6A
The infants radiograph confirms that the infant has a small left
pneumothorax. Because the infant has mild respiratory dis-
tress and a normal oxygen saturation in a 50% oxygen hood,
the resident does not intervene. A few hours later, the neonatal
nurse pages the resident because the infant has increased work
of breathing. The infants examination reveals the following:

RR = 80, HR = 180s, BP = 40/32, T = 99F (37.2C)


Oxygen saturation = 75% in 50% oxygen hood
Severe respiratory distress
Lack of breath sounds over the left lung
Increased anteriorposterior diameter of the left chest
FIGURE 2. Courtesy of Brodsky D Displaced point of maximal cardiac impulse to the right

4. Of the following, the preferred next step in the manage-


ment of this infant is:

A. Increase the Fio2 to 100%


B. Intubation
C. Needle thoracentesis
D. Normal saline bolus

FIGURE 3. Courtesy of Dukhovny D

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 6 Meconium aspiration syndrome33

CASE 6
Meconium aspiration syndrome

A neonatology team is called to the delivery of a full-term in- 2. Of the following, the most likely diagnosis in this infant is:
fant with thin meconium-stained amniotic fluid. The infant
A. Meconium aspiration syndrome
emerges without any respiratory effort, no activity, and a heart
B. Pneumothorax
rate of 55.
C. Respiratory distress syndrome
1. Of the following, the most appropriate next step in the man- D. Retained fetal lung fluid
agement of this infant is:
The neonatology fellow reviews the pathogenesis of this in-
A. Bag-mask ventilation fants disease with the pediatric resident.
B. Chest compressions
C. Intratracheal suctioning 3. Of the following, the pathophysiology that is least likely to
D. Intubation and positive pressure ventilation be occurring in this infant is:

After initial resuscitation, the team observes that the infant has A. Airway obstruction
severe intercostal and subcostal retractions with decreased aer- B. Chemical pneumonitis
ation and central cyanosis. The neonatology fellow intubates C. Pulmonary interstitial emphysema
the infant and the team transports the baby to the Neonatal D. Surfactant dysfunction
Intensive Care Unit. The infant is then placed on a synchro-
nized intermittent mechanical ventilator with high settings.
The infants abdomen appears distended and the nurse places
a nasogastric tube to remove air in the stomach. The infants
radiograph is shown in Figure 1.

FIGURE 1. From MacDonald G, Seshia MK, et al. Averys Neonatology:


Pathophysiology & Management of the Newborn. 6th ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 2005. Figure 29.9

(c) 2015 Wolters Kluwer. All Rights Reserved.


34Section II Pulmonology

CASE 7
Patchy lung fields

A male infant is delivered at 32 weeks gestation after his 1. Of the following, the diagnosis that is most likely in this
mother develops a fever of 102F (38.9C) in the setting of infant is:
ruptured membranes for 48 hours. The baby has respiratory
A. Congenital pneumonia
distress soon after birth, evident by grunting, severe intercostal
B. Pneumothorax
and subcostal retractions, and nasal flaring. His vital signs are:
C. Surfactant deficiency
Heart rate = 130 beats per minute D. Transient tachypnea of the newborn
Respiratory rate = 70 breaths per minute
The infant is then intubated and placed on synchronized in-
Oxygen saturation (right arm, room air) = 80%
termittent mechanical ventilation. Additional laboratory data
Oxygen saturation (right arm, facial continuous positive
include the following:
airway pressure [CPAP] 40%) = 91%
Blood pressure = 39/32 mm Hg White blood cell count = 1.5 103/L (1.5 109/L)
Differential = 25% neutrophils, 25% bands, 50%
His initial arterial blood gas while on CPAP is: pH = 7.17,
lymphocytes
Paco2 = 75 mm Hg, Pao2 = 32 mm Hg, HCO3 = 26 mEq/L,
Hemoglobin = 18.3 g/dL (11.3 mmol/L)
base excess = 1.3 mEq/L
Hematocrit = 55% (0.55)
His chest radiograph is shown in Figure 1.
Platelet count = 90 103/L (90 109/L)

2. Of the following, the pathophysiologic mechanism that


can contribute to this infants diagnosis is:

A. Ascending vaginal flora


B. Aspiration of contaminated amniotic fluid
C. Transplacental acquisition
D. All of the above

3. Of the following, the organism that is most likely respon-


sible for this infants illness is:

A. Chlamydia trachomatis
B. Flavobacteria
C. Listeria monocytogenes
D. Respiratory syncytial virus

FIGURE 1. From Sweet RL, Gibbs RS. Atlas of Infectious Diseases of the
Female Genital Tract. Philadelphia, PA: Lippincott Williams & Wilkins;
2005. Figure 4.4

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 8 Tachypnea35

CASE 8
Tachypnea

An obstetrician is closely monitoring a pregnant woman with 1. Of the following, the most likely cause of this infants
insulin-dependent diabetes mellitus. At 40 weeks gestation, tachypnea is:
a fetal ultrasound shows that the fetus is in a breech position
A. Cyanotic heart disease
and is macrosomic. The following day, the infant is delivered
B. Metabolic acidosis
by cesarean. After birth, the baby is noted to have a bluish
C. Retained fetal lung fluid
discoloration to the lips. The pediatric resident evaluates the
D. Surfactant deficiency
infant and finds the following:

Heart rate = 130 beats per minute 2. Of the following, the most appropriate next step in manag-
Respiratory rate = 95 breaths per minute ing this infant is to:
Oxygen saturation (right arm, room air) = 91%
Oxygen saturation (right arm, 25% blow by oxygen) = 99% A. Administer a normal saline bolus and an intravenous
Blood pressure = 62/38 mm Hg NaHCO3 bolus if repeated arterial pH is <7.35
B. Avoid supplemental oxygen and start a prostaglandin
The infants physical examination findings include the following: infusion
Active infant, appropriate during examination C. Initiate intravenous antibiotics
Slightly cyanotic lips in room air that become pink after D. Start maintenance intravenous fluid and provide sup-
25% blow by oxygen is applied plemental oxygen
Rapid respiratory rate without retractions and no evi- The pediatric resident meets with the family to discuss the in-
dence of grunting or nasal flaring fants expected clinical course.
Symmetric breath sounds with good aeration
Normal heart sounds without murmur, normal femoral 3. Of the following, the most likely clinical course for the in-
pulses, and well-perfused fant in this vignette is:
Normal abdominal and neurologic examination
A. Decreased distal perfusion at 48 hours of age
The infants laboratory data include the following: B. Increased severity of respiratory distress at 48 hours of
age
Arterial blood gas (25% blow by oxygen): pH = 7.32,
C. Resolution of tachypnea within 48 hours of age
Paco2= 50 mm Hg, Pao2 = 89 mm Hg, HCO3 = 25 mEq/L
D. Worsening cyanosis at 48 hours of age
Serum glucose = 65 mg/dL (3.6 mmol/L)

The babys chest radiograph is shown in Figure 1:

FIGURE 1. Courtesy of Brodsky D

(c) 2015 Wolters Kluwer. All Rights Reserved.


36Section II Pulmonology

CASE 9
Cystic lung disease

A female infant born at 26 weeks gestation had a complicated 2. Of the following, the infant in this vignette is at increased
medical course. She received two doses of surfactant and ini- risk of developing:
tially required high ventilator settings on the high-frequency
A. Cor pulmonale
oscillator. She was able to transition to the conventional ven-
B. Recurrent wheezing episodes
tilator at 12 days of life and extubated at 3 weeks of age af-
C. Respiratory infections
ter a 7-day course of steroids. Her feeding advancement went
D. All of the above
slowly initially, but she was on full-volume enteral feedings
by 3 weeks of age. She was treated for 1 week with antibiot- Five months after discharge, the pediatrician is concerned be-
ics for presumed chorioamnionitis. At 10 weeks of age, she cause the infants growth has been poor despite an increase
required 1-L flow by nasal cannula with 30% Fio2. Her most to 26 calories per ounce. The family meets with a gastroenter-
recent chest radiograph is shown in Figure 1. ologist to determine the approach to managing this infants
failure to thrive.

3. Of the following, the statement that the gastroenterologist


is most likely to make to the family is:

A. Failure to thrive is a rare complication in infants with


BPD.
B. Gastroesophageal reflux is unusual in infants with BPD.
C. Infants with BPD are unlikely to develop an oral
aversion.
D. Poor growth in infants with BPD is often related to the
infants oxygenation status.

FIGURE 1. From Fleisher GR, Ludwig W, Baskin MN. Atlas of Pediatric


Emergency Medicine. Philadelphia, PA: Lippincott Williams & Wilkins;
2004. Figure 16.03

1. Of the following, the diagnosis that is most likely in this


infant is:

A. Bronchogenic cyst
B. Bronchopulmonary dysplasia (BPD)
C. Congenital cystic adenomatoid malformation (CCAM)
D. Pulmonary interstitial emphysema (PIE)

At 42 weeks postmenstrual age, the baby was able to take full


oral feedings and was gaining weight on 24 calories per ounce.
She was discharged home with supplemental oxygen and had
follow-up arranged with several clinicians, including the pe-
diatrician, a pediatric pulmonologist, Early Intervention, and
the Infant Follow-up Clinic.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 10 Tracheoesophageal abnormalities37

CASE 10
Tracheoesophageal abnormalities

A neonatology team is asked to attend a delivery of a term 2. Of the following, the next best step in the management of
infant with a prenatal diagnosis of polyhydramnios of uncer- this infant is to:
tain etiology. The infant emerges with good activity but has a
A. Consult Interventional Radiology to place a nasogastric
large amount of oral secretions. A nasogastric tube is placed,
feeding tube into the infants stomach
and the radiograph is shown below (Figure 1). An abdominal
B. Place a cuffed endotracheal tube in the infants trachea
radiograph reveals that air is located in the stomach and proxi-
and consult Pediatric Surgery
mal intestines.
C. Place a suction catheter into the esophageal blind pouch
to remove secretions and consult Pediatric Surgery
D. Start intravenous prostaglandin infusion and consult
Pediatric Cardiology

The neonatologist meets with the family to discuss the man-


agement of TEF. The family has lots of questions about long-
term outcome.

3. Of the following, the least likely complication after surgical


repair of this infants TEF is:
FIGURE 1. Courtesy of Brodsky D
A. Apneic episodes
1. Of the following, the type of tracheoesophageal abnormal- B. Dysphagia
ity that is most likely in this infant (Figure 2) is: C. Esophageal stricture
D. Leakage at point of anastomosis

A B C D E

FIGURE 2. From Pillitteri, A. Maternal and Child Nursing. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2003. Figure 39.05

(c) 2015 Wolters Kluwer. All Rights Reserved.


38Section II Pulmonology

CASE 11
Congenital malformations of the lung

A term male infant delivered by cesarean is noted to have


mild to moderate respiratory distress at a few minutes of life.
A pediatric resident transports the infant to the Neonatal
Intensive Care Unit for further care. Initial evaluation shows
that the infant has normal oxygen saturations in room air
and the respiratory distress is improving. However, a chest
radiograph does demonstrate an abnormality.

1. Match the diagnosis with the corresponding chest radiograph:

A. Bronchogenic cyst
B. Congenital cystic adenomatoid malformation (CCAM)
C. Congenital diaphragmatic hernia (CDH)
FIGURE 3. From Mulholland W, Maier V, et al. Greenfields Surgery:
D. Pulmonary interstitial emphysema (PIE) Scientific Principles and Practice, 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006. Figure 109.04

FIGURE 1. Courtesy of Brodsky D

FIGURE 4. Courtesy of Dukhovny D

Upon further review of the infants prenatal history, the pedi-


atric resident learns that the infant had a prenatal diagnosis
of a CCAM, which is found on the postnatal radiograph. De-
spite this prenatal diagnosis, the infants respiratory distress
resolves at 30 minutes of age.

2. Of the following, the most appropriate management of the


infant in this vignette is:

A. Administer antibiotics because of the high likelihood


for intrapartum infection
B. Intubate the infant in anticipation of worsening respira-
tory distress by 48 hours of age
C. Nothing required because the mass will involute over
time
D. Reevaluate at 1 to 2 months of age with a computed
FIGURE 2. From Crapo JD, Glassroth J, Karlinsky JB, et al. Baums tomography scan to evaluate the lesion in more detail
Textbook of Pulmonary Diseases. 7th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2004. Figure 66.01A

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 11 Congenital malformations of the lung 39

After the infant is discharged home, the same pediatric resi- 3. Of the following, a possible cause of this infants respira-
dent is called again to the delivery room to evaluate another tory distress is:
term infant with respiratory distress. The pregnancy had been
A. Persistent pulmonary hypertension
complicated by severe oligohydramnios at 20 weeks gesta-
B. Pulmonary hypoplasia
tion. The infant has severe retractions and appears cyanotic.
C. Septic shock
The resident provides bag-mask ventilation and notes that the
D. All of the above
infant requires high peak inspiratory pressures and 100% Fio2
to maintain a preductal oxygen saturation over 85%.

(c) 2015 Wolters Kluwer. All Rights Reserved.


40Section II Pulmonology

SECTIONII
Answers

Increasing the PIP or increasing the inspiratory time will


CASE 1 ANSWERS
also increase mean airway pressures, but not as effectively. By
1. B. pH = 7.39, Paco2 = 44, Pao2 = 70 increasing the flow or rate on a ventilator, a small increase in
The normal pH of a neonate ranges between ~7.35 and 7.43. mean airway pressure may occur.
Normal Pao2 (i.e., arterial Po2) values range between 60 and 4. D. Increase the rate
90 mm Hg and Paco2 (i.e., arterial Pco2) values range between There are several ventilator strategies to decrease an infants
35 and 45 mm Hg. Thus, the arterial blood gas with a pH = Paco2, including:
7.39, Paco2 = 44, and Pao2 = 70 is normal for an infant.
An infant with an arterial Po2 of 30, as shown in option A, Increase the rate
has hypoxemia. Because an infant is unable to achieve a Pao2 Increase PIP (note: if the PEEP stays constant, an increase
of 140 in room air, option D is not possible. However, if an in PIP will increase tidal volume)
infant receives supplemental oxygen, the Pao2 can be greater Decrease PEEP (note: if the PIP stays constant, a decrease
than 150 if the baby does not have cardiac or respiratory dis- in PEEP will increase tidal volume)
ease. If an infant has an arterial Pco2 that is too low, as in op- Increase flow
tion C, this may lead to cerebral vasoconstriction. Increase the expiratory time

2. C. Respiratory acidosis However, each of these changes can lead to secondary conse-
The infant in this vignette has severe cyanosis and respiratory quences. For example, by increasing the ventilator rate, stacked
distress. An arterial blood gas is helpful to assess an infants breaths or inadvertent PEEP can occur, which may decrease
ventilation and oxygenation. If the pH is low (i.e., acidotic) tidal volume and increase Paco2. An increase in PIP or flow
and the Paco2 is high, this is consistent with a respiratory can induce barotrauma. While an infants tidal volume will
acidosis and demonstrates that an infant is not ventilating increase with a decrease in PEEP, the mean airway pressure
effectively because of lung disease. This infants blood gas is will also decrease, and this may lead to worsening hypoxemia.
consistent with a respiratory acidosis. Similarly, an increase in expiratory time can decrease mean air-
In contrast, if the pH is high (i.e., alkalotic) and the Paco2 way pressure and worsen an infants oxygenation.
is low, this is consistent with a respiratory alkalosis. A respi- 5. D. Veno-venous (VV)
ratory alkalosis is sometimes observed in infants with a urea Despite multiple strategies to treat the infant in this vignette,
cycle defect. the infant remains hypoxemic. ECMO is an option for in-
Metabolic acidosis is associated with a low pH and a low fants who fail maximal ventilator support with 100% Fio2
Paco2. The infants anion gap can be helpful to determine the and have an elevated alveolararterial O2 gradient and a high
cause of an infants metabolic acidosis. The anion gap is calcu- oxygenation index. ECMO is contraindicated in the following
lated by the difference between cations and anions: infants:
Anion gap = [Na+] ([Cl] + [HCO3]) Premature infants (typically those infants who are <34
A metabolic acidosis with an elevated anion gap is asso- weeks gestation)
ciated with shock, sepsis, renal failure, and metabolic disor- Irreversible lung disease
ders. A metabolic acidosis with a normal anion gap can result Irreversible severe neurologic abnormalities
from renal tubular acidosis, diarrhea, and congenital adrenal Severe intraventricular hemorrhage
hyperplasia. Significant coagulopathy
A metabolic alkalosis is associated with an elevated pH and Congenital anomalies incompatible with a good long-
Paco2. A metabolic alkalosis can be found in infants with em- term outcome
esis, diuretic use, and Bartter syndrome. There are two types of ECMO: VV and VA. In VV ECMO, blood
3. B. Increase the PEEP from an infants vein is circulated outside of the infant, oxy-
Oxygenation is most dependent on mean airway pressure. genated, and returned back to the infants venous circulation.
Themost effective way to increase mean airway pressure is by In VA ECMO (see Figure 1), blood is similarly removed from
increasing the PEEP. However, as the PEEP increases, the tidal an infants vein and oxygenated outside of the body. How-
volume decreases and can compromise ventilation. ever, blood is returned back to the infants arterial circulation,

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 2 Apnea41

bypassing the infants heart. VA ECMO is used when an in-


CASE 2 ANSWERS
fants cardiac dysfunction is partly responsible for the infants
hypoxemia. Because the infant in this vignette has hypoxemia 1. D. Pause in breathing that is less than 20 seconds fol-
primarily resulting from a respiratory process, VV ECMO will lowed by several rapid shallow breaths
be effective at oxygenating and ventilating this baby. Infants with period breathing have pauses in breathing that are
less than 20 seconds (typically a duration of 1015 seconds)
with interruptions of at least 3 seconds. Sometimes, an infant
will have several rapid shallow breaths after a pause in breath-
Aortic arch ing. Periodic breathing is not usually associated with cyanosis
Right atrium or a decrease in heart rate. This breathing pattern is a normal
variation of breathing in infants.
Term, healthy infants can have paradoxical breathing,
which describes the inward movement of the rib cage (i.e., col-
lapse of chest wall) while the abdomen moves outward during
inspiration. This typically happens during sleep.
Blood drainage
Blood return 2. A. Central apnea 1. Absent nasal airflow and
absent breathing efforts
B. Mixed apnea 3. Absent nasal airflow and absent
breathing efforts followed by
Bridge absent nasal airflow while
breathing efforts continued
Heat
exchanger C. Obstructive 2. Absent nasal airflow while
apnea breathing efforts continue
Servoregulation
Membrane lung D. Respiratory 4. Nasal airflow with increased
Heparin
distress work of breathing
Fluids
There are three types of apnea that can occur in premature
infants:

Central apnea is characterized by a complete absence of


Pump
inspiratory efforts without any evidence of obstruction. In
FIGURE 1. From Blackbourne LH. Advanced Surgical Recall. 2nd ed.
this type of apnea, an infant has absent nasal airflow and
Baltimore, MD: Lippincott Williams & Wilkins; 2004. Figure 64.2
absent breathing efforts.
Obstructive apnea is characterized by a breathing attempt
against an obstructed upper airway (typically the pharynx
AMERICAN BOARD OF PEDIATRICS or larynx). In this type of apnea, an infant has absent na-
CONTENT SPECIFICATIONS sal airflow despite breathing efforts.
Mixed apnea is characterized by central apnea followed by
Know the normal arterial blood gas values for a newborn obstructive apnea. In this type of apnea, an infant has a pe-
Review strategies to adjust mean airway pressure and im- riod of absent nasal airflow and absent breathing efforts fol-
prove oxygenation lowed by absent nasal airflow despite breathing efforts. This
Review approach to ventilator if infant has elevated Pco2 is the most common type of apnea in premature infants.
Recognize different modes of ventilation
Plan the evaluation of a full-term infant who has severe Apnea of prematurity is defined as absence of breathing for
respiratory failure at birth that does not respond to intu- more than 15 to 20 seconds, which is usually accompanied by
bation and assisted ventilation an oxygen desaturation and/or bradycardia. Although periodic
breathing is self-limited, an infant with apnea of prematurity
may not be able to reinitiate ventilation.
SUGGESTED READINGS 3. D. Reflux
There are many possible causes of apnea in an infant, such as:
Aly H. Respiratory disorders in the newborn: Identification and diag-
nosis. Peds Rev. 2004. 25;201208. Anemia
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; Electrolyte disturbance, such as hypoglycemia
2010.
Goldsmith JP, Karotkin EH (eds). Assisted Ventilation of the Neonate. Hypoxemia
5th ed. Philadelphia, PA; WB Saunders; 2010.

(c) 2015 Wolters Kluwer. All Rights Reserved.


42Section II Pulmonology

Infection, such as sepsis, meningitis, respiratory syncy- SUGGESTED READINGS


tial virus
Intracranial process, such as an intraventricular hemorrhage Baird TM, Martin RJ, Abu-Shaweesh JM. Clinical associations,
Medications, such as sedatives, magnesium, prostaglan- treatment and outcome of apnea of prematurity. NeoReviews.
2002;3:e66e70.
din E1 Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010.
Prematurity Martin RJ, Abu-Shaweesh JM, Baird TM. Pathophysiologic mechanisms
Seizures underlying apnea of prematurity. NeoReviews. 2002;3:e59e65.
Spinal cord abnormalities

Although apnea and gastroesophageal refux often coexist in CASE 3 ANSWERS


preterm infants, multiple studies have shown that these enti-
ties are not usually temporally related. When there is a rela- 1. B. Laryngomalacia
tionship between the two, apnea typically comes before the The infant described in this vignette most likely has laryngoma-
reflux, perhaps because the loss of central respiratory drive is lacia, the most common cause of congenital stridor. Affected
often accompanied by decreased lower esophageal tone. infants typically have inspiratory stridor that worsens with agi-
tation and improves in the prone position. It is typically benign
4. B. Decrease in minute ventilation and self-limited. Conservative management is common, par-
Caffeine therapy decreases apnea in premature infants by ticularly when the infant does not have any associated respira-
many different mechanisms, including: tory distress or feeding difficulties. The table below compares
Decreasing hypoxia-associated breathing depression the pathophysiology, clinical findings, diagnosis, management,
Decreasing periodic breathing and outcome of laryngomalacia and tracheomalacia.
Enhancing diaphragmatic activity
Improving CO2 sensitivity Tracheomalacia Laryngomalacia
Increasing minute ventilation
Pathophysiology Cartilaginous Collapse of epi-
To start therapy, an infant first receives a loading dose of caf- rings supporting glottis and/or ary-
the trachea are tenoids cartilages
feine, which is followed by maintenance dosing. Caffeine can
soft and tend to and/or larynx
be administered by an oral or intravenous route. Caffeine has collapse during leading to pro-
several advantages over theophylline therapy because it has a expiration lapse into glottis
greater therapeutic index, decreasing the risk for toxicity. Caf- Can be associ- during inspiration
feine also has a longer half-life than theophylline. ated with chronic Unknown etiology
There are also some nonpharmacologic approaches to ventilation
treat apnea of prematurity. Tactile stimulation of an infant Clinical Although most Most common
with apnea may terminate a short episode of apnea. CPAP common cause cause of congeni-
may help to splint the upper airway with positive pressure of intrinsic con- tal stridor
genital tracheal Coarse, inspira-
and decrease the obstructive component of the apnea. CPAP narrowing, it is tory stridor that is
also may provide an added benefit by increasing an infants rare worse with agita-
functional residual capacity, which improves oxygenation Expiratory stridor tion and improved
and decreases hypoxia-associated breathing depression. For in prone position
those infants with severe or extremely frequent apneic events, Can have expira-
endotracheal intubation and ventilator assistance may be nec- tory component
essary. Finally, if an infant has apnea in the setting of anemia, to stridor
a packed red blood cell transfusion may increase the infants Typically benign,
self-limited,
oxygen-carrying capacity and decrease hypoxia-induced respi- male> female
ratory depression. (2:1)
Presents with stri-
dor between birth
AMERICAN BOARD OF PEDIATRICS and first month
CONTENT SPECIFICATIONS of life
Majority without
Distinguish between apnea and periodic breathing respiratory dis-
Know the difference between central and obstructive tress or feeding
apnea difficulties
Know the differential diagnosis of central apnea in infancy Diagnosis Bronchoscopy Laryngoscopy
Know the treatment of idiopathic recurrent apnea in pre- (anterior and
mature infants posterior tra-
Understand the association between apnea and anemia cheal walls ap-
proximate during
in premature infants expiration)

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 3 Stridor43

Tracheomalacia Laryngomalacia Type of Differential


Obstruction Clinical Findings Diagnosis
Management Consider CPAP Conservative
If severe, Laryngeal Biphasic stridor Laryngomalacia
may need obstruction Usually worse most common
tracheostomy (vocal cords, with agitation congenital
subglottis, Because the laryngeal anomaly
Outcome Majority with Spontaneous res-
extrathoracic larynx is the Vocal cord
spontaneous res- olution by about
trachea) narrowest part paralysissecond
olution by 612 2 years of age
This region of the neonates most common
months of age Rare to require
is a fixed airway, this type laryngeal anomaly
tracheostomy
size during of stridor is most Congenital
Printed with permission from: Brodsky D, Martin C. Neonatology inspiration and common subglottic
Review. 2nd ed. Raleigh, NC: Lulu; 2010:96 expiration stenosisoften
unable to handle
secretions,
An infant with unilateral choanal atresia usually is as-
recurrent
ymptomatic unless the unaffected naris is obstructed with pneumonias;
a suction catheter or a feeding tube. An infant with bilateral if severe,
choanal atresia will have inspiratory stridor soon after birth tracheostomy and
that is associated with respiratory distress and cyanosis at rest. dilatations needed
These symptoms often improve with crying because of air en- Laryngeal web,
cyst
try through the mouth.
Infants with macroglossia may have inspiratory stridor Intrathoracic Expiratory stridor Tracheomalacia
that is worse in the supine position because gravity moves the obstruction Less common Tracheal stenosis
tongue posterior. Infants with macroglossia do not have an (intrathoracic than laryngeal External
trachea and stridor but often compression
expiratory component to their stridor. bronchi) more serious (vascular rings,
2. A. Biphasic stridor 2. Laryngeal obstruction This region mediastinal mass)
narrows during
B. Expiratory stridor 1. Intrathoracic obstruction expiration
C. Inspiratory stridor 3. Supraglottic obstruction
Printed with permission from: Brodsky D, Martin C. Neonatology
Review. 2nd ed. Raleigh, NC: Lulu; 2010:94
The location of an infants airway obstruction and associated
type of stridor are summarized in the table below. 3. D. Subglottic stenosis
Subglottic stenosis is caused by a narrowing of the subglottic air-
Type of Differential way (below the vocal cords and above the trachea) that can be
Obstruction Clinical Findings Diagnosis congenital or acquired. Acquired subglottic stenosis often occurs
after a baby has had a long period of intubation. It is associated
Supraglottic Inspiratory Pierre Robin
with biphasic stridor that worsens with agitation. The cause of this
obstruction stridor and Treacher
Collins (both with acquired stenosis is attributable to multiple factors, including:
(nose, Often less with
nasopharynx, crying micrognathia)
Endotracheal tube movement
oropharynx, Worse in supine Macroglossia
Gastroesophageal reflux
hypopharynx) position because (Beckwith
Wiedemann Infection
This region gravity moves
narrows during tongue posterior syndrome, Multiple intubations
inspiration hypothyroidism, Small cricoid region
glycogenstorage
diseases, The diagnosis of subglottic stenosis is confirmed by direct la-
trisomy21) ryngoscopy under general anesthesia. In this procedure, tubes
Choanal atresia of increasing sizes are passed through the obstructed region to
Thyroglossal duct determine the precise size of the smaller portion of the airway.
cyst (moves with Possible treatment options include:
swallowing due
to attachment to Reintubation and continued observation with possible
base of tongue or therapies such as antibiotics, antireflux medications, and
hyoid bone)
steroids
Tracheostomy
Surgical treatment (including possible laser surgery, dila-
tation, anterior cricoid split)

Infants who require chronic ventilation are also at increased


risk for tracheomalacia.

(c) 2015 Wolters Kluwer. All Rights Reserved.


44Section II Pulmonology

with gestational age, delaying preterm birth by tocolysis, when


AMERICAN BOARD OF PEDIATRICS possible, is important. Prior to an infants birth, antenatal ste-
CONTENT SPECIFICATIONS roid administration to the pregnant woman can help to de-
crease the severity of the disease. This effect is most evident
Know the differential diagnosis of congenital stridor
when a woman delivers the baby 48 hours after she has re-
Recognize subglottic stenosis as a complication of endo-
ceived the first of two doses of steroids. Administering CPAP
tracheal intubation
in the delivery room to premature infants with respiratory dis-
tress syndrome has been shown to decrease alveolar collapse
and lessen the severity of the illness. If CPAP is administered to
SUGGESTED READINGS
the infant after several hours of age, many alveoli lacking sur-
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; factant have had time to collapse, making CPAP less effective.
2010. The use of supplemental oxygen to full-term infants in the
Daniel M, Cheng A. Neonatal stridor. Int J Peds. 2012; Article ID delivery room has been shown to increase oxidative stress and
859104, 5 pages, doi:10.1155/2012/859104.
Wei JL, Bond J. Management and prevention of endotracheal intu- increase mortality in full-term infants. Although oxygen ad-
bation injury in neonates. Curr Opin Otolaryngol Head Neck Surg. ministration has been shown to increase the preterm infants
2011; 19:474477. risk for retinopathy of prematurity and chronic lung disease
(i.e., bronchopulmonary dysplasia), it has not been shown to
exacerbate respiratory distress syndrome.
CASE 4 ANSWERS

1. C. Recovery begins at ~72 hours of age AMERICAN BOARD OF PEDIATRICS


Premature infants with surfactant deficiency can have respi-
CONTENT SPECIFICATIONS
ratory distress syndrome, which is also known as hyaline
membrane disease. Affected infants typically have respiratory Recognize the characteristic clinical and radiographic ap-
distress soon after birth. The peak severity of illness usually pearance of respiratory distress syndrome
occurs at 1 to 3 days of age. The recovery phase of this disease Understand the effects of surfactant administration in an
usually begins at ~3 days of age, coinciding with an increase infant with respiratory distress syndrome
in diuresis. Although prenatal exposure to steroids has been Know appropriate treatments for respiratory distress
shown to decrease the risk and severity of illness, this antena- syndrome
tal therapy does not alter the timing of respiratory symptoms.

2. A. Decrease alveolar surface tension


There are various types of synthetic surfactant that can be ad- SUGGESTED READINGS
ministered through an endotracheal tube of an infant with
respiratory distress syndrome. This exogenous surfactant is Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010.
Warren JB, Anderson JM. Respiratory distress syndrome. NeoReviews.
preferentially distributed to alveoli that have not yet collapsed. 2009;10:e351e361.
Once the compound reaches open alveoli, it can help to de-
crease the alveolar surface tension and decrease the pressure
needed to keep those alveoli open. Exogenous surfactant does CASE 5 ANSWERS
not have an impact on bronchiolar patency.
1. B. Left pneumothorax
3. A. Air bronchograms
Clinical findings in an infant with a pneumothorax include:
Radiographic findings in this disease include:
Respiratory distress
Air bronchograms (visible because the air within the
Cyanosis
bronchi are outlined by the surrounding collapsed)
Affected side with decreased breath sounds
Diffuse homogenous reticulogranular pattern, also
Affected side with increased anteriorposterior diameter
known as a ground-glass appearance that corresponds
of the chest
with multiple collapsed alveoli
Acute decrease in blood pressure if pneumothorax under
Low lung volumes
tension
All of these findings are evident in the chest radiograph of the
An infant with bilateral pneumothoraces will have bilaterally
infant in the vignette.
decreased breath sounds and a symmetric anteriorposterior
4. B. Avoidance of supplemental oxygen in the delivery chest diameter. The symptoms of the infant described in this
room vignette are most consistent with a left pneumothorax that is
There are multiple approaches to attempt to decrease the not under tension. Only a minority of infants with a pneumo-
severity of hyaline membrane disease in preterm infants. Be- mediastinum will have symptoms, which include tachypnea,
cause the severity of surfactant deficiency correlates indirectly distant heart sounds, and cyanosis.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 6 Meconium aspiration syndrome45

2. A. Bilateral pneumothoraces 2 Although this infant may ultimately need to be intubated,


B. Left pneumothorax 4 this is not the next best step in managing an infant with a
tension pneumothorax because the pressures from the ventila-
C. Pneumomediastinum 1
tor will increase the size of the pneumothorax. If an infant is
D. Right pneumothorax 3 already receiving ventilator-assisted breaths at the time of a
pneumothorax, the pressures should be decreased.
The hypotension in the infant in this vignette is caused by
A chest radiograph is helpful to diagnose a pneumothorax by
the tension pneumothorax. Treatment with a normal saline
demonstrating a hyperlucent area without pulmonary paren-
bolus will not improve this infants blood pressure. Instead,
chymal markings. If the anteroposterior radiographic view is
removal of the external air will improve the infants blood
not definitive, a lateral decubitus film with the suspected side
pressure.
of the pneumothorax positioned up will delineate the external
air more clearly. Bilateral pneumothoraces are shown in the
radiograph 2. In this anteroposterior chest radiograph, there is
a large right-sided pneumothorax, a left-sided pneumothorax, AMERICAN BOARD OF PEDIATRICS
and some mediastinal air extending into the neck region. CONTENT SPECIFICATIONS
A pneumomediastinum is evident in the first radiograph.
Recognize the characteristic clinical and radiographic ap-
In this anteroposterior chest radiograph, the thymic lobes are
pearance of a pneumothorax in a newborn
elevated by mediastinal air (white arrows on the right side and
Recognize that pulmonary air leaks are common in new-
black arrowheads on the left). This is often described as a spin-
borns who are treated with assisted ventilation
naker sail sign or angels wings sign.
A large right pneumothorax is evident on the third radio-
graph resulting in a collapsed right lung. The fourth chest
radiograph is consistent with a moderate left pneumothorax,
SUGGESTED READINGS
leading to a rightward shift of mediastinal structures. There Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
is also a suggestion of pulmonary interstitial emphysema 2010.
throughout the left upper and mid lung. Posner K, Needleman JP. Pneumothorax. Peds Rev. 2008;29:6970.

3. A. Esophageal atresia
A pneumothorax occurs when air enters the space between the CASE 6 ANSWERS
parietal pleura that lines the chest wall and the visceral pleura
that covers the lung. A pneumothorax occurs in the following 1. C. Intratracheal suctioning
situations: The most recent Neonatal Resuscitation Program guide-
lines from 2012 recommend that an apneic, inactive infant
Excessive bag-mask ventilation
born through meconium-stained amniotic fluid should un-
Severe lung disease requiring high ventilator pressures
dergo intratracheal suctioning immediately after delivery.
Spontaneous occurrence
This procedure is performed based on the newborns de-
Intubated infant with improving compliance
gree of activity rather than the degree of thickness of the
Intubated infant with expiratory efforts that oppose the
meconium-stained fluid. Meconium in an infants trachea
ventilator breaths
is then removed, preventing this meconium from being as-
Infants with esophageal atresia can have various symptoms, pirated. It is uncertain if the amount of meconium in an
depending on the communication with the trachea. Infants infants trachea is sufficient to cause meconium aspiration
can present with excessive oral secretions, feeding intolerance, syndrome, and most studies have shown that the aspiration
respiratory distress with feeding, and abdominal distention. occurs prior to birth.
Bag-mask ventilation is indicated if the baby in the vignette
4. C. Needle thoracentesis
remains apneic or bradycardic after the intratracheal intuba-
The left pneumothorax of the infant in this vignette has now
tion. Chest compressions are not indicated for initial brady-
increased in size. This is evident by the infants symptoms of
cardia until effective ventilation with bag-mask ventilation has
severe respiratory distress, hypotension, tachycardia, cyanosis,
been established. If bag-mask ventilation is ineffective at im-
and a displaced point of maximal cardiac impulse to the right.
proving the infants respiratory or cardiovascular status, intu-
These findings are consistent with a tension pneumothorax
bation to provide more effective positive pressure ventilation
that requires emergent removal of air by a needle thoracente-
is indicated.
sis. If the leak is continuous after needle aspiration, placement
of a chest tube may be necessary. 2. A. Meconium aspiration syndrome
If an infant has minimal symptoms associated with a pneu- Similar to the infant in this vignette, an infant with meconium
mothorax, conservative management is appropriate. This in- aspiration syndrome typically presents soon after birth with
cludes close observation for worsening symptoms.

(c) 2015 Wolters Kluwer. All Rights Reserved.


46Section II Pulmonology

respiratory distress and cyanosis. This infants chest radio-


graph shows the following: AMERICAN BOARD OF PEDIATRICS
CONTENT SPECIFICATIONS
Coarse, diffuse infiltrates
Hyperinflated lungs (the left and right diaphragms are Recognize the characteristic clinical and radiographic
located at ribs 10 and 11, respectively) appearance of meconium aspiration syndrome
Heterogenous lung disease
Areas of overdistention as a result of air trapping from
SUGGESTED READINGS
airway obstruction

These findings are consistent with meconium aspiration Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010.
Yeh TF. Meconium aspiration syndrome: Pathogenesis and current
syndrome. management. NeoReviews. 2010;11:e503e512.
An infant with a pneumothorax will have a hyperlucent
area in the lung region that does not have pulmonary paren-
CASE 7 ANSWERS
chymal markings. Radiographic findings in an infant with
respiratory distress syndrome include low lung volumes, dif- 1. A. Congenital pneumonia
fuse reticulogranular pattern, and air bronchograms. An infant The chest radiograph of the infant in this vignette is most
with retained fetal lung fluid (i.e., transient tachypnea of the consistent with pneumonia. Classic radiographic findings of
newborn) has hyperinflated lung fields, fluid in the pleural congenital pneumonia include unilateral or bilaterally streaky
effusion, perihilar linear densities, and, sometimes, pleural ef- densities, opacifications, a pleural effusion, and, sometimes,
fusions evident on the chest radiograph. a granular appearance with air bronchograms. Because the ra-
3. C. Pulmonary interstitial emphysema diographic findings of congenital pneumonia can mimic im-
After experiencing intrauterine stress, a fetus may pass meco- ages of surfactant deficiency, it is often difficult to distinguish
nium. If the fetus becomes hypoxemic and has fetal gasping, between these two diseases. Thus, premature infants with re-
the risk of intrauterine aspiration is increased. When meco- spiratory distress are often treated initially with antibiotics.
nium enters the infants lung, it causes a(n): The infants clinical course and blood culture results will then
help to determine the length of antibiotic treatment.
Acute airway obstruction
Possible chemical pneumonitis 2. D. All of the above
Pulmonary vasoconstriction and pulmonary hypertension The infant in this vignette has other findings consistent with
Surfactant dysfunction pneumonia, including a low white blood cell count, an abnor-
mal differential with increased immature white blood cells, and
Infants with severe chronic lung disease of prematurity (i.e., bron- thrombocytopenia. Congenital pneumonia can be a cquired by
chopulmonary dysplasia) may have pulmonary interstitial em- aspiration of contaminated amniotic fluid, ascending vaginal
physema; this complication is not typically found in infants with flora, or a transplacental route
meconium aspiration syndrome. A general overview of the patho-
genesis of meconium aspiration syndrome is outlined in Figure 2. 3. C. Listeria monocytogenes
A newborn can acquire pneumonia in utero, intrapartum, or
postnatally. Because this infant presented soon after birth, his
Maternalfetal compromise
pneumonia was most likely acquired during pregnancy or
delivery. The specific organisms that are associated with intra-
Perinatal asphyxia
uterine, intrapartum, and postnatal acquisition of pneumonia
are summarized in the table below.
Fetal Passage of meconium
gasping
Acquisition
Aspiration of meconium Period Associated Organisms

Chemical Pulmonary Intrauterine Adenovirus, cytomegalovirus, herpes


pneumonitis vasoconstriction simplex virus, human immunodeficiency
Acute airway virus, rubella, mumps
obstruction Alevolar edema Intrapulmonary Listeria monocytogenes
and or Mycobacterium tuberculosis
Increased surfactant dysfunction intracardiac Toxoplasma gondii
airway resistance shunt
Treponema pallidum
Hypoxia
Varicella zoster
Air trapping
Intrapartum Group B Streptococcus
Hypoxemia
Escherichia coli, Klebsiella sp
FIGURE 2. From MacDonald G, Seshia MK, et al. Averys Neonatology:
Pathophysiology & Management of the Newborn. 6th ed. Philadelphia, C. trachomatis (clinical presentation typi-
PA: Lippincott Williams & Wilkins; 2005. Figure 29.8 cally at approximately age 3 weeks)

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 8 Tachypnea47

demonstrates an acute respiratory acidosis without a meta-


Acquisition
bolic component (i.e., normal HCO3).
Period Associated Organisms
In addition to TTN, a full-term infant born to a mother with
Postnatal Adenovirus, respiratory syncytial virus insulin-dependent diabetes is also at increased risk for surfac-
Gram-positive bacteria (groups A, B, and tant deficiency. Infants with surfactant deficiency typically have
G streptococci, Staphylococcus) signs of respiratory distress and a chest radiograph that shows
Gram-negative enteric bacteria (Klebsiella a reticulogranular pattern, air bronchograms, and decreased
sp, Proteus sp, Pseudomonas aeruginosa,
aeration. None of these findings were evident in this vignette.
flavobacteria, Serratia marcescens, E. coli)
Congenital heart disease is more likely to occur in an infant
born to a mother with insulin-dependent diabetes. However,
AMERICAN BOARD OF PEDIATRICS the infant in this vignette is unlikely to have cyanotic heart dis-
CONTENT SPECIFICATIONS ease because the infant has a normal arterial Po2 with a small
amount of supplemental oxygen.
Differentiate between the normal results of a newborns
chest X-ray and the radiographic patterns that reflect 2. D. Start maintenance intravenous fluid and provide
pneumonia supplemental oxygen
Recognize that neonatal pneumonia can mimic respira- Infants with TTN may need a small amount of oxygen supple-
tory distress syndrome mentation to maintain a normal oxygen saturation; mechani-
cal ventilation is rarely required. Because the infant in this
vignette is breathing rapidly, most neonatologists would hold
SUGGESTED READINGS off on allowing the baby to feed and instead provide mainte-
nance intravenous fluid.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; For infants with a metabolic acidosis, treatment may in-
2010. clude a normal saline bolus if the infants cardiac output is
Flidel-Rimon O, Shinwell ES. Respiratory distress in the term and
near-term infant. NeoReviews. 2005;6:e289e297.
decreased (evident by decreased distal pulses, poor perfusion,
and a low blood pressure). Intravenous NaHCO3 is indicated
only if an infant has a significant metabolic acidosis with nor-
CASE 8 ANSWERS mal ventilation.
Supplemental oxygen is avoided in infants with a left-sided
1. C. Retained fetal lung fluid obstructive lesion (e.g., left hypoplastic heart syndrome, aortic
The infant in this vignette is an infant of a diabetic mother stenosis, mitral stenosis) to prevent a decrease in pulmonary
who was born by cesarean and presents soon after birth with vascular resistance. By maintaining a high pulmonary vascu-
mild cyanosis that improves with a small amount of supple- lar resistance, shunting across the patent ductus arteriosus can
mental oxygen. The baby also has tachypnea without respi- continue to be right-to-left (i.e., pulmonary artery to aorta)
ratory distress and is well-appearing with a normal blood to provide systemic cardiac output. Infants with a left-sided
pressure and normal perfusion. The chest radiograph demon- cardiac obstruction will also require a prostaglandin infusion
strates perihilar vascular densities, streaky opacities of intersti- to maintain ductal patency.
tial edema, and fluid in the horizontal fissure of the right lung. Although antibiotics will not alter the clinical course of in-
The most likely cause of the infants tachypnea is retained fetal fants with TTN, they can be administered to treat a bacterial
lung fluid, also known as transient tachypnea of the newborn infection (e.g., pneumonia, sepsis, urinary tract infection).
(TTN).
3. C. Resolution of tachypnea within 48 hours of age
TTN is caused by a delay in fetal lung fluid reabsorption.
Infants with TTN typically have a normal respiratory rate
Risk factors for developing TTN include:
within 1 to 5 days of life and usually by 48 hours of age. In-
Cesarean birth without a period of labor fants may require oxygen and, in some cases, continuous posi-
Perinatal depression tive airway pressure. It is unlikely that an infant with TTN will
Maternal diabetes or asthma have decreased distal perfusion (as might occur with ductal
Anesthesia during labor closure in an infant with a ductal-dependent left-sided cardiac-
obstructive lesion) or worsening cyanosis (as might occur with
Affected infants present soon after birth with comfortable
ductal closure in an infant with a ductal-dependent right-sided
tachypnea (as high as 120 breaths per minute) without sig-
cardiac-obstructive lesion).
nificant respiratory distress.
An infant with a metabolic acidosis can also have tachy-
pnea without significant respiratory distress. Affected infants AMERICAN BOARD OF PEDIATRICS
may have a gray or ashen color associated with poor perfusion CONTENT specifications
and a low blood pressure because of decreased cardiac out-
Identify and manage transient tachypnea of the newborn
put. The infant in this vignette has an arterial blood gas that

(c) 2015 Wolters Kluwer. All Rights Reserved.


