Prematurity

Dr Waddah Khreisat
Done By Ahmad Shyoukh

Prematurity refers to the broad category of neonates born at less than 37 completed
weeks' gestation (less than 259 days after the first day of the last menstrual period (LMP) of
the mother). <<<< WHO and AAP definition
Why are we interested in premature infants ?
Because premature newborns have many physiologic challenges when adapting to
the extrauterine environment, due to their relative physiologic and metabolic
immaturity, so they are prone to high morbidity and mortality. So they need to be
monitored the whole time, and the practitioners who are taking care of this
problem should be ready to take action immediately.
Definitions:

STILLBIRTH: Infant expelled from birth canal at or after 24weeks of

pregnancy who shows no signs of life and has no heartbeat. <<<< in the slides it is
24 weeks, but most internet sources say that it is after 20 weeks of gestational
age.
This term is quite distinct from the two other entities "live birth" and
"miscarriage". While the former points out to the process in which the fetus, be it
of any gestational age, shows signs of life after exiting the maternal body, the
latter indicates the spontaneous end of a pregnancy at a stage where the embryo
or fetus is incapable of surviving independently, taking into consideration that it is
to occur 20 weeks prior to gestation.
The American Academy of Pediatrics (AAP) and WHO reports show that medical
advances in any country are measured depending on the neonatal and infantile
mortality rates, so it is of great importance to take into account the number of

stillbirths within a country and find out solutions that help in minimizing the
incidence.

GESTATIONAL AGE: This is calculated from the first day of the last normal
menstrual period to the date of birth, and is expressed in completed weeks. By
convention, only completed weeks of gestation are reported. Thus, infants born five days after
completing 35 weeks are reported as 35 weeks gestation, and are not rounded up to 36 weeks
gestation <<< from uptodate >>>>. We can say that this baby was born in 28 weeks, 36
weeks sometimes if there is additional days like 5 days we can say 28 weeks plus 5
days, so it's expressed by complete weeks plus if there is any days after.

TERM DELIVERY: Occurs when the infant is born at or after 37 and before 42
weeks gestation.

PRETERM DELIVERY: Occurs if the infant is born after less than 37 weeks
gestation (6-7% for all deliveries, but some sources say it up to 11% worldwide),
and this is a huge number. And it is considered the major cause of neonatal
morality in the developed countries.

POST-TERM DELIVERY: For infant born after 42 completed weeks (3%)

Different degrees of prematurity are defined by gestational age (GA), or birth
weight (BW). And based upon birth weight the classification is:
Low birth weight (LBW) BW less than 2500 g regardless of gestational
age at the time of birth (6% of all deliveries). These infants are 1) either born
too early (i.e prematurity is a cause of LBW) or 2) have grown inadequately
in the uterus and are classified as Small for Gestational Age (SGA).
Very low birth weight (VLBW) BW less than 1500 g (1-1.5% of all
deliveries)
Extremely low birth weight (ELBW) BW less than 1000 g (0.7% of all
deliveries)
Prematurity is also defined by gestational age (GA) as follows: (from uptodate)
Late preterm infants GA between 34 weeks and 36 weeks and 6 days
Very premature infants (VPT) GA at or below 32 weeks
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 Extremely premature infants (EPT) GA at or below 25 weeks

SMALL FOR GESTATIONAL AGE (SGA): The assessment of the baby

depends on accurate assessment of gestational age and plotting of weight on an
appropriate specific growth charts. There is no consensus on the definition of SGA
which varies from less than the 10th, 5th or 3rd percentiles, or more than 2 standard
deviation below the mean birth weight. BUT The most common definition of

small gestational age (SGA) refers to a weight below the 10th percentile for
gestational age
Small for gestational age newborns are mainly due to intrauterine growth
restriction or they are constitutionally small (due to maternal ethnicity, sex,
multiparity)

Intrauterine growth restriction (IUGR) is the term used to designate a fetus that has
limited growth and has not reached its growth potential because of genetic or environmental
factors.
It may be caused by fetal, placental, or maternal factors.
IUGR results in the birth of an infant who is small for gestational age (SGA).
Mortality and morbidity are increased in SGA infants compared to those who are
appropriate for gestational age (AGA)

The Corrected Gestational Age (CGA): Is the age of the preterm infant
which combines both the gestational age and the postnatal age. For example: an
infant of 28 weeks GA, and is 14 days old (2 weeks), has a CGA of 30 weeks.