48Section II Pulmonology

SUGGESTED READINGS require greater than 100% of the recommended dietary allow-
ance of calories in order to grow. This is a result of increased
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; energy expenditure associated with their respiratory disease.
2010. Poor growth in infants with BPD may be a sign of insufficient
Flidel-Rimon O, Shinwell ES. Respiratory distress in the term and
near-term infant. NeoReviews. 2005;6:e289e297. oxygenation.
Infants with BPD are also at greater risk of developing an
oral aversion and of having gastroesophageal reflux that may
CASE 9 ANSWERS worsen their respiratory status. In addition, affected infants are
also at increased risk for neurodevelopmental disabilities.
1. B. Bronchopulmonary dysplasia (BPD)
The infant described in this vignette has a postmenstrual age
of 36 weeks gestation. Her chest radiograph shows general- AMERICAN BOARD OF PEDIATRICS
ized overaeration, a heterogeneous pattern of lung disease, CONTENT SPECIFICATIONS
and multiple cystic regions bilaterally. These radiographic
Recognize that BPD can develop in a newborn, regard-
findings are consistent with BPD. BPD is caused by multiple
less of gestational age, who has been treated with artifi-
factors that impact the prenatal (e.g., infection, intrauterine
cial ventilation and an enriched oxygen concentration
stress, glucocorticoid exposure) and postnatal (e.g., mechani-
Recognize that infants with BPD may require home oxy-
cal ventilation, glucocorticoid therapy, nutritional deficien-
gen therapy
cies, inflammation) development of the lung. An overview of
Recognize that infants with BPD are prone to cor pul-
the pathogenesis of BPD is shown in Figure 2.
monale, recurrent wheezing with infections, and severe
Pathogenesis of BPD respiratory infections
Recognize that failure to thrive is common in infants
Infection/Cytokines Initiation with BPD
of Glucocorticoids
Stress
Know that infants with BPD often require greater than
ventilation
Nutrition 100% of the recommended dietary allowance of calories
in order to grow
Intrauterine lung Postnatal lung Lung injury,
development development inhibition of Know that poor growth may be a sign of insufficient oxy-
lung genation in an infant with BPD
development Recognize that aversive oral motor behavior is associ-
Antenatal
Inflammation ated with BPD
glucocorticoids
Recognize that gastroesophageal reflux is a common as-
Oxygen Overdistention Infection sociation in infants with BPD and that it may aggravate
FIGURE 2. Adapted from Jobe AH. The new BPD: An arrest of lung
their respiratory status
development. Pediatr Res. 1999;46:641, with permission

Although most infants who develop BPD are born prema-


SUGGESTED READINGS
turely, this lung disease can develop in any newborn, regard- Adams JM, Stark AR. Outcome of infants with bronchopulmonary
less of gestational age, who has been treated with artificial dysplasia. UpToDate. Accessed on March 1, 2013.
ventilation and exposed to increased oxygen concentrations. Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
2. D. All of the above Jobe AH. The new BPD. NeoReviews. 2006;7:e531e545.
Infants with severe BPD are prone to pulmonary artery
hypertension that can lead to cor pulmonale (i.e., right heart
failure). These outcomes result from both structural and func- CASE 10 ANSWERS
tional changes of the infants lung. Recurrent wheezing epi-
1. A. Esophageal atresia with a distal tracheoesophageal
sodes are also common in children with BPD less than 2 years
fistula (TEF)
of age. Infants with BPD are also prone to respiratory infec-
The infant in this vignette presented with increased oral secre-
tions, especially respiratory syncytial virus (RSV). Thus, infants
tions and the neonatology team was unable to pass a nasogas-
with BPD receive a vaccination containing a monoclonal anti-
tric tube into the infants stomach. This suggests that the infant
body against RSV during their first winter to decrease the risk
has an esophageal atresia. This diagnosis explains the prena-
of hospitalization if they acquire this virus.
tal finding of polyhydramnios because of the fetuss inability
3. D. Poor growth in infants with BPD is often related to to swallow amniotic fluid. Because air is noted in the infants
the infants oxygenation status stomach and proximal intestines, a connection between the
As exemplified by the infant in this vignette, failure to thrive is trachea and the distal esophagus must exist. Of the five types of
common in infants with BPD. Indeed, infants with BPD often tracheoesophageal abnormalities shown in the options, only

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 11 Congenital malformations of the lung 49

option A (esophageal atresia with a distal TEF) and option E SUGGESTED READINGS
(esophageal atresia with a distal and proximal TEF, a rare type
of TEF) correlate with this infants clinical findings. Because op- Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
tion A is more common, occurring in 86% of infants with a 2010.
Hansen TN, Cooper TR, Weisman LE. Contemporary Diagnosis and
TEF, this is the infants most likely diagnosis. Management of Neonatal Respiratory Diseases. 2nd ed. Newtown, CT:
An infant with option B (esophageal atresia without a TEF, Handbooks in Health Care; 1998.
5%8%) or option D (esophageal atresia with proximal TEF, Kovesi T, Rubin S. Long-term complications of congenital esophageal
atresia and/or tracheoesophageal fistula. Chest. 2004;126;915925.
a rare type of TEF) will present with increased oral secretions
but air will not be present in the stomach or intestines. In-
fants with an H-type TEF without esophageal fistula (option
CASE 11 ANSWERS
C, 2%3%) may present later with recurrent pneumonias or
difficulty with feedings. Infants with any of these types of tra- 1. A. Bronchogenic cyst 2
cheoesophageal abnormalities can also present with cyanosis,
B. Congenital cystic adenomatoid 3
coughing or choking with feedings.
malformation (CCAM)
2. C. Place a suction catheter into the esophageal blind C. Congenital diaphragmatic hernia (CDH) 4
pouch to remove secretions and consult Pediatric Surgery D. Pulmonary interstitial emphysema (PIE) 1
After an infant is diagnosed with a TEF, it is important to
place a suction catheter into the esophageal blind pouch to
A bronchogenic cyst is evident in radiograph 2 because of a
continuously remove secretions. Following, the neonatology
well-defined hyperaerated area within the right lower lobe. Ra-
team should consult with a Pediatric Surgery.
diograph 3 reveals a fluid-filled mass that appears as a density in
The other options in this question are all incorrect. A na-
the right hemithorax, which is consistent with a CCAM. A left-
sogastric feeding tube cannot be placed in an infant with an
sided congenital diaphragmatic hernia is evident in radiograph
esophageal atresia and distal TEF. Positive pressure ventilation
4 shown by intestinal contents within the left lung and a shift in
should be avoided in the infant in this vignette because gastric
the heart to the right side. Radiograph 1 demonstrates an infant
distention will be excessive. Intravenous prostaglandin is indi-
with pulmonary interstitial emphysema in the left lung.
cated only if an infant with a TEF also has a ductal-dependent
cardiac defect. 2. D. Reevaluate at 1 to 2 months of age with a computed
tomography scan to evaluate the lesion in more detail
3. A. Apneic episodes
An infant with a prenatal diagnosis of a CCAM can have a vari-
An infant with a TEF requires surgical repair to resect any
able outcome. If the mass is large, an infant may present with
fistula and anastomose any incongruent esophageal seg-
respiratory distress soon after birth. However, some lesions
ments. After surgery, infants can have the following potential
regress or disappear and, similar to the infant in this vignette,
complications:
an affected infant may be asymptomatic after birth. Asymp-
Dysphagia because of impaired esophageal peristalsis tomatic infants with a prenatal diagnosis of a CCAM should
Esophageal stricture as a result of acidic gastric fluid erod- have a postnatal radiograph after birth and a computed to-
ing the shortened esophagus mography scan at 1 to 2 months of age to evaluate the lesion
Gastroesophageal reflux in more detail. Although ~20% of asymptomatic infants with
Leakage of esophageal contents at the point of anastomosis radiographic evidence of a CCAM have complete regression of
Recurrence of the fistula the abnormality, the remaining 80% have persistence of the
lesions. Symptomatic infants will require surgical resection.
Infants with a TEF may have respiratory complications (e.g.,
Because of the concern that a persistent CCAM may lead to
recurrent pneumonia, aspiration, poor coordination with
recurrent infections or pose a malignancy risk, most surgical
feedings) as a result of reflux, tracheomalacia, recurrent fistula,
centers resect the mass of asymptomatic infants as an elective
and esophageal stricture.
procedure during childhood.

3. D. All of the above


AMERICAN BOARD OF PEDIATRICS
A decrease in amniotic fluid volume (i.e., oligohydramnios)
CONTENT SPECIFICATIONS
can be caused by renal agenesis, renal obstruction (associated
Recognize the signs and symptoms of esophageal atresia with hydronephrosis), uteroplacental insufficiency, or a rup-
with tracheoesophageal fistula ture of chorioamniotic membranes. Because maintenance of
Know how to evaluate an infant with a tracheoesopha- amniotic fluid is important for fetal lung growth, the fetus may
geal fistula develop pulmonary hypoplasia and extremity contractures if
Know that tracheoesophageal fistula may result in the oligohydramnios is prolonged and severe (see Figure 5).
tracheomalacia Infants with pulmonary hypoplasia often have persistent pul-
monary hypertension because the pulmonary vasculature has

(c) 2015 Wolters Kluwer. All Rights Reserved.


50Section II Pulmonology

developed poorly. The infant in this vignette is also prone to


septic shock from chorioamnionitis if the cause of the oligohy- AMERICAN BOARD OF PEDIATRICS
dramnios results from rupture of membranes. CONTENT SPECIFICATIONS
Recognize that congenital malformations of the lung
(e.g., hypoplastic lung, cystic adenomatoid malforma-
tion) may cause respiratory signs and symptoms

SUGGESTED READINGS
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
DiPrima FA, Bellia A, Inclimona G, et al. Antenatally diagnosed
congenital cystic adenomatoid malformations. J Prenat Med.
2012;6:2230.

FIGURE 5. Image from Rubin E, Farber JL. Pathology. 3rd ed.


Philadelphia, PA: Lippincott Williams & Wilkins; 1999. Figure 6.04

(c) 2015 Wolters Kluwer. All Rights Reserved.


S E C T I ON III Cardiology

(c) 2015 Wolters Kluwer. All Rights Reserved.


52Section III Cardiology

CASE 1
Congenital heart disease

A nurse in the Neonatal Intensive Care Unit (NICU) asks


about the difference in the mean blood pressure of the infant
born at 40 weeks gestation she is caring for today compared
to the 24-week-gestational-age infant she was caring for the
day before. Although the gestational age-specific blood pres-
sure that provides adequate organ perfusion is uncertain, you
A
are aware that linear regression models for gestational age and
blood pressure exist.

60 C
Mean BP (mm Hg)

B
40

A
20

22 42
Week of gestation
FIGURE 1.
B
1. Of the following, the line in the Figure 1 that best repre- PICTURE A. From MacDonald G, Seshia MK, et al. Averys Neonatology:
Pathophysiology & Management of the Newborn. 6th ed. Philadelphia,
sents the correlation between mean blood pressure and
PA: Lippincott Williams & Wilkins; 2005. Figure 38.3AB
gestational age is:

A. Line A
B. Line B
C. Line C
D. None of the above

The nurse then comments that the term infant has dysmorphic
features and a murmur. You remember that some infants with
dysmorphic features are at increased risk for congenital heart
disease (CHD).

2. Match the following pictures of patients (Pictures AE)


with dysmorphic features to the appropriate CHD (listed
as iv):
A

B
PICTURE B. From MacDonald G, Seshia MK, et al. Averys Neonatology:
Pathophysiology & Management of the Newborn. 6th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2005. Figure 38.4AB

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 1 Congenital heart disease53

A. _____ i. Atrioventricular canal


B. _____ ii. Coarctation of the aorta
C. _____ iii. Conotruncal defect
D. _____ iv. Atrial septal defect
E. _____ v. Ventricular septal defect

3. Match the syndrome with the corresponding increased risk


for CHD:

A. CHARGE Association i. 25%


B. Rubinstein-Taybi syndrome ii. 4550%
PICTURE C. From Sadler T. Langmans Medical Embryology. 9th ed.
Image Bank. Baltimore, MD: Lippincott Williams & Wilkins; 2003.
C. Trisomy 18 iii. 5070%
Figure 6.08B D. Trisomy 21 iv. >90%

A. _____
B. _____
C. _____
D. _____

4. Of the following, the most appropriate evaluation of an in-


fant with increased risk for CHD includes:
A. Physical examination, chest radiography, and
electrocardiography
B. Pre- and postductal oxygen saturations and a hyper-
oxia test
C. Echocardiography
D. All of the above

PICTURE D. From Roberts R. Atlas of Infectious Diseases. Mandell G


(series ed), Wilfert CM, eds. Philadelphia, PA: Current Medicine, Inc;
1998. Figure 21.2

PICTURE E. From MacDonald G, Seshia MK, et al. Averys Neonatology:


Pathophysiology & Management of the Newborn. 6th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2005. Figure 38.6AB

(c) 2015 Wolters Kluwer. All Rights Reserved.


54Section III Cardiology

CASE 2
Cyanosis

A full-term female infant in the well-baby nursery is noted to 3. Refer to the oxyhemoglobin dissociation curve below and
be cyanotic. select the most likely Pao2:

1. Which of the following statements about cyanosis in the A. 15 mm Hg


newborn is true? B. 30 mm Hg
C. 50 mm Hg
A. Central cyanosis is evident in mucous membranes and D. 70 mm Hg
is observed if there is >3 to 5 g of reduced hemoglobin
per deciliter of capillary blood.
B. Peripheral cyanosis (i.e., acrocyanosis) is a common 100
finding in healthy full-term newborns.
90
C. Peripheral cyanosis (i.e., acrocyanosis) is limited to the
extremities. 80
Newborn
D. All of the above HbO2 Saturation (%)
70 2 months

The infant has cyanotic mucous membranes and a bluish- 60 Adult


colored tongue but does not have any respiratory distress.
50

2. Select potential etiologies for this infants central cyanosis: 40

A. Idiopathic persistent pulmonary hypertension of the 30


newborn (PPHN)
20
B. Tetralogy of Fallot (TOF), pulmonary valve atresia, tri-
cuspid atresia 10
C. Surfactant deficiency 0
D. A and B 0 20 40 60 80 100
PO2 (torr, pH 7.4)
The nurse places a pulse oximeter on the infants right hand
and the oxygen saturation is 60%. The infants color does not FIGURE 1. From Hodson WA, Truog WE. In: Avery GB, Fletcher MA,
MacDonald MG, eds. Neonatology: Pathophysiology and Management of
improve after being placed in a 100%-oxygen hood.
the Newborn. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins;
1999, with permission

CASE 3
Cardiogenic shock

A 3-day-old full-term male infant, born via spontaneous vagi- 1. Select the information you feel would be most helpful for
nal delivery, was scheduled to go home when he is noted to be your preliminary diagnosis:
acutely cyanotic, tachypneic, and poorly perfused. His room
A. Complete blood count with differential and blood
air oxygen saturation (Sao2) is 54% and his blood pressure is
culture
40/28 (32).
B. Electrolyte measurements and blood glucose
concentration
C. Family history
D. Physical examination, four extremity blood pressures,
pre- and postductal oxygen saturations, chest radiogra-
phy, electrocardiography, and arterial blood gas

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 4 Non-cardiogenic shock55

The infants physical examination findings include central cya- 3. Because the infant in this vignette had of symptoms of
nosis, tachypnea, tachycardia, delayed capillary refill of 3 to cardiogenic shock on day 3 of life, the infants most likely
4 seconds, and cool extremities. Laboratory results and imag- heart lesion is:
ing for this infant reveal increased lung markings on the chest
A. Hypoplastic left heart syndrome (HLHS)
radiograph, arterial blood gas findings of metabolic acidosis
B. Pulmonary valve stenosis
and hypoxemia, pre- and postductal differential in oxygen
C. Tetralogy of Fallot (TOF)
content of 15 mm Hg, a complete blood count without a
D. Tricuspid atresia
left shift, normal serum electrolytes, and a blood glucose of
62mg/dL. The family history is not significant. Although you
have ordered an electrocardiogram and echocardiography, the
technician will not be available for one hour.

2. Select the initial therapeutic management for this infant:

A. Administer bicarbonate bolus to correct the infants


metabolic acidosis
B. Consider intubation and mechanical ventilation
C. Consult with a cardiologist and start prostaglandin E1
(PGE1)
D. All of the above

CASE 4
Non-cardiogenic shock

A 25-year-old pregnant woman at 37 weeks gestation presents 2. From the choices below, select the next most appropriate
to the labor and delivery floor with copious vaginal bleeding. therapy for this infant:
Her pregnancy has been uncomplicated. The male infant is
A. Antibiotics
born via stat cesarean under general anesthesia. He emerges
B. Emergency administration of O-negative blood
floppy with marked pallor, perioral cyanosis, and no pulse or
C. Normal saline (NS) bolus until O-negative blood arrives
respiratory rate.
D. B and C
1. With the limited data above, select the best choice for the The infants HR is now 170 beats per minute with a BP mean
infants preliminary diagnosis: of 32 mm Hg. He remains extremely pale with cool extremi-
A. ABO blood type incompatibility ties. His birth hematocrit is 21%. He has received a total of
B. Hypovolemic shock as a result of a placental abruption 20 ml/kg of NS and 10 ml/kg of O-negative blood.
and blood loss
3. From the choices below, select the next most appropriate
C. Reaction to maternal general anesthesia
therapy for this infant:
D. Sepsis
A. Additional 10 ml/kg of NS
The resuscitation team acts swiftly, following the Neonatal Re-
B. Another 10 ml/kg of O-negative blood
suscitation Program guidelines. The team intubates the infant,
C. Intravenous 2 ml/kg bolus of glucose
places an umbilical venous catheter (UVC), and administers
D. Intravenous 1 mEq/kg bolus of bicarbonate
two doses of intravenous epinephrine. The infants heart rate
(HR) is now 100.

(c) 2015 Wolters Kluwer. All Rights Reserved.


56Section III Cardiology

CASE 5
Cyanotic heart disease: Diagnosis and management

A male infant was born via spontaneous vaginal delivery at 4. Of the following, the congenital cardiac lesions associated
39 3/7 weeks gestation to a 24-year-old G2 P0 woman with with decreased pulmonary blood flow are:
reassuring prenatal screens, including negative Group B Strep-
A. ASD, VSD, AS, coarctation of the aorta, atrioventricular
tococcus status. The membranes had spontaneously ruptured 4
canal (AVC) without PS
hours prior to delivery and the mother did not have a fever. The
B. Critical PS, tricuspid atresia, PA, TOF, Ebstein anomaly,
infants Apgar scores were 8 and 9 at 1 and 5 minutes, respec-
TAPVR with obstruction
tively. The infant stayed with his mother and attempted breast-
C. HLHS, TGA, truncus arteriosus, TOF with PA, TAPVR
feeding. During the second breastfeeding attempt at 4 hours of
without obstruction, single ventricle
age, the nurse noted that he had tachypnea and cyanosis.
D. B and C
1. Of the following, the preferred initial assessment to deter- The infants examination was notable for severe cyanosis, non-
mine whether this infants cyanosis results from a respira- dysmorphic features, and absence of murmur. He had a pre-
tory or cardiac cause is: ductal oxygen saturation (right arm) that was 20% lower than
A. Complete blood count, blood culture, and arterial his postductal oxygen saturation (leg). The infants chest radio-
blood gas (ABG) graph is shown in Figure 1. His electrocardiogram had a normal
B. Echocardiography QRS axis. Echocardiography revealed a cyanotic heart defect.
C. Family history
D. Physical examination, chest radiograph, electrocardio-
gram, hyperoxia test

This infants hyperoxia test results were consistent with cya-


notic heart disease.

2. Of the following, the technique that best describes the hy-


peroxia test is:
A. Assessment of the amount of supplemental oxygen re-
quired to obtain an oxygen saturation 95%
B. Measurement of the infants arterial Pao2 in room air
C. Measurement of the infants arterial Pao2 while receiv- FIGURE 1. Eisenberg L. An Atlas of Differential Diagnosis. 4th ed.
ing 50% Fio2 Philadelphia, PA: Lippincott Williams & Wilkins; 2003. Figure 10.2
D. Comparison of the infants arterial Pao2 in room air
with the infants Pao2 while receiving 100% Fio2
5. Of the following, the most appropriate next step(s) in the
3. Of the following, the congenital cardiac lesions that pres- management of this infant is (are):
ent with cyanosis are: A. Consult the cardiology service
A. Atrial septal defect (ASD), ventricular septal defect B. Educate parents about the lesion and discuss that a
(VSD), aortic stenosis (AS), coarctation of the aorta Rashkind procedure may be needed to increase the size
B. Critical pulmonary stenosis (PS), truncus arteriosus, of the foramen ovale
pulmonary atresia (PA) with intact ventricular septum, C. Initiate an intravenous prostaglandin (PGE1) infusion
Ebstein anomaly, total anomalous pulmonary venous to maintain patency of the ductus arteriosus
return (TAPVR) with obstruction D. All of the above
C. Hypoplastic left heart syndrome (HLHS), transposition
6. Of the following, the possible side effects of an intravenous
of the great arteries (TGA), tricuspid atresia, TOF with
PGE1 infusion is (are):
PA, TAPVR without obstruction, single ventricle
D. B and C A. Apnea
B. Flushing
C. Hypotension
D. All of the above

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 7 Differential cyanosis57

CASE 6
Cyanotic heart disease: Outcomes

A full-term female infant was discharged to home on day 3 of 2. From the choices below, select the statement that best re-
life. Her course was unremarkable until 3 weeks of age when flects her prognosis:
her mother noted that she was tiring with feedings and be-
A. Good long-term survival and excellent quality life
coming tachypneic. Her mother also noted that when the baby
B. Progressive RVH and heart failure
awakened from sleep, her lips and face turned blue while cry-
C. Unlikely to survive beyond age 30
ing. The mother brought the infant to the emergency room
D. A and B
(ER) where her room air oxygen saturations with crying are
found to be 70%. Her electrocardiogram shows right ventricu- The infant is followed regularly in a cardiology clinic that mon-
lar hypertrophy (RVH), and her chest radiograph is described itors patients with cyanotic congenital heart disease (CHD).
as a boot-shaped heart with a right aortic arch.
3. From the choices below, select the statement that reflects
1. Of the following, the diagnosis that most likely explains the prognosis for cognitive development for patients seen
this infants desaturation events while crying is: in the cyanotic CHD clinic:

A. Foreign body aspiration A. Improved neurodevelopmental outcome as a result of


B. Pneumonia environmental factors (e.g., early intervention programs
C. Pulmonary edema and school programs, including tutoring, special educa-
D. Tet spell tion, and speech therapy)
B. Increased risk for neurodevelopmental delay because of
The infant had a complete surgical repair and her symptoms
biologic risk factors (e.g., underlying genetic syndromes
resolved. She does not have an underlying genetic abnormal-
or developmental disorders)
ity or any confounding risk factors.
C. Potential for behavioral abnormalities with impaired
social interaction, inattention, and impulsive behavior
D. All of the above

CASE 7
Differential cyanosis

A 5-hour-old male infant born at 41 weeks gestation via spon- 1. Of the following, the diagnosis that is most likely in the
taneous vaginal delivery is noted to be cyanotic with retractions. infant in this vignette is:
He is brought to the Special Care Nursery, where his oxygen
A. Cyanotic congenital heart disease (CHD)
saturations are 80% in room air. His preductal oxygen satura-
B. Persistent pulmonary hypertension
tions are ~10% higher than his postductal oxygen saturations.
C. Surfactant deficiency
D. A or B

(c) 2015 Wolters Kluwer. All Rights Reserved.


58Section III Cardiology

The rest of his history reveals that he was born through thick He has a mixed acidosis on his arterial blood gas. Echocar-
particulate meconium-stained amniotic fluid. His first chest diography shows pulmonary pressures greater than systemic
radiograph after intubation is shown in Figure 1. pressures, evident by moderate tricuspid regurgitation, bow-
ing of the ventricular septum into the left ventricle, and right-
to-left (pulmonary artery to aorta) shunting across the patent
ductus arteriosus.

2. Of the following, the most effective therapy to increase this


infants pulmonary blood flow is:

A. Antibiotics
B. Inhaled nitric oxide
C. Thirty percent oxygen
D. All of the above

FIGURE 1. MacDonald G, Seshia MK, et al. Averys Neonatology:


Pathophysiology & Management of the Newborn. 6th ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 2005. Figure 29.9

CASE 8
Arrhythmias

A 37-year-old G4P0 pregnant woman presents for her regu- 1. Of the following, the most accurate statement about fetal
larly scheduled prenatal appointment at 28 weeks gestation. arrhythmias is:
Her obstetrician notes an intermittent fetal arrhythmia. She
A. About 1 to 2% of fetuses have fetal arrhythmias; of
undergoes fetal echocardiography with Doppler imaging
those, 10% have associated morbidity.
and, at a follow-up visit, also has fetal magnetocardiography
B. Fetal supraventricular tachycardia (SVT) represents 70%
to observe the fetal cardiogram signals. The womans sister
to 80% of fetal tachyarrythmias.
has lupus, and her sisters most recent pregnancy had been
C. Lupus is associated with fetal or neonatal complete
complicated by a fetal arrhythmia. This patient does not have
heart block.
lupus but has many questions about fetal arrhythmias.
D. All of the above

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 8 Arrhythmias59

The result of the fetal testing shows that the fetal arrhythmia is During the rest of the pregnancy, the fetus remains healthy.
most consistent with intermittent SVT. The fetal arrhythmia is not sustained, and intrauterine inter-
ventions are not required. The baby is born at term and ap-
2. Match the EKG with the corresponding arrhythmia. pears healthy. He is hemodynamically stable but continues to
1. QRS T have SVT after delivery and needs treatment.

3. Select the first-line treatment for intrauterine treatment and


the first-line treatment for postnatal treatment, respectively:

A. Adenosine, adenosine
B. Digoxin, vagal maneuvers
C. Sotalol, vagal maneuvers
D. Verapamil, adenosine
FIGURE 1. From Bickley LS, Szilagyi P. Bates Guide to Physical
Examination and History-Taking. 8th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2003. Figure 17.5

2.

FIGURE 2. From Harwood-Nuss A, Wolfson AB, et al. The


Clinical Practice of Emergency Medicine. 3rd ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2001. Figure 134.4

3.

FIGURE 3. From LifeART 2014 Lippincott Williams &


Wilkins. All rights reserved

4.

FIGURE 4. From AACN Clinical Simulations: Hemodynamic


Monitoring. [CD-ROM]. Philadelphia, PA. Lippincott Williams
& Wilkins, 2001.

A. Premature atrial contractions (PACs) ____


B. Premature ventricular contractions (PVCs) ____
C. Supraventricular ventricular tachycardia (SVT) ____
D. Ventricular tachycardia (VT) ____

(c) 2015 Wolters Kluwer. All Rights Reserved.


60Section III Cardiology

SECTIONIII
Answers

Picture D is a postoperative picture of an infant with 22q11


CASE 1 ANSWERS
microdeletion, also known as DiGeorge syndrome. This infant
1. A. Line A has misshapen ears, a prominent nose, and micrognathia.
Line A shows that an infants mean blood pressure value in- Picture E shows some findings in a patient with 45,XO or
creases with increasing gestational age. An infants mean arte- Turner syndrome, including pedal edema and a webbed neck.
rial blood pressure (MAP) can be calculated by the following 3. A. CHARGE Association iii. 5070%
formula:
B. Rubinstein-Taybi syndrome i. 25%
MAP = ([2 diastolic pressure] + systolic pressure)/3 C. Trisomy 18 iv. 90%
In general, the normal mean arterial pressure in preterm in- D. Trisomy 21 ii. 4550%
fants and newborns can be calculated by taking the infants
gestational age (in weeks) and adding 25. 4. D. All of the above
The appropriate evaluation of an infant with increased risk for
Normal MAP = gestational age (weeks) + 25 CHD includes a physical examination to evaluate the following:

Dysmorphic features
110 Upper 95% CL Presence or absence of murmur
100 Quality of femoral pulses
90 Presence or absence hepatomegaly
Systolic blood pressure

80 Degree of capillary refill


70
In addition, the evaluation should include a(n):
(mm Hg)

60
50 Chest radiography
Lower 95% CL
40 Electrocardiography
30 Pre- and postductal oxygen saturations
20 Hyperoxia test
10 When possible, an echocardiography is important to confirm
0 the diagnosis and delineate the complete structure of the
24 26 28 30 32 34 36 38 40 42 44 46
Postconceptional age (wk)
heart. For critically ill infants or those with severe cyanosis,
FIGURE 2. Linear regression of mean systolic blood pressure on
echocardiography may need to be obtained emergently.
postconceptional age (gestational age in weeks plus weeks after
delivery). Data from Zubrow AB, Hulman S, Kushner H, et al.
Determinants of blood pressure in infants admitted to Neonatal AMERICAN BOARD OF PEDIATRICS
Intensive Care Units: A prospective multicenter study. Philadelphia CONTENT SPECIFICATIONS
Neonatal Blood Pressure Study Group. J Perinatol. 1995;15:470479
Know that blood pressure values vary directly with gesta-
2. A. i. tional age
Recognize the increased risk and plan appropriate evalu-
B. v.
ation of congenital heart disease in a newborn with
C. iv. congenital anomalies (e.g., trisomy 21, trisomy 18, fetal
D. iii. alcohol syndrome, 22q11 microdeletion, 45,0)
E. ii.

Picture A represents an infant with facial stigmata of trisomy21. SUGGESTED READINGS


Picture B is of an infant with trisomy 18, also known as
Edwards syndrome. This infant has a small head, microgna- Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
thia, and clenched fists. 2010.
Tschudy M, Arcara K; Johns Hopkins Hospital, Childrens Medical and
Picture C represents a child with fetal alcohol syndrome Surgical Center, eds. The Harriet Lane Handbook: A Manual for Pediat-
with narrow, small eyes, and a smooth philtrum. rics House Officers. 19th ed. Philadelphia, PA: Mosby Elsevier; 2012.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 3 Cardiogenic shock61

Infants with surfactant deficiency typically present clini-


CASE 2 ANSWERS
cally with grunting, flaring, and retractions.
1. D. All of the above
Differentiating central versus peripheral (i.e., acrocyanosis) is a 3. B. 30 mm Hg
fundamental first step in managing the cyanotic infant. When Oxygen saturation is the percentage of hemoglobin that is
an infant has central cyanosis, the cyanosis is present through- combined with oxygen. The oxyhemoglobin dissociation
out the body and is evident in the mucous membranes and curve represents the nonlinear tendency for oxygen to bind to
tongue. Central cyanosis is observed if there is >3 to 5 g of hemoglobin. Thus, oxygen binding with hemoglobin increases
reduced hemoglobin per deciliter of capillary blood. The pres- as the partial pressure of oxygen increases in a nonlinear re-
ence of central cyanosis warrants immediate evaluation. lationship. Below an oxygen saturation (Sao2) of 90%, small
In contrast, peripheral cyanosis or acrocyanosis is limited differences in hemoglobin saturation reflect large changes in
to the extremities, is a common finding in healthy full-term Pao2. In a newborn, an Sao2 of 60% would correlate with a
newborns, and does not require further evaluation in the im- Pao2 of 30 mm Hg. Some practitioners describe this relation-
mediate newborn period. ship as the 30-60-90 rule:

At a Pao2 of 30 mm Hg, the Sao2 is ~60%


2. D. A and B
At a Pao2 of 60 mm Hg, the Sao2 is ~90%
Cyanosis can be secondary to cardiac, respiratory, hemato-
At a Pao2 of 90 mm Hg, the Sao2 is ~95%
logic, and metabolic causes. Severe cyanosis in the newborn
is a prominent feature of congenital heart disease (CHD)
and is associated with varying degrees of pulmonary blood
flow (PBF). Infants who have cyanotic heart disease with AMERICAN BOARD OF PEDIATRICS
decreased PBF may present with severe cyanosis without any CONTENT SPECIFICATIONS
respiratory distress while infants with CHD with increased
Know that peripheral cyanosis is a common finding in
PBF may present with respiratory distress. The table below
healthy full-term newborns
lists cyanotic heart defects that are associated with varying
Distinguish between central cyanosis and acrocyanosis
degrees of PBF.
Know the common extrapulmonary causes of cyanosis:
right-to-left shunt, methemoglobinemia
CHD and Cyanosis with CHD and Cyanosis Know how to validate and quantitate a clinical obser-
Normal or Increased PBF with Decreased PBF vation of cyanosis: arterial blood gases, oxyhemoglobin
(may have respiratory (usually without respira- saturation
distress) tory distress) Know that cyanosis is not a sensitive indicator of oxyhe-
Transposition of the great TOF moglobin desaturation
arteries (TGA)
Truncus arteriosus Tricuspid atresia
Double outlet right Pulmonic atresia with in- SUGGESTED READINGS
ventricle tact septum or pulmonic
stenosis Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
Ebstein anomaly of the Ebstein anomaly of the 2010.
tricuspid valve tricuspid valve Tschudy M, Arcara K; Johns Hopkins Hospital, Childrens Medical and
Surgical Center, eds. The Harriet Lane Handbook: A Manual for Pe-
diatrics House Officers. 19th ed. Philadelphia, PA: Mosby Elsevier;
PPHN is the failure of the normal circulatory transition 2012.
that occurs after birth and is characterized by significant pul-
monary hypertension causing hypoxemia and right-to-left
shunting across the foramen ovale and ductus arteriosus. CASE 3 ANSWERS
PPHN most often occurs with parenchymal lung disease, such
1. D. Physical examination, four extremity blood pres-
as meconium aspiration. PPHN can be idiopathic, thought to
sures, pre- and postductal oxygen saturations, chest radi-
be in response to prolonged fetal stress. While infants with
ography, electrocardiography, and arterial blood gas
PPHN as a result of meconium aspiration syndrome present
Although all of the possible options would be part of the com-
with respiratory distress, infants with idiopathic PPHN more
plete evaluation for the infant in this vignette, this infants
often present without respiratory distress.
clinical findings most likely result from cardiogenic shock,
A rare extrapulmonary cause of cyanosis in the newborn is
which may be the initial finding in a newborn with cyanotic
methemoglobinemia. In this disease, the iron within hemo-
heart disease.
globin is oxidized from the ferrous state to the ferric state. Met-
hemoglobinemia occurs when red blood cells contain greater 2. D. All of the above
than 1% methemoglobin and the oxygen-carrying capacity of This infant has all of the cardinal findings of neonatal shock.
blood is decreased. Shock occurs when there is inadequate blood flow to the tissues

(c) 2015 Wolters Kluwer. All Rights Reserved.


62Section III Cardiology

to meet tissue metabolic requirements. This leads to tissue hy- SUGGESTED READING
poxemia, metabolic acidosis, irreversible cellular changes, and
possibly subsequent cellular death. Shock can be classified as Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
hypovolemic, distributive, or cardiogenic; common causes of 2010.
each include placental abruption/massive bleeding, sepsis,
and critical congenital heart disease (CHD), respectively. The
most common types of CHD causing shock are left-sided ob- CASE 4 ANSWERS
structive lesions. Blood shunting from the pulmonary artery to
1. B. Hypovolemic shock as a result of a placental abrup-
aorta across a patent ductus arteriosus will assist with provid-
tion and blood loss
ing systemic blood flow, lessening the symptoms of an infant
Hypovolemic shock is characterized by decreased blood vol-
with a left-sided obstructive lesion. With closure of the ductus
ume below a critical level. There is decreased ventricular filling
arteriosus (typically by 48 hours of age), an affected infant will
and decreased stroke volume (SV) with subsequent decreased
develop severe symptoms. The initial therapeutic management
cardiac output (CO) unless the infant is able to compensate
in an infant with cardiogenic shock includes:
with increased HR. Infants have poor peripheral perfusion,
Consulting with a cardiologist decreased distal pulses, hypotension, and decreased urine
Starting PGE1 with consideration for intubation because output.
of a potential side effect of apnea In contrast to hypovolemic shock, cardiogenic shock is
Correcting any metabolic acidosis with an intravenous bi- characterized by cardiac failure with impaired filling, poor
carbonate bolus or intravenous fluids with added acetate ventricular emptying, and decreased contractility. Distributive
Initiating inotropic agents to improve myocardial shock is characterized by inadequate relative intravascular vol-
function. ume secondary to vasodilation. A comparison of these three
types of shock is shown in the table below.
3. A. Hypoplastic left heart syndrome (HLHS)
The most common types of CHD causing shock are left-sided Hypovolemic Distributive Cardiogenic
obstructive lesions, such as: Shock Shock Shock

Aortic atresia or severe aortic stenosis Decreased blood Inadequate Cardiac failure
Coarctation of the aorta volume below a relative intra-
critical level vascular volume
Interrupted aortic arch
Most common secondary to
Mitral valve atresia or severe mitral stenosis (a type of vasodilation
type of shock in
HLHS) neonate
Total anomalous pulmonary venous return (TAPVR) with
Decreased ven- Normal circu- Impaired filling,
obstruction. tricular filling and lating blood impaired ven-
It is important to be aware that PGE1 is indicated in most decreased SV volume but tricular empty-
Decrease in CO insufficient for ing, impaired
cases where a newborn is critically ill with a presumed ductal- adequate cardiac contractility
unless able to
dependent lesion. However, it is important to recognize that compensate with filling
in a newborn with TAPVR with obstruction, PGE1 may worsen increased HR
symptoms by increasing pulmonary blood flow, further in-
Presents initially Presents with Presents with
creasing pulmonary congestion with an associated worsening with decreased decreased urine decreased urine
of systemic perfusion. urine output, output, increased output, increased
decreased BP, HR, decreased HR, decreased
increased HR BP BP
AMERICAN BOARD OF PEDIATRICS (note: prema- Often with CHF/pulmonary
CONTENT SPECIFICATIONS ture infants may bounding pulses edema
actually have de- Often with
Know that an electrocardiogram and echocardiography creased HR), no hepatomegaly,
congestive heart cardiomegaly
should be part of the evaluation of a patient with pos- failure (CHF)
sible cardiogenic shock
Know that cardiogenic shock may be the initial finding
in a newborn with congenital heart disease
Recognize the findings of cardiogenic shock in the
newborn
Know the treatment of cardiogenic shock in the newborn
Know what important lesions are associated with the
shock-like presentation in a newborn

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 5 Cyanotic heart disease: Diagnosis and management 63

Hypovolemic Distributive Cardiogenic


SUGGESTED READINGS
Shock Shock Shock
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
Severe Sepsis Metabolic 2010.
hemorrhage (e.g. hypo- Cloherty J, Eichenwald EC, Hansen A, et al., eds. Manual of Neonatal Care.
Anaphylaxis 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.
Severe fluid loss Vasodilators calcemia and
Can also be as- hypoglycemia)
Toxins
sociated with Congenital heart
sepsis (capillary disease CASE 5 ANSWERS
leakage into Cardiac
third spaces and/ tamponade 1. D. Physical examination, chest radiograph, electrocar-
or interstitial Severe perinatal diogram, hyperoxia test
spaces) depression To distinguish between cardiac and respiratory causes of cya-
Arrhythmias, nosis, the physical examination can be helpful. Infants with
myocarditis, cyanotic heart disease typically have milder respiratory distress
cardiomyopa- compared with infants with respiratory disease. Infants with
thy, myocardial
ischemia/ heart disease may have additional cardiac-specific findings,
infarction such as a hyperactive precordial impulse, delayed capillary
Can also be refill, a gallop rhythm, a single second heart sound, hepato-
associated megaly, and/or a murmur.
with sepsis The chest radiograph is also useful in distinguishing cardiac
(decreased from respiratory disease. Infants with respiratory disease typi-
contractility)
cally have lung disease evident on the radiograph. Infants with
Printed with permission from: Brodsky D, Martin C. Neonatology cardiac disease may have cardiomegaly, a distinctive shape of
Review. 2nd ed. Raleigh, NC: Lulu; 2010:117 the heart border, and increased or decreased pulmonary vas-
cular markings.
2. D. B and C
An electrocardiogram may also be helpful to assess for the
This infant has hypovolemic shock as a result of a placental
type of cyanotic heart disease. Infants with a complete atrio-
abruption and massive blood loss. Clinicians need to follow
ventricular canal or tricuspid atresia typically have a left supe-
the appropriate Neonatal Resuscitation Program steps. The in-
rior QRS axis.
fant should be given emergency release of O-negative blood as
The hyperoxia test is the most sensitive and specific method
soon as it is available. After an UVC is placed, a NS bolus may
to diagnose cyanotic heart disease.
be administered while awaiting arrival of the blood.

3. B. Another 10 ml/kg of O-negative blood 2. D. Comparison of the infants arterial Pao2 in room air
It must be recognized that immediate volume resuscitation of
with the infants Pao2 while receiving 100% Fio2
The hyperoxia test is a useful tool for diagnosing cyanotic
an infant in hypovolemic shock may require more than 20
heart disease. In this test, an ABG is obtained from the right ra-
ml/kg to improve the infants clinical status. This infant is pro-
dial artery (preductal) while the infant is in room air. Another
foundly anemic and his body is attempting to compensate for
ABG is obtained after the infant has inspired 100% oxygen for
his decreased ventricular filling and SV by increasing his HR.
a minimum of 15 minutes. If an infant has cyanotic heart dis-
Frequent clinical assessment of this infant is mandatory to
ease, there is little to no rise in Pao2 with 100% Fio2 (usually
provide ongoing appropriate medical management.
<100 torr), leading to a failed hyperoxia test result. Infants
receiving 100% Fio2 with a Pao2 between 100 and 250 torr
AMERICAN BOARD OF PEDIATRICS may have structural heart disease with intracardiac mixing and
CONTENT SPECIFICATIONS increased pulmonary blood flow. However, an infant receiv-
ing 100% Fio2 with a Pao2 >250 torr has passed the hyper-
Recognize the clinical signs of shock due to fluid loss oxia test, indicative of the absence of cyanotic heart disease.
Know the type of fluids to be administered in the treat-
ment of shock 3. D. B and C
Recognize that frequent clinical assessment is required Lesions with right-to-left shunting at the intracardiac level
in the treatment of shock cause infants to have cyanosis because blood is shunted away
Recognize that immediate fluid resuscitation of infants from the lungs. These cyanotic lesions can be remembered by
in shock may require more than 20 mL/kg of fluid to the five Ts rule:
improve their clinical conditions TOF
Tricuspid atresia

(c) 2015 Wolters Kluwer. All Rights Reserved.


64Section III Cardiology

TGA If a physician suspects that an infant has cyanotic heart


TAPVR disease, he/she should immediately consult the cardiology
Truncus arteriosus service. The infant should receive PGE1, a prostaglandin ana-
log that relaxes arterial smooth muscle and maintains ductal
Other cardiac lesions that lead to cyanosis include the
patency. Blood then shunts across the patent ductus based on
following:
vascular resistance in the distal aorta and pulmonary artery.
Double outlet right ventricle For infants with increased pulmonary vascular resistance, duc-
Ebstein anomaly tal shunting will occur from the pulmonary artery to aorta,
HLHS increasing systemic cardiac output. For infants with decreased
PA or severe PS pulmonary vascular resistance compared to systemic vascular
Single ventricle resistance, ductal shunting will occur from the aorta to pulmo-
nary artery, increasing pulmonary blood flow.
4. B. Critical PS, tricuspid atresia, PA, TOF, Ebstein Infants with TGA and an intact ventricular septum may not
anomaly, TAPVR with obstruction receive a tremendous benefit from PGE1 and may also require
These types of cyanotic heart disease are associated with de- an emergent Rashkind procedure, a technique developed in
creased PBF. These lesions are associated with a greater severity 1966. In this technique, a catheter with a deflated balloon
of cyanosis, and chest radiographs will reveal dark lung fields. at the tip is inserted through the foramen ovale. The balloon
is then filled with air and the catheter is rapidly pulled back
5. D. All of the above
through the foramen to create a large septostomy between the
TGA is the most likely cardiac defect in this infant. This in-
right and left atria. This opening increases intra-atrial mixing
fants difference in oxygen saturations with a preductal satura-
until arterial switch surgery can be performed.
tion being lower than the postductal saturation is consistent
with reversed differential cyanosis. This occurs when an infant 6. D. All of the above
has TGA, an intact ventricular septum, and a patent ductus ar- Although PGE1 is a life-saving treatment, it has several poten-
teriosus with shunting from the pulmonary artery to the aorta. tial side effects. These include flushing, hypotension, and ap-
The infant described in this vignette also has the classic nea. It is important to consider intubating any infant who is
egg on a string chest radiograph finding that is consistent receiving PGE1.
with TGA. This shape illustrates the narrowing of the supe-
rior mediastinum as a result of the anteriorposterior aorta
and main pulmonary artery relationship. A diagram of TGA is
AMERICAN BOARD OF PEDIATRICS
shown in Figure 2.
CONTENT SPECIFICATIONS
Know the cardiac causes of cyanosis in the newborn
Recognize that the absence of improvement in arterial
oxygen content with 100% oxygen in comparison with
room air is compatible with the diagnosis of cyanotic
Aorta
congenital heart disease
Ligamentum Recognize the clinical features and management of
arteriosum transposition of the great arteries
Understand the role of ductus arteriosus in cyanotic con-
genital heart disease and the use of prostaglandin E1 in
RA
LA treatment
Pulmonary
artery

SUGGESTED READINGS
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
RV LV Cloherty J, Eichenwald EC, Hansen A, et al., eds. Manual of Neona-
tal Care. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins;
2011.
Long WA (ed). Fetal and Neonatal Cardiology. Philadelphia, PA: WB
Saunders; 1990.

FIGURE 2. Rubin R, Strayer DS. Rubins Pathology: Clinicopathologic


Foundations of Medicine. 5th ed. Philadelphia, PA: Lippincott Williams
& Wilkins; 2008. Figure 11.10

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 7 Differential cyanosis65

2. A. Good long-term survival and excellent quality life


CASE 6 ANSWERS
Ninety percent of patients with complete repair of TOF dur-
1. D. Tet spell ing infancy develop a progressively leaky pulmonary valve in
Tetralogy of Fallot (TOF) is a congenital heart defect that in- adulthood. These patients have a good overall long-term sur-
volves the following four anatomic abnormalities: vival and they have an excellent quality of life. Affected infants
who are not surgically repaired will have progressive right ven-
Ventricular septal defect tricular hypertrophy and heart failure.
Obstruction of the right ventricular outflow tract
Overriding of the ventricular septum by the aortic root 3. D. All of the above
Right ventricular hypertrophy Children with cyanotic CHD are at increased risk of devel-
opmental disability or developmental delay. Developmental
This cardiac defect is depicted in Figure 1. disorders are common in infants with CHD, especially those
Tetrology of Fallot infants who require open heart surgery in the first year of life
or those with cyanotic CHD who are not repaired in the first
year of life. These high-risk patients require periodic develop-
mental surveillance, screening, evaluation, and reevaluation
Aorta
throughout childhood. This surveillance may enhance identi-
Pulmonary artery fication of significant deficits, allowing for appropriate thera-
Pulmonary artery
pies and education to enhance later academic, behavioral,
psychosocial, and adaptive functioning.
Pulmonary veins Pulmonary veins
Right ventricular
outflow tract Left atrium
obstruction AMERICAN BOARD OF PEDIATRICS
Overriding aorta
CONTENT SPECIFICATIONS
Right atrium Ventricular septal
defect
Right ventricle
Identify the clinical characteristics of a tetralogy spell
Understand the prognosis for a patient with tetralogy of
Right ventricular
Left ventricle
Fallot
hypertrophy
Understand the prognosis for cognitive development in
patients with cyanotic congenital heart disease

FIGURE 1. Courtesy of Anatomical Chart Co. 2014 Lippincott


Williams & Wilkins. All rights reserved SUGGESTED READINGS

Tet spells or hypercyanotic spells can be described as an Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
imbalance between pulmonary and systemic vascular resis- Marino B, Lipkin PH, Newburger JW, et al. Neurodevelopmental out-
tance favoring decreased pulmonary flow and increased right- comes in children with congenital heart disease: Evaluation and
to-left (i.e., pulmonary artery to aorta) shunting. Hypoxemia, managementa scientific statement from the American Heart As-
sociation. Circulation. 2012;126:11431172.
metabolic acidosis, hyperpnea, increased systemic venous re-
turn, excessive catecholamines, and pulmonary vasoconstric-
tion are thought to be involved in an interaction that results in
CASE 7 ANSWERS
a continuous cycle. The proposed mechanism for a tet spell
is shown in Figure 2. 1. D. A or B
Persistent pulmonary hypertension of the newborn (PPHN)
occurs in ~1 to 2 per 1,000 births. It is caused by a failure
Increased right-to-left shunt of transition from intrauterine to extrauterine pulmonary
physiology. Thus, affected infants have a persistent eleva-
tion in their pulmonary vascular resistance (PVR). This in-
Crying, Increased PVR, Decreased
stooling decreased SVR PBF
crease in PVR leads to right-to-left shunting at the atrial
(i.e., right-atrium-to-left-atrium shunting) or ductal level
(i.e., pulmonary-artery-to-aorta shunting), with the resultant
Decreased PO2, acidosis, decrease in pulmonary blood flow leading to hypoxemia.
increased PCO2
PPHN can be divided into two groups:
FIGURE 2. Printed with permission from: Brodsky D, Martin C.
Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010:120 Maladaptationnormal structure of the pulmonary vascu-
lar bed with elevated PVR (e.g., meconium aspiration syn-
drome, pneumonia, sepsis, hypoxia, perinatal depression)

(c) 2015 Wolters Kluwer. All Rights Reserved.


66Section III Cardiology

Maldevelopmentabnormal structure of the pulmonary arrhythmias represent deviations from this norm. Approxi-
vascular bed leading to vascular smooth muscle hypertro- mately 1% to 2% of fetuses have fetal arrhythmias; of those,
phy (e.g., CHD, pulmonary hypoplasia, diaphragmatic 10% have associated morbidity. The most common cause of a
hernia) fetal arrhythmia is premature atrial contractions (PACs) where
there is most often a 1:1 conduction of ectopic beats yielding
A newborn with cyanosis, low oxygen saturations, and a sig-
early ventricular contractions as well. PACs are most often be-
nificant differential in pre- and postductal oxygen saturations
nign and intermittent. In any fetus with frequent ectopy, the fe-
requires further evaluation to establish a definitive diagnosis.
tal heart rate should be auscultated at each prenatal visit and an
In the absence of meconium aspiration syndrome, it is diffi-
ultrasound should be done to evaluate structural abnormality
cult to distinguish between PPHN and cyanotic CHD.
of the fetal heart. Pregnant women with lupus are at increased
2. B. Inhaled nitric oxide risk of having a fetus or neonate with complete heart block.
The infant described in this vignette should have an echo-
cardiograph to rule out CHD and to confirm the presence of
2. A 2
PPHN. There are several strategies that are used to treat PPHN, B 3
including: C 1
Administration of 100% oxygen to increase pulmonary D 4
vasodilation
Use of inhaled nitric oxide, a selective pulmonary 3. B. Digoxin, vagal maneuvers
vasodilator A fetus with sustained SVT warrants treatment. First-line intra-
Use of sedation medications uterine treatment is digoxin administered intravenously to the
Maximization of an infants oxygen-carrying capacity by pregnant woman. If the fetus is sick, second-line treatment is
transfusing with packed red blood cells if the infant is amiodarone, while second-line treatment for a healthier fetus
anemic can be procainamide, flecainide, or sotalol. Lastly, delivery is
Maintenance of cardiac output an option for the fetus with mature lungs.
Avoidance of acidosis A newborn with SVT warrants treatment if the SVT is sus-
Administration of antibiotics as PPHN may be associated tained or if there are any signs or symptoms of cardiovascular
with sepsis/pneumonia compromise. If the infant is unstable, clinicians can perform
Utilization of ventilator support synchronized cardioversion at a dose of 0.5 to 2 J/kg. If the in-
Option of extracorporeal membrane oxygenation fant is stable, clinicians can perform vagal maneuvers (crushed
(ECMO) in term infants should all else fail ice to face; rectal stimulation) and administer adenosine intra-
venously if the arrhythmia persists.

AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATIONS AMERICAN BOARD OF PEDIATRICS
CONTENT SPECIFICATIONS
Know that it is difficult to distinguish between persistent
pulmonary hypertension without meconium aspiration Understand the significance and plan the management
and cyanotic congenital heart disease of fetal arrhythmias
Recognize the clinical presentation of a neonate with Using electrocardiographic patterns, identify premature
persistent pulmonary hypertension following meco- atrial contractions, premature ventricular contractions,
nium aspiration supraventricular tachycardia, and ventricular tachycardia
Know the strategy to manage persistent pulmonary hy- Understand the treatment of supraventricular tachycardia
pertension of the newborn

SUGGESTED READINGS
SUGGESTED READING
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010.
2010. Strasburger JF. Prenatal diagnosis of fetal arrhythmias. In: Wernovsky
G, Berger S, Rubenstein SD, eds. Congenital Heart Disease: Impact
on the Fetus, Pregnancy, Neonate and Family. Philadelphia, PA:
W B Saunders; 2005:891912. Clinics in Perinatology; vol 32.
CASE 8 ANSWERS

1. D. All of the above


The conduction of the fetal heart is functionally mature by 16
weeks gestation, yielding a normal fetal heart rate of 110 to
160 beats per minute for the remainder of the pregnancy. Fetal

(c) 2015 Wolters Kluwer. All Rights Reserved.


S E C T I ON IV Neurology

(c) 2015 Wolters Kluwer. All Rights Reserved.


68Section IV Neurology

CASE 1
Head growth

During a night shift, four full-term infants are admitted to 2. Of the following, a possible etiology of this babys head
the Special Care Nursery. The next day, the neonatologist re- growth from birth until 4 months of age is:
views each infants head circumference (HC). Her findings are
A. Acquired microcephaly as a result of craniosynostosis
shown below:
B. Acquired microcephaly from a perinatal insult
Baby boy Banks HC = 37 cm
C. Progressive microcephaly as a result of a neurodegenera-
Baby girl Gray HC = two to three standard
tive or neurogenetic process
deviations below the mean
D. All of the above
Baby boy Scott HC > three standard deviations
above the mean One of the babies in the scenario above has craniosynostosis
Baby girl Smith HC = 40 cm that requires surgery at age 4 months.

1. Match the infant with the corresponding description (the 3. Review the diagrams (Figure 2) and match the type of cra-
descriptions may be used more than once): niosynostosis to the corresponding head shape:

A. Baby boy Banks ____ 1. Macrocephaly


B. Baby girl Gray ____ 2. Microcephaly
C. Baby boy Scott ____ 3. Normal HC
D. Baby girl Smith ____
Sagittal
The continued head growth of one of these infants is plotted Coronal

on the growth chart (Figure 1). Referring to this growth chart, B


please answer the next question. A
bd ral

U
d
te

ni
oi
la

la
ni

or

te
U

on

ra
La

l
al

C
C

FIGURE 2. From MacDonald MG, Mullett MD, Seshia MM, eds. Averys
Neonatology: Pathophysiology & Management of the Newborn. 6th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2005

A. _____ 1. Brachycephaly
B. _____ 2. Plagiocephaly
C. _____ 3. Scaphocephaly or dolichocephaly
D. _____ 4. Trigonocephaly

4. For the baby in the Special Care Nursery who had mac-
rocephaly, what is the most likely etiology of this infants
abnormal head growth?

A. BeckwithWiedemann syndrome, neurofibromatosis,


Sotos syndrome, or fragile X syndrome
B. Benign familial macrocephaly
C. Intracranial mass
FIGURE 1. Developed by the National Center for Health Statistics in
D. Posthemorrhagic hydrocephalus
collaboration with the National Center for Chronic Disease Prevention
and Health Promotion (2000). http://www.cdc.gov/growthcarts

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 3 Seizures69

CASE 2
Brachial plexus injury at birth

You are called stat to labor room 2 due to possible shoulder The infant was diagnosed with an Erb palsy. You are asked to
dystocia. A large-for-gestational-age baby girl is delivered us- explain the management and prognosis to the parents.
ing McRoberts maneuver assistance. She is vigorous and cry-
ing at the perineum. She is brought to the warmer, where you 2. Select the most appropriate management and prognosis
provide routine care. You palpate her clavicles, and they are in- below:
tact. However, she has decreased movement of her right arm. A. Physical therapy; likely full recovery by 4 months
B. Immediate surgery; likely full recovery by 4 months
1. Match the following clinical signs and symptoms with the
C. Physical therapy and Botox injections; variable recovery
two types of brachial plexus injury listed to the right:
D. Neurosurgical consultation; if no improvement by
A. C5C7 ____ i. ErbDuchenne 2weeks, likely will persist
(proximal) palsy
B. Less common ____ ii. Klumpke (distal) palsy
C. Waiters tip ____
D. Absent shoulder Moro
reflex with presence of
hand Moro reflex ____

CASE 3
Seizures

A full-term female infant was born by an uncomplicated re- The infant undergoes the following laboratory tests and
peat cesarean delivery. Her Apgar scores were 8 and 9 at 1 and studies:
5 minutes, respectively. She had been doing well until day 5
A sepsis evaluation, including a lumbar puncture
of life when her mother noted that she had brief jerking move-
Electrolytes, calcium, magnesium, phosphorus
ments of her legs. As the covering pediatrician, you evaluate
An electroencephalography (EEG)
the infant.
Magnetic resonance imaging (MRI)
1. What would be your differential diagnosis? She develops unifocal clonic seizure activity and is diagnosed
A. Benign sleep myoclonus with a right middle cerebral arterial (MCA) infarct.
B. Exaggerated startle response, jitteriness
3. Which statement(s) below is(are) true?
C. Seizure
D. All of the above A. Abnormal interictal EEG has less favorable outcome
B. Overall outcome for infants with seizures after arterial
The infant is admitted to the Neonatal Intensive Care Unit
or venous vaso-occlusive disease is favorable
(NICU). While you are observing her, she has another event.
C. Seizures are the most common presentation of stroke
2. All of the following possible clinical findings would sup- in the newborn period, and stroke is the second most
port a diagnosis of seizure with the exception of: common cause of neonatal seizures
D. All of the above
A. Abnormal chewing
B. Bicycling or swimming movement of the extremities
C. Eye deviation
D. Sudden hypotension

(c) 2015 Wolters Kluwer. All Rights Reserved.


70Section IV Neurology

CASE 4
Hypoxic-ischemic encephalopathy

A 43-year-old primigravida woman presents to Labor and and ATN, respiratory distress with shunting from left to
Delivery 1 hour after feeling a decrease in fetal movement. The right across the patent ductus arteriosus (PDA) and pat-
fetal tracing is flat, prompting an emergent cesarean delivery. ent foramen ovale (PFO), intestinal ischemia
After birth, the baby girl requires resuscitation with intuba-
The infant is undergoing therapeutic hypothermia. Her sei-
tion, chest compressions, epinephrine, and volume. Her Apgar
zures have quelled with phenobarbital; she remains on do-
scores are 1, 3, and 4 at 1, 5, and 10 minutes, respectively. The
pamine at 5 mcg/kg/min; her laboratory values peaked with
cord pH is 6.82 in the umbilical artery and 6.93 in the umbili-
aspartate aminotransferase (AST) of 800 mg/dL and alanine
cal vein. While being observed in the Neonatal Intensive Care
aminotransferase of 675 mg/dL, blood urea nitrogen (BUN)
Unit (NICU), the infant has a seizure.
of 12 mg/dL, creatinine (Cr) of 1.3 mg/dL, and a platelet nadir
1. The most common timing of seizure activity in this infant of 72 109/L. She remains critically ill.
with hypoxic-ischemic encephalopathy (HIE) is:
3. The nurse has been talking with the father at the bedside.
A. 0 to 6 hours of life He is devastated and believes that his daughter will have
B. Within the first 24 hours of life a terrible outcome. The nurse suggests a family meeting
C. 24 to 48 hours of life as soon as possible. Before the meeting, the neonatology
D. >72 hours of life attending discusses HIE and outcomes with the pediatric
residents. Which statement(s) below is(are) true?
2. Multisystem organ effects may occur in the setting of severe
intrapartum asphyxia. Chose the answer below that reflects A. More individualized outcome predictors for infants
the type of end-organ injury seen as a result of severe HIE: with HIE depend on the severity of the encephalopathy,
the presence or absence of seizures, EEG findings, and
A. Hypotonia, seizures, hypertension, ventricular dysfunc- neuroimaging results
tion, tricuspid regurgitation, polyuria with sodium wast- B. The majority of term infants with seizures due to HIE do
ing, pulmonary hypertension, intestinal ischemia not manifest long-term neurodevelopmental sequelae
B. Hypotonia, seizures, other organ effect uncommon C. Therapeutic hypothermia in term infants with m oderate/
C. Hypotonia, seizures, transient myocardial ischemia, severe encephalopathy reduces mortality and/or neurode-
ventricular dysfunction, tricuspid regurgitation, oliguria velopmental outcomes (measured at 18months of age)
and acute tubular necrosis (ATN), pulmonary hyperten- D. All of the above
sion, intestinal ischemia
D. Hypotonia, seizures, transient myocardial ischemia,
ventricular dysfunction, tricuspid regurgitation, oliguria

CASE 5
Intracranial hemorrhage

The attending on service has selected three infants in the Neo- been complicated by respiratory distress syndrome, se-
natal Intensive Care Unit (NICU) for you to follow this week. vere hypotension, a patent ductus arteriosus (PDA), and
He has asked you to prepare a presentation on intracranial sepsis. His neurologic examination is currently appro-
hemorrhage by the end of the week. He suggests you design a priate for gestational age.
case-based presentation based on the following four patients. ii. A full-term female infant had a difficult delivery. Her
neurologic examination is significant for hypotonia,
i. A male infant was born at 24 weeks gestation to a
lateral eye deviation, unequal pupil size, and irregular
mother with chorioamnionitis. His hospital course has
respirations.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 6 Neonatal encephalopathy71

iii. A full-term male infant was born via uncomplicated 3. The critically ill patients described in vignettes ii and iv
spontaneous vaginal delivery. He had been well until need intervention. What steps would you take to evaluate
his second postnatal day when he developed seizures. and manage these infants?
He is currently hemodynamically stable and remains
A. Call neurology stat, but hold off on calling neurosurgery
in room air.
as you do not have imaging results yet
iv. A preterm infant was born via emergent cesarean de-
B. Follow guidelines for neonatal stabilization; secure the
livery for fetal distress. He required cardiopulmonary
airway (intubate); provide blood products and volume;
resuscitation after birth and now is showing signs of
start inotropes; obtain complete blood count with dif-
brainstem compression.
ferential, blood culture, electrolytes, disseminated intra-
1. Match the above cases to potential head imaging results vascular coagulation panel; call neurosurgery stat and
based on the risk factors in the short vignettes above: arrange for head imaging urgently
C. Monitor vital signs and call neurosurgery
A. Bilateral germinal matrix hemorrhages (GMH) on post- D. Send the infant urgently to radiology as there is no time
natal day 3, followed by periventricular leukomalacia to secure the airway
(PVL) noted on imaging at 1 month
B. Cerebellar hemorrhage
C. Subarachnoid hemorrhage
D. Subdural hemorrhage

2. Select the radiographic study that is most accurate at detect-


ing a specific neurologic finding (select one best answer for
each finding; answers may be used more than once or not
at all):

A. GMH and PVL i. Computed


tomography (CT)
B. Cerebellar hemorrhage ii. Magnetic resonance
imaging (MRI)
C. Hypoxic-ischemic iii. Ultrasonography
encephalopathy
D. Subdural hemorrhage

CASE 6
Neonatal encephalopathy

A full-term male infant was born at a community hospital via A. Ammonia level, electrolytes, blood urea nitrogen
repeat cesarean delivery to a 30-year-old gravida 3 para 2 now (BUN), creatinine (Cr), glucose
3 Caucasian woman with reassuring prenatal screens aside B. Arterial blood gas (ABG), complete blood count (CBC),
from Group B Streptococcus colonization. The infant did well blood culture
in the delivery room, with Apgar scores of 8 and 9 at 1 and C. Radiograph of chest and abdomen
5minutes, respectively. D. All of the above
On postnatal day 3, the infant was unable to breast-feed
The infant is now intubated and receiving intravenous fluids.
and became hypothermic and jittery. Within an hour, his
He also received a normal saline bolus, a 10% dextrose bo-
clinical condition deteriorates rapidly with tachypnea, tachy-
lus, and has been started on ampicillin and gentamicin. Test
cardia, and extreme lethargy. The pediatric hospitalist calls the
results are as follows:
transport team to transfer the infant to the closest level 3 Neo-
natal Intensive Care Unit (NICU). You are the resident who ABG: pH = 7.17, Paco2 = 55 mm Hg, Pao2 = 147 mm
will be admitting the infant to the NICU. Hg, base deficit = 15 mEq/L
Na = 149 mEq/L, K = 6.9 mEq/L, Cl = 111 mEq/L
1. Based on the clinical history thus far, you have created a Blood glucose = 90 mg/dL
differential diagnosis. What studies will you order upon Plasma ammonia level > 2,000 M/L
admission?

(c) 2015 Wolters Kluwer. All Rights Reserved.


72Section IV Neurology

CBC within normal limits 2. Which statement(s) is(are) true regarding neurologic se-
Chest radiograph within normal limits quelae and outcomes in infants diagnosed with a urea cycle
Newborn state screen pending defect?
The metabolism consult service has recommended sending A. Most patients with urea cycle defects live well into
quantitative plasma amino acids, urine amino acids, urine adulthood
ketones, liver function tests (LFTs), and frequent repeat se- B. Neurologic sequelae and survival depend on the length
rum ammonia levels via arterial puncture. The results lead of the hyperammonemic coma
to a diagnosis of a urea cycle defect. Despite maximal ther- C. There is a low risk for neurologic sequelae if the coma
apy with hemodialysis, the infant remains in a coma for lasts for 4 days
3days. D. All of the above

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 1 Head growth73

SECTION IV
Answers

initially suspected this diagnosis by physical examination


CASE 1 ANSWERS
findings and confirmed the diagnosis by a three-dimensional
1. A 3. Normal HC computed tomography (CT) scan. The baby underwent surgi-
B 2. Microcephaly cal repair at 4 months of age, which resulted in improved head
C 1. Macrocephaly growth.
D 1. Macrocephaly The management of an infant with craniosynostosis i nvolves
imaging and neurosurgical consultation. Head ultrasound
If a pregnancy is complicated by placental insufficiency, head has been used as a diagnostic tool for craniosynostosis, but it
growth is initially preserved and is the last growth parameter requires an experienced technician for maximum utility. Three-
to be adversely affected. The average HC for full-term infants dimensional CT now serves as the standard d iagnostic tool for
is 33 to 38 cm. After 3 weeks of life, an infants HC increases complete visualization of the skull and sutures. Indications for
~1 cm/week. surgery include:
Microcephaly describes an infant with a HC that is greater
than two to three standard deviations below the mean. Con- 1. Prevention of intracranial hypertension and associated
genital microcephaly, also known as primary microcephaly, is complications
microcephaly that is present at birth. Congenital microcephaly 2. Prevention of progressive skull and facial deformity
is more common than postnatal microcephaly (also known 3. Optimization of brain growth potential
as acquired or secondary microcephaly). This latter type of As most of an infants brain growth occurs in the first year
microcephaly occurs when there is failure of normal brain of life, it is important to recognize craniosynostosis as early
growth in an infant who had a normal-sized brain at birth. as possible with neurosurgical corrective repair at age 3 to
Macrocephaly describes an infant with a HC that is greater 9months of life.
than three standard deviations above the mean. Macroceph-
aly results from an increase in size of any component of the 3. A 3. Scaphocephaly or dolichocephaly
cranium (brain, cerebral spinal fluid [CSF], blood, skull), B 1. Brachycephaly
increased intracranial pressure, or presence of a mass (cyst, tu- C 2. Plagiocephaly
mor, abscess). D 4. Trigonocephaly
Hydrocephaly occurs when the cerebral ventricular system Scaphocephaly or dolichocephaly involves premature closure
contains excessive CSF, resulting in increased ventricular dila- of the sagittal suture and is the most common type of cranio-
tation and possibly increased ventricular pressure. synostosis. Frontal plagiocephaly, resulting from premature
closure of a unilateral coronal suture, is the next most com-
2. D. All of the above
mon type of craniosynostosis and is associated with C rouzon
The growth chart shown in Figure 1 corresponds with an in-
and Apert syndrome. Brachycephaly involves premature clo-
fant with postnatal microcephaly. This infants decrease in
sure of the bilateral coronal sutures; it occurs infrequently
head growth can be caused by:
and can be observed in infants with Carpenter syndrome.
A hemorrhagic or ischemic stroke Occurring even less frequently, trigonocephaly involves pre-
A neurodegenerative or neurogenetic process, such as mature closure of the metopic suture and is seen more often
an inborn error of metabolism or a genetic syndrome in males.
(e.g.,
MillerDieker syndrome, Rett syndrome, ataxia
4. B. Benign familial macrocephaly
telangiectasia)
Fifty percent of cases of macrocephaly are associated with
A perinatal insult, such as hypoxic ischemic
benign familial macrocephaly, which typically has an auto-
encephalopathy
somal dominant inheritance pattern and affects males more
Other etiologies such as craniosynostosis
often than females. Macrocephaly may also be associated with
Infants with craniosynostosis have premature closure of one genetic syndromes/disorders such as BeckwithWiedemann
or more cranial sutures, resulting in a decrease in head growth syndrome, neurofibromatosis, Sotos syndrome, and fragile X
noted at birth or, more often, postnatally. The baby who had syndrome. In addition, intracranial tumors and posthemor-
the growth curve shown in Figure 1 was diagnosed with pre- rhagic hydrocephalus can lead to macrocephaly as a result of
mature closure of the sagittal sutures. The babys pediatrician obstructive hydrocephalus.

(c) 2015 Wolters Kluwer. All Rights Reserved.


74Section IV Neurology

AMERICAN BOARD OF PEDIATRICS ErbDuchenne Klumpke


CONTENT SPECIFICATIONS Palsy (proximal) Palsy (distal)
C4/C5phrenic nerve Wrist, fingers ex-
Know the normal head circumference of a full-term in- paralysis, respiratory tended, digits in
fant at birth distress, decreased neutral position
Recognize the growth pattern of acquired microcephaly diaphragm movement, Biceps reflex
Recognize normal and abnormal variations in head CXR with elevated absent
shape hemidiaphragm Grasp reflex
Craniosynostosis C7flexion deformity absent
of the hand, winging Complete moro
Recognize the clinical findings of premature closure of of the scapula, absent
a cranial suture absent
Moro, intact grasp
Distinguish between the closure of cranial sutures reflex, cutaneous T1unilateral
sensory loss over the Horner syndrome
secondary to failure of brain growth (small, normally with miosis,
shaped head) and premature closure of a single cra- deltoids and radial
aspect of upper arm, ptosis, anhidro-
nial suture decreased tempera- sis, decreased
Plan appropriate management for a patient with ture and perspiration pigmentation of
craniosynostosis the iris

FIGURE 1. Printed with permission from: Brodsky D, Martin C.


Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010:173
SUGGESTED READINGS
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; Figure 2 shows an infant with an Erb palsy.
2010.
Tschudy M, Arcara K (Childrens Medical and Surgical Center, Johns
Hopkins Hospital), eds. The Harriet Lane Handbook: A Manual for
Pediatric House Officers. 19th ed. Philadelphia, PA: Mosby Elsevier;
2012.

CASE 2 ANSWERS

1. A. i. ErbDuchenne
B. ii. Klumpke
C. i. ErbDuchenne
D. i. ErbDuchenne
Figure 1 compares the clinical findings of an infant with an Erb
Duchenne palsy and those of an infant with a Klumpke palsy.

FIGURE 2. This picture shows an infant with Erb palsy. From


ErbDuchenne Klumpke MacDonald MG, Mullett MD, Seshia MM, eds. Averys Neonatology:
Palsy (proximal) Palsy (distal) Pathophysiology & Management of the Newborn. 6th ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 2005. Figure 52.17
Nerve C5C7 C8T1
roots Figure 3 shows how a brachial plexus injury can occur after
Clinical Most common (90%) Least common excessive stretching of the neck during delivery.
signs and Waiter tip position Rare to be iso-
symptoms with arm adducted, lated (often upper
internally rotated arm, roots involved as
extension of elbow, well, leading to
pronation of forearm, total palsy)
flexed wrist and fingers Weakness of flex-
Biceps reflex absent ors of wrist and
Intact palmar grasp fingers, and finger
Absent shoulder moro abduction
while hand moro is
present
FIGURE 3. From Moore KL, Agur AM, eds. Essential Clinical Anatomy. 2nd
ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002. Figure 7.6

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 3 Seizures75

2. A. Physical therapy; likely full recovery by 4 months The clinical diagnosis of neonatal seizures can be catego-
Some brachial plexus injuries heal without treatment; others rized into five subtypes, as summarized in the table below.
improve or recover by 3 to 4 months of age. Treatments used
for brachial plexus injuries are physical therapy and, in cer-
Seizure Preterm or
tain cases, surgery. Prognosis is based on location and type Subtype Clinical Manifestations Term Infant
of injury. For avulsion and rupture injuries, surgical interven-
tion is needed in a timely fashion to offer an opportunity for Subtle Oral, facial, or ocular Occurs in both
activity; swimming (most frequent
complete recovery.
or bicycling limb neonatal
movements; auto- subtype)
nomic changes with
tachycardia, apnea,
AMERICAN BOARD OF PEDIATRICS and increased blood
CONTENT SPECIFICATIONS pressure
Multifocal Clonic activity of one Term infant
Recognize the clinical manifestations of neonatal bra- clonic limb with movement to
chial plexus injuries another part of body in
Know the management and prognosis of neonatal bra- a nonordered manner;
chial plexus injuries may look like jitteri-
ness; not usually as-
sociated with apnea or
ocular movements
SUGGESTED READINGS Focal clonic Well-localized, repeti- Term infant >
tive, usually one limb, preterm infant
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; conscious throughout,
2010. may represent focal
Tschudy M, Arcara K (Childrens Medical and Surgical Center, Johns or diffuse disease (i.e.,
Hopkins Hospital), eds. The Harriet Lane Handbook: A Manual for metabolic disorder)
Pediatric House Officers. 19th ed. Philadelphia, PA: Mosby Elsevier;
2012.
Tonic Abrupt change in tone Preterm infant
that leads to change
in posture; described
as posturing,
CASE 3 ANSWERS stiffening, rigidity;
may have associated
1. D. All of the above apnea and ocular
Seizure mimics in the newborn period can make it difficult movements
to distinguish between normal immature activity, abnormal Myoclonic Rapid, sudden, shock- Term and
nonseizure activity, and true seizures. like jerks of flexion of preterm
both arms and/or legs;
True epileptic seizures are not usually stimulus-sensitive events may occur in
Epileptic seizures cannot be stopped by repositioning or brief series
passive restraint
Epileptic seizures most often have associated autonomic Adapted from: Brodsky D, Martin C. Neonatology Review. 2nd ed.
changes or ocular manifestations Raleigh, NC: Lulu; 2010:177178

Some seizure mimic examples are nonnutritive sucking, jit-


3. D. All of the above
teriness, and an exaggerated startle response.
Seizures are a marker for potential adverse neurologic out-
2. D. Sudden hypotension come. The overall prognosis for survival in an infant with neo-
All of the following are potential manifestations of seizure ac- natal seizures is 85% with a morbidity that varies between
tivity in the neonate: 35% and 60%. The three major predictors of outcome after a
neonatal seizure are:
Abnormal chewing
Bicycling or swimming movement of the extremities Underlying etiology
Eye deviation EEG
Tachycardia Gestational age
Apnea
Infants with hypoxic-ischemic encephalopathy and seizure ac-
Sudden hypertension
tivity have a 50% chance of normal neurologic development.
Hypotension would be unusual unless the infant had pro- Infants diagnosed with bacterial meningitis accompanied by
longed apnea with bradycardia and subsequent low blood seizures also have ~50% chance for a normal neurologic out-
pressure. come. Overall outcome for infants with seizures after arterial or

(c) 2015 Wolters Kluwer. All Rights Reserved.


76Section IV Neurology

venous vaso-occlusive disease is favorable. In infants with arte- of the images represents changes at day 3, at 4 months of age,
rial strokes, those with an abnormal interictal EEG background and at 2 years of life. Figure 1A shows generalized, decreased
have a less favorable outcome. Infants with benign neonatal sei- tissue attenuation in both cerebral hemispheres. Figure 1B
zures, also known as fifth day fits, have normal background and Figure 1C reveal multicystic e ncephalomacia and cerebral
EEG patterns with seizure resolution usually by day 15 of life; as atrophy.
the name implies, infants have a normal neurologic outcome.
Intracranial hemorrhage and subsequent seizure are seen in
both term and preterm infants, but the outcome depends on
parenchymal injury and gestational age with lower-gestational-
age infants at risk for significantly worse neurologic outcome.

AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATIONS

Know the differential diagnosis of neonatal seizures


Know the clinical manifestations of neonatal seizures
Know the prognosis following neonatal seizures
A

SUGGESTED READINGS
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010.
Cloherty J, Eichenwald EC, Hansen A, et al., eds. Manual of Neonatal
Care. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.
Olson D. Neonatal seizures. NeoReviews. 2012;13:e213e222.

CASE 4 ANSWERS

1. B. Within the first 24 hours of life


HIE is the most frequent cause of neonatal seizure in a full-term
infant, occurring in 20% to 50% of these infants. Seizures related
to HIE most often start between 6 and 24 hours after the insult. B

2. C. Hypotonia, seizures, transient myocardial ischemia,


ventricular dysfunction, tricuspid regurgitation, oliguria
and ATN, pulmonary hypertension, intestinal ischemia
Intrapartum asphyxiation can lead to multiorgan injury. Acute
asphyxia elicits the diving reflex where blood preferentially
flows to the most vital organs, such as the brain, heart, and
adrenal glands. Vasoconstriction occurs in organs such as the
kidneys, liver, lungs, and intestines. The kidney is the most
common organ affected in perinatal asphyxia as decreased per-
fusion to the proximal tubule leads to ATN. Cardiac dysfunc-
tion is caused by transient myocardial ischemia with clinical
findings of hypotension, ventricular dysfunction (right ventricle
worse than left ventricle), and tricuspid regurgitation. There
is increased risk for bowel ischemia and necrotizing entero- C
colitis. Hematologic effects include thrombocytopenia due FIGURE 1ABC. From MacDonald MG, Mullett MD, Seshia MM, eds.
to poor production in the bone marrow, poor production of Averys Neonatology: Pathophysiology & Management of the Newborn. 6th ed.
clotting factors due to liver dysfunction, and disseminated in- Philadelphia, PA: Lippincott Williams & Wilkins; 2005. Figure 50.1ABC
travascular coagulation due to damage to blood vessels. Peak
laboratory values for liver function studies, BUN, and serum 3. D. All of the above
Cr usually occur 1 to 4 days after the insult. The overall mortality rate in infants with HIE is 10% to
Figure 1 shows the brain of a full-term infant with severe HIE. 30%, and the incidence of neurodevelopmental sequelae
Figure 1A and Figure 1B are computed tomographic images, is 15% to 45% in surviving infants. Therapeutic hypother-
and Figure 1C is a magnetic resonance image. The progression mia in term infants with moderate/severe encephalopathy

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 5 Intracranial hemorrhage77

reduces mortality and/or neurodevelopmental outcomes


when measured at 18 months of age. Attempts to predict
Subependymal
individual patient outcomes depend on the severity of the germinal matrix
area
encephalopathy, the presence or absence of seizures, EEG
results, neuroimaging findings, and the infants clinical
examination.

AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATIONS

Know that hypoxic-ischemic encephalopathy is the most Grade ISubependymal Grade IIIntraventricular hemorrhage
hemorrhage only without ventricular dilation
frequent cause of neonatal seizure in a full-term infant
Recognize that neonatal seizures secondary to hypoxic-
ischemic encephalopathy characteristically occur within
24 hours of birth
Recognize that intrapartum asphyxiation can cause in-
jury to multiple organ systems (e.g., kidney, lung, intes-
tine, liver, brain, heart)
Recognize that the majority of full-term newborns who
have neonatal seizures secondary to hypoxic-ischemic
encephalopathy do not manifest long-term neurodevel-
opmental sequelae

Grade IIIIntraventricular hemorrhage Grade IVIntraventricular hemorrhage


with ventricular dilation with parenchymal hemorrhage
SUGGESTED READINGS FIGURE 1. From Rozmus C. Periventricular-intraventricular hem
orr
hage in the newborn. Matern Child Nurs. 1992;17:672, with
Allan W. The clinical spectrum and prediction of outcome in hypoxic- permission
ischemic encephalopathy. NeoReviews. 2002;3:e108e114.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010. Vignette iv describes a preterm infant showing signs of brain-
Cloherty J, Eichenwald EC, Hansen A, et al., eds. Manual of Neona-
tal Care. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; stem compression that can be associated with a cerebellar
2011. hemorrhage. Although uncommon, cerebellar hemorrhage
can be serious and can lead to long-term neurodevelopmental
deficits.
CASE 5 ANSWERS Vignette iii depicts a term infant with seizures on day 2.
A subarachnoid hemorrhage is the most frequent intracranial
1. A i hemorrhage and rarely is of clinical significance. If symptom-
B iv atic, infants may have early onset refractory seizures.
C iii Vignette ii describes a term infant who withstood a trau-
D ii matic delivery resulting in a subdural hemorrhage caused by
Vignette i describes a 24-week-gestational-age infant who trauma and tearing of the veins and venous sinuses. Figure2
has bilateral GMH (or a grade 1 intraventricular hemorrhage shows an extensive left subdural hemorrhage covering the
[IVH]) on his initial head ultrasound. The incidence of IVH frontal lobe (arrows) and extending into the midline along the
in an infant at this gestation is 30%. Approximately 78% of falx cerebri.
IVHs are ultrasonographically visible by postnatal day 3, and 2. A ii. and iii. MRI and Ultrasonography
90% of IVH are visible by one week of age. As described in B i. CT
this case, this infant develops PVL. His risks for developing C ii. MRI
PVL include prematurity, IVH, chorioamnionitis, and initial D i. CT
profound hypotension.
Figure 1 depicts the various grades of IVH. IVH is best visualized via ultrasonography or MRI. It is
routine to obtain head ultrasound imaging for infants born
<32 weeks gestation. For extremely premature infants, test-
ing is usually obtained on day 1 to 3, day 10, day 30, and

(c) 2015 Wolters Kluwer. All Rights Reserved.


78Section IV Neurology

SUGGESTED READINGS
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
Cloherty J, Eichenwald EC, Hansen A, et al., eds. Manual of Neonatal
Care. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.
Whitelaw A. Core concepts: Intraventricular hemorrhage. NeoReviews.
2011;12:e94e101.

C ase 6 A nswers

1. D. All of the above


A newborn presenting at postnatal day 3 with poor feeding,
hypothermia, jitteriness, followed by tachypnea, tachycar-
dia, and extreme lethargy, prompts a vast differential diag-
nosis. There are two broad categories that initially should be
considered:

FIGURE 2. Courtesy of Robert A. Zimmerman, MD Disorders resulting from infection, cardiorespiratory


compromise, congenital brain abnormalities, trauma (in-
tracranial hemorrhage versus other), or toxins
term gestational age, with more frequent testing if an infant is Disorders caused by an inborn error of metabolism (in-
acutely ill or has abnormal radiographic findings. cluding carbohydrate disorders, protein abnormalities,
Subdural, subarachnoid, and cerebellar hemorrhages are organic acidemias, fatty acid abnormalities, lysosomal
best visualized via CT. Although CT delivers radiation to the storage diseases, mitochondrial disorders)
infant as opposed to ultrasound and MRI, newer protocols
have been developed to minimize radiation exposure. How- Thus, all the studies listed in the options would be helpful
ever, because of these radiation concerns, MRI is sometimes initial tests to narrow the differential diagnosis.
used for detection of these hemorrhages. The initial laboratory findings that may lead to a diagnosis
of an inborn error of metabolism are acidosis and hyperam-
3. B. Follow guidelines for neonatal stabilization; secure monemia. A mild increase in ammonia (typically <500 M/L)
the airway (intubate); provide blood products and vol- may be seen in sepsis, perinatal asphyxia, or disseminated
ume; start inotropes; obtain complete blood count with herpes simplex infection. A moderate increase in ammonia
differential, blood culture, electrolytes, disseminated in- (>500 M/L) may be seen in:
travascular coagulation panel; call neurosurgery stat and
arrange for head imaging urgently Deficiencies of urea cycle enzymes
The two infants described in vignettes ii and iv represent Organic acidemias
neurosurgical emergencies until proven otherwise. They Lysinuric protein intolerance
need urgent stabilization and neurosurgery needs to be con- Hyperammonemiahyperornithinemiahomocitrul-
sulted. In the case of a subdural hemorrhage with severe linemia syndrome
neurologic decompensation, surgical evacuation must be Transient hyperammonemia of the newborn
performed. Congenital hyperinsulinism with hyperammonemia

AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATIONS

Recognize the clinical and laboratory findings associated


with intracranial hemorrhage in a neonate
Plan the evaluation and management of a neonate with
intracranial hemorrhage

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 6 Neonatal encephalopathy79

Hyperammonemia

Assess for acidosis


and ketonuria

Acidosis + ketonuria No acidosis, no ketonuria Acidosis, no ketonuria

Propionic, methylmalonic,
and isovaleric acidemia; Fatty acid oxidation
lactic acidemia; glutaric Plasma citrulline abnormalities
aciduria; pyruvate
carboxylase deficiency;
-methylcrotonyl glycinuria

Absent or trace Normal to Very high


moderately
increased

Check urine orotic acid


Check urine arginino- Argininosuccinic
succinic acid acid
synthetase
deficiency
Low or normal High

Absent Present

Carbamyl
phosphate Ornithine
synthetase transcarboxylase
deficiency, Check plasma Argininosuccinic acid
deficiency arginine
N-acetylglutamate lyase deficiency
synthetase
FIGURE 1. Printed with permission from: deficiency
Brodsky D, Martin C. Neonatology Review.
2nd ed. Raleigh, NC: Lulu; 2010:420; Normal or low Elevated
Modified from: Ward JC. Inborn errors of
metabolism of acute onset in infancy. Pediatr
in Rev. 1990;11:210 and An Approach to Transient neonatal
Inborn Errors of Metabolism in the Neonate. hyperammonemia, Arginase deficiency
Lecture by Korson M. Childrens Hospital, lysine protein
intolerance
Boston, MA. August 1990

See Figure 1 for the workup and steps to further delineate the
etiology of hyperammonemia:
AMERICAN BOARD OF PEDIATRICS
CONTENT SPECIFICATIONS
2. B. Neurologic sequelae and survival depend on the
length of the hyperammonemic coma Formulate a differential diagnosis of lethargy and coma
Infants diagnosed with a urea cycle defect at a few days of in the neonate
life may succumb to their illness unless management is swift.
Neurologic sequelae and survival depend on the length of the
hyperammonemic coma. In infants with a duration of hyperam- SUGGESTED READINGS
monemia coma that is <2 days, there is potential for minimal
neurologic sequelae. Many infants who survive the newborn Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010.
Cloherty J, Eichenwald EC, Hansen A, et al., eds. Manual of Neonatal
period have developmental delay, cognitive deficits, seizures, Care. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.
cortical atrophy, and spastic quadriparesis. Further morbidity Enns G, Packman S. Diagnosing inborn errors of metabolism in the
or death may result from acute illness due to protein intake or newborn: Clinical features. NeoReviews. 2001;2:e183e191.
Joseph M, Hageman J. Neonatal transport: A 3-day-old neonate with
infection. hypothermia, respiratory distress, lethargy, and poor feeding.
JPerinat. 2002;22:506509.