This is important because the development of the infant depends on the CGA,
and regarding vaccination, we take into consideration the postnatal age.

A graph suggests that a baby born in 28 weeks and his weight is 1000g and this
is the 50th percentile so this is normal. Now after 4 weeks when this baby becomes
32 weeks (corrected gestational age) what will be his expected weight?

The difference is 4 weeks (28 days) and as the normal baby will gain 20- 30
g/day, so 28 days * 20 g/day this equals 560grams so this baby in his 32nd week his
50th percentile must be 1560 grams.
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Specific problems of the preterm infant:

We divide them into:
Acute problems that appear immediately once those babies are born.
Sub-acute problem that occur several days after the delivery.
Chronic problems that may happen after one or two months of their birth.
1) Birth asphyxia:- AKA perinatal asphyxia or asphyxia neonatorum ( low
oxygen at birth )

It is a medical condition resulting from deprivation of oxygen to a newborn

infant before, during, or immediately after birth, that lasts longer enough to cause
physical harm, usually to the brain. There is an inability of an infant to establish
regular respiration following birth. These babies will not cry immediately after
birth and they dont have good muscle strength.

Prematurity is a cause of perinatal asphyxia as premature infants have

immaturity of their systems, so because of immaturity of the lungs, the gas
exchange will be decreased, and their circulatory system isnt mature enough to
regulate blood pressure and its fluctuations, leading to asphyxia.
EXTRA NOTE:
Perinatal asphyxia results from compromised placental or pulmonary gas exchange. This
disorder can lead to hypoxia and hypercarbia in the blood. Severe hypoxia results in anaerobic
glycolysis and lactic acid production first in the peripheral tissues (muscle and heart) and then in
the brain. Hypoxia and acidosis can depress myocardial function, leading to hypotension and
ischemia. Ischemia can impair oxygen delivery, causing further compromise, as well as disrupt
delivery of substrate and removal of metabolic and respiratory by-products (eg, lactic acid,
carbon dioxide), leading to hypoxic-ischemic encephalopathy.
Hypoxic damage can occur to most of the infant's organs (heart, lungs, liver, gut, kidneys), but
brain damage is of most concern and perhaps the least likely to quickly or completely heal.
In the more pronounced cases, an infant will survive, but with damage to the brain manifested
as either mental, such as developmental delay or intellectual disability, or physical, such as
spasticity in fact, spastic diplegia and the other forms of cerebral palsy almost always
feature asphyxiation during the birth process as a major, if not defining, factor.
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Other causes of perinatal asphyxia are:

Umbilical Cord compression, causing decreased blood flow

Anesthetic drugs: either inhalational or intravenous drugs, they will cross the placenta and

sedate the fetus causing respiratory depression, or they will affect the mother, she may have
insufficient oxygen in her blood that directly impacts the fetus oxygen levels.
Maternal conditions such as 1) Low blood pressure, 2) early separation of the placenta from the
uterus, called placental abruption, 3) hypertension leading to poor placenta function, 4) Inadequate
relaxation of the uterus during labor that prevents oxygen circulation to the placenta

Signs of perinatal asphyxia:

1) Cyanosis, bluish or purple discoloration of skin and mucous membranes, when blood has > 2.5 mg/dl
of deoxyhemoglobin
2) Slow heart beat (bradycardia), and weak breathing or gasping
3) hypotonia
4) Weak cry, poor response to stimulation (grimace)

Fortunately the preterm can tolerate asphyxia better than babies who are born
at term.