(c) 2015 Wolters Kluwer. All Rights Reserved.


S E C T I ON V Musculoskeletal
System

(c) 2015 Wolters Kluwer. All Rights Reserved.


82Section V Musculoskeletal System

CASE 1
Clubfoot

A 32-year-old pregnant woman has a benign prenatal course 2. Of the following, the most likely classification for this
with a normal early risk assessment and 16-week fetal ultra- infants deformity is:
sound. She delivers a full-term female infant with a left-sided
A. Genetic
foot abnormality. The infants pediatrician is unable to ma-
B. Isolated
nipulate the foot back to the midline position. A diagram of
C. Positional
this infants feet is shown in Figure 1.
D. Syndromic

The pediatrician meets with the infants family to discuss the


management of clubfoot. A pediatric orthopedist is consulted,
who suggests an intervention to prevent long-term disability,
deformity, and pain.

3. Of the following, the most appropriate next best manage-


ment for this infant is:

A. Casting
B. Observation
C. Surgical correction
D. All of the above

The family wants to discuss the likelihood of having a second


child with a clubfoot. Neither parents had this abnormality.

FIGURE 1. Courtesy of LifeArt 2014 Lippincott Williams & Wilkins. 4. Of the following, the recurrence risk that is most likely in
All rights reserved this baby girls future sibling is:

1. Of the following, the most likely structural abnormality in A. 0%


this newborn is: B. 2% to 5%
C. 10%
A. Talipes equinovarus D. 15%
B. Talipes equinus
C. Talipes valgus
D. Talipes varus

CASE 2
Developmental dysplasia of the hips

A pediatrician is rounding with a third-year medical student pediatrician and medical student review the perinatal histo-
in the newborn nursery. This is the students second day of ries and then examine the 15 neonates who are currently in
his clinical rotation in the nursery. He expresses interest in the nursery.
learning more about the newborns hip examination. The

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 3 Torticollis83

Four newborns have a distinct perinatal history, as described 2. Of the following, match the infant scenarios listed above
below; all have a normal hip examination: (vx) with the most appropriate next management:
i. Female full-term infant with a history of breech position A. No actions required, routine newborn care
between 24 and 26 weeks gestation but then changed to B. Obtain hip radiographs
vertex position and was delivered vaginally C. Schedule hip ultrasonography at 4 to 6 weeks of age
ii. Female infant born at 36 weeks gestation by cesarean D. Obtain a hip ultrasound and consult a pediatric orthopedist
delivery because of breech presentation
iii. Male full-term infant born by cesarean delivery because The remaining five newborns have a benign perinatal history
of breech presentation and a completely normal hip examination.
iv. Male infant who was born to a mother with develop-
3. Which statement is true about the risk of DDH in the five
mental dysplasia of the hips (DDH)
remaining newborns?
1. Of the following, match the infant scenarios listed above A. If an orthopedist confirms that the hip examinations are
(iiv) with the most appropriate next management: normal, the infants have no risk of DDH.
A. No actions required, routine newborn care B. It would be extremely rare that these infants later have a
B. Obtain hip radiographs diagnosis of DDH.
C. Schedule hip ultrasonography at 4 to 6 weeks of age C. Only the female infants need to be monitored for a
D. Obtain a hip ultrasound and consult a pediatric orthopedist potential risk of DDH.
D. The pediatricians will still need to monitor the infants
Six newborns have specific physical examination findings:
hip examinations because they are still at risk for DDH.
v. Male infant with asymmetric thigh and posterior gluteal folds
vi. Male infant with disproportionate length of legs
vii. Female infant with bilateral hip clicks
viii. Female infant with unilateral hip clunk
ix. Male infant with bilateral hip clunks
x. Female infant with abnormal Barlow maneuver but nor-
mal Ortolani test

CASE 3
Torticollis

A full-term male infant is born by cesarean delivery because of 1. Of the following, the most likely cause of this infants phys-
breech presentation. The baby does well in the newborn nurs- ical examination finding is injury to the right:
ery and is discharged after 2 days. At a routine appointment at
A. Clavicle
2 weeks of age, the pediatrician observes that the infant prefers
B. Facial nerve
to hold his head toward the right side. The pediatrician is able
C. Sternocleidomastoid muscle
to move the infants head to the left side without difficulty
D. Trapezius muscle
but movement toward the right side is restricted and seems
to cause pain to the infant. The infant is pictured in Figure 1. The pediatrician needs to determine if this infants torticollis
is congenital or acquired. He recalls that there are different
reasons for acquired torticollis, including the following:

Brachial plexus palsy


Brain abnormalities, such as posterior fossa syndrome
Cervical spinal abnormalities
Craniosynostosis
KlippelFeil syndrome
Ocular dysfunction

FIGURE 1. From Avery GB, Fletcher MA, MacDonald MG. Neonatology:


Pathophysiology and Management of the Newborn, 5th ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 1999. Figure 13.23

(c) 2015 Wolters Kluwer. All Rights Reserved.


84Section V Musculoskeletal System

However, based on a complete physical examination of the The pediatrician discusses management options with the
infant, the pediatrician believes that this infant most likely has infants mother.
isolated congenital torticollis.
3. Of the following, the management that is most likely to be
2. Of the following, the finding that is most consistent with helpful in this infant is:
congenital, instead of acquired, torticollis is:
A. Await spontaneous resolution (i.e., no treatment
A. A low posterior hairline required)
B. A palpable neck mass B. Passive stretching exercises
C. Microcephaly C. Surgical removal of any neck mass
D. Strabismus D. Temporary stabilization of the neck

CASE 4
Contractures

A neurologist is asked to evaluate a full-term male infant who The neurologist meets with the infants parents to obtain a
was born with contractures of all his extremities. A photo- detailed prenatal and family history.
graph of the infant is shown in Figure 1.
2. Of the following, the intrauterine history that corresponds
with this infants findings is a(n):

A. Abnormal maternal glucose tolerance test


B. Decrease in fetal movements
C. Low resting heart rate
D. All of the above

The neurologist also discusses the possible causes of the


infants joint contractures.

3. An abnormality in which of the following organ systems


can lead to joint contractures?

A. Connective tissue
B. Muscular system
C. Neurologic system
D. All of the above
FIGURE 1. From MacDonald MG, Mullett MD, Seshia MM, eds. Averys
Neonatology: Pathophysiology & Management of the Newborn. 6th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2005. Figure 52.15

1. Of the following, the most accurate name for this infants


findings is:

A. Achondrogenesis
B. Achondroplasia
C. Arthrochondritis
D. Arthrogryposis

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 5 Osteogenesis imperfecta85

CASE 5
Osteogenesis imperfecta

A full-term male newborn has the following radiograph The neonatologist obtains a complete skeletal survey, with the
(Figure 1) on the first day of life. skull film shown in Figure 2.

FIGURE 2. Courtesy of C.H. Quay, MD, Melbourne, Australia

3. Of the following, the finding that is exemplified in this ra-


FIGURE 1. Eisenberg RL. An Atlas of Differential Diagnosis. 4th ed. diograph is:
Philadelphia, PA: Lippincott Williams & Wilkins; 2003. Figure 6.11
A. Cloverleaf skull shape
B. Craniosynostosis
1. Of the following, the abnormal findings that are consistent C. Widely split sutures
with osteogenesis imperfecta (OI) type II in this radiograph D. Wormian bones
are:
Genetic testing confirms that the neonate has OI type II. The
A. Deformed and crumpled femurs neonatologist discusses the infants prognosis with the family.
B. Diffuse osteoporosis The parents had been counseled about this likely diagnosis
C. Multiple rib fractures with callus formation prenatally. However, because they have a distant relative with
D. All of the above OI who is doing well at age 48, they are surprised by their
Indeed, OI type II had been diagnosed prenatally. infants prognosis. They inform the neonatologist that their
relative has OI type I evident by blue sclerae, several fractures
2. Of the following, the statement that is most consistent with during childhood but only two since puberty, easy bruisabil-
OI type II is: ity, and hyperextensible joints.
A. Most affected newborns have deep blue sclerae 4. Of the following, the most likely additional finding in this
B. OI type II has an X-linked recessive inheritance pattern adult relative with type I OI is (are):
C. The majority of affected patients survive to adulthood
D. This disorder is caused by a mutation in the fibroblast A. Cataracts
growth factor receptor 3 gene B. Early menopause
C. Hearing loss
D. Mitral valve prolapse

(c) 2015 Wolters Kluwer. All Rights Reserved.


86Section V Musculoskeletal System

CASE 6
Achondroplasia

A geneticist is following several children with achondropla- Children with achondroplasia require frequent monitoring to
sia in her outpatient clinic. All of her patients have the same assess for potential complications.
mutation in the fibroblast growth factor receptor 3 (FGFR3)
gene. They also have similar clinical characteristics, including 2. Of the following, the most likely potential complication of
the following: children with achondroplasia is:

Flat vertebrae with abnormally shaped pelvis A. Cognitive disabilities


Hearing loss B. Fractures
Hypotonia during early infancy C. Retinal detachment
Macrocephaly D. Spinal complications
Short limbs with relatively normal trunk length None of the parents or siblings of the affected children whom
Trident hand shape with short, wide, and cone-shaped the geneticist is following up has achondroplasia.
phalanges
3. Of the following, the inheritance pattern that is associated
1. Of the following, the skeletal dysplasia that is also caused with achondroplasia is:
by a mutation in the FGFR3 gene and has similar clinical
features as achondroplasia is: A. Autosomal dominant
B. Autosomal recessive
A. Achondrogenesis C. X-linked dominant
B. Hypochondrogenesis D. X-linked recessive
C. Osteogenesis imperfecta
D. Thanatophoric dysplasia

CASE 7
Limited neck movements

A neonatologist is asked to evaluate a 6-hour-old full-term in- The neonatologist speaks with the family about the infants
fant with limited neck movements. The neonatologist finds likely diagnosis. Lateral flexion-extension radiographs of the
that the infant also has a low posterior hairline and a short infants cervical spine reveal fused cervical vertebrae. Because
neck. of possible associated findings, the neonatologist recom-
mends additional testing.
1. Of the following, the most likely diagnosis in this infant is:
2. Of the following, the most likely associated finding in this
A. Ellisvan Creveld syndrome
infant is (are):
B. KlippelFeil syndrome
C. Stickler syndrome A. Deafness
D. Thanatophoric dysplasia B. Genitourinary abnormalities
C. Structural heart defects
D. All of the above

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 2 Developmental dysplasia of the hips 87

SECTION V
Answers

4. B. 2% to 5%
CASE 1 ANSWERS
If an affected infants parents did not have a clubfoot, as in
1. A. Talipes equinovarus this vignette, then the overall risk of an isolated clubfoot in the
The infant in this vignette has a left clubfoot, which is caused siblings depends on the sex of the affected child. If the affected
by abnormal bone formation that also involves the local child is male, the recurrence risk is 2%. If the affected child is
muscles, nerves, tendons, and blood vessels. There are several female, the recurrence risk is 5%.
structural abnormalities that can lead to a clubfoot, including: If an affected infant (without respect to gender) has a par-
ent who had a clubfoot, the recurrence risk is 3% to 4%. If
Talipes varusthe foot is turned inward, leading to the both parents had a clubfoot, this risk increases to 15%. It is
appearance of the leg and foot of the letter J likely that a single gene is involved, but both autosomal reces-
Talipes valgusthe foot rotates outward, leading to the sive and X-linked recessive inheritance patterns have been de-
appearance of the letter L scribed in affected families. Less commonly, variably penetrant
Talipes equinusthe foot points downward, similar to a autosomal dominant inheritance has also been observed.
ballerinas position
Talipes calcaneusthe foot points upward with the heel
AMERICAN BOARD OF PEDIATRICS
pointing downward
CONTENT SPECIFICATIONS
The infant in this vignette has talipes equinovarus, the most
common cause of clubfoot. In this deformity, the foot ap- Know that the most common component of clubfoot is
pears to be pointed downward (i.e., equinus) and inward (i.e., equinovarus deformity
varus). Clubfoot can be unilateral or bilateral and involve a Be aware that early treatment of clubfoot is critical
mild or severe deformity. Recognize that the treatment for talipes equinovarus is
casting or splinting of the affected foot
2. B. Isolated
Clubfoot can be classified into three types:

1. Isolated: the most common type (80%), often first identi-


SUGGESTED READING
fied after birth Magriples U. Prenatal diagnosis of talipes equinovarus (clubfoot).
2. Positional: caused by a fixed intrauterine position of the UpToDate (Subscription required). http://www.uptodate.com/
foot, often associated with a restricted uterine environ- contents/prenatal-diagnosis-of-talipes-equinovarus-clubfoot.
Accessed March 21, 2013.
ment (e.g., uterine anomalies, oligohydramnios); this
is not a true clubfoot because the foot is structurally
normal CASE 2 ANSWERS
3. Syndromic or genetic: associated with other anomalies,
usually attributable to a multifactorial etiology 1. A. i, iii
B. none
While a positional clubfoot is flexible and can be moved back
C. ii, iv
to midline easily, infants with an isolated or syndromic club-
foot have fixed abnormalities. D. none
When determining a newborns risk for DDH, a pediatrician
3. A. Casting
needs to assess the infants perinatal history, observe the babys
Even for mild deformities, all affected newborns require treat-
movements at rest and with activity, and perform a hip ex-
ment. For neonates with isolated clubfoot, the ideal initial
amination. There are several easily identifiable risk factors for
management is serial casting or splinting of the affected foot.
DDH, including:
This should be initiated within the first week of life with cast
changes every few weeks for 2 to 3 months. Most infants will Extended breech positioning, particularly in late gestation
then require surgery with a tenotomy to release and lengthen Female infant (females have a 4- to 8-fold risk of DDH
the Achilles heel. Following, a bracing regimen is instituted for compared with males because of their increased sensitiv-
several years to minimize recurrence. ity to maternal relaxin)
Conservative treatment with stretching exercises is recom- Maternal hip dysplasia because genetic factors increase
mended for infants with positional clubfoot. the offspring risk

(c) 2015 Wolters Kluwer. All Rights Reserved.


88Section V Musculoskeletal System

In the setting of a normal hip examination, the recognition Finally, when the infant is in a supine position, the Orto-
of these risk factors, such as the infants in scenario ii and sce- lani and Barlow tests are helpful in the detection of DDH. In
nario iv, should prompt a hip evaluation by ultrasonography the Barlow maneuver (shown in Figure 2B), the clinicians fin-
at 4 to 6 weeks of age. Hip ultrasonography is preferred over gers are placed over the greater trochanters and the hips and
radiographies because it is the most precise imaging modality knees are flexed at 90 degrees. Following, a gentle backward
to confirm the diagnosis of DDH in infants. pressure is applied while adducting the thighs. If the femo-
For the infant in scenario i with a short intrauterine period ral head dislocates out of the acetabulum, the test is positive.
of breech positioning and for the male infant in scenario iii In the Ortolani test, the clinicians fingers are placed on the
who was born breech, further actions are not required because infants greater trochanters and the thumbs grip the femurs
these infants are at low risk for DDH. (shown in Figure 2A). While applying upward pressure over
the trochanters, the thighs are abducted. If the femoral head
2. A. vii
is dislocated, this can be felt as a clunk. Thus, the Barlow
B. none maneuver dislocates a dislocatable hip and the Ortolani test
C. none relocates a dislocated hip. Any male or female infant with a
D. v, vi, viii, ix , x unilateral or bilateral positive Barlow and/or Ortolani test
(e.g., scenarios viii, ix, and x) requires a hip ultrasound and a
An infant with DDH can have one or more abnormal physical pediatric orthopedist consult.
examination findings, including:
Asymmetry of the thigh and posterior gluteal folds
Limited abduction of the affected hip
Galeazzi test (also known as the Allis sign): with knee
flexion, while the infants feet are flat on a surface, the
knee on the affected side appears lower

Thus, the infants in scenarios v and vi require a hip ultrasound


and a pediatric orthopedist consult. These findings are shown in
Figure 1. Figure 1A shows increased folds on the affected right
side, Figure 1B shows limited abduction of the right leg, and
Figure 1C shows a lower knee position of the affected left side. A

B
A B
FIGURE 2AB. From MacDonald MG, Mullett MD, Seshia MM, eds.
Averys Neonatology: Pathophysiology & Management of the Newborn. 6th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2005. Figure 52.1AB

Isolated hip clicks are unlikely indicators of DDH, and


without any other concerning signs for DDH, the infant in
scenario vii should receive routine newborn care.

3. D. The pediatricians will still need to monitor the


infants hip examinations because they are still at risk
for DDH.
The term congenital hip dislocation had previously been
C used to describe DDH. However, because neonates may not
FIGURE 1ABC. Klossner NJ, Hatfield NT. Introductory Maternity and
have any abnormal findings of hip dislocation initially, the
Pediatric Nursing. 2nd ed. Philadelphia , PA: Lippincott Williams & term was changed to developmental dysplasia of the hips.
Wilkins; 2009. Figure 21.24AC During newborn visits, pediatricians still need to monitor

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 4 Contractures89

the infants hip examinations even if prior examinations therapy, such as placing visual effects on the side of the torti-
were normal because the babies are still at risk for DDH. collis, will help encourage infants to rotate their head in that
direction. A physical therapist may also be involved in moni-
toring an infants progress. After 6 months of age, additional
active stretching movements are recommended. If children
AMERICAN BOARD OF PEDIATRICS
continue to have limited neck motion, severe plagiocephaly,
CONTENT SPECIFICATIONS
or facial asymmetry beyond 6 to 12 months of age, surgical
Know that developmental dysplasia of the hips is more intervention may be warranted.
likely in girls and in infants who are born by breech
presentation
AMERICAN BOARD OF PEDIATRICS
Know that ultrasonography is the most precise imaging
CONTENT SPECIFICATIONS
modality for confirmation of the diagnosis of develop-
mental dysplasia of the hip(s) in young infants Understand the etiology of congenital torticollis
Recognize asymmetry of the gluteal and thigh folds as a Recognize that the differential diagnosis of torticollis in-
sign of possible subluxation of the hip cludes head tilt secondary to malformation of the cervical
Know that isolated hip clicks are unlikely indicators of spine, a visual disturbance, and a posterior fossa tumor
dysplasia Differentiate between congenital and acquired torticollis
Know that initially there may be no abnormal signs of Understand that physical therapy (stretching) of the
subluxation of the hip in developmental dysplasia of the neck by a pediatric physical therapist and/or a parent
hip(s) may be successful treatment for torticollis

SUGGESTED READING
SUGGESTED READING
Macias CG, Gan V. Congenital muscular torticollis. UpToDate (Subscrip-
Wilkinson AG, Wilkinson S. Neonatal hip dysplasia: A new perspec- tion required). http://www.uptodate.com/contents/congenital-
tive. NeoReviews. 2010;11:e349e362. muscular-torticollis. Accessed March 18, 2013.

CASE 3 ANSWERS CASE 4 ANSWERS

1. C. Sternocleidomastoid muscle 1. D. Arthrogryposis


The infant described in this vignette most likely has congeni- The infant described in this vignette has contractures of his
tal muscular torticollis. Although the precise etiology is un- joints, known as arthrogryposis. This term describes joints
known, most affected infants have an injury to and shortening (i.e., arthro) that are curved or hooked (i.e., gryposis).
of the sternocleidomastoid muscle. Achondrogenesis is an autosomal dominant skeletal dys-
plasia associated with short limbs caused by a defect in type
2. B. A palpable neck mass
II collagen.
The diagnosis of congenital torticollis can usually be made
Achondroplasia is an autosomal dominant skeletal dys-
clinically. Infants typically present in the first 2 to 4 weeks
plasia leading to abnormal formation of cartilaginous tissues
of age with head tilting to the affected side. A characteristic
with short limbs. It is caused by a mutation in the fibroblast
circumscribed and firm mass may be palpable in the inferior
growth factor receptor 3 gene.
part of the affected sternocleidomastoid muscle. Radiographs
Arthrochondritis is an inflammation of articular cartilage;
of the cervical spine may be helpful to assess for C1-C2 sub-
this condition is not typically found in newborns.
luxation and other bone abnormalities. In addition, an ultra-
sound of the neck mass may be helpful to confirm that it is 2. B. Decrease in fetal movements
part of the muscle. The prenatal history of an infant with arthrogryposis may
A low posterior hairline with a short neck is found in in- identify one or more of the following:
fants with KlippelFeil syndrome. Microcephaly is not as-
Abnormal amniotic fluid volumepolyhydramnios or
sociated with torticollis. Strabismus may contribute to the
oligohydramnios
development of acquired torticollis.
Infants with a neurologic abnormality may have joint
3. B. Passive stretching exercises contractures because of lack of fetal movements. These in-
Infants with congenital torticollis can be treated by conservative fants may also have associated polyhydramnios because
therapy with passive and active stretching therapy. It is ideal if of decreased fetal swallowing as a result of abnormal neu-
passive stretching is initiated prior to 1 month of age. Parents rologic function. In contrast, infants with severe oligohy-
are taught specific exercises to attempt to stretch the short- dramnios may develop joint contractures as a result of
ened sternocleidomastoid muscle. In addition, environmental fetal crowding.

(c) 2015 Wolters Kluwer. All Rights Reserved.


90Section V Musculoskeletal System

Decreased fetal movements 2. A. Most affected newborns have deep blue sclerae
Intrauterine breech positioning Type II is the most severe form of OI with a high intrauterine
mortality or death in early infancy as a result of respiratory
The maternal glucose tolerance test and fetal resting heart rate
failure. Affected infants have short broad long bones, short
will be unaffected in infants with arthrogryposis.
limbs, multiple fractures, and deep blue sclerae. The skull is
3. D. All of the above often poorly mineralized with a soft calvarium and large fon-
Joint contractures in a fetus can be caused by intrinsic fetal tanels. This type of OI typically has an autosomal dominant
abnormalities in the fetal neurologic, muscular, or connective inheritance pattern (although some rare subtypes have an au-
tissue systems. A neurologic problem is the most common tosomal recessive inheritance pattern) and is usually caused by
cause of arthrogryposis. Potential neurologic abnormalities an abnormality in type I collagen genes.
include meningomyelocele, motor horn cell deficiency, and
3. D. Wormian bones
structural brain abnormalities, such as anencephaly, hydran-
This skull film demonstrates multiple Wormian bones, which
encephaly, and holoprosencephaly. Muscular abnormalities,
are small bony fragments along a suture line. As shown in this
such as muscle agenesis, myopathy, and myotonic dystro-
radiograph, these bones are often observed along the lamb-
phy, can also lead to arthrogryposis. A fetus with a significant
doid suture. Wormian bones can be found as a normal variant
connective tissue disorder (e.g., synostosis, lack of joint de-
or in infants with OI or cleidocranial dysplasia.
velopment, abnormal fixation of joints) is at increased risk
for developing arthrogryposis. All of these abnormalities can 4. C. Hearing loss
lead to decreased intrauterine joint mobility resulting in joint Even though OI types I and II are both autosomal dominant dis-
fixations. orders that impact the same collagen gene, patients have different
In addition to intrinsic fetal abnormalities, arthrogrypo- clinical manifestations. This occurs because type I OI is caused
sis can occur because of an extrinsic etiology leading to fetal by a quantitative defect in the type I collagen genes (COL1A1 or
crowding or constraint. Examples of these external/environ- COL1A2), while type II OI results from a qualitative defect of the
mental causes are: same genes. While OI type 2 is associated with a poor prognosis,
patients with OI type 1 have an excellent prognosis. Individuals
Multiple births
with type I OI have blue sclerae, Wormian skull bones, a normal
Severe oligohydramnios as a result of renal agenesis or
stature, hyperextensibility, and infrequent fractures that often
early persistent amniotic fluid leakage; affected infants
decrease after puberty. Approximately 50% of affected patients
may have a Potter facies with abnormal ear lobation, mi-
have adult-onset hearing loss as a result of osteosclerosis.
crognathia, flattened nose, and infraorbital folds
There are a total of nine types of OI. Type I is the mildest
form; type II is the most severe form; types III through IX lead
AMERICAN BOARD OF PEDIATRICS to moderate or severe bone fragility. All types have an autoso-
CONTENT SPECIFICATION mal dominant or recessive pattern of inheritance.

Recognize the clinical features of arthrogryposis


AMERICAN BOARD OF PEDIATRICS
CONTENT SPECIFICATIONS
SUGGESTED READINGS
Know the clinical features of osteogenesis imperfecta
Jones K. Smiths Recognizable Patterns of Human Malformation. 6th ed. Recognize the association of deafness with osteogenesis
Philadelphia, PA: Saunders; 2006. imperfecta
Swarr DT, Sutton VR. Skeletal dysplasias in the newborn: Di-
agnostic evaluation and development genetics. NeoReviews.
2010;11:e290e305.
SUGGESTED READINGS
Jones K. Smiths Recognizable Patterns of Human Malformation. 6th ed.
CASE 5 ANSWERS Philadelphia, PA: Saunders; 2006.
Swarr DT, Sutton VR. Skeletal dysplasias in the newborn: Diagnostic eval-
1. D. All of the above uation and development genetics. NeoReviews. 2010;11:e290e305.
The abnormal findings that are evident in this radiograph are:

Deformed and crumpled femurs and humeri CASE 6 ANSWERS


Diffuse osteoporosis
Multiple rib fractures with callus formation leading to a 1. D. Thanatophoric dysplasia
beaded or wavy rib appearance Mutations in the FGFR3 gene can cause three different types of
Short ribs and long bones skeletal dysplasias:

These radiographic findings are consistent with OI. OI is a het- 1. Thanatophoric dysplasia
erogeneous disorder of increased bone fragility that is catego- 2. Achondroplasia
rized into nine types. 3. Hypochondroplasia

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 7 Limited neck movements91

The most significant difference between these disorders is


CASE 7 ANSWERS
the severity of the dysplasia. Infants with thanatophoric dys-
plasia have a high mortality rate in the first few days of life 1. B. KlippelFeil syndrome
because of respiratory failure from pulmonary hypoplasia. The infant described in this vignette has the classic clinical
In contrast, infants with achondroplasia have an excellent triad of KlippelFeil syndrome:
prognosis and typically survive into adulthood. In both of
these disorders, affected infants have a large head and short Low hairline
limbs with a normal-sized trunk. Hypochondroplasia is the Short neck
mildest of the three dysplasias, with onset during the second Limited neck movements
decade of life. These symptoms are attributable to fused cervical vertebrae.
Achondrogenesis and hypochondrogenesis are colla- KlippelFeil syndrome is also commonly associated with
gen disorders with mutations in the type 2 collagen gene other skeletal abnormalities, with more than half of affected
(COL2A1). Affected infants have abnormalities of the spine children having scoliosis.
and epiphyses of the long bones. The vast majority (90%) of Ellisvan Creveld syndrome, also known as chondroecto-
infants with osteogenesis imperfecta have a mutation in a gene dermal dysplasia, is associated with skeletal abnormalities,
for type I collagen (either COL1A1 or COL1A2), which leads to such as a narrow thorax, polydactyly, and fused metacarpals
an increase in bone fragility. or phalanges. In addition, affected individuals can have pel-
2. D. Spinal complications vic dysplasia, gingival frenulum, congenital heart defects,
Approximately 46% of patients with achondroplasia have hypoplastic nails, and dental abnormalities.
spinal complications, and close follow-up by an orthopedist Infants with Stickler syndrome typically have midfacial hy-
and neurologist is important. While almost all children with poplasia, micrognathia, joint hypermobility, cleft palate, sen-
achondroplasia have a small foramen magnum, brainstem or sorineural hearing loss, and ophthalmologic abnormalities.
upper cervical cord compression leading to respiratory failure Infants with thanatophoric dysplasia typically have the
and sudden death occurs rarely. following clinical features:
Although affected children can have speech delay, their Central nervous system malformations (e.g., megalen-
cognitive abilities are typically normal. While bone com- cephaly, neuronal migration disorders)
pression can occur in children with achondroplasia, osteo- Depressed nasal bridge with a prominent forehead
arthritis and fractures are not commonly found. Children Narrow thorax, often associated with pulmonary
with achondroplasia may have short eustachian tubes, re- hypoplasia
sulting in middle-ear infections and conductive hearing Very short extremities with a normal trunk length
loss. However, their vision is normal without risk for retinal
detachment. The infant in Figure 1 has thanatophoric dysplasia, evident by
frontal bossing and short limbs and fingers.
3. A. Autosomal dominant
Achondroplasia has an autosomal dominant inheritance pat-
tern. However, parents and siblings are not usually affected
because 90% of cases are caused by new mutations.

AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATIONS
Recognize the clinical features and complications of
achondroplasia
Recognize the inheritance pattern of achondroplasia

SUGGESTED READINGS
Jones K. Smiths Recognizable Patterns of Human Malformation. 6th ed.
Philadelphia, PA: Saunders; 2006.
Swarr DT, Sutton VR. Skeletal dysplasias in the newborn: Di-
agnostic evaluation and development genetics. NeoReviews.
2010;11:e290e305. FIGURE 1. Courtesy of Paul S. Matz, MD

(c) 2015 Wolters Kluwer. All Rights Reserved.


92Section V Musculoskeletal System

Infants with thanatophoric dysplasia type II have a charac- 2. D. All of the above
teristic cloverleaf skull deformity, shown in Figure 2. Approximately 30% of infants with KlippelFeil syndrome
also have conductive or neural deafness. Affected infants can
have congenital heart defects, with ventricular septal defect be-
ing the most common. Genitourinary abnormalities are also
found in infants with KlippelFeil syndrome. The most com-
mon renal abnormalities include renal agenesis, renal ectopia,
or a pelvic kidney.

AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATION
Know the clinical and radiologic features of KlippelFeil
syndrome congenital abnormalities

SUGGESTED READINGS
Jones K. Smiths Recognizable Patterns of Human Malformation. 6th ed.
Philadelphia, PA: Saunders; 2006.
FIGURE 2. Reprinted with permission from: Stevenson RE, Hall JG, Swarr DT, Sutton VR. Skeletal dysplasias in the newborn: Di-
Goodman RM (eds). Human Malformations and Related Anomalies. agnostic evaluation and development genetics. NeoReviews.
NewYork, NY: Oxford University Press;1993 2010;11:e290e305.

(c) 2015 Wolters Kluwer. All Rights Reserved.


S E C T I ON VI Genetics

(c) 2015 Wolters Kluwer. All Rights Reserved.


94Section VI Genetics

CASE 1
Postnatal genetic testing

A 40-year-old gravida 6 para 0 woman is currently pregnant at The infants clinical features are not consistent with any of
12 weeks gestation. Her past medical history is complicated by the common gene defects, and the FISH results are normal.
five spontaneous abortions with one fetus with a postmortem Further testing will need to be done. The consulting geneti-
diagnosis of Turner syndrome. The prenatal fetal ultrasound cist recommends sending comparative genomic hybridization
for this pregnancy is concerning for a thickened nuchal fold. (CGH).
The parents have declined prenatal testing. Six months later, a
male infant is born at term, and his examination reveals dys- 2. Which of the following statements is true regarding CGH?
morphic features. A. CGH has replaced high-resolution chromosomal
analysis.
1. Which of the following gene defects could be diagnosed
B. CGH is inexpensive.
via fluorescent in situ hybridization (FISH) to provide the
C. CGH is less likely than karyotype analysis to provide a
family with information as soon as possible?
genetic diagnosis.
A. 22q11 deletion C. Trisomy 18 syndrome D. CGH only detects large deletions.
B. Down syndrome D. All of the above

CASE 2
Inheritance patterns

A 42-year-old woman is pregnant. Her family history is re- fetus with a postmortem diagnosis of Turner syndrome. You
viewed and is significant for a maternal uncle with Marfan also learn that her cousin with intellectual disability was diag-
syndrome, a paternal aunt with cystic fibrosis, and a cousin nosed with fragile X syndrome and her father had hemophilia.
with intellectual disability. To understand the implications to
The medical records include the pedigree charts
the fetus, you need to review the inheritance patterns in the
(Figure1AD).
womans family.

1. Match the inheritance pattern (AD) with the descriptions


below:
A. Autosomal i. An affected father will transmit
dominant the carrier state to his daughters
but cannot transmit the disease
A B
or carrier state to his sons
B. Autosomal ii. An affected female has a 50%
recessive chance of passing the disease
to her sons or daughters
C. X-linked iii. If both parents are affected, 1 2
dominant recurrence risk is 75%
A parents are affected, B
D. X-linked iv. If both 3 5
recessive recurrence risk is 100%

C From Topol EJ, Califf RM, et al. Textbook


FIGURE 1. AC: D of 4
The pregnant woman signs a medical release form so that you Cardiovascular Medicine. 3rd ed. Philadelphia, PA: Lippincott
can obtain and review records from a genetics consultation Williams & Wilkins; 2006. D: Courtesy of Genica Pharmaceuticals
1 2
she had 3 years ago after recurrent pregnancy losses and one Corporation, Worcester, MA

3 5 9

C D
(c) 2015 Wolters Kluwer. All Rights Reserved. 4 6 7 8
A B

Case 3 Autosomal trisomy syndromes95

1 2 2. Match the potential inheritance patterns indicated by the


pedigree charts (Figures 1A-D) to the diseases listed below.
B 3 The5inheritance patterns
9 can be used more than once or not
atall:
C D 4 i. Cystic
6 fibrosis
7 8

ii. Fragile X syndrome


iii. Hemophilia B
1 2
iv. Marfan syndrome

3 5 9

D 4 6 7 8
FIGURE 1. AD: (Continued)

CASE 3
Autosomal trisomy syndromes

A full-term male infant is born via spontaneous vaginal de- 2. Match the trisomy (AC) with the most commonly associ-
livery to a 27-year-old primigravida woman. Her pregnancy ated cardiac lesion (i through iv). Of note, i, ii, iii, or iv may
was unremarkable, and she declined prenatal testing. As the be used more than once:
pediatric resident covering the delivery room, you are called to
A. Trisomy 13 i. Endocardial cushion
evaluate the infant shortly after birth because of a concern for
(Patausyndrome) defect, ventricular septal
dysmorphic features. On your examination, you find that the
defect (VSD), patent ductus
baby has features consistent with trisomy 21 syndrome.
arteriosus (PDA), cardiac
1. Match the trisomy (AC) with the descriptions (i through iv) anomalies seen in 40% to
below. Of note, i, ii, iii, or iv may be used more than once: 50% of patients
B. Trisomy 18 ii. Mitral valve prolapse, aortic
A. Trisomy13 i. Duodenal atresia, increased risk (Edwardsyndrome) regurgitation, anomalous
(Patau of Hirschsprung disease subclavian artery
syndrome) C. Trisomy 21 iii. VSD, PDA, bicuspid aortic
B. Trisomy 18 ii. Hypoplastic nails, clenched (Downsyndrome) valve, pulmonary stenosis,
(Edward hand, overlapping of second coarctation of the aorta,
syndrome) finger over third finger or fifth tetralogy of Fallot, cardiac
finger over fourth finger, rocker- anomalies seen in 95% to
bottom feet, micrognathia, small 99% of patients
mouth, malformed low-set ears, iv. VSD, PDA, cardiac anoma-
occipital prominence lies seen in 80% to 90%
C. Trisomy21 iii. Transverse palmar crease, cutis ofpatients
(Down aplasia, polydactyly, cleft lip/
syndrome) palate, colobomas, narrow
hyperconvex fingernails
iv. Transverse palmar crease; flat
facies; upslanting palpebral fis-
sures; wide gap between first and
second toes; broad, short hands
and feet; inner epicanthal folds;
large protruding tongue; nuchal
redundancy; hypotonia

(c) 2015 Wolters Kluwer. All Rights Reserved.


96Section VI Genetics

The infants karyotype is shown in Figure 1. 3. Match the clinical finding that can be observed in infants
with this diagnosis with the corresponding incidence. Of
note, i, ii, iii, and iv may be used more than once or not at all:
A. Atlantoaxial subluxation with i. 1%
spinal cord compression
B. Early Alzheimer disease by ii. 2% to 5%
60years of age
C. Hearing loss (associated chronic iii. 70% to 75%
otitis media effusions or
sensorineural)
D. Hypothyroidism iv. 100%
The parents ask about future pregnancies and whether they
have an increased risk of having another child with Down
syndrome. You recall that the mother and father are 27 and
FIGURE 1. Klossner NJ, Hatfield NT. Introductory Maternity and Pediatric 29years old, respectively.
Nursing. 2nd ed. Philadephia, PA: Lippincott Williams & Wilkins;
2009. Figure 21.27 4. Select the true statement(s) below about recurrence risk
and trisomy 21 syndrome:
He has a VSD but otherwise is doing well, tolerating feedings A. Fifty percent of new diagnoses are sporadic.
and has a normal stooling pattern. He is at risk for several B. Three percent to 4% result from an unbalanced translo-
medical problems. cation between chromosome 21 and another acrocentric
chromosome, usually chromosome 14.
C. If both parents have normal karyotypes, recurrence risk
is 10%.
D. Recurrence risk is higher in a 45-year-old woman than
for a 25-year-old woman with a balanced translocation.

CASE 4
Turner syndrome

A 33-year-old pregnant woman has a finding of a cystic hy- The infant in the vignette has an evaluation that includes
groma observed by fetal ultrasonography at 16 weeks gesta- echocardiography, a renal ultrasound, and a genitourinary
tion. A fetal ultrasound at 35 weeks gestation shows that the ultrasound. The parents ask about their daughters ability to
hygroma is decreasing in size. Fetal echocardiography is unre- have children in the future.
markable. The woman declines any invasive testing. She deliv-
ers a full-term female infant with dysmorphic features that are 2. Select the correct statement about fertility in a patient with
suggestive of Turner syndrome. Turner syndrome:
A. Gonadal dysgenesis is universal in patients with Turner
1. Select the collection of clinical findings that are most con-
syndrome; about 50% will bear children.
sistent with Turner syndrome:
B. Gonadal dysgenesis is universal in patients with Turner
A. Coloboma, genital hypoplasia, ear anomalies, murmur, syndrome; however, fertility is unaffected.
microcephaly, anal atresia C. Gonadal dysgenesis is universal in patients with Turner
B. Edema of hands and feet, short stature, broad chest syndrome; infertility is most likely.
with wide-spaced nipples, webbed neck, low posterior D. None of the above.
hairline
The pediatrician meets with the family to describe the physi-
C. Micrognathia, glossoptosis, cleft palate
cal features and relay the presumptive diagnosis of Turner
D. Short/webbed neck, low posterior hairline, hyper-
syndrome. He tells them that a definitive diagnosis of Turner
telorism, low-set ears, low nasal bridge, pectus excava-
syndrome requires chromosomal analysis.
tum, ptosis

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 5 Syndromes of tall stature97

3. Select the karyotype below that would be mostly likely in


this vignette:

A. Figure 1 C. Figure 3
B. Figure 2 D. Figure 4

FIGURE 3. Scott JR, Gibbs RS, Karlan BY, et al. Danforths Obstetrics and
Gynecology. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins;
2003. Figure 6.03

FIGURE 1. Klossner NJ, Hatfield NT. Introductory Maternity and Pediatric


Nursing. 2nd ed. Philadephia, PA: Lippincott Williams & Wilkins;
2009. Figure 21.27

FIGURE 4. Reprinted with permission from Gelehrter TD, Collins FS,


Ginsburg D. Principles of Medical Genetics. 2nd ed. Baltimore, MD:
Lippincott Williams & Wilkins; 1998:166. Figure 1.6B

FIGURE 2. From Beckmann CRB, Ling FW, Laube DW, et al. Obstetrics
4. Select the therapy that is recommended in patients with
and Gynecology. 4th ed. Baltimore, MD: Lippincott Williams & Wilkins; Turner syndrome as soon as their height falls below the
2002 fifth percentile:

A. Androgen
B. Estrogen
C. Growth hormone
D. No therapy should be initiated

CASE 5
Syndromes of tall stature

A 45-year-old woman delivers a full-term nondysmorphic, 1. Select the syndrome below that would be most consistent
average-weight male infant via cesarean for failure to progress. with the presentation above:
The infant does well throughout the neonatal period and early
A. EhlersDanlos syndrome
childhood. By age 6, he is diagnosed with autism. By age 15,
B. Klinefelter syndrome
he is significantly taller than anyone in his class and the class
C. Marfan syndrome
above his. His mother and father are average height. At his
D. None of the above
next pediatrician appointment, his physician notes his growth
velocity and detects small testes by physical examination.

(c) 2015 Wolters Kluwer. All Rights Reserved.


98Section VI Genetics

CASE 6
Genetic associations

A 27-year-old primigravida woman from Korea presents to Further workup and examination of the infant reveal hemiver-
Labor and Delivery with a cervical dilation of 8 cm. All of her tebrae, anal atresia, single umbilical artery, dysplastic kidneys,
prenatal care has been in Korea. She tells the obstetrician on and thumb hypoplasia.
call that her pregnancy was uncomplicated except for intra-
uterine growth restriction. The neonatologist is called to at- 2. Select whether the infants diagnosis is consistent with a
tend the delivery. The infant is born with multiple congenital syndrome or an association and the corresponding likely
anomalies, including a cardiac defect and renal/genitourinary neurological outcome and recurrence risk:
anomalies. A. Association, as there is currently no known genetic
cause; it is not associated with developmental disabili-
1. Select the syndrome(s)/association that would most likely
ties; there is a low recurrence risk.
fit this description:
B. Syndrome, as it represents a pattern of congenital anom-
A. Alagille syndrome and VACTERL association alies with a known genetic cause; it is often associated
B. CHARGE syndrome and VACTERL association with developmental disabilities; there is a significant
C. HoltOram syndrome and CHARGE syndrome recurrence risk.
D. None of the above C. Both A and B
D. None of the above

CASE 7
Deletion syndromes

A 39-year-old gravida 6 para 0 woman pregnant with twins 2. Select the syndrome (AD) with the pictures below. Each
presents with spontaneous rupture of membranes at 35weeks syndrome can be used only once:
gestation. The twins are delivered via cesarean because of A. Angelman syndrome i. Figure 1
breech presentation in the presenting twin. The mothers
B. BeckwithWiedemann syndrome ii. Figure 2
medical history is significant for infertility, and this pregnancy
C. DiGeorge syndrome iii. Figure 3
had been conceived by in vitro fertilization. One of the twins
D. PraderWilli syndrome iv. Figure 4
(twin A) has hypotonia, almond-shaped palpebral fissures,
and undescended testes. Although his twin brother (twin B)
currently has no stigmata of a syndrome, each twin has a dis-
tinct syndrome. One has a microdeletion of maternal origin,
while the other has a microdeletion of paternal origin.

1. Explain the most plausible etiology for the syndromes in


the vignette above by completing the following sentence:
The two distinct syndromes may represent:

A. Autosomal dominant inheritance


B. Contiguous gene syndromes
C. Single-gene defects
D. None of the above
FIGURE 1. Courtesy of Gorlin RJ. Department of Oral Pathology and
Genetics, University of Minnesota

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 7 Deletion syndromes99

FIGURE 2. From MacDonald MG, Mullett MD, Seshia MM, eds. Averys
Neonatology: Pathophysiology of the Newborn. 6th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2005. Figure 38.13

FIGURE 4. Courtesy of Gorlin RJ. Department of Oral Pathology and


Genetics, University of Minesota

3. Match the syndrome (AD) with an appropriate manage-


ment. All cases will require genetics consultation and close
follow-up. Each syndrome can be used only once:
A. Angelman syndrome i. Monitor for delayed
developmental mile-
stones and risk for
seizure
B. BeckwithWiedemann ii. Monitor for
syndrome hypocalcemia
C. DiGeorge syndrome iii. Monitor for
hypoglycemia
D. PraderWilli syndrome iv. Monitor for risk of fail-
ure to thrive in infancy

The twins were diagnosed with PraderWilli syndrome


(twinA) and Angelman syndrome (twin B), as represented by
Figure 5 on the next page. This Southern blot analysis shows
that the patient with PraderWilli syndrome has a 6.0-kb frag-
FIGURE 3. From Roberts R. Atlas of Infectious Diseases. Mandell G ment from the mother but lacks the 4.4-kb fragment from the
(series ed.), Wilfert CM, ed. Philadelphia, PA: Current Medicine, Inc; father. This results from either a deletion on the paternal chro-
1998. Pediatric Infectious Diseases, vol 11
mosome 15 or maternal uniparenteral disomy. In contrast, the
patient with Angelman syndrome has a 4.4-kb fragment from
the father but lacks the maternal 6.0-kb fragment. This results
from either a deletion on the maternal chromosome 15 or a
paternal uniparental disomy (see Figure 5).

(c) 2015 Wolters Kluwer. All Rights Reserved.


100Section VI Genetics

The nurse caring for the twins assists with a blood draw for an
infant in the adjacent bed space. She notices that the infant is
markedly jittery and has dysmorphic facial features consisting
of hypertelorism, short palpebral fissures, a small mouth, and
a prominent nose with a square nasal root and narrow alar
base. The infants ionized calcium result is 0.69 mmol/L.

4. Select the genetic syndrome that best fits the description above:

A. Angelman syndrome
B. BeckwithWiedemann syndrome
FIGURE 5. From Schad CR, Jalal SM, Thibodeau SN. Genetic C. DiGeorge syndrome
testing for PraderWilli and Angelman syndromes. Mayo Clin Proc. D. PraderWilli syndrome
1995;70:11951196, with permission

CASE 8
Treacher Collins syndrome and PierreRobin sequence

An 18-year-old gravida 1 para 0 woman presents in active labor


at term gestational age. The fetal heart rate tracing is reassur-
ing, but there is meconium-stained amniotic fluid. The neo-
natologist is present at the delivery. Intubation is attempted,
following the Neonatal Resuscitation Program guidelines for
an infant born floppy, without respiratory effort, in the pres-
ence of meconium-stained amniotic fluid. The intubation at-
tempt is unsuccessful likely because of the infants physical
findings of micrognathia, glossoptosis, and a U-shaped cleft
palate. The infant begins to cry vigorously at 40 seconds of life,
and routine care is resumed.

1. Of the craniofacial defects shown (Figure 1AD), select the


defect that is thought to result from hypoplasia of the man-
dible, occurring before the ninth week of development:

FIGURE 1. (Continued)

2. Match the photographs (Figure 1AD) with the corre-


sponding syndromes (iiv):

i. DiGeorge syndrome ____


ii. Goldenhar syndrome ____
iii. PierreRobin sequence ____
iv. Treacher Collins syndrome ____

3. Select the true statement(s) below regarding the infants in


photographs A and B above:

FIGURE 1. A: Courtesy of Warkany J. Reprinted with permission from A. One is a sequence and one is a syndrome.
Warkany J. Congenital Malformations. Chicago, IL: Yearbook publishers; B. One is caused by a single-gene defect, while the other
1971. BD: Courtesy of Gorlin RJ. Department of Oral Pathology and is a condition secondary to hypoplasia of the mandible
Genetics, University of Minnesota before the ninth week of development.
C. A and B
D. None of the above

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 8 Treacher Collins syndrome and PierreRobin sequence 101

The infant in the vignette is diagnosed with PierreRobin se- A systolic murmur
quence. After several weeks in the hospital, he was discharged Coarse breath sounds bilaterally
to home on a monitor, stable in room air, with nasogastric
An electrocardiography is consistent with biventricular
tube feedings. Close follow-up was arranged, with plans for
hypertrophy.
cleft palate repair at a later date. Parents were also told that
he may need a gastrostomy tube and tonguelip adhesion, 4. From the list below, which is the most likely clinical
depending on his clinical course. By 5 weeks of life, he devel- diagnosis?
ops rapid weight gain, progressive respiratory difficulty, and
cyanosis in room air. He is admitted to the hospital with the A. Aspiration pneumonia
following findings: B. Cyanotic congenital heart disease
C. Sepsis
Heart rate = 180 beats per minute D. Upper airway obstruction leading to cor pulmonale
A third heart sound

(c) 2015 Wolters Kluwer. All Rights Reserved.


102Section VI Genetics

SECTION VI
Answers

CASE 1 ANSWERS AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATIONS
1. D. All of the above
FISH is a laboratory technique where a single-stranded DNA FISH
probe, complementary to the sequence of interest, is tagged Know the common gene defects that can be diagnosed
with a fluorescent marker. The cultured cells from the patient with fluorescent in situ hybridization
are exposed to the fluorescent probe. The signal is easily identi- Comparative genomic hybridization
fied using ultraviolet light. FISH is available for the following: Understand that comparative genomic hybridization has
Angelman syndrome replaced high-resolution chromosome analysis to screen
Chromosome 4p deletion patients suspected of having a chromosome abnormality
Cri du chat syndrome
DiGeorge syndrome/velocardiofacial syndrome SUGGESTED READINGS
MillerDieker syndrome
Trisomy 13 Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
Trisomy 18 2010.
Schrijver I, Zehnder JL, Cherry AM. Cytogenetic and molecular ge-
Trisomy 21 netic diagnostic tools. UpToDate (Subscription required). http://
PraderWilli syndrome www.uptodate.com/contents/cytogenetic-and-molecular-genetic-
Williams syndrome diagnostic-tools. Accessed March 30, 2013.

2. A. CGH has replaced high-resolution chromosomal CASE 2 ANSWERS


analysis
CGH, or chromosomal microarray analysis, is a molecular- 1. A. Autosomal dominant iii
cytogenetic method for the analysis of copy number changes B. Autosomal recessive iv
(gains/losses) in the DNA content in a patients DNA. CGH C. X-linked dominant ii
detects only unbalanced chromosomal changes. This tech- D. X-linked recessive i
nique has replaced high-resolution chromosomal analysis,
is still relatively expensive, is more likely to provide a genetic Single-gene disorders refer to Mendelian inheritance. The
diagnosis than karyotyping, and is able to detect very small table below characterizes some common features that occur
deletions or duplications of genetic material. in autosomal dominant, autosomal recessive, X-linked
dominant, and X-linked recessive disorders.

Mendelian
Inheritance
Patterns Incidence Characteristics Recurrence Risk

Autosomal 1/200 Wide variation of expression For offspring of one carrier


dominant individuals Vertical transmission of disease phenotype parent, recurrence risk is 50%
No skipped generations If both parents are affected,
Males and females equally likely to transmit recurrence risk is 75%
tooffspring
Autosomal Rare in Less variation in expression than autosomal For offspring of two carrier
recessive population dominant diseases parents, recurrence risk is 25%
Clustering of the disease among siblings If an affected homozygote
Males and females are equally likely to transmit mates with a heterozygote,
the disease to offspring recurrence risk is 50%
If both parents are affected
homozygotes, recurrence risk
is 100%

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 3 Autosomal trisomy syndromes103

Mendelian
Inheritance
Patterns Incidence Characteristics Recurrence Risk
X-linked Rarer than Twice as common in females than in males Dependent on genotype of
dominant X-linked reces- Fathers cannot transmit the disease to sons each parents and the sex of
sive diseases Rare to have skipped generations their offspring
Heterozygote females may be less severely
affected than affected males
An affected female has a 50% chance of passing
the disease to her sons or daughters
X-linked More common Since females have two copies of the X chro- Dependent on genotype of
recessive than X-linked mosome and males have only one, X-linked each parents and the sex of
dominant recessive diseases are usually clinically evident their offspring
diseases inmales
Fathers cannot transmit the disease to sons
Can have skipped generations
An affected father will transmit the disease to all
of his daughters, who will be carriers and pass
the disease onto ~ half of their sons

Adapted from Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010:162163

2. A iv. Marfan syndrome (Autosomal dominant) Know that Factor VIII and IX deficiencies can be diag-
B i. Cystic fibrosis (Autosomal recessive) nosed prenatally
C iii. Hemophilia B (X-linked recessive) Recognize that fragile X syndrome is associated with
D ii. Fragile X syndrome (X-linked dominant) X-linked mental retardation
X-linked dominant
Affected individuals in the pedigree charts are shown as filled
Recognize the inheritance patterns of X-linked dominant
circles or squares and unaffected individuals are shown as
disorders
empty symbols. Figure 1D represents a pedigree of a family
with fragile X syndrome. Figure 1D also has symbols with a
central dot, representing a premutation. All of these genetic dis-
orders (i.e., cystic fibrosis, fragile X syndrome, hemophiliaB, SUGGESTED READINGS
and Marfan syndrome) can be diagnosed prenatally.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
Jorde LB, Carey JC, Bamshad MJ. Medical Genetics. 3rd ed. St. Louis,
AMERICAN BOARD OF PEDIATRICS MO: Mosby; 2009.
CONTENT SPECIFICATIONS
Autosomal dominant CASE 3 ANSWERS
Recognize the inheritance pattern associated with an au-
tosomal dominant disorder with incomplete penetrance 1. A. Trisomy 13 Answer is iii.
Autosomal recessive B. Trisomy 18 Answer is ii.
Recognize the clinical and laboratory features associated C. Trisomy 21 Answer is i and iv.
with an autosomal recessive disorder
X-linked recessive
Recognize the inheritance patterns of X-linked recessive
disorders
Recognize the clinical features associated with an
X-linked recessive disorder

(c) 2015 Wolters Kluwer. All Rights Reserved.


104Section VI Genetics

Figure 2 shows an infant with trisomy 21. Figure 4 shows an infant with trisomy 13 syndrome who has a
cleft lip and palate, a sloping forehead, microphthalmia, and
polydactyly.

A B

A B
FIGURE 4. From Sadler T. Langmans Medical Embryology. 9th ed.
Image Bank. Baltimore, MD: Lippincott Williams & Wilkins; 2003.
Figure 1.10AB

B
FIGURE 2. From MacDonald MG, Mullett MD, Seshia MM, eds. Averys
Neonatology: Pathophysiology & Management of the Newborn. 6th ed. 2. A. Trisomy 13 Answer is iv
Philadelphia, PA: Lippincott Williams & Wilkins; 2005. Figure 52.15 B. Trisomy 18 Answer is iii
C. Trisomy 21 Answers are i and ii

Cardiac lesions are found in 40% to 50% of patients with


Down syndrome, with endocardial cushion defects predomi-
nating. Cardiac anomalies are found in the vast majority
(95%99%) of patients with Edward Syndrome. The associ-
ated cardiac defects include a VSD, PDA, bicuspid aortic valve,
pulmonary stenosis, coarctation of the aorta, and tetralogy of
Fallot. In patients with trisomy 13, cardiac lesions are also very
common (80%90% of affected individuals) and most often
are either a VSD or a PDA.

3. A i. 1%
B iii. 70% to 75%
FIGURE 3. From Sadler T. Langmans Medical Embryology. 9th ed. Image
C iii. 70% to 75%
Bank. Baltimore, MD: Lippincott Williams & Wilkins; 2003. Figure 1.9 D ii. 2% to 5%

An infant with trisomy 18 syndrome is shown in Figure 3; The karyotype of this infant confirms the diagnosis of trisomy
clinical findings include a prominent occiput, micrognathia, 21 syndrome. There is an increased incidence of congenital
low-set ears, and a flexed finger. malformations and acquired diseases in patients with Down

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 4 Turner syndrome105

syndrome. The two leading causes of death for these patients


CASE 4 ANSWERS
are congenital heart disease and pneumonia. Hearing loss and
ophthalmologic disorders occur in 70% and 60% of patients, 1. B. Edema of hands and feet, short stature, broad chest
respectively. Early Alzheimer disease affects 75% of patients by with wide-spaced nipples, webbed neck, low posterior
age 60. Atlantoaxial subluxation with spinal cord compression hairline
occurs with an incidence of <1%. Other medical complica- A newborn with Turner syndrome often demonstrates mini-
tions include epilepsy (5%10%), gastrointestinal problems mal to no findings at birth and subsequently is diagnosed after
(duodenal atresia and Hirschsprung disease, 5%), hypothy- an evaluation for growth failure or failure to enter puberty. The
roidism (5%), and leukemia (1%). classic features that may be present at birth include:
4. B. Three percent to 4% result from an unbalanced Cardiac (35%)coarctation of the aorta, bicuspid aortic
translocation between chromosome 21 and another acro- valve, aortic stenosis, mitral valve prolapse
centric chromosome, usually chromosome 14. Extremitiescubitus valgus, knee anomalies
It is imperative that the practitioner be able to explain recur- Facial/neckcystic hygroma in utero, short/webbed neck
rence risk and trisomy 21, as this information may be very im- (especially posteriorly), low posterior hairline
portant to families. Ninety-five percent of cases are sporadic. Genitourinarygonadal dysgenesis with subsequent
If both parents have normal karyotypes, the recurrence risk is infertility (majority of patients)
1%. Three to 5% of cases result from an unbalanced trans- Renalhorseshoe kidney
location between chromosome 21 and another acrocentric Otheredema of hands and feet (congenital lymph-
chromosome, usually chromosome 14; seventy-five percent of edema), short stature, broad chest with wide-spaced nip-
these translocations are de novo while the remainder occurs ples, bone dysplasia
because of familial translocations. The risk of having another
child with Down syndrome is greater for a young woman with As affected individuals get older, additional clinical manifesta-
a balanced translocation than for a middle-aged woman with tions can be found, including the following:
normal chromosomes. Aortic dissection
Hypertension
Increased risk for gonadoblastoma
AMERICAN BOARD OF PEDIATRICS
Poor coordination
CONTENT SPECIFICATIONS
Visual spatial deficits
Recognize the prominent features of trisomy 21 in a Importantly, Noonan syndrome can sometimes be confused
newborn with Turner syndrome, as these syndromes have some over-
Recognize the prominent features of trisomy 13 in a lapping features. Infants with Noonan syndrome often have
newborn short/webbed neck, low posterior hairline, hypertelorism, low-
Recognize the prominent features of trisomy 18 in a set ears, low nasal bridge, pectus excavatum, and ptosis. More
newborn than 50% of patients with Noonan syndrome have cardiac
Know the associated medical problems in children with anomalies, which most often include dysplastic pulmonary
Down syndrome valve, atrial septal defect, and cardiomyopathy. In utero, pa-
Recognize that the risk of having another child with tients with Noonan syndrome may also have a cystic hygroma.
Down syndrome is greater for a young woman who is Micrognathia, glossoptosis, and a cleft palate are found in
a balanced translocation carrier than for a middle-aged patients with PierreRobin sequence.
woman CHARGE syndrome is described as:

Coloboma (80%)
SUGGESTED READINGS Heart defect (50%70%)
Atresia of choanae (60%)
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; Retarded growth (90%, most often noted postnatally)
2010. Genital hypoplasia (in males, 75%)
Bull M. Health supervision for children with Down syndrome. Pediat-
rics. 2011;128(2):393406. Ear anomalies (90%), often with deafness
Newberger D. Down syndrome: Prenatal risk assessment and diagno-
sis. Am Fam Physician. 2000;62(4):825832.

(c) 2015 Wolters Kluwer. All Rights Reserved.


106Section VI Genetics

Figure 5 depicts features of Turner syndrome. 2. C. Gonadal dysgenesis is universal in patients with
Turner syndrome; infertility is most likely.
Spontaneous fertility is rare among patients with Turner syn-
Heart-shaped face drome. If a woman with Turner syndrome successfully becomes
pregnant, the womans karyotype would most likely represent
Low hairline on neck Wide, webbed neck
mosaicism for a normal 46, XX cell lineage or 47, XXX cell lin-
Coarctation eage. In addition, it is unlikely she would carry the fetus to term.
of aorta
Broad, flat chest with
widely separated 3. B. Figure 2
nipples Figure 2 shows a karyotype in a patient with Turner syndrome,
demonstrating 45, X with one of the X chromosomes m issing.
Outwardly angled The karyotype in Figure 1 is consistent with trisomy 21 because
forearms
there are three chromosomes in the 21st position. Figure 3
shows a normal male human karyotype. The karyotype in
Figure 4 depicts translocation of chromosome 21 into 14, re-
sulting in Down syndrome.

Streak ovaries, 4. C. Growth hormone


Multiple
amenorrhea,
pigmented Growth hormone may be an effective treatment in patients
infertility
nevi with Turner syndrome to increase final height at adulthood.
It should be initiated as soon as the patients height falls be-
low the fifth percentile for age. The combination of growth
hormone with low-dose estrogen replacement therapy may
improve growth in addition to other benefits. Ninety per-
cent of patients with Turner syndrome will require estrogen
therapy to initiate puberty and complete growth. An added
FIGURE 5. From McConnell TH. The Nature of Disease Pathology for the health benefit of estrogen therapy in women with Turner syn-
Health Professions. Philadelphia, PA: Lippincott Williams & Wilkins; drome who do not have spontaneous puberty is a reduced risk
2007. Figure 7.17 for osteoporosis and heart conditions. Adding an androgen
to growth hormone therapy at age 9 to 12 years should be
Figure 6 shows two features of Turner syndrome: webbed considered in girls with Turner syndrome who have extreme
neckand pedal edema. short stature.

AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATIONS
Recognize the features of the Turner phenotype in a
newborn
Recognize that growth retardation may be the only clini-
cal manifestation of Turner syndrome
Know that gonadal dysgenesis is uniformly present in
Turner syndrome
Know that a definitive diagnosis of Turner syndrome
requires chromosomal analysis
Recognize that growth hormone may be an effective
treatment for Turner syndrome

SUGGESTED READINGS
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
Saenger P. Management of Turner syndrome (gonadal dysgenesis).
UpToDate (Subscription required). http://www.uptodate.com/
contents/management-of-turner-syndrome-gonadal-dysgenesis.
FIGURE 6. From MacDonald MG, Mullett MD, Seshia MM. Averys Accessed April 8, 2013.
Neonatology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, Sybert V, McCauley E. Turners syndrome. N Engl J Med. 2004;351:
2005. 12271238.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 6 Genetic associations107

Patients with Klinefelter syndrome are at higher risk for behav-


CASE 5 ANSWERS
ioral difficulties (immaturity, shyness), learning disabilities,
1. B. Klinefelter syndrome and autism.
Klinefelter syndrome (47, XXY) has an incidence of 1 in 500 EhlersDanlos is an inherited connective-tissue disorder
to 1,000 male births and is derived equally from maternal caused by a defect in the synthesis of collagen. These patients
or paternal errors. The mother in this vignette is 45 years may be tall and have joint hypermobility and skin hyperexten-
old. Importantly, if Klinefelter is maternally derived, there sibility, among other findings.
is a higher risk with advanced maternal age. Male infants Marfan syndrome is also a connective-tissue disorder and
with Klinefelter syndrome are phenotypically normal as the is secondary to abnormal fibrillin gene. Patients with Marfan
manifestations do not appear until after the newborn period. syndrome tend to be unusually tall, with long limbs and long,
Figure 1 depicts a male patient with clinical features of Kline- thin fingers. Marfan syndrome is an autosomal dominant con-
felter syndrome. dition that may be associated with advanced paternal age.

AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATION
Mild mental
retardation Know the major clinical manifestations of Klinefelter
syndrome
Lack of beard
and body hair
SUGGESTED READINGS
Enlarged Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
breasts 2010.
Snyder P. Causes of primary hypogonadism in males. UpToDate (Sub-
scription required). http://www.uptodate.com/contents/causes-of-
primary-hypogonadism-in-males. Accessed April 8, 2013.
Long arms
Lack of
pubic hair
Female-like CASE 6 ANSWERS
hips
1. B. CHARGE syndrome and VACTERL association
CHARGE syndrome is described as:

Coloboma (80%, usually involving the retina)


Heart defect (50%70%, tetralogy of Fallot, double-
outlet right ventricle, ventricular septal defect, atrial septal
defect, patent ductus arteriosus, right-sided aortic arch)
Testicular Atresia of choanae (60%)
atrophy and Retarded growth (90%, most often noted postnatally)
infertility
Genital hypoplasia (in males, 75%)
Ear anomalies (90%, often with deafness)
Other findings: neurocognitive impairment, cranial nerve
Long legs dysfunction

VACTERL/VATER is described as:

Vertebral (70%, e.g., hemivertebrae)


Anal atresia (80%, may have fistula)
Cardiac (50%, ventricular septal defect more common
than tetralogy of Fallot or coarctation of the aorta)
Tracheoesophageal fistula (70%, typically with Esopha-
FIGURE 1. From McConnell TH. The Nature of Disease Pathology for the geal atresia)
Health Professions. Philadelphia, PA: Lippincott Williams & Wilkins;
Renal anomalies (90%, most often noted postnatally)
2007. Figure 7.16
Limb dysplasia (65%, typically radial, may also have pre-
axial polydactyly or syndactyly)
Other findings: intrauterine growth restriction, ear anom-
alies, spinal anomalies

(c) 2015 Wolters Kluwer. All Rights Reserved.


108Section VI Genetics

VATER association was first named in the early 1970s; shortly 2. A. Angelman syndrome i. Figure 1
thereafter, the C and the L were added, with the subse- B. BeckwithWiedemann syndrome ii. Figure 2
quent change to the acronym VACTERL. Vertebral and cardiac C. DiGeorge syndrome iii. Figure 3
anomalies are features of patients with either CHARGE or D. PraderWilli syndrome iv. Figure 4
VACTERL syndrome.
Alagille syndrome is a genetic disorder that predominantly Table 1 summarizes the clinical features in these syndromes.
affects the liver, heart, and kidney and is associated with bile
duct paucity and cholestasis. Renal anomalies have been re- Table 1. Clinical Features

ported in Alagille syndrome but are uncommon. HoltOram


Syndrome Features
syndrome is a disorder that affects bones in the upper limbs,
most typically with absent radial bones, and may also cause Angelman syndrome Profound intellectual
cardiac conduction defects. HoltOram typically does not disability
have associated genitourinary abnormalities. Postnatal microcephaly
Gait ataxia (puppet-like
2. A. Association, as there is currently no known genetic gait)
cause; it is not associated with developmental disabilities; Happy demeanor
there is a low recurrence risk. Large mouth
Protruding tongue
The additional findings in the infant in this vignette suggest a
Widely spaced teeth
diagnosis of VACTERL association. Affected individuals are un- Seizures
likely to have developmental disabilities, and there is a low risk
BeckwithWiedemann Macroglossia
of recurrence. VACTERL is an association because there is cur- syndrome Macrosomia
rently no known genetic cause for the clinical manifestations. Midline abdominal wall
Syndromes represent a pattern of congenital anomalies defects (omphalocele,
with a known genetic cause. They are often associated with de- umbilical hernia, diastasis
velopmental disabilities, and there can be a significant recur- recti)
Ear creases or pits
rence risk for the parents or the affected individual. CHARGE Neonatal hypoglycemia
syndrome was known as an association until 2004 when the
DiGeorge syndrome Hypoplasia of thymus
responsible gene (CHD7) was identified.
and/or parathyroid gland
Neonatal hypocalcemia
AMERICAN BOARD OF PEDIATRICS Susceptibility to infection
Predisposition to
CONTENT SPECIFICATION autoimmune diseases
Mild/moderate learning
Recognize the clinical manifestations of genetic associa- disabilities
tions (e.g., CHARGE, VACTERL)
PraderWilli syndrome Hypotonia
Poor feeding in infancy
Increased appetite and
SUGGESTED READINGS obesity in adolescence
Genital hypoplasia
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; Small hands and feet
2010. Almond-shaped eyes
Kaplan J, Hudgins L. Neonatal presentations of CHARGE syndrome Mild intellectual disability
and VATER/VACTERL association. NeoReviews. 2008;7:e299e305. in two-third of cases

CASE 7 ANSWERS
3. A. Angelman i. Monitor for delayed develop-
1. B. Contiguous gene syndromes syndrome mental milestones and risk
Microdeletions are chromosomal deletions that are too small for seizure
to be detected by conventional cytogenetic methods. They are B. Beckwith- iii. Monitor for hypoglycemia
usually only a few megabases (Mb) long and involve contigu- Wiedemann
ous genes. The twins in the vignette have a small deletion be- syndrome
tween 15q11 and 15q13, resulting in two completely different C. DiGeorge syndrome ii. Monitor for hypocalcemia
syndromes depending on the parental origin of the chromo- D. Prader-Willi iv. Monitor for risk of failure to
some. In contrast to contiguous gene syndromes, single-gene syndrome thrive in infancy
disorders (Mendelian inheritance) include the following in-
heritance patterns: autosomal dominant, autosomal recessive,
X-linked dominant, and X-linked recessive.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 8 Treacher Collins syndrome and PierreRobin sequence 109

Table 2 below summarizes the management of these SUGGESTED READINGS


syndromes.
Bacino C. Microdeletion syndromes (chromosomes 12 to 22).
Table 2. Management UpToDate (Subscription required). http://www.uptodate.com/con
tents/microdeletion-syndromes-chromosomes-12-to-22. Accessed
Syndrome Management April8, 2013.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
Angelman syndrome Genetics consultation
May be asymptomatic in
newborn period
Monitoring for delayed CASE 8 ANSWERS
developmental milestones
and seizures 1. B. PierreRobin sequence is thought to result from
BeckwithWiedemann Genetics consultation mandibular hypoplasia occurring prior to 9 weeks of
syndrome If omphalocele present, development.
surgical consultation The other photographs represent the following syndromes:
Close monitoring for A. Treacher Collins syndrome, C. DiGeorge syndrome, and
neonatal hypoglycemia
D.Goldenhar syndrome.
DiGeorge syndrome Genetics and cardiology
consultations 2. i. DiGeorge syndrome Figure 1C
Monitoring for ii. Goldenhar syndrome Figure 1D
hypocalcemia
iii. PierreRobin sequence Figure 1B
PraderWilli syndrome Genetics consultation iv. Treacher Collins syndrome Figure 1A
Monitoring for failure to
thrive in infancy
Risk for obesity in Features of each are listed in Table 1.
adolescence
Table 1. Syndrome/Sequence Features

Syndrome/
4. C. DiGeorge syndrome
Sequence Features
Newborn infants with DiGeorge syndrome can have the fol-
lowing physical findings: DiGeorge Majority with 22q11.2 deletion
syndrome Also described as Velocardiofacial
Cleft palate
syndrome
Hypertelorism CATCH 22 (Cardiac, Abnormal facies,
Micrognathia Thymic hypoplasia, Cleft palate,
Misshapen ears Hypocalcemia)
Murmur Autosomal dominant with variable
expression
Prominent nose with square nasal root and narrow alar
base Goldenhar Hemifacial microsomia
Short palpebral fissures syndrome Short neck, low posterior hairline,
limited movement of head, facial
Short philtrum asymmetry, deafness (conductive or
Hypoplastic parathyroid glands in patients with DiGeorge neural)
Abnormal cervical vertebrae (typically
syndrome result in hypocalcemia with clinical findings of jit- fused)
teriness. None of the other syndromes fit with the clinical pic- Unknown etiology
ture of the infant in this vignette.
PierreRobin Triad: micrognathia; glossoptosis
sequence (normally sized tongue in a small oral
cavity); cleft palate (U-shaped)
AMERICAN BOARD OF PEDIATRICS Feeding intolerance
CONTENT SPECIFICATIONS Conductive hearing loss; normal
intelligence
Understand the cause(s) of contiguous gene syndromes Posterior airway obstruction with
Appreciate that contiguous gene syndromes (deletion or potential for cor pulmonale
May be isolated or associated with
alteration of multiple gene pairs that are adjacent to one
genetic disorders such as Treacher
another) can cause syndromes with multiple apparent Collins syndrome
unconnected defects (e.g., Angelman, PraderWilli)
Recognize contiguous gene syndromes, including
PraderWilli, Angelman, BeckwithWiedemann, and
DiGeorge, and manage appropriately
Recognize the signs of DiGeorge syndrome

(c) 2015 Wolters Kluwer. All Rights Reserved.


110Section VI Genetics

Treacher Collins syndrome is caused by a single-gene defect


Syndrome/
from a mutation in the TCOF1 gene (chromosome 5).
Sequence Features
4. D. Upper airway obstruction leading to cor pulmonale
Treacher Lower eyelid coloboma; down-slanting
Collins of palpebral fissures; malformed The infant in this vignette has clinical findings consistent with
syndrome ears; mandibular hypoplasia; malar cor pulmonale. The most likely cause of cor pulmonale in an
hypoplasia with or without a cleft in infant with PierreRobin sequence is severe and persistent
the zygomatic bone; absence of lower upper airway obstruction.
eyelashes; possible cleft palate; scalp
hair that may extend to lateral cheek
Conductive hearing loss; visual deficit;
normal intelligence
AMERICAN BOARD OF PEDIATRICS
Respiratory difficulties as a result of a CONTENT SPECIFICATIONS
narrow airway
Results from a single gene defect; Know that the features of PierreRobin sequence are sec-
autosomal dominant with variable ondary to micrognathia
expression; 60% because of a new Know the clinical features of Treacher Collins syndrome
mutation and that it is due to a single-gene defect
Know that upper airway obstruction caused by glossop-
3. C. A and B tosis may cause cor pulmonale in infants with Pierre
PierreRobin is a sequence, while Treacher Collins is a syn- Robin sequence
drome. A sequence occurs when a single primary developmental
defect results in a chain of secondary defects. The primary defect SUGGESTED READINGS
in PierreRobin sequence is mandibular hypoplasia leading to
posterior displacement of the tongue, which does not allow clo- Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
sure of the palatal arches. This sequence is secondary to hypo- 2010.
Buchanan E, Cole P, Hollier L. Syndromes with craniofacial abnor-
plasia of the mandible before the ninth week of development. malities. UpToDate (Subscription required). http://www.uptodate.
Treacher Collins is a syndrome, which represents a pattern com/contents/syndromes-with-craniofacial-abnormalities. Accessed
of many primary malformations as a result of one etiology. April 8, 2013.

(c) 2015 Wolters Kluwer. All Rights Reserved.


S E C T I ON VII Infectious
Diseases

(c) 2015 Wolters Kluwer. All Rights Reserved.


112Section VII Infectious Diseases

CASE 1
Sepsis

A 28-year-old pregnant woman contacts her obstetrician af- 3. If this pregnant woman also had a flu-like illness and
ter her water breaks at 25 weeks gestation. Her obstetrician brown-colored amniotic fluid, the most likely organism
urges her to come to the hospital for an evaluation. Testing in involved would be:
the hospital confirms that the woman has experienced rupture
A. Group B Streptococcus (GBS)
of the membranes of the amniotic sac and chorion, leading
B. Escherichia coli
to complete loss of amniotic fluid. The fetus appears active
C. Enterococcus
with a normal heart rate tracing. The woman is afebrile and is
D. Listeria monocytogenes
not having any contractions. She is admitted to the hospital
for observation and bed rest. She meets with the neonatology After 2 days, the infant stabilizes. The infants blood culture
team to discuss the prognosis of an infant born at this gesta- is negative and cerebrospinal fluid testing is normal. How-
tional age. ever, because of initial clinical concerns for sepsis, the infant
receives 14 days of antibiotics. Because of some initial intoler-
1. Of the following, a potential complication in a new- ance of enteral feedings and a need for slow feeding advance-
born with preterm premature rupture of membranes ment, a percutaneous central-line catheter is placed to provide
(PPROM) is: TPN. At 2 weeks of age, the infant has an increase in apneic
A. Infection events and appears lethargic. The neonatology team is con-
B. Pulmonary hyperplasia cerned about late-onset sepsis.
C. Renal dysfunction
4. Match the characteristics listed below with the type of sep-
D. All of the above
sis (of note, some characteristics may be found in both
Four weeks later, the woman is noted to have a high fever, types of sepsis):
abdominal pain, and contractions. Her obstetrician suspects
A. Presents in the first week of i. Early-onset sepsis
chorioamnionitis, and the infant is born at 29 weeks gestation
life
after unstoppable preterm labor. The baby has severe respira-
B. Acquired from the maternal ii. Late-onset sepsis
tory distress requiring intubation and surfactant administra-
genital tract
tion, hypotension requiring volume and inotropic support,
and a coagulopathy requiring platelet and fresh frozen plasma C. Acquired from the postnatal
transfusions. The infant receives total parenteral nutrition environment
(TPN) by an umbilical venous catheter. The neonatology D. Caused by GBS
team treats the baby with antibiotics for presumed early-onset E. Caused by Staphylococcus
sepsis. coagulase-negative
F. Focal involvement more
2. Of the following, the antibiotic regimen that is most common than multisystem
appropriate for this infant is: involvement
G. Associated with central-line
A. Ampicillin and gentamicin
catheter
B. Cefotaxime
H. Mortality between 15%
C. Gentamicin
and45%
D. Vancomycin and gentamicin

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 2 Group B Streptococcus113

CASE 2
Group B Streptococcus

At 36 weeks gestation, a pregnant woman has a vaginal culture The pregnant woman remains extremely anxious about the
that is positive for Group B Streptococcus (GBS). The woman is possibility of GBS infection in her baby. Thus, the obstetrician
concerned about the possibility that her infant will develop a asks a neonatologist to discuss care of her infant after birth.
GBS infection. The neonatologist reviews the three possible options that may
occur after delivery:
1. Of the following, the time period that an infant can acquire
a GBS infection is: Observation of the baby and/or
Evaluation of the baby with blood tests and/or
A. Shortly before delivery C. Postnatally Initiation of antibiotic therapy
B. During delivery D. All of the above

The obstetrician discusses the factors that would increase the 6. Match the clinical description (A through F) with the initial
babys risk of acquiring a GBS infection in the first week of life. approach in the neonate (i, ii, or iii):

2. Of the following, the characteristic that is least likely to A. Asymptomatic, well- i. Observation
increase this babys risk for early-onset GBS infection is: appearing infant born to a (i.e., no
GBS-positive woman with evaluation
A. Advanced maternal age adequate intrapartum GBS or antibiotic
B. Maternal GBS bacteriuria prophylaxis and no signs of initiation)
C. Preterm birth chorioamnionitis ii. Observation
D. Sibling with invasive GBS disease in the neonatal period and evaluation
B. Asymptomatic, well-appearing
To minimize the risk of acquisition of GBS disease in this infant born to a GBS-positive with blood tests
infant, the obstetrician describes the approach to and im- woman with inadequate iii. Observation,
pact of maternal intrapartum antimicrobial prophylaxis (i.e., intrapartum GBS prophylaxis evaluation, and
chemoprophylaxis). with duration of membrane initiation of
rupture <18 hours and no antibiotics
3. Chemoprophylaxis is indicated in all of the following sce- maternal fever
narios except for a woman with:
C. Asymptomatic, well-appearing
A. A prior infant with invasive GBS disease, regardless of infant born to a GBS-positive
current GBS status woman with inadequate GBS
B. GBS bacteriuria during current pregnancy prophylaxis with duration of
C. GBS colonization during a prior pregnancy, regardless membrane rupture 18 hours
of current GBS status D. Asymptomatic, well-appearing
D. Unknown GBS status and is in preterm labor infant born to a GBS-positive
woman with adequate
4. Of the following, the optimal intravenous antibiotic for
intrapartum GBS prophylaxis
intrapartum chemoprophylaxis is:
and signs of chorioamnionitis
A. Cefazolin C. Penicillin E. Asymptomatic, well-appearing
B. Clindamycin D. Vancomycin infant born to a GBS-positive
woman with inadequate
5. Of the following, the most likely impact of chemoprophy- intrapartum GBS prophylaxis
laxis in a GBS-positive pregnant woman is: and signs of chorioamnionitis
A. A decreased incidence of late-onset neonatal GBS dis- F. Symptomatic, ill-appearing
ease by 50% infant born to a GBS-positive
B. A lower incidence of early-onset neonatal GBS disease woman with adequate
by 80% intrapartum GBS prophylaxis
C. A lower risk of early-onset neonatal GBS disease in
future pregnancies
D. Prolongation of labor by 2 to 4 hours

(c) 2015 Wolters Kluwer. All Rights Reserved.


114Section VII Infectious Diseases

After the infant is born and the appropriate approach is taken, 8. Of the following, the most appropriate management ap-
the infant is discharged home. At 3 weeks of age, the infant is proach in an infant with GBS infection is:
admitted to the hospital with late-onset GBS disease.
A. Change broad-spectrum antibiotic coverage to intrave-
7. Of the following, the clinical manifestation(s) that is (are) nous penicillin G after isolation of the GBS organism
more common in late- rather than early-onset GBS disease B. Length of treatment is dependent on the location of
is (are): infection
C. Use of oral penicillin is inadequate in the treatment of
A. Meningitis C. Septicemia GBS disease in an infant
B. Pneumonia D. All of the above D. All of the above

CASE 3
Herpes simplex virus

A pregnant woman presents to the hospital in labor at 32weeks The neonatology team is asked to evaluate the baby because of
gestation. She reports that her water had broken 6hours ago his mothers primary genital herpes lesion.
and she is now having contractions every 2 minutes. On
examination, her obstetrician observes a genital lesion that is 3. Of the following, the most appropriate management of an
most consistent with herpes simplex virus (HSV). This is the asymptomatic infant born to a mother with a primary active
first time the woman has had a genital lesion. genital lesion at the time of delivery is:

A. Consider empirical intravenous acyclovir


1. Which of the following statements is (are) true?
B. Monitor infant closely
A. A pregnant woman with a primary genital herpes lesion C. Obtain surface cultures at 12 to 24 hours of age
during delivery has a greater than 25% chance of having D. All of the above
a neonate who is infected.
B. A pregnant woman with a secondary genital herpes le- 4. Of the following, the most appropriate management of an
sion during delivery has a greater than 25% chance of asymptomatic infant with a maternal history of genital her-
having a neonate who is infected. pes but no active lesions at the time of delivery is:
C. The majority of neonates who acquire a herpes infection A. Consider empirical intravenous acyclovir
are born to women without a history of genital herpes. B. Monitor the infant closely
D. The majority of neonates who acquire a herpes infection C. Obtain surface cultures at 12 to 24 hours of age
are born to women who are asymptomatic. D. B and C
E. B and C E. All of the above
F. A, C, and D
G. All of the above The infant described in the vignette has surface cultures that
are positive for HSV, confirming HSV infection. However, the
The womans labor progresses rapidly and a male infant is infant needs to be assessed for HSV disease; the neonatologist
born by vaginal delivery 10 minutes after the mothers arrival orders the following studies:
to the hospital. This neonate has several risk factors for acquir-
ing a herpes infection. Complete blood cell count with differential
Lumbar puncture for cerebrospinal fluid (CSF) indices
2. For each of the following, determine which scenario is as- and HSV polymerase chain reaction (PCR)
sociated with a higher risk of a neonate acquiring HSV if Serum hepatic transaminases
the mother has a genital herpes lesion: Whole blood for PCR

A. Cesarean birth vs. vaginal delivery The neonatologist meets with the infants family to discuss the
B. Maternal genital lesion in the first trimester vs. maternal different approach for HSV infection and HSV disease. He ex-
genital lesion at delivery plains that their neonate has HSV infection and requires 10
C. Premature infant vs. term infant to 14 days of intravenous acyclovir to prevent progression to
D. Rupture of membranes for less than 2 hours prior to de- HSV disease. If the babys test results are consistent with HSV
livery vs. rupture of membranes more than 6 hours prior disease, longer treatment with acyclovir will be needed.
to delivery
E. Use of a fetal scalp monitor vs. noninvasive fetal monitoring

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 4 Lower respiratory tract infections115

The neonatologist meets with the family a few days later be- 7. Of the following, the appropriate management of an
cause the CSF and whole blood PCR tests are consistent with infant with HSV disease with central nervous system (CNS)
HSV disease. The baby does indeed develop clinical symptoms involvement is:
consistent with HSV disease.
A. Oral acyclovir 3 weeks
5. Of the following, the most likely timing of neonatal symp- B. Intravenous acyclovir 3 weeks
toms caused by peripartum acquisition of HSV is: C. Oral acyclovir 3 weeks, followed by oral acyclovir sup-
pressive therapy 6 months
A. Immediately after delivery C. Two to 3 weeks of age D. Intravenous acyclovir 3 weeks, followed by oral acy-
B. Forty-eight hours of age D. Four months of age clovir suppressive therapy 6 months
6. Of the following, the examination finding(s) that is (are)
consistent with HSV disease in an infant is:

A. Encephalitis leading to lethargy and seizures


B. Conjunctivitis, chorioretinitis, papulovesicular lesions,
mucous membrane involvement
C. Systemic findings, including coagulopathy, shock,
pneumonitis
D. All of the above

CASE 4
Lower respiratory tract infections

An infant born at 27 weeks gestation has a postnatal course The infant has an evaluation and is found to have an RSV
significant for: infection. The parents are surprised by their infants diagno-
sis because the baby had been receiving monthly palivizumab
Intubation and surfactant therapy
since November to protect against RSV. The pediatrician
Transition to continuous positive airway pressure (CPAP)
explains the benefit of this prophylaxis.
on the second day of life
Continuation of CPAP for 6 weeks, then transitioned to 2. Of the following, the benefit of palivizumab prophylaxis in
room air premature infants is to decrease the:
Apnea of prematurity that resolved
Feeding immaturity that resolved A. Mortality rate
Mild retinopathy of prematurity that resolved B. Rate of acquisition
C. Rate of hospitalization
The baby is discharged home in June. Initially, the babys D. Rate of transmission
mother is the primary care provider. However, the mother re-
turns to work in September and enrolls the baby in full-time 3. Of the following, the population that should receive RSV
daycare. At the end of March, the parents bring the baby to the prophylaxis during the first winter season includes:
pediatrician because of a low-grade fever, tachypnea, cough,
A. All infants with a small ventricular septal defect
wheezing, and nasal congestion.
B. All infants with cystic fibrosis
1. Of the following, the most common cause of lower respira- C. All premature infants with a diagnosis of chronic lung
tory infections in infants is: disease
D. All premature infants born less than 35 weeks gestation
A. Chlamydia
B. Influenza
C. Respiratory syncytial virus (RSV)
D. Ureaplasma

(c) 2015 Wolters Kluwer. All Rights Reserved.


116Section VII Infectious Diseases

CASE 5
Hepatitis B virus

A full-term 3,400-g female infant is born by vaginal delivery The mothers HBsAg status is negative. However, she converts
to a mother with an unknown hepatitis B surface antigen to a positive HBsAg status during her second pregnancy. She
(HBsAg) status. delivers this second baby at term gestational age.

1. Of the following, the most appropriate management of this 3. Of the following, the most appropriate management of this
infant is to: infant is to:
A. Administer hepatitis vaccine (HBV) by 12 hours of age A. Administer HBV and HBIG by 12 hours of age
B. Administer hepatitis immune globulin (HBIG) as soon B. Administer HBV by 12 hours of age and HBIG by 1 week
as possible if the mother is positive for HBsAg or by of age
1week of age if she remains HBsAg-unknown C. Test the infant for HBsAg and antibodies to HBsAg (anti-
C. Test the infants mother for HBsAg HBs) at 1 month of age
D. All of the above D. B and C

2. If this infant had weighed 1,900 g at birth, the most appro- The infant receives the appropriate management after birth.
priate management for this infant would have been to:
4. Of the following, the transmission of hepatitis B infection
A. Administer HBV by 12 hours of age to this mothers second child is highest during:
B. Administer HBIG by 12 hours of age
A. Breast-feeding C. Labor and delivery
C. Test the infants mother for HBsAg
B. Gestation (i.e., in utero) D. Postpartum
D. All of the above

CASE 6
Syphilis

A female infant is born at 35 weeks gestation by vaginal de- 2. Of the following, the route by which this 1-month-old
livery. The pregnancy had been complicated by a diagnosis of infant most likely acquired syphilis is during:
syphilis in the infants mother at 32 weeks gestation.
A. Breast-feeding
1. Of the following, the scenario in which this infant would B. Direct contact with the mother
require an evaluation for syphilis is: C. Gestation (by transplacental route)
D. Labor and delivery
A. If the mother was appropriately treated during preg-
nancy and had a twofold decrease in viral titers 3. Additional clinical findings in this infant with syphilis in-
B. If the mother was appropriately treated during preg- clude all of the following, except:
nancy less than 4 weeks prior to delivery
A. Desquamating maculopapular rash
C. If the mother was treated with a nonpenicillin antibiotic
B. Hepatosplenomegaly
D. All of the above
C. Hutchinson triad
At 1 month of age, the infant has clinical findings that are D. Osteochondritis
consistent with syphilis, including the following:
To confirm the diagnosis of syphilis in this infant, the neonatolo-
Copious nasal secretions gist orders an RPR (rapid plasma reagin) test and a fluorescent
Hemolytic anemia treponemal antibody absorption (FTA) test on the infant and com-
Lymphadenopathy pares these findings with the mothers test results. The maternal
Pneumonia and neonatal testing are consistent with neonatal infection.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 7 Toxoplasmosis117

4. Of the following, the test results most consistent with con- All of these test results are abnormal and consistent with sys-
genital syphilis is: temic and neurologic evidence of syphilis.
A. Mother: negative RPR, positive FTA; infant: negative 5. Of the following, the most effective treatment for this in-
RPR, positive FTA fant is:
B. Mother: positive RPR, negative FTA; infant: positive
RPR, negative FTA A. Ampicillin administered intravenously 10 days
C. Mother: positive RPR, positive FTA; infant: negative B. Aqueous crystalline penicillin G administered intrave-
RPR, positive FTA nously 10 days
D. None of the above C. Penicillin G benzathine administered intramuscularly
once per week three doses
The neonatologist also performs a complete evaluation for D. All of the above are acceptable options
syphilis, including the following:

Complete blood count


Direct bilirubin
Liver function tests
Cerebrospinal fluid (CSF) examination for cell count,
protein, and quantitative VDRL (Venereal Disease Re-
search Laboratory) test
Chest radiograph
Long-bone radiographs
Ophthalmologic examination

CASE 7
Toxoplasmosis

A full-term male infant is born to a woman with normal pre- 2. Of the following, the mode of transmission that might
natal screening tests. He is discharged to home after 2 days in have led this mother to acquire toxoplasmosis is:
the hospital. The pediatrician meets with the infants parents
A. Oocyst from contaminated food
the day after discharge to discuss a positive toxoplasmosis re-
B. Oocyst from contaminated water
sult that was found on the infants state screening test. The
C. Tissue cyst from undercooked meat
infants examination is normal. The pediatrician reviews the
D. All of the above
maternal history and learns that the woman had been healthy
throughout her pregnancy and is currently asymptomatic. Maternal Toxoplasma gondii-specific IgG and IgM antibody lev-
els and neonatal T. gondii-specific IgG, IgM, and IgA antibody
1. Of the following, the most accurate statement by the pedia- levels confirm that the baby has congenital toxoplasmosis.
trician about this baby is: The infant is asymptomatic and has normal ophthalmologic,
A. Congenital toxoplasmosis is unlikely because the baby auditory, and neurologic evaluations.
is asymptomatic.
3. Of the following, the clinical issues that are likely to de-
B. Congenital toxoplasmosis is unlikely because the
velop in this infant several months to years later include
mother is asymptomatic.
the following:
C. The baby most likely has congenital toxoplasmosis from
a primary maternal infection. A. Hearing impairment
D. The baby most likely has congenital toxoplasmosis from B. Mental deficiency
a secondary maternal infection. C. Visual impairment
D. All of the above
The parents have many questions for the pediatrician. In par-
ticular, the mother wants to know how she might have ac- The pediatrician consults with infectious diseases experts to
quired toxoplasmosis. determine the management plan.

(c) 2015 Wolters Kluwer. All Rights Reserved.


118Section VII Infectious Diseases

4. Of the following, the appropriate management of this in- 5. Of the following, the clinical manifestation of T. gondii
fant is: infections acquired after birth is:
A. Close monitoring but no medications until the infant A. Easy bruisability, petechial rash, hematochezia
becomes symptomatic B. Fever, rash, myalgia, cervical lymphadenopathy
B. Pyrimethamine only 1 year C. Lethargy, seizures, hearing loss
C. Sulfadiazine only 1 year D. Nausea, emesis, diarrhea
D. Pyrimethamine and sulfadiazine 1 year

The parents are concerned that the infants 3-year-old sibling


might have acquired toxoplasmosis.

CASE 8
Human immunodeficiency virus

A 32-year-old pregnant woman has routine blood testing dur- After following all of the recommendations by the infectious
ing the first trimester. Her testing reveals the following: disease specialist to attempt to minimize HIV transmission to
her infant, the woman delivers a full-term infant girl.
Blood type O positive
Rapid plasma reagin nonreactive 3. Of the following, the preferred method to diagnosis HIV
Hepatitis B surface antigen negative infection in a newborn is:
Rubella immune
Human immunodeficiency virus (HIV) antibody positive A. Detection of p24 antigen
B. Enzyme immunoassay
The womans HIV-positive status is confirmed with additional C. Nucleic acid amplification
testing. The womans obstetrician reviews these new findings, D. Viral isolation by culture
discusses the preventive strategies to decrease the risk of HIV
transmission to her baby, and refers her to an infectious dis- While waiting for the infants test results, the woman asks the
ease specialist. pediatrician to describe the most likely clinical presentation in
an infant with a maternally acquired HIV infection.
1. Of the following, the most likely period of mother-to-child
transmission of HIV in the United States is: 4. Of the following, the most likely clinical diagnosis in an
untreated infant with a maternally acquired HIV infection is:
A. During the first trimester
B. During the third trimester A. Disseminated candidiasis
C. Intrapartum B. Pneumocystis jirovecii pneumonia
D. Postnatally C. Toxoplasmosis
D. All of the above
2. Of the following, the approach(es) to minimize the risk of
transmission is:

A. Oral antiretroviral medication to the pregnant woman


during pregnancy
B. Intravenous antiretroviral medication to the pregnant
woman during delivery
C. Oral antiretroviral medication to the infant postnatally
for 6 weeks
D. All of the above

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 10 Immunizations119

CASE 9
Cytomegalovirus

A 6-month-old female infant with a diagnosis of cytomega- The infant was symptomatic with classic findings of congeni-
lovirus (CMV) infection has an appointment in the Pediatric tal CMV infection after birth.
Infectious Diseases Clinic. The pediatric resident rotating in
the clinic reviews the infants medical records prior to the visit. 3. Of the following, the most likely clinical finding in the in-
fant in this vignette is:
1. Of the following, acquisition of CMV infection may have
A. Large for gestational age
occurred in this infant:
B. Macrocephaly
A. By a blood transfusion C. Periventricular intracerebral calcifications
B. During delivery D. Thrombocytosis
C. Via infected breast milk
Upon further review of the infants records, the resident finds
D. All of the above
that the infant had three normal hearing screens (day of life2,
The resident learns that the infant acquired CMV by transpla- age 2 months, and age 4 months). The parents report that their
cental passage in utero. baby is able to hear noises and have no concerns about her
hearing.
2. Of the following, the most accurate statement about the
intrauterine transmission of CMV is: 4. Of the following, this infants risk of hearing loss is:
A. A fetus is at greater risk of acquiring CMV infection if A. 1% to 5% because the infants hearing screen was nor-
maternal infection occurs during the second half of mal soon after birth
pregnancy instead of the first half of pregnancy. B. 10% to 15% because the 6-month-old infants hearing
B. CMV is the most common intrauterine infection seems appropriate to the parents
worldwide. C. 30% to 40% because of the diagnosis of symptomatic
C. More than 80% of infants with congenital CMV are congenital CMV infection
symptomatic and have clinical sequelae. D. 80% to 90% because of the diagnosis of symptomatic
D. All of the above congenital CMV infection

CASE 10
Immunizations

A male infant is born at 28 weeks gestation with a birth weight 1. Of the following, the least accurate statement is:
of 960 g. He has a typical clinical course in the Neonatal Inten-
A. Most preterm infants have an adequate immune
sive Care Unit (NICU), complicated by surfactant deficiency,
response postvaccination to prevent disease.
apnea of prematurity, feeding immaturity, anemia of prema-
B. Preterm infants should receive a lower vaccine dose than
turity, and mild retinopathy of prematurity. He is discharged
term infants.
home at 35 weeks postmenstrual age, weighing 1,995 g. At
C. Preterm infants should receive inactivated vaccines
his first pediatric appointment at 36 weeks postmenstrual age,
while in the hospital.
the pediatrician meets with the family and discusses the ap-
D. Very-low-birth-weight infants may have an increase in
proach to immunizations in a former preterm infant.
cardiorespiratory events postvaccination.

(c) 2015 Wolters Kluwer. All Rights Reserved.


120Section VII Infectious Diseases

The pediatrician then plans the vaccination schedule for this To protect the preterm infant until he can be vaccinated
infant. against influenza and receive the complete set of pertussis
vaccinations, the pediatrician also discusses that household
2. Of the following, the most appropriate timing of this members should receive influenza each year and an acellular

infants 2-month set of vaccinations is: pertussis booster dose.
A. Simultaneously at 36 weeks postmenstrual age (i.e., at
2months chronologic age)
B. Simultaneously at 48 weeks postmenstrual age (i.e.,
2months after the estimated due date)
C. Simultaneously once the infants weight is over 2,500 g
D. Separation of vaccines in 1-week intervals, starting at
36weeks postmenstrual age

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 1 Sepsis121

SECTION VII
Answers

4. A i
CASE 1 ANSWERS
B i and ii
1. A. Infection C ii
Premature rupture of membranes (PROM) describes the rup- D i and ii
ture of the amniotic sac prior to the onset of labor. If the rup- E ii
ture occurs prior to 37 weeks gestation and prior to labor, F ii
this is termed preterm premature rupture of membranes G ii
(PPROM). In either situation, the fetus becomes susceptible; H i
bacteria from the maternal vaginal flora can ascend and lead The characteristics of early-onset and late-onset sepsis are
to chorioamnionitis and a fetal infection. If a womans mem- compared in Table 1.
branes rupture prematurely, she will need to be monitored
closely for signs of infection. If there is a concern for chorio- Table 1. Early-Onset and Late-Onset Comparisons
amnionitis, the obstetrician will need to deliver the baby.
For infants born after several weeks of PPROM without re- Early-Onset Sepsis Late-Onset Sepsis
accumulation of the amniotic fluid, there is an increased risk
for pulmonary hypoplasia. Renal function in these infants is Timing Presents 0 to 6 days Presents 7 to
not usually affected. of life (some studies 10days of life
narrow to 03days) (may occur later in
2. A. Ampicillin and gentamicin premature infant)
For a newborn with suspected sepsis, the appropriate antibi-
Acquisition From maternal Either maternal
otic regimen should provide a broad coverage of gram-negative genital tract genital tract
and gram-positive organisms that are present in the maternal or postnatal
genital tract. These organisms include the following: environment
Organisms GBS, E. coli, Listeria, Staphylococcus
Group B Streptococcus
nontypeable H. (Staph)
Escherichia coli influenzae (H flu), coagulase-negative,
Listeria monocytogenes and Enterococcus Staph aureus,
Nontypeable Haemophilus influenzae Pseudomonas, GBS,
Enterococcus E Coli, and Listeria
Clinical Fulminant Usually slowly
Because Listeria monocytogenes is a possible cause of neonatal Multisystem progressive
sepsis, coverage with ampicillin is important. involvement (greater Focal involvement
risk of pneumonia) (greater risk of
3. D. Listeria monocytogenes meningitis)
A pregnant woman can acquire a Listeria monocytogenes in-
Mortality Greater mortality Lower mortality
fection by consuming unpasteurized milk, unpasteurized
(15%45%) (10%20%)
soft cheeses, unwashed raw vegetables, or uncooked meat.
Approximately 65% of pregnant women infected with Listeria
Printed with permission from: Brodsky D, Martin C. Neonatology
will have a prodromal flu-like illness with headache, malaise, Review. 2nd ed. Raleigh, NC: Lulu; 2010:223
fever, and gastrointestinal symptoms. Infants can then acquire
early-onset disease by transplacental transmission (most com-
mon) of the gram-positive rod or by ingestion or aspiration of
infected amniotic fluid. The amniotic fluid of infected infants
may have a brown-colored appearance, sometimes mistaken
for meconium. Infants can also acquire a late-onset Listeria
infection by a nosocomial route or from a colonized mother.

(c) 2015 Wolters Kluwer. All Rights Reserved.


122Section VII Infectious Diseases

3. C. GBS colonization during a prior pregnancy, regard-


AMERICAN BOARD OF PEDIATRICS
less of current GBS status
CONTENT SPECIFICATIONS
To minimize the risk of neonatal GBS disease, 2010 guidelines
Know the significance for infection of prolonged prema- from the Centers for Disease Control and Prevention and the
ture rupture of the membranes American Academy of Pediatrics recommend maternal intra-
Know the appropriate antibiotic treatment for suspected partum chemoprophylaxis in the following scenarios:
sepsis in the immediate newborn period A woman with GBS bacteriuria during current pregnancy
Recognize Listeria monocytogenes as a cause of neonatal A woman with prior infant with invasive GBS disease, re-
sepsis gardless of current GBS status
Understand the risk of sepsis from the use of intravascu- A woman with unknown GBS status and any of the
lar catheters following:
Preterm labor
Duration of membrane rupture for 18 hours or longer
SUGGESTED READING Intrapartum temperature 38C (100.4F)

A woman with GBS colonization during a prior pregnancy


Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010.
does not require intrapartum chemoprophylaxis unless she is
GBS-positive in the current pregnancy. For those women who
have a cesarean prior to the onset of labor and have intact am-
CASE 2 ANSWERS
niotic membranes, intrapartum antimicrobial prophylaxis is
1. D. All of the above not indicated.
GBS can be found in human gastrointestinal and genitouri- 4. C. Penicillin
nary tracts. Between 15% and 35% of pregnant women are To obtain adequate intrapartum GBS prophylaxis, the preg-
colonized with this organism. Transmission of GBS from a nant woman needs to receive the appropriate antibiotic 4 or
colonized mother to her infant can occur: more hours prior to delivery. The preferred antibiotic for ma-
Shortly before delivery ternal intrapartum chemoprophylaxis is intravenous penicillin
During delivery G because of its high efficacy and narrow antimicrobial activ-
Postnatally from a colonized caregiver or healthcare pro- ity. Alternatively, intravenous ampicillin can be administered.
fessional with inadequate hand hygiene For women who are mildly allergic to penicillin, intravenous
cefazolin can be used to prevent early-onset neonatal GBS dis-
Because of the high risk of neonatal GBS disease, all pregnant ease. For those women at high risk for anaphylaxis with peni-
women are screened for GBS vaginal/rectal colonization be- cillin exposure, intravenous clindamycin can be administered
tween 35 and 37 weeks gestation. if the GBS isolate is sensitive to clindamycin. For those women
2. A. Advanced maternal age with unknown GBS sensitivity or clindamycin-resistant GBS,
Early-onset GBS disease is characterized by a systemic infec- intravenous vancomycin can be used. However, the efficacy of
tion in a neonate less than 7 days of age. In contrast, late-onset clindamycin or vancomycin is uncertain. Oral antimicrobials
GBS disease usually occurs at 3 to 4 weeks of age with a range are not appropriate for chemoprophylaxis.
between 7 and 89 days of life. Risk factors of early-onset dis- 5. B. A lower incidence of early-onset neonatal GBS dis-
ease include the following: ease by 80%
Black race Prior to the implementation of GBS chemoprophylaxis, the
Chorioamnionitis incidence of early-onset GBS neonatal disease was 1 to 4cases
High inoculum of maternal genital GBS per 1,000 live births and 1 to 2 infants per 100 colonized
Intrauterine fetal monitoring women. After implementing widespread maternal intrapar-
Low maternal antibody concentration to the capsular tum antibiotic prophylaxis, this incidence of early-onset dis-
polysaccharide of the infecting strain ease decreased by 80% to 0.28 cases per 1,000 live births
Maternal age less than 20 years (2008 data). In contrast, maternal chemoprophylaxis has not
Maternal GBS bacteriuria during the current pregnancy had any impact on the incidence of late-onset disease, the
Maternal fever 38C (100.4F) risk of neonatal disease in future pregnancies, or the length
Preterm birth (i.e., <37 weeks gestation) of labor.
Rupture of membranes >18 hours
Sibling with invasive GBS disease in the neonatal period

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 3 Herpes simplex virus123

6. A i Oral penicillin is inadequate in the treatment of GBS disease


B i in infants.
C ii The length of treatment of a GBS infection in an infant de-
D iii pends on the location of the infection. For example, a 10-day
E iii course of antibiotics is appropriate for an infant with bacte-
F iii remia, while a minimum of 14 days is recommended for un-
complicated meningitis, and an infant with septic arthritis or
In a symptomatic newborn, the clinician should perform a
osteomyelitis requires 3 to 4 weeks of therapy.
complete diagnostic evaluation (complete blood count with
differential, blood culture, and lumbar puncture) and initiate
antibiotics, regardless of adequacy of intrapartum GBS pro-
phylaxis (option F). However, for well-appearing infants who AMERICAN BOARD OF PEDIATRICS
are born to a GBS-colonized mother, the approach is more CONTENT SPECIFICATIONS
targeted. If the mother received adequate intrapartum prophy-
Know the mode of transmission of Group B Streptococcus
laxis and there are no signs of chorioamnionitis (option A)
Understand the importance of maternal screening for
or the mother had inadequate intrapartum prophylaxis with
Group B Streptococcus and the appropriate treatment of
duration of membrane rupture less than 18 hours without
women with positive results
a maternal fever (option B), observation of the infant is rec-
Know the recommendations for evaluation of an infant
ommended. If the infant is born <37 weeks gestation or the
whose mother is colonized with Group B Streptococcus
duration of membrane rupture is 18 hours with inadequate
and how the administration of intrapartum antibiotic
prophylaxis (option C), then the infant requires a limited eval-
therapy affects the evaluation
uation (complete blood count/differential and blood culture)
Recognize the major clinical manifestations of Group
and observation for a minimum of 48 hours. If the culture
B streptococcal infection: early-onset septicemia and
is positive or the infants clinical status changes, antibiotic
pneumonia; late-onset bacteremia, pneumonia, menin-
therapy is needed. If chorioamnionitis is suspected, a limited
gitis, pyogenic arthritis, osteomyelitis
evaluation with a complete blood count with differential and
Know the treatment of Group B Streptococcus infection
a blood culture and initiation of antibiotics is warranted, re-
gardless of whether there is adequate intrapartum GBS pro-
phylaxis (options D and E).

7. A. Meningitis
SUGGESTED READING
Early-onset GBS disease is characterized by systemic infec- Baker CJ, Long SS, Pickering LK, eds. Red Book: 2012 Report of the
tion in a neonate less than 7 days of age. Newborns with Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL:
early-onset GBS disease typically have the following clinical American Academy of Pediatrics; 2012.
manifestations:

Apnea CASE 3 ANSWERS


Pneumonia
Respiratory distress 1. F. A, C, and D
Septicemia A pregnant woman with a primary genital herpes lesion at de-
Shock livery has a 25% to 60% chance of having a neonate who is
infected with herpes. This high risk is because of the following:
Meningitis occurs less frequently (5%10% of affected
newborns). High viral replication
In contrast, late-onset GBS disease usually occurs at 3 to Longer excretion of virus from a primary lesion (3 weeks
4 weeks of age with a range between 7 and 89 days of life. if primary infection vs. 25 days of shedding if recurrent
Affected infants typically have bacteremia or meningitis. Less herpes)
frequently, late-onset GBS disease can manifest with focal in- Lack of maternal antibodies transferred to neonate
fections, including cellulitis, osteomyelitis, pneumonia, and/
In contrast, a pregnant woman with a secondary genital her-
or pyogenic arthritis.
pes lesion during delivery has less than a 5% chance of hav-
8. D. All of the above ing a neonate who is infected because of protective maternally
When an infant has a presumptive GBS infection, use of in- transmitted antibodies. More than 75% of neonates who ac-
travenous ampicillin and an aminoglycoside is the initial quire a herpes infection are born to women who are asymp-
preferred antimicrobial regimen. Once the GBS organism has tomatic or without a history of genital herpes.
been identified, intravenous penicillin G can be administered.

(c) 2015 Wolters Kluwer. All Rights Reserved.


124Section VII Infectious Diseases

2. Higher risk is associated with: experts would not recommend intravenous acyclovir unless sur-
A. Vaginal birth face cultures are positive.
B. Maternal genital lesion at delivery
4. B. Monitor the infant closely
C. Premature infant
For an asymptomatic infant born by vaginal delivery to a
D. Rupture of membranes more than 6 hours prior to delivery
woman with a history of genital herpes but no active lesions at
E. Use of a fetal scalp monitor
the time of delivery, the following is recommended:
The risk of a neonate acquiring HSV is greatest if the mother
Monitor the infant closely and educate the family to
has a primary genital lesion at the time of a vaginal delivery.
monitor for signs and symptoms of HSV disease during
Additional risk factors include the following:
the first 6 weeks of life.
Prematurity because of low transplacental antibodies It is not necessary to obtain surface cultures for HSV.
Fetal scalp monitoring because of the potential that an Empiric acyclovir therapy is not indicated.
infants skin barrier is broken, allowing easier entry of
herpetic cells
5. C. Two to 3 weeks of age
The most likely timing of neonatal symptoms from perinatal
Rupture of membranes more than 4 hours because of the
acquisition of HSV is between 2 and 3 weeks of age. In con-
increased risk of ascending infection
trast, infants with congenital HSV will be symptomatic imme-
3. D. All of the above diately after delivery.
For an asymptomatic infant born by vaginal delivery to a
woman with a primary active genital lesion, infectious diseases 6. D. All of the above
experts recommend the following: There are three types of clinical presentations of neonatal
herpes:
Obtain surface cultures of conjunctivae, nasopharynx,
mouth, and rectum at 12 to 24 hours of age; the delay 1. Disseminated (systemic) disease
in obtaining surface cultures in an asymptomatic infant 2. Encephalitis (CNS involvement)
will allow the cultures to reflect viral replication instead 3. Skin, eye, mucous membranes (SEM)
of contamination from an exposure. There is some overlap with each of these disorders. Table 1
Monitor the infant closely. compares the timing, incidence, clinical features, morbidity,
Some experts suggest empirical intravenous acyclovir after and mortality of these three types. Of note, while skin find-
surface cultures are obtained. ings are common, they are not always present in neonates with
For asymptomatic infants born by vaginal delivery to a woman herpes.
with a secondary genital lesion at the time of delivery, most

Table 1. Neonatal Herpes Disease

Disseminated (Systemic) SEM Encephalitis (CNS)


Timing 4 to 10 days of life 6 to 9 days of life 10 to 18 days of life
Incidence 20% 40% to 45% 30% to 35%
Clinical Fever, lethargy, irritability, poor oral intake Most common Initially with fever, lethargy,
Respiratory distress may be presenting Eyes: conjunctivitis, keratitis, and seizures
sign in 20% secondary to pneumonitis chorioretinitis, retinal dysplasia Irritability, apnea
Hepatomegaly, adrenal gland Skin (80%85%): papulovesicular Bulging fontanel
involvement lesions, often pustular and with Pyramidal tract signs
Coagulopathy, shock erythematous base, often occurs
at sites of trauma, risk of scar 60% with skin involvement
60% with skin involvement formation CNS involvement (probably
May also have CNS (60% 75%, results results from retrograde axonal
from hematogenous spread) or SEM (80%) transmission to brain)

Morbidity 30% to 80% normal development if Treatment minimizes risk of 30% with normal development
treated progression to disseminated or Increased risk of microcephaly,
CNS disease spasticity, blindness,
Normal development in >90% if chorioretinitis, developmental
treated delay
Greatest risk of neurologic
sequelae if 3 skin recurrences
Mortality 30% (despite treatment) Minimal 4% to 10% (despite treatment)
Printed with permission from: Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 2010:236237

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 4 Lower respiratory tract infections125

7. D. Intravenous acyclovir 3 3 weeks, followed by oral Nasal congestion


acyclovir suppressive therapy 3 6 months Respiratory distress
Infants with SEM disease require intravenous acyclovir for Tachypnea
2 weeks. Those with CNS disease or disseminated disease Wheezing
should be treated for a minimum of 3 weeks. Oral acyclovir
Preterm infants who acquire RSV during the first few weeks
suppressive therapy for 6 months after treatment of acute HSV
to months of life often present with lethargy, irritability, poor
disease has been shown to improve neurodevelopmental out-
oral intake, and apnea.
comes in those infants with HSV CNS disease. This approach
also has been shown to prevent additional skin lesions, 2. C. Rate of hospitalization
regardless of the type of HSV. Infants with ophthalmologic Palivizumab has been shown to decrease the rate of RSV-
involvement require a topical ophthalmologic medication in associated hospitalizations in infants at high risk for RSV. Trials
addition to intravenous acyclovir. have not shown a significant decrease in mortality attributable
to an RSV infection, in the rate of recurrent wheezing after an
RSV infection, or in the transmission rate of RSV. Palivizumab
administration is not helpful in the treatment of RSV disease.
AMERICAN BOARD OF PEDIATRICS
CONTENT SPECIFICATIONS 3. C. All premature infants with a diagnosis of chronic
lung disease
Know that newborns of mothers with primary herpes The American Academy of Pediatrics Red Book summarizes
infections are more likely to be infected than infants the most recent eligibility criteria for RSV prophylaxis of high-
born to mothers with recurrent genital herpes simplex risk infants. The 2012 guidelines recommend RSV prophylaxis
infections with palivizumab during the first winter season in the follow-
Recognize that herpes simplex virus can be transmit- ing infants:
ted from a person with a primary or recurrent infection
regardless of whether any symptoms are present All infants with a diagnosis of chronic lung disease (i.e.,
Know the appropriate tests for the diagnosis of herpes receiving supplemental oxygen, bronchodilator, diuretic,
simplex infection or chronic corticosteroid treatment); those infants with
Recognize the clinical manifestations of herpes s implex severe disease who continue to need these therapies dur-
virus infection in the neonatal period and that skin ing their second winter season may benefit from a second
lesions are not always present prophylactic course.
Plan the appropriate management of a neonatal herpes All infants born 31 6/7 weeks gestation
simplex infection Infants born at 32 0/7 weeks gestation and <35 weeks
gestation who attend child care or have a sibling <5 years
of age (prophylaxis should be continued until the infant is
3 months of age for a maximum of three doses)
SUGGESTED READINGS Infants with airway abnormalities or neuromuscular disease
Infants with cyanotic heart disease, symptomatic heart
Baker CJ, Long SS, Pickering LK, eds. Red Book: 2012 Report of the
Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: disease requiring medication to treat congestive heart fail-
American Academy of Pediatrics; 2012. ure, and moderate or severe pulmonary hypertension
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010. Prophylaxis is not recommended for infants with any of the
Westhoff GL, Little SE, Caughey AB. Herpes simplex virus and preg- following:
nancy: A review of the management of antenatal and peripartum
herpes infections. Obstet Gynecol Surv. 2011;66:629638. Mild cardiomyopathy without requiring medications
Mild coarctation of the aorta
Patent ductus arteriosus
CASE 4 ANSWERS Pulmonic stenosis
Secundum atrial septal defect
1. C. Respiratory syncytial virus (RSV)
Small ventricular septal defect
RSV is the most common cause of lower respiratory infections
Surgically corrected structural heart disease unless medi-
in infancy. Most children acquire this infection during the first
cation is still required to treat congestive heart failure
year of life. Affected infants typically have an upper respira-
Uncomplicated aortic stenosis
tory illness, and 20% to 30% also have a lower respiratory
illness, such as bronchiolitis or pneumonia. Infants often pres- Infants with severe immunodeficiencies may benefit from RSV
ent with the following symptoms: prophylaxis. Because of limited data in patients with cystic
fibrosis, there is no current recommendation for routine RSV
Cough
prophylaxis in this population.
Low-grade fever

(c) 2015 Wolters Kluwer. All Rights Reserved.


126Section VII Infectious Diseases

Complete the hepatitis B immunization series with a total


AMERICAN BOARD OF PEDIATRICS of three doses for infants with a birth weight 2,000 g
CONTENT SPECIFICATIONS and provide a total of four doses for infants with a birth
weight <2,000 g
Know that respiratory syncytial virus is the most com-
Test the infant for HBsAg and anti-HBs at 9 to 18 months
mon cause of lower respiratory infections in infancy
of age; earlier testing leads to false-positive results be-
Identify patients at high risk for morbidity and mortal-
cause of possible detection of antibodies from the HBIG
ity from respiratory syncytial virus infection (e.g., those
administration after birth. In addition, earlier testing may
with congenital heart disease, bronchopulmonary dys-
not detect late-onset Hepatitis B virus infections.
plasia, prematurity) and those who may benefit from
prophylaxis Concurrent dosing of HBV and HBIG should be administered
at different anatomic sites.
A positive maternal HBeAg status increases the chance of
SUGGESTED READING transmission because of the associated high degree of rep-
lication. Without prophylaxis, an infants risk of acquiring
Baker CJ, Long SS, Pickering LK, eds. Red Book: 2012 Report of the Com-
mittee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American hepatitis B from a mother who is HBsAg-positive and HBeAg-
Academy of Pediatrics; 2012. positive is 70% to 90%. For women who are HBsAg-positive
but HBeAg-negative, the risk of neonatal transmission is 5%
CASE 5 ANSWERS to 20%. Infants born to an HBsAg-positive woman receive two
types of immunoprophylaxis: HBV and HBIG. While the HBV
1. D. All of the above provides long-term protection, the HBIG provides short-term
The management of a full-term infant who weighs over 2,000g protection (up to 1 week after administration).
at birth and is born to a woman with an unknown HBsAg sta-
4. C. Labor and delivery
tus includes the following:
Transmission of hepatitis B virus from an infected mother
Test the infants mother for HBsAg as soon as possible to her baby typically occurs by blood exposure during labor
Administer the first HBV within 12 hours of age to the infant and delivery. There is no additional risk of hepatitis B viral
Administer HBIG as soon as possible if the mother transmission to infants who have been breast-fed by HBsAg-
is positive for HBsAg or by 1 week of age if she remains positive mothers and have received appropriate immunopro-
HBsAg-unknown phylaxis with HBV and HBIG. Intrauterine transmission of this
Complete hepatitis B immunization series with a total of virus is very small, accounting for less than 2% of perinatal
three doses infections. Postpartum transmission of hepatitis B is unlikely
for infants who have received the appropriate HBV.
This rationale for delaying the HBIG is because the vaccine is
effective at preventing hepatitis infection in term infants.

2. D. All of the above AMERICAN BOARD OF PEDIATRICS


The management of an infant who weighs less than 2,000 g at CONTENT SPECIFICATION
birth and is born to a woman with an unknown HBsAg status
includes the following: Plan the treatment of an infant born to a woman who is
a hepatitis B carrier (e.g., combination of hepatitis vac-
Test the infants mother for HBsAg as soon as possible
cine and hepatitis B immune globulin [HBIG] at birth)
Administer the first HBV within 12 hours of age to the infant
Administer HBIG within 12 hours of age if the mother is
positive for HBsAg or if she remains HBsAg-unknown
Complete hepatitis B immunization series with a total of SUGGESTED READINGS
four doses
Baker CJ, Long SS, Pickering LK, eds. Red Book: 2012 Report of the Com-
Earlier administration of HBIG in this lower-birth-weight mittee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American
population is recommended because the immune response of Academy of Pediatrics; 2012.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
these infants is less reliable. 2010.
3. A. Administer HBV and HBIG by 12 hours of age
The management of an infant who is born to a woman with a
positive HBsAg status includes the following:
Administer the first HBV to the infant within 12 hours of
age, regardless of birth weight
Administer HBIG to the infant within 12 hours of age,
regardless of birth weight

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 6 Syphilis127

Cognitive deficits
CASE 6 ANSWERS
Eighth cranial nerve deafness (evident at 10 to 40 years
1. D. All of the above of age)
A neonate must be evaluated for syphilis soon after birth in Frontal bossing
the following scenarios: Hutchinson teeth (peg-shaped, notched central incisors)
Interstitial keratitis (evident at 5 to 20 years of age)
If the baby is born to a seropositive mother with un-
treated syphilis Hutchinson triad refers to the combination of eighth cranial
If the mother is treated for syphilis during pregnancy with nerve deafness, Hutchinson teeth, and interstitial keratitis.
a nonpenicillin antibiotic These late findings of congenital syphilis can be prevented
If the mother was appropriately treated during pregnancy with appropriate early treatment.
but this treatment occurred less than 4 weeks prior to de- 4. C. Mother: positive RPR, positive FTA; infant: negative
livery; evaluation is necessary because of the potential for RPR, positive FTA
a treatment failure The RPR or VDRL test is a nontreponemal antibody test that
If the mother was appropriately treated during pregnancy detects cell membrane cardiolipin nonspecific IgG antibod-
but did not show a fourfold (or more) decrease in viral titers. ies. It is reported as a titer, and it correlates with disease activ-
If the mother was appropriately treated during pregnancy ity. In contrast, FTA detects a specific antibody to Treponema
but had insufficient follow-up pallidum, remains active for life, and does not correlate with
If the baby has symptoms that are consistent with syphilis disease activity. Because of potential false-positive results, a
2. C. Gestation (by transplacental route) diagnosis of syphilis requires both nontreponemal and trepo-
The transplacental route is the most common mode of acqui- nemal testing.
sition of syphilis in the neonate. If a pregnant woman has pri- If a mother tests positive for RPR and FTA with an infant
mary syphilis that is untreated, there is a 70% to 100% risk of who is negative or positive for RPR and positive for FTA, this
fetal acquisition. is consistent with a mother with syphilis and an infected
An infant can acquire syphilis by contact with an active neonate.
vaginal lesion during delivery, but this is less common than in- If a mother tests negative for RPR and positive for FTA with
trauterine acquisition. Transmission of syphilis by direct ma- an infant who is negative for RPR and positive for FTA, the
ternal contact and breast-feeding is unlikely. Acquired syphilis mother has been successfully treated for syphilis or has a false-
in children and adults almost always occurs through sexual positive serology.
contact with infected lesions or mucous membranes If a mother tests positive for RPR and negative for FTA with
an infant who is also positive for RPR and negative for FTA,
3. C. Hutchinson triad this is consistent with a false-positive nontreponemal test.
Congenital syphilis can result in prenatal findings, including Thus, the mother does not have syphilis and there has been
stillbirth, hydrops fetalis, or preterm birth. Affected infants passive transfer of RPR antibodies to the neonate.
can be asymptomatic at birth (23) or have clinical findings that
present within the first 2 months of age (13). These symptoms 5. B. Aqueous crystalline penicillin G administered intra-
include the following: venously 3 10 days
For neonates with a definite or likely diagnosis of congenital
Chorioretinitis and/or uveitis syphilis, the most appropriate treatment is aqueous crystal-
Copious nasal secretions (also known as snuffles) line penicillin G administered intravenously for 10 days. An
Desquamating maculopapular rash involving the palms alternative treatment is procaine penicillin G administered
and soles or bullous eruptions intramuscularly for 10 days; although procaine penicillin G
Erb palsy has low entry into the CSF, treatment failures have not been
Hemolytic anemia reported. For neonates who are at risk for congenital syphi-
Hepatosplenomegaly lis but have a benign examination with normal radiographic
Leptomeningitis imaging and laboratory testing, some infectious diseases
Lymphadenopathy experts recommend treatment with penicillin G benzathine
Nephrotic syndrome intramuscularly for 10 days. There is no data to support am-
Osteochondritis picillin for the treatment of congenital syphilis. After treat-
Pneumonia ment, infants need to be followed closely with serum and CSF
Pseudoparalysis VDRLtests.
Thrombocytopenia

Untreated infants with congenital syphilis have additional


findings that are evident after 2 years of age, including:

Anterior bowing of shins (known as saber shins)


Clutton joints (symmetric, painless knee swelling)

(c) 2015 Wolters Kluwer. All Rights Reserved.


128Section VII Infectious Diseases

AMERICAN BOARD OF PEDIATRICS


CONTENT SPECIFICATIONS

Know the mode of transmission of Treponema pallidum


Recognize the clinical manifestations of congenital and
acquired syphilis
Plan the laboratory diagnosis of congenital syphilis
Know the treatment of congenital syphilis (i.e., penicil-
lin), and that CNS involvement must always be consid-
ered when planning the treatment

SUGGESTED READINGS
Baker CJ, Long SS, Pickering LK, eds. Red Book: 2012 Report of the Com-
mittee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American
Academy of Pediatrics; 2012.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.

CASE 7 ANSWERS

1. C. The baby most likely has congenital toxoplasmosis


from a primary maternal infection.
Almost all infants with congenital toxoplasmosis acquire the
illness from a primary maternal infection during pregnancy.
Most women are asymptomatic or have mild symptoms dur- FIGURE 1. From Tsieh S. Parasitic Disorders: Pathology, Diagnosis, and
ing this infection. Approximately 70% to 90% of infants with Management. 2nd ed. Baltimore, MO: Lippincott Williams & Wilkins;
1999. Figure 14.1
congenital toxoplasmosis are asymptomatic at birth.

2. D. All of the above


The organism that causes toxoplasmosis is a protozoan and 3. D. All of the above
an intracellular parasite. Members of the cat family serve as Infants with congenital toxoplasmosis have two possible clini-
primary hosts. Cats usually acquire this parasite by eating in- cal presentations:
fected animals (e.g., mice), uncooked household meats, or 1. Clinical findings in the neonatal period (least common)
water or food contaminated with their own feces that contain 2. Subclinical infection in the neonatal period with symp-
oocysts. After replication in the cats intestinal epithelium, toms during the first few months to years of life (most
oocysts are excreted for up to 2 weeks. These excreted oocysts common)
can then become sporulated in a maturation process that takes Infants with congenital toxoplasmosis usually present with vi-
1 to 2 days. Once sporulated, oocysts can survive in soil for sual impairment, hearing loss, learning disabilities, or mental
months to years. Sheep, pigs, and cattle can be intermediate deficiency during the first few months to years of life.
hosts and have cysts located in their tissues. Clinical findings in the neonatal period are less common.
Humans can acquire toxoplasmosis by eating undercooked Affected neonates may have neurologic findings, such as:
animal tissues containing cysts or by ingesting sporulated oo- Chorioretinitis
cysts found in soil, water, or contaminated food. In addition, Cortical brain calcifications
transmission of T. gondii can occur by organ transplantation, Hydrocephalus
laboratory accidents, or blood transfusions. Human-to-human Meningoencephalitis
transmission can occur only from a pregnant woman to her fe- Microcephaly
tus. The life cycle of the T. gondii parasite is shown in Figure 1. Seizures

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 8 Human immunodeficiency virus129

The triad of chorioretinitis, cortical brain calcifications, and SUGGESTED READINGS


hydrocephalus is highly suggestive of congenital toxoplasmo-
sis. Affected neonates may also have a blueberry muffin rash Baker CJ, Long SS, Pickering LK, eds. Red Book: 2012 Report of the Com-
from dermal erythropoiesis, hearing loss, growth restriction, mittee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American
Academy of Pediatrics; 2012.
hepatosplenomegaly, lymphadenopathy, maculopapular rash, Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
and thrombocytopenia. 2010.

4. D. Pyrimethamine and sulfadiazine 3 1 year


For both symptomatic and asymptomatic infants with congen-
CASE 8 ANSWERS
ital toxoplasmosis, treatment with pyrimethamine and sulfa-
diazine is recommended. Infants need to be followed by an 1. C. Intrapartum
infectious diseases expert to determine the dose and length of Maternal transmission of HIV to an infant can occur by the
treatment; typically, infants are treated for 1 year. Folinic acid following routes:
is recommended while infants are receiving sulfadiazine. For
those infants with mild toxoplasmosis, sometimes this regi- Breast-feeding
men is alternated monthly with spiramycin during treatment Intrapartum route (most common mode of transmission
months 7 to 12. in the United States)
Transplacentally throughout gestation
5. B. Fever, rash, myalgia, cervical lymphadenopathy
Infants, children, or adults who acquire a T. gondii infection Breast-feeding is not recommended for HIV-positive women
after birth are usually asymptomatic. For those who develop in the United States because formula is a safe alternative to
symptoms, findings include the following: human milk. However, for HIV-positive women in underde-
veloped countries, the 2010 World Health Organization rec-
Arthralgia ommends breast-feeding because a safe alternative to human
Fever milk is not available.
Headache
Lymphadenopathy, cervical (this is the most common 2. D. All of the above
sign) The risk of transmission of HIV infection from an untreated
Malaise HIV-positive mother to her infant is 21% to 25% in the United
Myalgia States. Table 1 summarizes the highest risks associated with
Sore throat transmission of HIV from an HIV-positive pregnant woman
to her infant.
Some patients may present with isolated ocular toxoplasmosis
with chorioretinitis, leading to visual changes or visual distur- Table 1. High Risks Associated with Transmission of HIV From an
bances. Less common symptoms include a mononucleosis- HIV-Positive Pregnant Woman to Her Infant
like illness, macular rash, and hepatosplenomegaly. Affected
individuals typically have a self-limited clinical course. Immu- Maternal-disease Advanced maternal illness
nocompromised patients may have more severe effects, such specific risks Low maternal CD4 T-lymphocyte
as myocarditis, myositis, hepatitis, pericarditis, pneumonia, or count
brain abscesses. Increased maternal viral load
Newly acquired infection during the
last trimester of pregnancy (because
a primary infection is associated with
AMERICAN BOARD OF PEDIATRICS a greater viral load)
CONTENT SPECIFICATIONS Labor-specific Chorioamnionitis
risks Fetal scalp electrode
Recognize that the majority of newborns with congenital
toxoplasmosis are asymptomatic in the neonatal period Preterm delivery
Know the epidemiology of toxoplasmosis: hosts, inter- Prolonged labor
mediate hosts, modes of transmission (vertical trans- Prolonged rupture of membranes,
mission from mother to infant, ingestion of cysts from regardless of delivery mode
contaminated food or soil) Vaginal delivery (particularly if
Know the clinical manifestations of congenital prolonged rupture of membranes)
toxoplasmosis Postnatal Breast-feeding
Recognize the importance of prompt treatment of con- Other Increased exposure of fetus to
genital toxoplasmosis maternal blood in utero
Identify the clinical manifestations of Toxoplasma gondii Motherinfant human leukocyte
infections acquired after birth antigen concordance

(c) 2015 Wolters Kluwer. All Rights Reserved.


130Section VII Infectious Diseases

Approaches to decrease the transmission rate of HIV from Mycobacterium avium infection (10%)
an HIV-positive mother to her infant include the following: Herpes simplex virus infection (5%)
Cryptosporidiosis (5%)
Oral antiretroviral medications to the woman during
pregnancy A childs risk of acquiring these opportunistic infections is sig-
Intravenous antiretroviral medication to the woman dur- nificantly decreased with highly active antiretroviral therapy.
ing delivery Unless an infant is receiving total parenteral nutrition or
Oral antiretroviral prophylaxis to the infant for 6 weeks has a central venous catheter, disseminated candidiasis is un-
after birth common in an HIV-infected child. Similarly, toxoplasmosis is
Avoidance of breast-feeding (recommended approach in not a common illness in HIV-infected children.
the United States)
Cesarean delivery before the onset of labor and before
rupture of membranes if maternal viral load > 1,000 AMERICAN BOARD OF PEDIATRICS
copies/mL or unknown viral load CONTENT SPECIFICATIONS
Because these approaches have markedly decreased the Know the means of maternal transmission of HIV to her
risk of perinatal HIV transmission, the American Academy of infant (e.g., vaginal delivery, breast-feeding, transplacen-
Pediatrics currently recommends that all pregnant women, tally, intrapartum)
with their consent, undergo HIV testing. For those women Know that cesarean delivery and treatment of an HIV-
with an unknown HIV status, clinical providers should o
btain positive mother with antiretroviral drugs decrease the
rapid HIV antibody testing on the mother or infant after risk of transmission of virus to her infant
state-specific consent is obtained. Know the preferred method of diagnosis of HIV infec-
3. C. Nucleic acid amplification tion in infancy (i.e., nucleic acid amplification test)
Nucleic acid amplification by HIV-DNA polymerase chain Know the effect of a mothers HIV-positive status on her
reaction (PCR) assay is the preferred method of diagnosis of infants HIV test
HIV infection in a neonate. Although 30% of HIV-infected Know the clinical manifestations of human immunode-
neonates will test positive for HIV-DNA by PCR at 48 hours ficiency virus infection in neonates
of age, almost all HIV-infected neonates will have a positive
DNA PCR assay result at 1 month of age. When an infant has a
positive HIV-DNA PCR result, repeat testing is recommended SUGGESTED READINGS
at 1 to 2 months of age and again at 2 to 4 months of age. An
Baker CJ, Long SS, Pickering LK, eds. Red Book: 2012 Report of the
infant is diagnosed with an HIV infection if two separate sam- Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL:
ples are positive by DNA PCR assays. In non-breast-feeding American Academy of Pediatrics; 2012.
infants, two negative HIV DNA PCR assays confirm that the Brodsky D. Clinical presentation of neonatal HIV. NeoReviewsPlus.
April 5, 2008:Q7.
infant is not infected. Brodsky D. Diagnostic criteria of HIV. NeoReviewsPlus. July 5, 2008:Q2.
Detection of p24 antigen is less sensitive than testing by Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
HIV-DNA PCR and may yield false-negative results because of 2010.
Maldonado YA. Acquired immunodeficiency syndrome in the infant.
a low amount of circulating antigen in asymptomatic infected In: Remington JS, Klein JO, Wilson CB, et al. , eds. Infectious Disease
infants. Detection of HIV antibody by enzyme immunoassay of the Fetus and Newborn Infant. 6th ed. Philadelphia, PA: Elsevier
may yield false-positive results because of passively acquired Inc; 2006:667692.
maternal antibodies remaining in the infant until 18 months
of age. Viral isolation by culture is not an ideal test in neonates
because it is expensive and often requires up to 1 month to CASE 9 ANSWERS
attain positive results.
1. D. All of the above
4. B. Pneumocystis jirovecii pneumonia An infant can acquire CMV by different modes, including:
P. jirovecii (previously known as Pneumocystis carinii) pneumonia
By a blood transfusion (less common because of use of
is the most likely clinical presentation in an untreated infant with
CMV-negative blood)
a maternally acquired HIV infection, occurring in approximately
By intrauterine transmission (all trimesters)
one-third of affected infants. Other c linical manifestations in an
During delivery (from cervical secretions; term infants usu-
infant infected with HIV include the following:
ally asymptomatic because of passively transferred mater-
Lymphocytic interstitial pneumonitis (25%) nal antibodies; preterm infants at risk for clinical findings)
Recurrent bacterial infections (20%) Secretions (requires close contact)
Encephalopathy (15%) Via infected breast milk (term infants are usually asymp-
Candida esophagitis (15%) tomatic because of passively transferred maternal anti-
Cytomegalovirus infection (10%) bodies; preterm infants are at risk for clinical findings)

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 10 Immunizations131

2. B. CMV is the most common intrauterine infection loss in an infant with congenital CMV infection. Approximately
worldwide. half of affected infants are at risk for neurologic sequelae, includ-
Worldwide, CMV is the most common intrauterine infec- ing cognitive deficits, developmental delays, and seizures.
tion. Seroconversion from a positive to a negative status dur- In contrast, infants who acquire CMV infection intrapar-
ing pregnancy is not very common, occurring in 1% to 4% tum or postnatally from infected breast milk or blood prod-
of pregnant women and the majority of these women are as- ucts typically are asymptomatic. However, some infants, such
ymptomatic. Approximately 40% of fetuses will acquire CMV as preterm infants, may have clinical manifestations, such as
if the pregnant woman acquires a primary CMV infection. The pneumonitis, thrombocytopenia, hepatitis, poor head growth,
risk of neonatal disease and the severity of the neonates ill- and/or hearing loss.
ness are highest if the pregnant woman acquires an infection
4. C. 30% to 40% because of the diagnosis of symptom-
during the first half of gestation. Of those fetuses who become
atic congenital CMV infection
infected with CMV, 85% to 90% will be asymptomatic and
Sensorineural hearing loss is the most common clinical con-
have normal development. These infants have asymptomatic
sequence of symptomatic congenital CMV infection, occurring
congenital CMV. Of the remaining 10% to 15% who become
in 30% to 40% of affected children. In contrast, hearing loss
infected, 90% will have clinical sequelae (i.e., symptomatic
occurs in 5% to 10% of children with asymptomatic congenital
congenital CMV).
CMV. In those children with symptomatic congenital CMV and
3. C. Periventricular intracerebral calcifications hearing loss, half will be identified during the newborns hear-
Infants with symptomatic congenital CMV infection can have ing screening test and the remainder will be diagnosed during
the following findings: childhood. Thus, frequent audiology screening is necessary to
identify children with late-onset CMV-related hearing loss.
Chorioretinitis
Coagulopathy
Dermal hematopoiesis
AMERICAN BOARD OF PEDIATRICS
Growth restriction
CONTENT SPECIFICATIONS
Hearing loss, sensorineural (most common clinical
sequela of congenital CMV infection) Recognize that perinatal infection with cytomegalovirus
Hepatosplenomegaly may be acquired in utero, during delivery, or in the neo-
Indirect hyperbilirubinemia natal period (e.g., breast milk, blood transfusion)
Microcephaly Recognize the clinical manifestations of symptomatic
Periventricular intracerebral calcifications congenital cytomegalovirus disease, including congeni-
Thrombocytopenia tal hearing loss and mental retardation
The computed tomography image in Figure 1 reveals periventric-
ular calcifications, enlarged ventricles, and white matter volume
SUGGESTED READINGS
Baker CJ, Long SS, Pickering LK, eds. Red Book: 2012 Report of the Com-
mittee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American
Academy of Pediatrics; 2012.
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.

CASE 10 ANSWERS

1. B. Preterm infants should receive a lower vaccine dose


than term infants
Preterm infant should receive the same total vaccine dosage as
term infants. Clinicians should not divide the vaccine into
multiple doses.
While data do show that some preterm infants (born
<1,500 g and/or < 29 weeks gestation) have a decreased im-
mune response to some of the vaccines, most preterm infants
have an adequate immune response postvaccination to pre-
vent disease.
If a preterm infant remains in the hospital at the time of
vaccination, inactivated vaccines should be administered to
FIGURE 1. From MacDonald MG, Mullett MD, Seshia MM, eds. Averys
Neonatology: Pathophysiology & Management of the Newborn. 6th ed. medically stable infants (i.e., without current infection or
Philadelphia, PA: Lippincott Williams & Wilkins; 2005. Figure 48.3 acute illness).

(c) 2015 Wolters Kluwer. All Rights Reserved.


132Section VII Infectious Diseases

Preterm infants have a similar tolerance to vaccines as term


infants. However, very-low-birth-weight infants (i.e., weight
AMERICAN BOARD OF PEDIATRICS
<1,500 g) have a higher incidence of cardiorespiratory events
CONTENT SPECIFICATIONS
(apnea, bradycardia, and/or desaturation) after being vacci-
Know that preterm infants should be immunized at the
nated. These events are more likely if the infant has had apnea
same postnatal age as full-term infant
within 24 hours prior to being vaccinated, is of younger post-
Plan an immunization schedule for a patient born three
menstrual age, or has a current weight < 2,000 g.
months prematurely
2. A. Simultaneously at 36 weeks postmenstrual age
(i.e., at 2 months chronologic age)
Preterm infants and infants should receive routine childhood SUGGESTED READING
vaccinations at the same chronologic age as do term infants.
Baker CJ, Long SS, Pickering LK, eds. Red Book: 2012 Report of the Com-
Thus, the infant in this vignette should receive the 2-month
mittee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American
set of vaccinations at 36 weeks postmenstrual age (i.e., at 2 Academy of Pediatrics; 2012.
months chronologic age). Unless an infant is medically unsta-
ble or lacks vaccination sites, the 2-month set of vaccinations
should be administered simultaneously.

(c) 2015 Wolters Kluwer. All Rights Reserved.


S E C T I ON VIII Fluids,
Electrolytes,
and Nutrition

(c) 2015 Wolters Kluwer. All Rights Reserved.


134Section VIII Fluids, Electrolytes, and Nutrition

CASE 1
Fluid, caloric, and nutritional requirements

Two infants with respiratory distress are admitted to the Neo- 2. Match the findings below (AF) with the appropriate gesta-
natal Intensive Care Unit soon after birth. One infant is born tional age (iiv):
at 28 weeks gestation, and the other infant is born at term.
A. Decreased ability to digest i. Both full-term and
Both infants are started on maintenance intravenous fluids.
fats and absorb fat-soluble preterm infants
1. Select the most appropriate initial total fluid order for the vitamins
infant born at 28 weeks gestation and the infant born at B. Greater fluid requirement ii. Full-term infants
term, respectively: per kilogram of body
weight
A. 60 mL/kg/day for both
B. 60 mL/kg/day and 100 mL/kg/day C. Greater insensible water iii. Preterm infants
C. 100 mL/kg/day and 60 mL/kg/day loss (IWL)
D. 100 mL/kg/day for both D. Greater protein require- iv. Neither full-term
ment for adequate growth nor preterm infants
E. Lower caloric requirement
per kilogram for adequate
growth
F. Most regain birth weight by
2 weeks of life

CASE 2
Acidosis and alkalosis

A 1,300-g male infant is born at 30 5/7 weeks gestation af- Bicarbonate = 15 mEq/L
ter unstoppable preterm labor. His mother is a 28-year-old Arterial blood gas: pH = 7.2, Pco2 = 41 mm Hg,
woman with unremarkable prenatal screens aside from un- bicarbonate = 15 mEq/L
known Group B Streptococcus status. The infant is treated for Urinalysis: pH = 7.5, no glucose, no protein
respiratory distress syndrome with intubation and adminis-
The neonatology team stops his enteral feedings, starts anti-
tration of surfactant. He is extubated to continuous positive
biotic therapy, and provides more supplemental alkali. His
airway pressure (CPAP) on postnatal day 2 and begins enteral
bicarbonate normalizes, and the team restarts enteral feedings.
feedings. On postnatal day 5, he has pronounced, frequent ap-
nea and bradycardia episodes. The results of the sepsis evalu- 1. Using the laboratory results from above, calculate the an-
ation and abdominal radiograph are reassuring. His serum ion gap:
electrolytes, blood gas, and urinalysis are as follows:
A. 12 C. 18
Sodium = 137 mEq/L B. 14 D. 44
Potassium = 4.2 mEq/L
Chloride = 108 mEq/L

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 3 Electrolyte abnormalities135

2. For each of the causes of metabolic acidosis (AI), choose His course has consisted of treatment for surfactant deficiency,
the corresponding selection (i, ii): a 48-hour rule-out sepsis with antibiotics, and phototherapy
for indirect hyperbilirubinemia. His current settings on syn-
A. Acute renal failure i. Elevated anion gap
chronized intermittent mandatory ventilation are:
B. Congenital adrenal ii. Normal anion gap
hyperplasia Peak inspiratory pressure = 20 mm Hg
Peak end-expiratory pressure = 5 mm Hg
C. Congenital
Rate = 40 breaths per minute
hypothyroidism
D. Galactosemia He continues to breathe above the set rate of 40 breaths per
E. High-protein formula minutes. His blood gas is as follows:
pH = 7.5, Pco2 = 30 mm Hg, bicarbonate = 16 mEq/L
F. Inborn errors of
metabolism 3. Select the most likely acidbase disorder:
G. Lactic acidosis A. Acute metabolic acidosis
H. Organic acidemias B. Acute respiratory alkalosis
I. Toxins C. Chronic metabolic acidosis with compensation
D. Chronic respiratory alkalosis with compensation
The infant in the next bed space was born at 28 weeks gesta-
tion, is now postnatal day 5, and remains on the ventilator.

CASE 3
Electrolyte abnormalities

A 690-g female infant is born at 24 weeks gestation after un- 2. Select the EKGs below (see Figure 1AD) that would be con-
stoppable preterm labor. She is born to a 21-year-old woman sistent with cardiac changes in the setting of hyperkalemia:
with unremarkable prenatal screens aside from unknown
A. Figure 1A
Group B Streptococcus status. Starter parenteral fluid is initi-
B. Figure 1B
ated and consists of dextrose, sodium, and protein. The in-
C. Figure 1C
fants serum electrolytes at 36 hours are as follows:
D. Figure 1D
Sodium = 143 mEq/L
Potassium = 8.2 mEq/L
Chloride = 110 mEq/L A.
Bicarbonate = 18 mEq/L

1. Select the most likely etiology of her hyperkalemia:

A. Excess exogenous potassium B.


B. Necrotizing enterocolitis
C. Potassium shifts from the intracellular fluid (ICF) to the
extracellular fluid (ECF) space
D. Renal failure C.

Soon after these results are reported, the bedside nurse notices
a possible arrhythmia on the cardiorespiratory monitor.

D.

FIGURE 1.

(c) 2015 Wolters Kluwer. All Rights Reserved.


136Section VIII Fluids, Electrolytes, and Nutrition

3. Choose the next step(s) in medical management for this she is on full feedings and her nutrition laboratory values are
patient: notable for:

A. Defibrillation Phosphorus = 3 mg/L


B. Remove all exogenous potassium sources; give 10% Ionized calcium = 1.9 mg/L
calcium gluconate; give glucose and insulin; consider
Lasix, NaHCO3, and Kayexalate 4. Of the following, the most likely cause(s) of this infants
C. Synchronized cardioversion laboratory findings is:
D. Vagal maneuvers; administration of adenosine; con-
A. Congenital hyperparathyroidism
sider digoxin, propranolol, procainamide, flecanide, or
B. Prolonged hyperalimentation with inadequate balance
verapamil
of calcium and phosphorus
The infant is stabilized, and her serum potassium normalizes. C. Transition to breast milk with limited nutritional
A week later, she develops necrotizing enterocolitis and has a supplementation
prolonged course of hyperalimentation. At 1 month of age, D. All of the above

CASE 4
Mineral deficiencies

An 880-g male infant born at 28 weeks gestation is now 2. Match the clinical findings below (AD) with the most
6 months old and has hypochromic anemia unresponsive appropriate trace mineral deficiency (iiv). Each mineral
to iron therapy, neutropenia, and osteoporosis. In addition, deficiency may be used more than once or not at all:
he has decreased skin pigmentation, diarrhea, and failure to
A. Erosive skin changes, alopecia, i. Chromium
thrive (FTT).
diarrhea, FTT, and oral candidiasis
1. Select the most likely mineral deficiency that is consistent B. Often diagnosed as eczema or impetigo ii. Copper
with this infants clinical findings:
C. Often seen with late-onset iii. Magnesium
A. Chromium C. Magnesium hypocalcemia
B. Copper D. Zinc D. Wiry hair iv. Zinc

CASE 5
Vitamin deficiencies

A 760-g male infant born at 27 weeks gestation is now ap- 2. Select the signs or symptoms that would not typically be
proaching 2 months old. He is status-post necrotizing entero- present in an infant or child with MBD:
colitis at 4 weeks of age and has now reached full-volume
A. Frontal bossing, craniotabes, prominence of costochon-
enteral feedings with unfortified breast milk. He remains on
dral junction (rachitic rosary)
mechanical ventilation because of severe chronic lung disease.
B. Manifestation between 6 and 12 weeks of age
His laboratory values and radiographs reveal that he has meta-
C. Nonpainful fractures
bolic bone disease (MBD) consistent with rickets.
D. Poor weight gain and failure to wean off mechanical
1. Select the primary risk factor for the development of MBD ventilation because of excessive chest wall compliance
in this infant:

A. Chronic lung disease


B. Necrotizing enterocolitis
C. Prematurity
D. Prolonged NPO (nothing by mouth) status

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 6 Breast-feeding137

3. Choose the most appropriate management once a diagno- reviews the importance of supplementing breast-fed infants
sis of MBD of prematurity has been established: with Vitamin D. Next, he discusses that breast-fed infants have
lower vitamin K levels when compared with infants receiving
A. Ask the infants mother to double her intake of multivi-
cows milk.
tamins if she is breast-feeding
B. Give preterm or transitional formula and human milk 4. Choose the additional neonatal risk factor(s) that
fortification, consider supplementation with calcium predispose(s) the newborn to vitamin K deficiency:
and phosphorus, and avoid administration directly to
A. An immature newborn liver
milk to prevent precipitation
B. Initial lack of gastrointestinal (GI) microorganisms that
C. Offer breast milk at a higher volume
synthesize vitamin K
D. All of the above
C. Maternal medications (e.g. anticonvulsants, warfarin,
The medical student rotating in the Neonatal Intensive Care and antituberculosis medications)
Unit (NICU) this month presents a talk about breast milk. He D. All of the above

CASE 6
Breast-feeding

A primigravida 26-year-old woman is wondering if she should 2. For the clinical scenarios below (AD), select the most ap-
breast-feed or formula-feed her newborn. The pediatrician propriate choice (iiii). You may use each selection more
rounding in the nursery explains the differences between than once or not at all:
breast milk and infant formula. He also describes the benefits
A. Mother continues to take i. Breast milk is
of breast milk and the limited contraindications.
lithium. contraindicated.
1. Match each description below (AJ) with the most appro- B. Mother had an oral herpes ii. Breast milk is
priate type of milk (iiv): simplex virus (HSV) infec- recommended.
A. Contains bile salt-dependent lipase i. Breast milk tion 2 weeks prior to deliv- iii. There is no American
ery, was treated with Valtrex, Academy of Pediat-
B. Contains consistent caloric density ii. Formula
and the lesion has healed. rics (AAP) guideline
C. Contains secretory IgA iii. Both She took Lithium for 5 for this clinical
D. Increases lactobacilli growth iv. Neither years as a teenager and she scenario.
E. Has consistent protein content has no symptoms of active
F. Has fewer long-chain unsaturated tuberculosis with a negative
fatty acids chest radiograph.

G. Lactose is the source of C. Mother has several open


carbohydrate HSV lesions on her breasts.

H. Provides protective and bacteri- D. Mother stopped taking


cidal enzymes lithium prior to this preg-
nancy. She has no current
I. Recommended as primary source
HSV lesions (oral, breast, or
of enteral feeding until 6 months,
genital). She had a positive
followed by introduction of cows
PPD 3 years ago and is cur-
milk
rently asymptomatic with a
J. Yields lower incidence of gastro- negative chest radiograph.
intestinal (GI) and respiratory
infections Ultimately, breast milk is recommended for the mother in this
case. The pediatrician asks the medical student to review pro-
Further discussion with the mother and detailed chart review tein, electrolyte, and iron concentrations in colostrum, mature
reveal that the mother has taken lithium for a bipolar disorder. breast milk, and cows milk.
In addition, under medical history, cold sores and a positive
postpartum depression (PPD) are listed.

(c) 2015 Wolters Kluwer. All Rights Reserved.


138Section VIII Fluids, Electrolytes, and Nutrition

3. Refer to the table below and fill in the correct heading i. Cows milk
(iiv) for the columns listed A, B, and C: ii. Human colostrum
iii. Mature breast milk
A B C iv. None of the above
Protein (g/L) 22.9 10.6 32.5
Whey:casein 80:20 55:45 20:80
Lactalbumin (g/L) 3.6 2.4
Na (mg/dL) 48 15 58
K (mg/dL) 74 55 138
Cl (mg/dL) 85 43 103
Ca (mg/dL) 39 35 130
Fe (g/dL) 70 100 70

Modified from: Behrman RE, Kliegman RM, Arvin AM, eds. Nelson
Textbook of Pediatrics. 15th ed. Philadelphia, PA: WB Saunders;
1996:158 and Lawrence RA, Lawrence RM. Breastfeeding: A
Guide for the Medical Profession. 5th ed. St. Louis, MO: Mosby;
1999:128129

CASE 7
Formula-feeding

A full-term male infant was born to a 19-year-old woman ounce was based on carbohydrate source, protein source, iron
with a family history of asthma, allergies, and colic. The in- fortification, mineral content, and caloric density.
fants mother decided that she did not want to breast-feed and
sought out advice from family and friends to help guide her 2. Identify the carbohydrate source (iiii), protein source (iv
on what to feed her newborn infant. Her neighbor told her to vii), fat source (viiiix), and iron fortification (xxii) for
give fresh goats milk from the familys farm; her aunt said to Neocate:
use cows milk; her sister told her to use soy formula, while her A. Carbohydrate source _____ i. Lactose
uncle, who is a phlebotomist in the local community hospital, ii. Sucrose and g lucose
said to use protein hydrolysate infant formula. polymers
At 3 months of age, the infant was brought to the Emer- iii. Glucose polymers
gency Department with failure to thrive (FTT), pallor, and
B. Protein source_____ iv. Cows milk protein
lethargy. His laboratory values revealed megaloblastic anemia,
v. Soy protein
severe hypernatremia, and azotemia.
vi. Hydrolysate
1. Which feeding regimen would be most likely to lead to the vii. Free amino acids
above laboratory findings? C. Fat source_____ viii. Long-chain
triglycerides
A. Cows milk
ix. Medium-chain
B. Fresh goats milk
and long-chain
C. Protein hydrolysate infant formula
triglycerides
D. Soy formula
D. Iron fortification_____ x. Low dose
After being hospitalized for a week with normalization of his xi. High dose
physical examination and laboratory values, the infant was xii. Formula without
discharged to home on Neocate 24 calories per ounce. The any iron
neonatologists decision to choose Neocate 24 calories per

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 7 Formula-feeding139

At age 3 months, the infant reaches the 15th percentile for 3. Select true or false (iii) for the following statements
weight on the growth chart, after having been at less than the related to MPA in infants:
3rd percentile. He tolerates this new formula well.
i. True
His cousin, now 3 weeks old, is having frequent episodes
ii. False
of regurgitation, followed by crying, after his feedings of Enfa-
mil. By 4 weeks of life, the regurgitation and crying after feed- A. An infant with MPA may appear healthy but have a history
ings continues and his stools have become more frequent and of fussiness, regurgitation, increased frequency of stools,
watery. His weight is 4,150 g, and he is gaining only 10 g per and presence of blood-tinged and/or mucous stools.
day over the past week. He has also developed a rash on his B. Some infants demonstrate extreme irritability as the
cheeks and buttocks. His pediatrician suspects milk protein al- only symptom of MPA.
lergy (MPA). C. The prevalence of MPA in infants is low.
D. Skin prick testing and in vitro immunoassays (com-
monly called RAST tests) are recommended.
E. It is not recommended that an infant with cows MPA be
changed to soy formula as the initial next step, as a signif-
icant percentage of infants are sensitive to both proteins.
F. Up to 50% of infants with cows MPA or soy-induced proc-
titis are intolerant to hydrolysated cows milk formula.
G. Lactose intolerance is the same as MPA, as both involve
the immune system.
H. Almost all infants will be able to tolerate cows milk and
soy products by 1 year of age.

(c) 2015 Wolters Kluwer. All Rights Reserved.


140Section VIII Fluids, Electrolytes, and Nutrition

SECTION VIII
Answers

70
CASE 1 ANSWERS
60
1. C. 100 mL/kg/day and 60 mL/kg/day
Knowledge of a neonates insensible water losses (IWLs) is re-
50
quired to provide the appropriate maintenance fluid. IWL in-

IWL (mL/kg/day)
creases as gestational age decreases because immature infants 40
have a high surface area to body mass ratio and water-permeable
skin. Table 1 summarizes the mechanisms of IWL in neonates. 30
Table 1. Mechanisms of IWL
20
Neonatal evaporative 1/3 via respiratory tract,
water loss 2/3 via skin 10

Factors leading to Increased environmental and


0
increased IWL body temperature
<1000 10011250 12511500 15011750 17512000
Decreasing gestational age
Birth weight (g)
Skin breakdown
FIGURE 1. Data from Wu PY, Hodgman JE. Insensible water loss in
Congenital skin defects preterm infants: Changes with postnatal development and non-
Radiant warmer ionizing radiant energy. Pediatrics. 1974;54:704712, as redrawn in
Phototherapy Shaffer SG, Weismann DN. Fluid requirements in the preterm infant.
Clin Perinatol. 1992;19: 233250, with permission
Factors leading to Humidity
decreased IWL Plastic heat shield
Premature infants also have greater caloric requirements per
kilogram to attain adequate growth. A term infants protein re-
Adapted from: Brodsky D, Martin C. Neonatology Review. 2nd ed.
quirement ranges between 1.8 g/kg/day to 2.2 g/kg/day, while
Raleigh, NC: Lulu; 2010:269
the very-low-birth-weight (VLBW) infant requires 3 g/kg/day
Although there is some variation in fluid requirements be- to 3.5 g/kg/day. Full-term infants generally regain their birth
cause of an infants individual clinical status, in general, the weight by 2 weeks of life. Preterm infants who are fed enterally
estimated total fluid requirement at birth for an infant born (i.e., without intravenous fluids or parenteral nutrition) usu-
at 28 weeks gestation ranges from 80 mL/kg/d for infants in ally require longer than 2 weeks to regain their birth weight.
incubators to 100 mL/kg/day for infants placed on radiant
warmers. In contrast, the estimated total fluid requirement for
AMERICAN BOARD OF PEDIATRICS
an infant born at term is about 60 mL/kg/day.
CONTENT SPECIFICATIONS
2. A iii. Preterm infants
Recognize that preterm infants have a greater daily fluid
B iii. Preterm infants
requirement per kilogram of body weight than full-term
C iii. Preterm infants
infants
D iii. Preterm infants Recognize that insensible water loss is increased with
E ii. Full-term infants prematurity
F ii. Full-term infants Recognize the difference in preterm and full-term in-
fants ability to digest fat and absorb fat soluble vitamins
Premature infants have a decreased ability to digest fats and Know the protein requirements for premature and full-
absorb fat-soluble vitamins. Premature infants have reduced term infants
bile salt content and decreased secretion of pancreatic lipase, Know the caloric requirements for infant
which leads to fat malabsorption. In addition, body fat is in- Recognize that the caloric requirement per kilogram for
creased in late gestation; thus, preterm infants are born with adequate growth is greater for preterm infants than for
fewer fat-soluble vitamins and minimal caloric reserves. full-term infants
Premature infants have a greater fluid requirement per kilo- Know that most full-term infants will regain their birth
gram of body weight than full-term infants because of greater weight within two weeks
IWL. Figure 1 shows the relationship of IWL and birth weight.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 2 Acidosis and alkalosis141

SUGGESTED READINGS Metabolic Acidosis


with Normal Anion Metabolic Acidosis with
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
Gap Elevated Anion Gap
2010.
Poindexter B, Denne S. Protein needs of the preterm infant. NeoRev-
Gastrointestinal Acute renal failure
iews. 2003;4:e52e59.
diarrhea; ileal drainage, Inborn errors of metabolism
cholestyramine Organic acidemiase.g.,
administration, small- methylmalonic acidemia
bowel drainage
CASE 2 ANSWERS Lactic acidosise.g., pyruvate
Decreased dehydrogenase or carboxylase
aldosteronecongenital deficiency
1. B. 14
adrenal hyperplasia
This presentation is consistent with a normal anion gap hy- Mitochondrial respiratory chain
Hyperalimentation and abnormalities
perchloremic acidosis caused by renal tubular acidosis (RTA). administration of excess
RTA is generally caused by decreased renal reabsorption of acid and amino acids Glycogen storage disease type 1
bicarbonate ion or impaired urinary acidification. High-protein formula Galactosemia
Metabolic acidosis is defined as a loss of bicarbonate or a Congenital Hereditary fructose intolerance
gain of hydrogen ions resulting in an arterial pH less than 7.4. hypothyroidism Toxins
It is a concern in preterm infants because of the effect on tissue
metabolism and is a potential initial marker for underlying Adapted from: Brodsky D, Martin C. Neonatology Review. 2nd ed.
pathology. Raleigh, NC: Lulu; 2010:277

The formula for calculating a metabolic acidosis anion gap is: 3. D. Chronic respiratory alkalosis with compensation
Anion gap = [Na+] ([Cl] + [HCO3]) There are many causes of respiratory alkalosis, including:

Hypoxia
2. A i
Parenchymal lung disease
B ii
Medications (salicylate, xanthine, catecholamine)
C ii Mechanical ventilation
D i Central nervous system disorders
E ii Metabolic disorders
Hyperventilation syndrome
F i

G i The infant in this vignette is being overventilated with a set rate


of 40 breaths per minute (in addition to his own breaths), and
H i
his CO2 is being blown off. If the respiratory alkalosis persists
I i
for more than 2 to 6 hours, renal compensatory changes occur,
Metabolic acidosis may coincide with a normal anion gap such as decreased hydrogen secretion and increased bicarbon-
acidosis or an elevated anion gap acidosis. Normal anion ate excretion. Renal compensation results in a 4-mEq/L reduc-
gap acidosis is caused by loss of bicarbonate via the gastro- tion in plasma [HCO3] for every 10 mm Hg reduction in Pco2.
intestinal tract or the urinary system or by failure to excrete
hydrogen ions. An elevated anion gap acidosis is usually
AMERICAN BOARD OF PEDIATRICS
caused by increased organic acid production, inborn errors
CONTENT SPECIFICATIONS
of metabolism, or decreased excretion of acid in the setting
of renal failure. Know how to calculate the anion gap
Table 1 lists the causes of metabolic acidosis (normal anion Formulate a differential diagnosis of acidosis with a nor-
gap and elevated anion gap): mal anion gap
Know the renal compensatory changes seen in primary
Table 1. Causes of Metabolic Acidosis
respiratory alkalosis
Metabolic Acidosis
with Normal Anion Metabolic Acidosis with SUGGESTED READINGS
Gap Elevated Anion Gap
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
RenalRTA; Lactic acidosis (hypoxemia,
2010.
acetazolamide shock, sepsis) Ringer S. Renal tubular acidosis. NeoReviews. 2010;11(5);e252e256.
administration, renal Schwaderer A, Schwartz G. Back to basics: Acidosis and alkalosis. Ped
dysplasia, obstructive Rev. 2004;25:350357.
uropathy, early uremia

(c) 2015 Wolters Kluwer. All Rights Reserved.


142Section VIII Fluids, Electrolytes, and Nutrition

3. B. Remove all exogenous potassium sources; give 10%


CASE 3 ANSWERS
calcium gluconate; give glucose and insulin; consider
1. C. Potassium shifts from the intracellular fluid (ICF) Lasix, NaHCO3, and Kayexalate
to the extracellular fluid (ECF) space Initial treatment of symptomatic hyperkalemia includes the
Up to 25% to 50% of very-low-birth-weight (VLBW) infants following:
develop hyperkalemia in the first 24 to 72 hours of life, even
Remove all exogenous potassium sources
without receiving any exogenous potassium intake or renal
Give 10% calcium gluconate
failure. The hyperkalemia results from a potassium shift from
Give glucose and insulin
the ICF to the ECF space, and the magnitude of the shift seems
Consider Lasix, NaHCO3, and Kayexalate
to correlate with the degree of prematurity. The underlying
physiologic explanation is unknown. Generally, adding po- Options C and D may be warranted in an infant with supra-
tassium to intravenous fluids or parenteral fluids for VLBW ventricular tachycardia (SVT). A newborn with SVT warrants
infant is not recommended until adequate urine output is treatment if the SVT is sustained or if there are any signs or
established and potassium values are checked and are within symptoms of cardiovascular compromise. If the infant is un-
normal limits. stable, clinicians can perform synchronized cardioversion at a
dose of 0.5 to 2 J/kg. If the infant is stable, clinicians can per-
2. D. Figure 1D
form vagal maneuvers (crushed ice to face, rectal stimulation)
Table 1 describes the EKG findings that correlate with the
and administer adenosine intravenously if the arrhythmia per-
corresponding electrolyte abnormalities.
sists. Additional therapeutic agents are sometimes warranted if
Table 1. EKG Findings and Correlations to Electrolyte Abnormalities first-line medication fails.

Electrolyte 4. D. All of the above


Abnormality EKG EKG Findings The etiology of hypophosphatemia and hypercalcemia in a
1-month old preterm infant could be consistent with con-
Normal PR = 0.080.11 sec genital hyperparathyroidism, prolonged hyperalimentation
QRS = 0.040.07 sec
with inadequate calcium and phosphorus, or transition to
Hypercalcemia Shortened QT interval breast milk with limited nutritional supplementation. Further
workup is warranted.
Hypophosphatemia is a common finding in preterm in-
Hypocalcemia Prolonged QT interval fants with osteopenia of prematurity (or rickets) and results
from insufficient intake of calcium and phosphorus. Enteral
intake selection in preterm infants is crucial as breast milk
Hyperkalemia Tall peaked T Wave is low in phosphorus and full-term formula also has lower
>6.0 mEq/L Shortened QT interval phosphorus content than preterm formula. Therefore, careful
Depressed ST segment calculation of phosphorus and calcium content and ratio is
>7.5 mEq/L Prolonged PR interval needed to provide sufficient supplementation to the preterm
Widened QRS complex infant. Calcium to phosphorus ratios should be in the 1.2:1
Flattened P wave to 1.7:1 range; ratios <1:1 are not recommended. Congenital
>9.0 mEq/L Absent P wave hyperparathyroidism is a rare cause of hypophosphatemia.
Sinusoidal QRS wave In contrast, hyperphosphatemia can be caused by:
Asystole and ventricular
fibrillation can occur Ingestion of formula with high phosphorus concentration
Hypokalemia Slightly widened QRS Excessive phosphorus concentration in parenteral nutrition
U
<2.5 mEq/L T
complex Impaired phosphorus excretion as a result of renal failure
Depressed ST segment
Metastatic calcifications and hypocalcemia can develop if hy-
Biphasic T wave
attributable to visible perphosphatemia is severe and untreated.
U wave
1.0 mEq/L Prominent U wave
Flat T wave
If sustained, may
develop prolonged PR
interval and sinoatrial
block

Printed with permission from: Brodsky D, Martin C. Neonatology


Review. 2nd ed. Raleigh, NC: Lulu; 2010:143

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 4 Mineral deficiencies143

Figure 1AC reveals features of Menkes disease, includ-


American Board of Pediatrics ing frayed and split internal elastic lamina (A), cherubic
Content Specifications facies(B), and abnormal hair shaft (C).
Hyperkalemia
Recognize that severe cardiac rhythm changes may begin
abruptly in patients with hyperkalemia
Know the signs of hyperkalemia
Know the emergency treatment of hyperkalemia
Plan the treatment for a patient with hyperkalemia
Phosphorus
Know the problems associated with inadequate and ex-
cessive amounts of phosphorus in the diet of a prema-
ture infant
A

SUGGESTED READINGS
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
2010.
Kenner C. Comprehensive Neonatal Care: An Interdisciplinary Approach.
ST. Louis, MO: Saunders (Elsevier); 2007.

CASE 4 ANSWERS

1. B. Copper
The neonate in the scenario has copper deficiency, which can
manifest with findings of: B C
FIGURE 1. Menkes JH, Sarnat HB, Maria, BL. Child Neurology. 7th ed.
FTT Philadelphia, PA: Lippincott Williams & Wilkins; 2005. Figure 1.32
Pallor/decreased pigmentation
Hypothermia 2. A iv
Apneic events
B iv
Hypotonia
Poor feeding C iii
Skeletal changes D ii
Abnormal elastic connective tissue
Anemia Chromium deficiency in an infant is most often caused by long-
Hypoceruloplasminemia term parenteral nutrition and may manifest with impaired
Hepatosplenomegaly glucose tolerance, weight loss, peripheral neuropathy, and
Diarrhea confusion.
Copper deficiency is described in Answer 1.
Most fetal accretion of copper occurs during the third trimes-
Magnesium deficiency in a neonate is often a manifestation
ter. Thus, preterm infants are born deficient. The exact neona-
of late-onset hypocalcemia and can cause hypokalemia, vom-
tal requirements are unknown, but reasonable guidelines have
iting, arrhythmia, tremor, muscle spasm, and tetany.
been made on the basis of current evidence.
Similar to copper, Zinc is mostly accumulated in the fetus
Almost all cases of copper deficiency in neonates result
during the third trimester when liver stores are established.
from a nutritional deficiency or genetic disorder of copper
Typical manifestations of zinc deficiency are:
metabolism. The X-linked recessive lethal multisystem disor-
der is called Menkes disease, which consists of neurodegen- Dermatitis
eration, connective tissue disturbances, and peculiar kinky Alopecia
hair. The levels of copper and ceruloplasmin are low, and FTT
the confirmatory test is presence of mutation analysis of the Oral candidiasis
ATP7A gene. Irritability

(c) 2015 Wolters Kluwer. All Rights Reserved.


144Section VIII Fluids, Electrolytes, and Nutrition

Manifestations later in life may include delayed sexual matu- Thickening of the skull
ration, reduced taste sensitivity, poor night vision, immune Delayed anterior fontanelle closure
compromise, and impaired wound healing. Long-bone abnormalities with cupping or flaring of the
metaphyses because of uncalcified osteoid formation

AMERICAN BOARD OF PEDIATRICS Infants with severe hypocalcemia may present with seizures.
CONTENT SPECIFICATION Children older than 2 years of age may succumb to greenstick
fractures, kyphoscoliosis, and short stature. They may also be
Know the diseases that are associated with trace mineral at increased risk for autoimmune disease as vitamin D is a
deficiency (zinc, copper, magnesium, chromium) modulator for B- and T-lymphocyte function.
Figure 1 demonstrates some radiographic features of MBD,
including profound demineralization, frayed, irregular cup-
ping of the end of the metaphysis, and poorly defined cortex.
SUGGESTED READINGS
The chest radiograph (Figure 2) shows an 11-month with rick-
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; ets, evident by demineralization and cupping of the distal end
2010. of ribs and humerus.
Cloherty J, Eichenwald EC, Hansen A, et al., eds. Manual of Neonatal
Care. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.
Giles E, Doyle L. Copper in the extremely low-birthweight or very pre-
term infants. NeoReviews. 2007;4: e159e164.
Giles E, Doyle L. Zinc in the extremely low-birthweight or very preterm
infants. NeoReviews. 2007;4: e165e171.

CASE 5 ANSWERS

1. C. Prematurity
Prematurity is the single most important risk factor for the
development of MBD. There is an inverse relationship to ges-
tational age and birth weight and the frequency of MBD. Ad-
ditional risk factors for MBD are:

Enteral feeding practices (delayed initiation of enteral


feedings, prolonged parenteral nutrition, use of breast
milk without fortification)
Lack of movement (e.g. sedation/paralysis, neuromuscu-
lar disorders)
Malabsorption of vitamin D or vitamin D deficiency FIGURE 1. From Fleisher GR, Ludwig S, Baskin MN. Atlas of Pediatric
Emergency Medicine. Philadelphia, PA: Lippincott Williams & Wilkins;
Medications (steroids, caffeine, Lasix)
2004. Figure 7.14

2. C. Nonpainful fractures
MBD typically manifests between 6 and 12 weeks of age. Rap-
idly growing premature infants with low intake of either cal-
cium or phosphorus are at high risk. The primary nutritional
reason for MBD in preterm infants is a deficiency of vitaminD.
Vitamin D is a prohormone essential for normal absorption
of calcium from the intestines. When vitamin D deficiency
occurs, growing children may develop MBD or rickets while
adults may develop osteomalacia.
Infants may demonstrate poor weight gain, failure to thrive,
and can have respiratory difficulties with potential for difficulty
weaning off mechanical ventilation as a result of excessive chest
wall compliance. Physical findings may include the following:

Generalized hypotonia
Pain in spine, pelvis, and legs FIGURE 2. From Fleisher GR, Ludwig S, Baskin MN. Atlas of Pediatric
Painful fractures Emergency Medicine. Philadelphia, PA: Lippincott Williams & Wilkins;
Bowing of the legs 2004. Figure 7.15

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 6 Breast-feeding145

3. B. Give preterm or transitional formula and human


CASE 6 ANSWERS
milk fortification, consider supplementation with calcium
and phosphorus, and avoid administration directly to milk 1. A. Contains bile salt-dependent i. Breast milk
to prevent precipitation lipase
Option B is the most appropriate management, as administra-
B. Contains consistent caloric ii. Formula
tion of unfortified breast milk provides very little vitaminD
density
and not enough for catch-up of bone mineralization. In fact,
C. Contains secretory IgA i. Breast milk
feeding preterm infants unfortified breast milk or term for-
mula can lead to MBD in up to 50% of very-low-birth-weight D. Increases lactobacilli growth i. Breast milk
infants. Vitamin D intake in pregnant women is important to E. Has consistent protein content ii. Formula
prevent fetal vitamin D deficiency, but doubling a womans F. Has fewer long-chain unsatu- ii. Formula
multivitamin intake would not be the appropriate manage- rated fatty acids
ment for a breast-feeding infant with MBD. The AAP recom-
G. Lactose is the source of iii. Both
mends daily supplementation of 400 international units (IU)
carbohydrate
of vitamin D for all breast-fed infants and for nonbreast-
fed infants and children who do not ingest at least 1 L of H. Provides protective and bacte- i. Breast milk
vitaminD-fortified milk daily. ricidal enzymes
I. Recommended as primary iv. Neither
4. D. All of the above source of enteral feeding until
Receiving an intramuscular dose of vitamin K at birth is 6 months, followed by intro-
strongly recommended for every newborn to prevent hemor- duction of cows milk
rhagic disease of the newborn (HDN). Vitamin K is an essen-
J. Yields lower incidence of gas- i. Breast milk
tial cofactor for factors II, VII, IX, and X and for proteins C and
trointestinal (GI) and respira-
S. Deficiency of vitamin K leads to a bleeding diathesis with
tory infections
classic HDN findings presenting at 2 to 7 days of life with GI
bleeding, umbilical cord bleeding, intracranial hemorrhage,
and/or prolonged bleeding after circumcision. The composition of breast milk provides many benefits to the
newborn. Breast milk contains immunologic and antibacterial
factors such as secretory IgA that can:
AMERICAN BOARD OF PEDIATRICS
CONTENT SPECIFICATIONS Bind to viruses and bacteria to prevent invasion of mucosa
Provide protective and bactericidal enzymes
Recognize the presenting signs and symptoms of rickets Increase lactobacilli growth
and manage appropriately
Recognize the effects of vitamin D deficiency in children Colostrum has increased amounts of lymphocytes, macro-
of various ages, including breast-fed infants and older phages, and immunoglobulins. Breast milk contains bile salt-
children dependent lipase that can aid with digestion. As breast milk
Know that rickets may develop in rapidly growing prema- matures, protein levels decrease in conjunction with advanc-
ture infants with low intake of either calcium or phosphorus ing gestational age of the infant. Whey-to-casein ratio in colos-
Recognize the clinical manifestations of vitamin K trum is 80:20, while that in mature breast milk is 55:45. The
deficiency whey-to-casein ratio of cows milk is consistently 20:80.
The predominant carbohydrate in breast milk is lactose and
is greater in foremilk versus hind milk. Many but not all for-
SUGGESTED READINGS mulae have lactose as the carbohydrate source.
The AAP supports breast-feeding until an infant is at least
Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu; 12months. If an infant is weaned off breast milk prior to age 12
2010. months, iron-fortified formula is recommended. Cows milk
Cloherty J, Eichenwald EC, Hansen A, et al., eds. Manual of Neona-
tal Care. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; may be introduced after 1 year of life. The AAP also recom-
2011. mends daily supplementation of 400 international units (IU)
Misra M, Pacaud D, Petryk A, et al.; Drug and Therapeutics Commit- of vitamin D for all breast-fed infants and for nonbreast-fed
tee of the Lawson Wilkins Pediatric Endocrine Society. Vitamin
D deficiency in children and its management: Review of current infants and children who do not ingest at least 1 L of vitamin
knowledge and recommendations. Pediatrics. 2008;122:398417. D-fortified milk daily.
Vachharajani A, Mathur A, Rao R. Metabolic bone disease of prematu-
rity. NeoReviews. 2009;10:e402e411.

(c) 2015 Wolters Kluwer. All Rights Reserved.


146Section VIII Fluids, Electrolytes, and Nutrition

2. A i
AMERICAN BOARD OF PEDIATRICS
B ii CONTENT SPECIFICATIONS
C i
D ii Breast milk
Content
Understand the qualitative and quantitative differences
Table 1 summarizes breast-feeding contraindications in the
between human milk and infant formulas
United States.
Recognize that human and cow milk proteins differ in
Table 1. Contraindications to Breast-Feeding in the United States quality and quantity
Know that breast milk is deficient in vitamin D
Infection Maternal human immunodeficiency
virus Benefits
Mother with herpes simplex lesions Know that human milk contains antibodies against cer-
on breast tain bacteria and viruses, including high concentrations
Symptomatic mother with positive PPD of secretory IgA antibodies
and chest radiograph Know that ingested antibodies from human colostrum
Active breast abscess and milk provide local gastrointestinal immunity against
Relative infection contraindications organisms entering the body via this route
Premature very-low-birth-weight infant Understand that human milk provides protection
and cytomegalovirus-seropositive against many gastrointestinal and respiratory infections
mother, maternal oral HSV lesion Know that there is a lower incidence of gastrointestinal
Galactosemia Caused by lactose being the infections in infants fed with human milk
predominant carbohydrate in breast milk
Contraindications
Drugs Cocaine Know the drugs that are contraindicated in breast-feeding
Cyclosporine Know that maternal ingestion of drugs with sedative
Lithium properties has the potential to cause sedation in breast-
Methotrexate feeding infants
Phencyclidine Know the disorders of the breast that may interfere with
Radioactive agents breast-feeding
Judge for which maternal breast infections breast-feeding
Adapted from: Brodsky D, Martin C. Neonatology Review. 2nd ed. should be interrupted
Raleigh, NC: Lulu; 2010:306
Know for which maternal chronic viral infections breast-
3. A ii feeding is not recommended

B iii
C i

SUGGESTED READINGS
Human Mature Cows
Component Colostrum Breast Milk Milk Brodsky D, Martin C. Neonatology Review. 2nd ed. Lulu. 2010.
Cloherty J, Eichenwald EC, Hansen A, et al., eds. Manual of Neona-
Protein (g/L) 22.9 10.6 32.5 tal Care. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins;
2011.
Whey:casein 80:20 55:45 20:80
Lactalbumin 3.6 2.4
(g/L)
CASE 7 ANSWERS
Na (mg/dL) 48 15 58
K (mg/dL) 74 55 138 1. B. Fresh goats milk
False and potentially dangerous information can lead parents
Cl (mg/dL) 85 43 103
to select an inappropriate feeding regimen for their newborn.
Ca (mg/dL) 39 35 130 It is important for pediatricians and neonatologists to dispel
Fe (g/dL) 70 100 70 any myths about unsafe feeding practices. Fresh goats milk is
not an appropriate selection for enteral feedings in a newborn.
Obtained from: Brodsky D, Martin C. Neonatology Review. Goats milk contains 50 mg sodium and 3.56 g of protein per
2nd ed. Raleigh, NC: Lulu; 2010. Modified from: Behrman RE, 100 ml, which is almost three times that in breast milk. A new-
Kliegman RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 15th born requires 100 mg/day to 200 mg/day of sodium and 9 g/day
ed. Philadelphia, PA: WB Saunders; 1996:158 and Lawrence RA,
Lawrence RM. Breastfeeding: A Guide for the Medical Profession.
to 11 g/day of protein. The laboratory values for the infant in
5th ed. St. Louis, MO: Mosby; 1999:128129

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 7 Formula-feeding147

this case reveal megaloblastic anemia (see Figure 1) as a result


of folate deficiency (6 mcg folate/L in fresh goats milk vs. 50 Type of
Carbohydrate Formula Name
mcg/L in human breast milk). Figure 1 demonstrates hyper-
segmented neutrophils and well-hemoglobinized macrocytes, Glucose polymers Enfamil Lactofree
consistent with megaloblastic anemia. Neocate
Neosure (also contains lactose)
Nutramigen
Pregestimil
ProSobee
Similac Lactose Free

Obtained from: Brodsky D, Martin C. Neonatology Review. 2nd ed.


Raleigh, NC: Lulu; 2010:306. Modified from: Gunn VL, Nechyba
C, eds. The Harriet Lane Handbook: A Manual for Pediatric House
Officers. 16th ed. Philadelphia, PA: Mosby; 2002:467

Table 2. Proteins

Type of Protein Formula Name


Cows milk protein Enfamil (standard, AR, Enfacare,
Lipil, Premature)
Portagen
FIGURE 1. From McClatchey KD. Clinical Laboratory Medicine. 2nd ed. Similac (standard, Lactose Free,
Philadelphia, PA: Lippincott Williams & Wilkins; 2002. Figure 41.10 60/40, Neosure, and Special
Care)
Soy protein Isomil
Soy protein-based formulas are recommended in the fol- ProSobee
lowing limited clinical scenarios:
Hydrolysate Alimentum
Galactosemia Nutramigen
Hereditary lactase deficiency Pregestimil
Desire for strict vegetarian-based diet Free amino acids Neocate
The AAP recommends that all infants fed with breast milk or
Obtained from: Brodsky D, Martin, C. Neonatology Review. 2nd
iron-fortified formula should receive iron supplementation
ed. Raleigh, NC: Lulu; 2010:307. Modified from: Gunn VL, Nechyba
for the first year of life. C, eds. The Harriet Lane Handbook: A Manual for Pediatric House
Officers. 16th ed. Philadelphia, PA: Mosby; 2002:470471
2. A. Carbohydrate source iii. Glucose polymers
Table 3. Fats
B. Protein source vii. Free amino acids
C. Fat source viii. Long-chain triglycerides Type of Fat Formula Name
D. Iron fortification xi. High dose
Long-chain triglycerides Enfamil (standard, AR, Lipil,
Lactofree)
Tables 1 to 3 summarize the type of carbohydrate, fat, and Isomil
protein that are contained in different formulas. Neocate
Nutramigen
Table 1. Carbohydrates
ProSobee
Type of Similac (standard, 60/40, and
Carbohydrate Formula Name Lactose Free)
Medium and long-chain Enfamil (Enfacare and
Lactose Enfamil (standard, AR, Lipil, triglycerides Premature)
Enfacare, and Premature) Neosure
Neosure (also contains glucose Portagen
polymers) Pregestimil
Similac (standard, 60/40, and Similac (Special Care)
Special Care)

Sucrose and Alimentum Obtained from: Brodsky D, Martin C. Neonatology Review. 2nd ed.
glucose polymers Isomil Raleigh, NC: Lulu; 2010:307. Modified from: Gunn VL, Nechyba
C, eds. The Harriet Lane Handbook: A Manual for Pediatric House
Portagen, Monogen
Officers. 16th ed. Philadelphia, PA: Mosby; 2002:472

(c) 2015 Wolters Kluwer. All Rights Reserved.


148Section VIII Fluids, Electrolytes, and Nutrition

The quality of fat content in preterm and full-term infant MPA, an amino acid-based formula may be trialed. In the set-
formula is important to recognize. Formulas are designed to ting of cows MPA, soy protein-based formulas are generally
attempt to mimic the fat content in gestationally appropriate not recommended as there is a 10% or greater allergen cross-
breast milk. There are greater amounts of long-chain unsatu- reactivity. However, almost all infants will be able to tolerate
rated fatty acids in breast milk compared with cows milk. In cows milk and soy products by1 year of age.
addition, there are increased amounts of arachidonic acid and Lactose intolerance is a separate entity from MPA, as the
docosahexaenoic acid in breast milk; infant formulas now also later involves the immune system and causes intestinal mu-
contain arachidonic acids. The minimum fat content of infant cosal injury. Lactose is a disaccharide comprised of glucose
formulas is 3.4g/100 kcal. Most infant formulas contain at and galactose. Lactose requires lactase to be absorbed in the
least 10% of their total fatty acids as linoleic acid. small intestine. Lactose intolerance most often presents with
The American Academy of Pediatrics recommends iron sup- abdominal pain, diarrhea, gas, and bloating. Milk intolerance
plementation in breast-fed infants and the use of iron-fortified may be attributed to lactose or protein components.
infant formula when a mother chooses not to breast-feed. The
rate of iron-deficiency anemia in infancy has decreased to a
great extent as a result of iron fortification. Low-iron formulas AMERICAN BOARD OF PEDIATRICS
should not be used, since they do not provide enough iron to CONTENT SPECIFICATIONS
provide optimal support to the growing infant.
Formula feeding
3. A i True Content
B i True Recognize that infants fed with goat milk exclusively are
C i True prone to megaloblastic anemia due to folate deficiency
D ii False Know which infant formulas contain lactose
Know the indications for the use of protein hydrolysate
E ii False
formulas
F ii False Know the indications for the use of soy formula
G ii False Recognize the importance of the quality of fat content in
H i True preterm and full-term infants formulas
Understand the rationales for the use of iron-fortified
MPA is a problem in infancy that may affect up to 15% of new- formulas and recognize the misuse of low-iron formulas
borns. MPA manifests as an immunologic reaction to dietary Allergy
proteins via IgE-mediated and nonIgE-mediated pathways. Recognize the signs and symptoms of milk protein
The IgE-mediated pathway is also known as a type I hypersen- allergy
sitivity reaction occurring when an antigen binds to mast cells. Understand the difference between milk protein allergy
NonIgE-mediated MPA is likely multifactorial and involves and lactose intolerance
immune complexes (IgA or IgG antibodies) and T cells. The Recognize soy as a potential allergen in gastrointestinal
distinction is important because IgE-mediated MPA is associ- protein allergy
ated with multiple food allergies and atopic conditions. Skin
prick testing and in vitro immunoassays are not recommended
in infants as this testing will fail to diagnose the infants with
nonIgE-mediated immunologic reaction and testing is usu- SUGGESTED READINGS
ally negative in protein-induced proctitis/proctocolitis.
An infant with MPA may appear healthy but have a his- Basnet S, Schneider M, Gazit A, et al. Fresh goats milk for infants:
Myths and realitiesa review. Pediatrics. 2010;125:e973e977.
tory of fussiness, regurgitation, increased frequency of stools, Brodsky D, Martin C. Neonatology Review. 2nd ed. Raleigh, NC: Lulu;
and presence of blood-tinged and/or mucous stools. How- 2010.
ever, some infants demonstrate extreme irritability as the only Committee on Nutrition, American Academy of Pediatrics. Hypoal-
lergenic infant formulas. Pediatrics. 2000;106:346348.
symptom of MPA. An elevated serum eosinophil count as well Heyman MB. Lactose intolerance in infants, children, and adolescents.
as presence of eosinophils in stool may be detected. Protein Pediatrics. 2006;18:12791286.
hydrolysate formula or strict diet modification in mothers Lake A. Food protein-induced proctitis/colitis and enteropathy of
infancy. UpToDate (Subscription required). http://www.uptodate.
who continue to breast-feed is recommended for infants with com/contents/food-protein-induced-proctitis-colitis-and-
MPA. If the infant continues to have signs and symptoms of enteropathy-of-infancy. Accessed July 10, 2013.

(c) 2015 Wolters Kluwer. All Rights Reserved.


S E C T I ON IX Renal System

(c) 2015 Wolters Kluwer. All Rights Reserved.


150Section IX Renal System

CASE1
Anuria in a newborn

A nurse in the Newborn Nursery pages the pediatric resident 2. Of the following, the most helpful noninvasive test to diag-
because she is concerned that an 18-hour-old term newborn nose the cause of this babys renal failure is:
has not voided.
A. Complete blood cell count
1. Of the following, the most appropriate initial response to B. Urinalysis
this nurses concern is to: C. Urinary biomarkers
D. Urine specific gravity
A. Meet with the babys parents and obtain a family history
B. Obtain a blood sample to test the babys serum creati- The neonatologist discontinues potassium in the babys intra-
nine concentration venous fluids and orders several blood tests, urine tests, and
C. Recommend continued observation and an evaluation an imaging study. While waiting for the results of these initial
if the baby does not void by 24 hours of age studies, the neonatologist speaks with the pediatric interns to
D. Review the babys prenatal ultrasonographic findings review the potential etiology of the babys renal failure, divid-
ing the cause into three possible categories:
The newborn is admitted to the Neonatal Intensive Care Unit Prerenal failure as a result of decreased renal perfusion
at 48 hours of age with the following data: Intrinsic renal disease, such as renal vascular thrombosis
Benign family history, normal prenatal ultrasonog- or congenital renal disorders
raphy, normal prenatal course, and normal physical Postrenal failure as a result of an obstructive uropathy
examination 3. Of the following, the finding that is most consistent with
Rising serum creatinine concentration with most intrinsic renal disease is:
recent measurement at 48 hours of age of 2.0 mg/dL
(177mol/L) A. Fractional excretion of sodium (FENa) = 6%
Urine output = 0.4 mL/kg/hr B. High urine osmolality
C. Lack of urination following a fluid challenge of 5 mL/kg
The neonatologist suspects that this infant has acute renal D. Presence of a metabolic acidosis
failure.

CASE 2
Multicystic dysplastic kidney

A pregnant woman undergoes routine fetal ultrasonography at The womans obstetrician reviews the possible causes of
17 weeks gestation. The study reveals an abnormal left kidney cystic renal disease, including the following:
(see Figure 1) with cysts and abnormal renal parenchyma. The
Autosomal dominant polycystic kidney disease
fetal right kidney, pancreas, and liver appear normal.
Autosomal recessive polycystic kidney disease
Medullary cystic kidney disease
Multicystic dysplastic kidney (MCDK)

On the basis of the current information, the obstetrician be-


lieves that MCDK (also known as multicystic renal dysplasia)
is the most likely etiology for this renal abnormality.

FIGURE 1. Reproduced with permission from: 2011 NeoReviewsPlus:


March: Question 10 by the American Academy of Pediatrics

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 3 Autosomal dominant polycystic kidney disease 151

1. Of the following, the characteristic(s) most consistent with The neonate is transferred to the Newborn Nursery and
MCDK is: discharged at 2 days of life with a follow-up nephrology
appointment.
A. Abnormal renal parenchyma of the involved kidney
B. Early intrauterine detection of cysts 3. Of the following, possible outcome(s) in this neonate with
C. Isolated, unilateral renal involvement MCDK is:
D. All of the above
A. Compensatory growth of the unaffected kidney
The rest of the pregnancy is uncomplicated, and the woman B. Involution of the affected kidney
delivers the baby at 39 weeks gestation. A neonatologist ex- C. Vesicoureteral reflux in the unaffected kidney
amines the newborn soon after birth. D. All of the above
2. Of the following, the most likely clinical finding in this
newborn is:

A. Costovertebral angle tenderness


B. Distended abdomen
C. Hematuria
D. Unilateral flank mass

CASE 3
Autosomal dominant polycystic kidney disease

A 15-year-old girl has an elevated blood pressure on routine After obtaining the laboratory and radiographic results, the
examination. Her father reports that he has cysts in his kid- pediatrician meets with the girl and her parents to discuss the
neys that have not impacted his health. The pediatrician or- outcome of her renal disease.
ders some laboratory and radiographic tests.
3. Of the following, possible extrarenal manifestation(s) for
1. Of the following, the preferred diagnostic procedure in the child in this vignette is:
children suspected of having a cystic renal disease is: A. Cyst formations in the liver, spleen, and/or pancreas
A. Magnetic resonance imaging B. Intracranial aneurysms
B. Radionuclide scintigraphy C. Mitral valve ballooning
C. Ultrasonography D. All of the above
D. Voiding cystourethrogram

The pediatrician also reviews the childs fetal records and finds
a late second-trimester fetal ultrasound that had noted some
echogenicity of the renal cortices but no evidence of renal
cysts.

2. Of the following, the most likely etiology for this childs


cystic renal disease is:

A. Autosomal dominant polycystic kidney disease (ADPKD)


B. Autosomal recessive polycystic kidney disease (ARPKD)
C. Medullary cystic kidney disease
D. Multicystic dysplastic kidney (MCDK)

(c) 2015 Wolters Kluwer. All Rights Reserved.


152Section IX Renal System

CASE 4
Autosomal recessive polycystic kidney disease

A 36-year-old pregnant woman with diabetes mellitus is mon- The neonate is born at 39 weeks gestation by cesarean deliv-
itored closely by her obstetrician. She has a first-trimester fetal ery. The neonatology team is present in the delivery room to
ultrasonography and a second-trimester fetal echocardiogra- assess the baby.
phy that are normal. Because the woman has a uterine size
that is greater than anticipated by dating, she has a second 2. Of the following, the most likely associated clinical abnor-
fetal ultrasound at 29 weeks gestation. This fetal ultrasound mality in this neonate is/are:
reveals the following: A. Congenital hepatic fibrosis
Multiple small cysts in both kidneys that are confined to B. Hemolytic anemia
the collecting ducts C. Tracheoesophageal abnormalities
Enlarged kidneys with increased echogenicity D. Vertebral anomalies
Decreased corticomedullary differentiation A neonatologist discusses possible outcomes of ARPKD.
The obstetrician is concerned about autosomal recessive poly-
3. Of the following, the most likely outcome in this neonate is:
cystic kidney disease (ARPKD).
A. Absence of clinical manifestations in the neonatal
1. Of the following, the renal finding(s) consistent with period
ARPKD in a fetus is: B. Development of renal vein thromboses in the neonatal
A. Renal cysts visible by fetal ultrasonography before period
20weeks gestation C. Early renal failure with hypertension in the neonatal
B. Small cysts that are usually confined to the collecting ducts period
C. Unilateral renal involvement D. Resolution of renal abnormalities by the second decade
D. All of the above of life

CASE 5
Renal agenesis

A 28-year-old gravida 6 para 0 woman is now pregnant. Be- The woman is admitted to the hospital for close observation.
cause of her prior pregnancy complications, she is being moni- A high-risk obstetrician meets with the couple and discusses
tored extremely closely by her obstetrician with frequent fetal possible pregnancy outcomes. Specifically, the obstetrician is
ultrasounds. A fetal ultrasound at 26 weeks gestation reveals concerned that the woman is at higher risk of acquiring cho-
severe oligohydramnios. rioamnionitis, which would prompt immediate delivery of
the baby. The couple also meets with a neonatologist who re-
1. Of the following, a possible mechanism of severe oligohy- views the potential associated complications after birth.
dramnios is:
2. Of the following, a potential complication for this fetus
A. A complete intestinal obstruction
with severe oligohydramnios is:
B. Continuous leakage of amniotic fluid
C. Deep implantation of the placenta A. Esophageal atresia
D. Poor fetal swallowing of amniotic fluid B. Pulmonary hypoplasia
C. Severe hearing loss
D. Visual deficits

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Case 6 Abnormalities of the collecting system, kidney, and bladder 153

Follow-up fetal ultrasounds show that the severe oligohy- 3. Identify the two renal disorders that can be associated with
dramnios persists. However, the fetus remains active with this infants physical examination findings:
appropriate growth and the woman does not have any signs
A. Bilateral renal agenesis
of labor. At 35 weeks gestation, the woman develops a high
B. Bilateral multicystic dysplastic kidneys
fever, abdominal tenderness, and an elevated white blood
C. Medullary cystic renal disease
cell count. Because of the concern for chorioamnionitis, the
D. Unilateral renal agenesis
high-risk obstetrician delivers the infant by cesarean. The neo-
natology team is present at the delivery. The infant requires Postnatal ultrasounds reveal that the infant has normal kid-
initial resuscitation with bag-mask ventilation and then needs neys, and laboratory findings show that the infant has normal
an endotracheal tube because of persistent severe respiratory renal function. The neonatologist is uncertain about the cause
distress. A thorough examination reveals the following: of the prenatal oligohydramnios but focuses on managing the
infants lung disease.
Clubbed feet
Distinctive facial features: flattened facies, parrot-beak
nose, skin fold of tissue from medial canthus across the
cheek
Multiple flexion contractures of the hands, feet, arms,
and legs
Severe respiratory distress

CASE 6
Abnormalities of the collecting system,
kidney, and bladder

At 20 weeks gestation, a pregnant woman has an ultrasound 2. Match the potential causes of prenatal hydronephrosis
that reveals fetal hydronephrosis and oligohydramnios. There with the prenatal ultrasonographic findings:
are no other fetal abnormalities. The obstetrician discusses
A. Isolated mild i. Cystic mass in
these findings with the expectant parents.
hydronephrosis the bladder with
1. Of the following, the current approach to characterizing B. Posterior urethral hydroureteronephrosis
fetal hydronephrosis is based on the: valves ii. Hydronephrosis and di-
C. Ureterocele lated ureter to the level
A. Appearance of the intrarenal collecting system
of the bladder
B. Degree of oligohydramnios D. Ureteropelvic junc-
C. Gestational age at which the hydronephrosis is initially tion obstruction iii. Moderately or severely
observed radiographically dilated renal pelvis with-
E. Ureterovesical junc-
D. Underlying cause of the hydronephrosis out dilation of ureter or
tion obstruction
bladder
Because the findings are consistent with severe hydronephro-
iv. Physiologic, transient
sis, the obstetrician refers the expectant parents to a pediatric
finding
urologist. The urologist reviews the potential causes of the hy-
v. Posterior urethral dila-
dronephrosis with the parents.
tion, a full bladder with
thickened wall, de-
creased amniotic fluid

(c) 2015 Wolters Kluwer. All Rights Reserved.


154Section IX Renal System

Follow-up fetal ultrasounds reveal the following: 3. Of the following, the most likely additional finding in this
Bilateral hydroureter and hydronephrosis infant is:
Distended, thin-walled bladder A. Bilateral cryptorchidism
Severe oligohydramnios B. Choanal atresia
Because of the concern for renal injury, the urologists decom- C. Hypertonia
press the fetal urinary system by inserting a vesicoamniotic D. Neural tube defect
shunt. This procedure was successful and the oligohydramnios
improved. The male infant is born by cesarean delivery at 35
weeks gestation. His abdominal findings are shown in Figure 1.

FIGURE 1. Photo courtesy of Karen M. Polise, MSN, RN, Division of


Nephrology, The Childrens Hospital of Philadelphia.

CASE 7
Posterior urethral valves

A 28-year-old pregnant woman with chronic hypertension has The neonatology team then contacts the consulting urologist
a fetal ultrasound performed at 32 weeks gestation to monitor to establish a plan.
fetal growth. The radiologist is concerned about a new diag-
3. Of the following, the most definitive test to diagnose PUV
nosis of posterior urethral valves (PUV). A neonatologist and
postnatally is:
urologist then meet with the family to discuss this diagnosis.
A. Abdominal radiography
1. Of the following, the ultrasonographic finding(s) most B. Magnetic resonance imaging
consistent with PUV is (are): C. Renal ultrasonography
A. Unilateral hydroureteronephrosis D. Voiding cystourethrography (VCUG)
B. Polyhydramnios After confirming the diagnosis of PUV, the urologist places a
C. Thickened bladder wall catheter into the neonates bladder to relieve the urinary tract
D. All of the above obstruction and decrease pressure on the proximal urinary
The rest of the prenatal course is stable, and the baby boy is tract. The neonatology team closely monitors the babys serum
born at term gestational age. He is then evaluated by the neo- electrolytes and renal function. The baby is also given antibi-
natology team soon after birth. otics to prevent of a urinary tract infection. By day of life 5,
the infants creatinine concentration and degree of hydrone-
2. Of the following, the most likely clinical symptom(s) in phrosis has decreased and the baby undergoes transurethral
this newborn is (are) (a): ablation of the valves.

A. Palpable midline bladder


B. Straining during urination
C. Weak urinary stream
D. All of the above

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 1 Anuria in a newborn155

SECTION IX
Answers

Additional studies that might be useful in the evaluation of


CASE 1 ANSWERS
an infant with acute renal failure are:
1. C. Recommend continued observation and an evalua- Urine sodium excretion and calculation of FENa to distin-
tion if the baby does not void by 24 hours of age guish between prerenal and intrinsic renal disease
The first void in a newborn is highly variable. More than half Urine osmolality with a concentrated urine in a hypovolemic
of newborns void by 8 hours of age, and almost all babies infant correlating with prerenal disease and a diluted urine
urinate by 24 hours of age. An evaluation is recommended in a hypovolemic infant suggesting intrinsic renal disease.
in newborns without a documented void by 24 hours of age. Renal ultrasonography to determine presence/absence of
Although the serum creatinine concentration is helpful to kidneys, assess renal size and shape, assess renal paren-
estimate renal function, measurement of this protein at this chyma and presence/absence of echogenicity and/or cysts,
babys age would reflect the mothers serum creatinine. Thus, and identify urinary tract obstruction; simultaneous Dop-
the serum creatinine concentration should be measured in a pler examination can be helpful to assess for renal vessel
newborn after the first 24 hours of age to avoid a falsely el- occlusion
evated result. Because absence of a void at 18 hours of age is Voiding cystourethrography to diagnose obstructive urop-
still within normal, it is not necessary to meet with the babys athy and/or vesicoureteral reflux
parents or review the prenatal ultrasonographic findings. Radionuclide scintigraphy to determine renal structure
2. B. Urinalysis and function
Clinicians should suspect a diagnosis of acute renal failure in 3. A. Fractional excretion of sodium (FENa) = 6%
a newborn with the following: The FENa can be calculated as follows:
Lack of urine output by 48 hours of age or decreased Urine Na concentration Plasma creatinine
urine output (<1 mL/kg/hr) FENa(%) =
Plasma Na concentration Urine creatinine
Rising, abnormal serum creatinine concentration
If an infants FENa is less than 2%, the diagnosis is most likely
The diagnosis of acute renal failure is confirmed if the babys
prerenal disease because the reabsorption of most of the filter
serum creatinine concentration is greater than 1.5 mg/
dL
sodium is an appropriate renal response to a decrease in renal
(133 mol/L) or increasing by >0.2 mg/dL to 0.3 mg/dL
perfusion. When the FENa is above 2.5% to 3%, the infant
(17267 mol/L) per day. Although serum creatinine con-
most likely has intrinsic renal disease.
centrations estimate the glomerular filtration rate and can
A high urine osmolality often corresponds to prerenal dis-
help determine the extent and progression of renal disease,
ease. If an infant voids after a fluid challenge, prerenal failure
an elevated value is not helpful in diagnosing the cause of the
is a likely etiology of the renal failure. However, the volume
renal failure.
of the fluid challenge needs to be at least 10 to 20 mL/kg. The
A urinalysis is the most helpful noninvasive test to diag-
presence of a metabolic acidosis is an abnormality found in
nose the cause of this babys renal failure because there may be
infants with both prerenal failure and intrinsic renal disease.
specific microscopic findings in the urine sediment that corre-
late with a specific diagnosis. The urinalysis is usually normal
in infants with prerenal disease and the majority of cases of
AMERICAN BOARD OF PEDIATRICS
urinary tract obstruction. If an infant has acute tubular necro-
CONTENT SPECIFICATIONS
sis, muddy brown granular and epithelial casts are usually vis- Know that a newborn who does not urinate by 24 hours
ible. If there are red blood cells, tubular cells, and proteinuria, of age warrants evaluation
the infant may have intrinsic renal disease. Plan the evaluation of an anuric infant
While a complete blood cell count result may be a bnormal,
the results are not specific nor helpful in determining the
etiology of the renal injury. Urine specific gravity is extremely SUGGESTED READINGS
variable, altered by protein and glucose concentrations and
does not correlate with urine osmolality in the newborn. Mattoo TK. Acute kidney injury (acute renal failure) in the newborn.
UpToDate (Subscription required). http://www.uptodate.com/
Measurement of urinary biomarkers of renal injury to d iagnose contents/acute-kidney-injury-acute-renal-failure-in-the-newborn.
acute renal failure is investigational. Accessed June 25, 2013.

(c) 2015 Wolters Kluwer. All Rights Reserved.


156Section IX Renal System

infancy. This disorder involves a large number of noncom-


CASE 2 ANSWERS
municating cysts that are surrounded by dysplastic renal tis-
1. D. All of the above sue. Although bilateral involvement can occur, most affected
MCDK occurs in 0.3 to 1 in 1,000 live births, with more than individuals have unilateral involvement. Cysts are typically
50% of cases being diagnosed prenatally by early fetal ultra- isolated to the involved kidney without involvement of the
sonography. Although autosomal dominant polycystic kid- contralateral kidney, pancreas, or liver.
ney disease is the most common cystic renal disease in all age A comparison of renal cystic diseases is shown in Table 1.
groups, MCDK is the most common cystic renal disorder of

Table 1. Comparison of Renal Cystic Diseases

Type of Re- Timing of


nal Disease Epidemiology Diagnosis Renal Findings Clinical Findings Prognosis

Autosomal Most common Second Bilateral Abdominal mass Most have


Dominant cystic renal decade involvement Flank pain worsening renal
Polycystic disease in all of life Large cysts Hematuria disease with
Kidney age groups Cysts increase in Hypertension advancing age
Disease 1 in 800 to size and number Extra renal
1,000 live over time manifestations
births cysts in liver,
Autosomal spleen, pancreas,
dominant hepatic fibrosis,
intracranial
aneurysm, mitral
valve ballooning
Of note, varied
clinical findings
because of genetic,
environmental, and
hormonal modifiers

Autosomal Autosomal After Bilateral Abdominal mass Broad range


Recessive recessive 20weeks involvement High risk of of outcomes,
Polycystic 1 in 20,000 gestation Small cysts confined congenital hepatic including
Kidney to 40,000 live to collecting ducts fibrosis intrauterine fetal
Disease births Renal failure, demise, Potter
hypertension, syndrome, early
esophageal varices renal failure with
hypertension
If survive neonatal
period, 40% with
renal disease and
poor growth
Majority require
renal transplant
prior to 2nd
decade of life

Medullary Autosomal Adulthood Cystic dilation of Gout Most with end-


Cystic dominant medullary part of Hyperuricemia stage renal
Kidney Rare collecting ducts Renal failure disease
Disease

MCDK Most common Cysts are Noncommunicating Palpable flank mass Unilateralvery
cystic renal visible by large cysts good prognosis
disease of ultrasound Dysplastic renal with affected
infancy prior to tissue kidney involuting
0.3 to 1 in 20 weeks Most are unilateral months to years,
1,000 live gestation Usually no some contralateral
births (>50%) involvement of changes can
No familial contralateral kidney, occur (reflux,
recurrence pancreas, or liver obstruction,
compensatory
growth)

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Case 3 Autosomal dominant polycystic kidney disease 157

2. D. Unilateral flank mass corticomedullary differentiation), affected individuals typi-


A physical examination of a neonate or infant with unilateral cally develop bilateral renal cysts during or after the second
MCDK will reveal a palpable flank mass. The affected individ- decade of life. These renal cysts increase in both number and
ual will not have a distended abdomen, abdominal tenderness size with advancing age, resulting in hypertension and/or re-
or costovertebral angle tenderness, or hematuria. Complica- nal failure.
tions are rare. The child in this vignette is unlikely to have multicystic dys-
plastic kidney because in this disorder, cysts are usually identi-
3. D. All of the above
fied by 20 weeks gestation and there is no familial occurrence.
Although newborns with bilateral MCDK typically have a poor
Individuals with autosomal recessive polycystic kidney disease
prognosis because of the associated pulmonary hypoplasia, neo-
have an autosomal recessive inheritance pattern with cysts that
nates with unilateral MCDK have a very good prognosis. In most
are evident after 20 weeks gestation by fetal ultrasonography.
cases, the affected kidney involutes over a period of months to
Medullary cystic kidney disease has an autosomal dominant
years. Contralateral renal changes have been observed, including
pattern of inheritance, but affected individuals present during
compensatory growth, vesicoureteral reflux, and u reteropelvic
adulthood with gout and renal failure.
junction obstruction in the unaffected kidney. While some stud-
ies suggest an increased risk for hypertension, other reports are 3. D. All of the above
inconclusive. Some patients develop renal impairment. Patients with ADPKD typically present later in childhood
or adolescence. Symptoms can include one or more of the
following:
American Board of Pediatrics
Abdominal mass
Content SPECIFICATION
Flank pain
Recognize that multicystic dysplastic kidney frequently Hematuria
presents as a unilateral flank mass in neonates or infants Hypertension
Extra renal manifestations can also occur, including:
Cyst formation in the liver, spleen, or pancreas
SUGGESTED READINGS Hepatic fibrosis
Intracranial aneurysm
American Academy of Pediatrics. Renal cystic disorders. NeoReviews Mitral valve ballooning
Plus. March 2011, Question 10. Clinical manifestations vary among affected individuals be-
Niaudet P. Autosomal recessive and dominant polycystic kidney dis-
ease in children. UpToDate (Subscription required). http://www.
cause there can be genetic, environmental, and/or hormonal
uptodate.com/contents/autosomal-recessive-polycystic-kidney- modifiers. Thus, the child in this vignette may have different
disease-in-children. Accessed May 18, 2013. clinical manifestations compared with her father. Many af-
Wiener JS. Multicystic dysplastic kidney. In: Belman AB, King LR,
Kramer SA, eds. Clinical Pediatric Urology. 4th ed. London: Martin
fected individuals are asymptomatic during childhood but
Dunitz; 2002. have worsening renal disease with age.

AMERICAN BOARD OF PEDIATRICS


CASE 3 ANSWERS
CONTENT SPECIFICATIONS
1. C. Ultrasonography
Know that abdominal ultrasonography is the preferred
Abdominal ultrasonography is the preferred diagnostic proce-
diagnostic procedure in children suspected of having au-
dure in children suspected of having cystic renal disease.
tosomal dominant polycystic kidney disease
Although magnetic resonance imaging will be able to iden-
Know that children with autosomal dominant polycystic
tify renal cysts, it is a more expensive test that is unnecessary
kidney disease may have hypertension
for initial diagnosis. Radionuclide scintigraphy is helpful to
Know that autosomal dominant polycystic kidney dis-
measure renal function and blood flow. A voiding cystoure-
ease may be associated with intracranial aneurysms
thrography can assess for an obstructive uropathy or vesico-
ureteral reflux.

2. A. Autosomal dominant polycystic kidney disease SUGGESTED READINGS


(ADPKD)
ADPKD is the most common cystic renal disease, occurring American Academy of Pediatrics. Renal cystic disorders. NeoReviews
Plus. March 2011, Question 10.
in 1 in 800 to 1 in 1,000 live births. This autosomal domi- Cohen JN, Ringer SA. Congenital kidney abnormalities: Diagnosis,
nant disorder is caused by mutations in polycystin, resulting management, and palliative care. NeoReviews. 2010;11:e226e235.
in renal tubular epithelium abnormalities. Although there Niaudet P. Autosomal recessive and dominant polycystic kidney dis-
ease in children. UpToDate (Subscription required). http://www
may be some subtle renal abnormalities detected prenatally .uptodate.com/contents/autosomal-recessive-polycystic-kidney-
(e.g., increased echogenicity of the renal cortex, increased disease-in-children. Accessed May 18, 2013.

(c) 2015 Wolters Kluwer. All Rights Reserved.


158Section IX Renal System

CASE 4 ANSWERS SUGGESTED READINGS


American Academy of Pediatrics. Renal cystic disorders. NeoReviews
1. B. Small cysts that are usually confined to the collect- Plus. March 2011, Question 10.
ing ducts Cohen JN, Ringer SA. Congenital kidney abnormalities: Diagnosis,
ARKPD is an uncommon cystic renal disease with an inci- management, and palliative care. NeoReviews. 2010;11:e226e235.
Niaudet P. Autosomal recessive and dominant polycystic kidney dis-
dence of 1 in 20,000 to 40,000 live births. It is caused by
ease in children. UpToDate (Subscription required). http://www
abnormalities in the fibrocystin protein, leading to abnor- .uptodate.com/contents/autosomal-recessive-polycystic-kidney-
malities of tubular cilia formation in the collecting tubules disease-in-children. Accessed May 18, 2013.
and biliary tree. Findings consistent with ARKPD include the
following:
Bilateral renal involvement CASE 5 ANSWERS
Renal cysts visible radiographically after 20 weeks
gestation 1. B. Continuous leakage of amniotic fluid
Small cysts that are usually confined to the collecting Fetal urine becomes the major component of amniotic fluid
ducts at the beginning of the second trimester, with fetal urine ac-
counting for more than 90% of amniotic fluid content by 20
2. A. Congenital hepatic fibrosis weeks gestation. The amniotic fluid then gets swallowed by
Many infants with ARKPD also have congenital hepatic fibro- the fetus. Following, the fluid is absorbed in the gastrointes-
sis, which can lead to portal hypertension. The degree of liver tinal tract and then reintroduced into the amniotic fluid with
disease has an indirect correlation with the severity of renal urination. Thus, a constant amount of amniotic fluid volume
disease; individuals with severe kidney disease tend to have is maintained.
a milder amount of liver involvement. Affected patients also Severe oligohydramnios can occur in the following
are at high risk for developing hypertension and esophageal scenarios:
varices. Amniotic fluid leakage
3. C. Early renal failure with hypertension in the neona- Bilateral severe renal disease
tal period Urinary tract obstruction
There is a broad range of outcomes for individuals with Severe placental insufficiency
ARPKD, including intrauterine fetal demise, Potter syndrome, A fetus with a complete intestinal obstruction may develop
and early renal failure with hypertension. Early mortality from polyhydramnios because the fetus will be unable to adequately
respiratory failure and/or sepsis occurs in more than one- absorb amniotic fluid. Similarly, a fetus with a poor abil-
fourth of affected patients. Approximately 40% of infants with ity to swallow amniotic fluid, as occurs in severe neurologic
ARPKD develop chronic renal disease and delayed growth in disorders, can develop excessive amounts of amniotic fluid.
infancy and early childhood. For those individuals who sur- Although shallow placental implantation is associated with
vive infancy, the majority require renal transplantation before placental insufficiency and pregnancy-induced hypertension,
their second decade of life. A small number of children with deep placental implantation does not impact amniotic fluid
ARPKD initially have normal renal function with progressive production.
hepatic fibrosis in adulthood. 2. B. Pulmonary hypoplasia
Affected individuals are not at increased risk for renal vein With loss of amniotic fluid, fluid within the fetal lungs will
thrombosis. Clinical manifestations are typically apparent preferentially egress from the trachea and airways into the
during infancy, and renal abnormalities are not reversible. amniotic sac. Because fetal lung growth requires an adequate
amount of fetal lung fluid, pulmonary development is limited
in fetuses with severe oligohydramnios, and after birth, the in-
AMERICAN BOARD OF PEDIATRICS fant is at risk for pulmonary hypoplasia. This risk is greatest if
CONTENT SPECIFICATIONS the oligohydramnios is severe, long-standing, and occurs early
in gestation.
Know the clinical presentation of autosomal reces- Esophageal atresia, severe hearing loss, and visual deficits
sive polycystic kidney disease in neonates, infants, and are not directly associated with severe oligohydramnios.
children
Know the association of autosomal recessive polycystic
kidney disease with congenital hepatic fibrosis

(c) 2015 Wolters Kluwer. All Rights Reserved.


Case 6 Abnormalities of the collecting system, kidney, and bladder 159

3. A and B Potter sequence occurs in a fetus with severe, prolonged


The clinical findings of the infant in this vignette (clubbed oligohydramnios. Possible reasons for this extreme degree of
feet; distinctive facies; multiple flexion contractures of the oligohydramnios include:
hands, feet, arms and legs; and severe respiratory distress as Autosomal polycystic kidney disease (recessive type
a result of pulmonary hypoplasia) are most consistent with more often than dominant type)
Potter sequence (see Figure 1). Bilateral renal agenesis
Bilateral multicystic dysplastic kidneys
Complete ureteral obstruction
The majority of infants with unilateral renal agenesis have
normal renal function; oligohydramnios is not an associated
finding with this abnormality because the other kidney can
produce adequate amounts of urine prenatally.

American Board of Pediatrics


Content SPECIFICATION
Recognize the association of bilateral renal aplasia or
severe dysplasia with pulmonary hypoplasia (Potter
syndrome)

SUGGESTED READINGS
American Academy of Pediatrics. Renal cystic disorders. NeoReviewsP
lus. March 2011, Question 10.
Waters AM, Rosenblum ND. Evaluation of congenital anomalies of
the kidney and urinary tract. UpToDate (Subscription required).
http://www.uptodate.com/contents/evaluation-of-congenital-
anomalies-of-the-kidney-and-urinary-tract-cakut. Accessed May
18, 2013.

CASE 6 ANSWERS

1. A. Appearance of the intrarenal collecting system


Although an infant with hydronephrosis can present with
an abdominal mass on postnatal examination, most af-
fected infants are diagnosed prenatally by fetal ultrasonog-
raphy. Indeed, fetal hydronephrosis is the most common
abnormality detected by routine fetal ultrasonography. Cur-
rently, the challenge for clinicians is to determine which
infants have clinically significant fetal hydronephrosis
that could impair renal function. At present, there are two
main approaches used to standardize the severity of fetal
hydronephrosis:
1. Measurement of the anteriorposterior (AP) diameter of
the renal pelvis by fetal ultrasonography:
In this method, the size of the renal pelvis is considered
clinically significant (moderate or severe) if the AP diame-
ter is greater than 8 mm in the second trimester and above
10 mm in the third trimester.
2. Appearance of the intrarenal collecting system:
This method was described by the Society for Fetal Urol-
ogy in 1993, and it classifies the severity of fetal hydrone-
phrosis based on the degree of collecting system dilation
and renal parenchymal findings. Figure 2 summarizes this
FIGURE 1. Image from: Rubin E, Farber JL. Pathology. 3rd ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 1999. Figure 6.04 classification system.

(c) 2015 Wolters Kluwer. All Rights Reserved.


160Section IX Renal System

reflux. Less-common causes of antenatal hydronephrosis in-


clude ureterovesical junction obstruction (5%15%), multi-
cystic dysplastic kidney disease (2%5%), posterior urethral
valves (1%5%), and ureterocele (1%3%). Less than 1% of
cases result from an ectopic ureter, urethral atresia, prune belly
syndrome, polycystic kidney disease, and renal cysts.

3. A. Bilateral cryptorchidism
The abdominal findings shown in the figure are consistent
with EagleBarrett syndrome, also known as prune belly syn-
drome. Antenatal findings in this rare syndrome include:
Bilateral hydroureter and hydronephrosis
Distended, thin-walled bladder
Severe oligohydramnios
After birth, affected infants typically have a low-pressure di-
lated urinary tract from the renal pelvis to the urethra. The ure-
ters are often elongated and tortuous because smooth muscle
has been replaced by collagen and fibrous tissue. Most affected
FIGURE 2. From MacDonald MG, Mullett MD, Seshia MM, eds. Averys
infants also have vesicoureteral reflux.
Neonatology: Pathophysiology & Management of the Newborn. 6th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2005. Figure 43.13
Affected individuals also have the following clinical
findings:
Bilateral cryptorchidism
In both the approaches described earlier, there is a corre- Deficient or absent abdominal wall musculature
lation between the degree of prenatal involvement and the Hypotonia
risk of persistent postnatal uropathy. Although the earlier in Less commonly, patients can have pulmonary hypoplasia
gestation that the hydronephrosis is found has been shown (60%), structural heart disease (25%), gastrointestinal abnor-
to correlate with clinically significant postnatal pathology, the malities (25%), and/or musculoskeletal fi