The other problem in birth asphyxia is false negative in APGAR score, if we see
APGAR score, 2 of its elements depends on the muscle strength of the baby.
Mostly, the preterm baby they don't have enough muscle power, he cannot sneeze
nor do the usual flexion movements. Yet the baby is doing fine, but at the same
time he is normal, he is not asphyxiated or not having hypoxia. So this may delay
the role of APGAR score of those babies once they are delivered.
2) Thermal instability:- The preterm infants at higher risk for thermal
instability because of:a- conductive heat loss: once the baby delivered he is covered by the amniotic
fluid, and this fluid is very good surface for conduction of the heat so the
first step in any resuscitation to the baby (full term or not) is the drying of
the body. The baby is covered with Vernix caseosa which is a white cheesy
substance that covers and protects the skin of the fetus, facilitates passage through the
birth canal, and is still all over the skin of a baby at birth. It is composed of sebum (oil) and
cells that have sloughed off the fetus' skin.
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After birth, a newborn remains covered by amniotic fluid and situated in a cold environment (20
C to 25 C). An infant's skin temperature may decrease 0.3 C/min, and the core temperature may
decrease 0.1 C/min in the delivery room. In the absence of an external heat source, the infant must
increase metabolism substantially to maintain body temperature.
Heat loss occurs through four basic mechanisms. In the cold delivery room, the wet infant loses
heat predominantly by evaporation (cutaneous and respiratory loss when wet or in low humidity),
radiation (loss to nearby cold, solid surfaces), and convection (loss to air current). When the
infant is dry, radiation, convection, and conduction (loss to object in direct contact with infant)
are important causes of heat loss. <<<< NELSON ESSENTIALS.
b- Lack of brown fat: the preterm infants don't have the brown fat which is
the heat generating fat in the body, and it is rich in mitochondria, so they
cannot produce ATP to produce heat, for that reason they are subjected to
hypothermia. Brown fat produces heat by non-shivering thermogenesis, as
infants cant shiver like adults. Brown fat is highly vascular, contains many
mitochondria per cell, and is situated around large blood vessels, resulting in rapid heat
transfer to the circulation. The vessels of the neck, thorax, and interscapular region are
common locations of brown fat. These tissues also are innervated by the sympathetic
nervous system, by norepinephrine, which serves as a primary stimulus for heat production
by brown adipose cells after exposure to cold. Shivering does not occur in newborns.<<<<
NELSON ESSENTIALS
c- Lack of shivering reflex: - if we are cold we make involuntary muscle
contractions which cause production of heat (conversion of mechanical
energy into thermal energy), the preterm infants don't have these reflexes so
they can't shiver so they are more subjected to hypothermia.
d- Large surface area compared to the body weight, and basically the
premature have large head so they can lose heat from that
hypothermia
e- Lack of keratinazation in the skin that develops in 34 -35 weeks, so the
preterm infants have very elastic skin which induces more heat loss.

During resuscitations of the preterm infants we put them in warm

resuscitators, dried immediately after delivery and we cover them by dry and preheated material in order to protect them from hypothermia.
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After resuscitation we put them in the incubators. In the incubators we keep

their temperature through neutral thermal environment, the temperature in the
incubator is fixed according to the gestational age and the weight of the baby.

Neutral thermal environment: the temperature at which there is the lowest

oxygen consumption and caloric expenditure so the preterm infants in the
incubators don't use their energy to keep up their temperature, they use it to
increase their metabolic rate which also increase their growth rate.
Ambient temperatures less than the neutral thermal environment first result in increasing rates
of oxygen consumption for heat production, which is designed to maintain normal body
temperature. If the ambient temperature decreases further or if oxygen consumption cannot
increase sufficiently (due to hypoxia, hypoglycemia, or drugs), the core body temperature
decreases.<<<< NELOSN ESSENTIALS
3) Lack of primitive survival reflexes: - (sucking, swallowing)

The sucking and swallowing reflexes happens at different gestational age,

usually the sucking reflex develops around 28 weeks so before this age there is no
sucking reflex. The swallowing usually happens while the baby is in the uterus, for
example 16 weeks of GA have swallowing reflex (in many studies it has been
demonstrated to occur at 1012 weeks GA), but the problem is coordination
between the sucking, breathing and swallowing that develops not before 32-34
weeks GA. So we feed them very small amount through nasogastric tube or
orogastric tube.

Trophic feeding (AKA minimal enteral feeding): (very small amount like 1 cc
of milk every 6 hours, and it varies from 5-20 ml/kg/day) we use it only as
stimulation to the GI and the enzymes that are present in the GI to start
working, after that we advance feeding gradually until we reach their full feeding.
For premature infants, with very low birth weight, they have extremely immature
gastrointestinal function, which limits their enteral feeding. However, some degrees of nutrient
exposure are essential to prevent intestinal mucosal atrophy, by stimulating blood supply to the
gut, thus maintaining its viability, and to stimulate the development of the immature
gastrointestinal tract, and to prime the gut for later feeding, with establishment of the normal gut
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microflora. But the infant will be taking parenteral nutrition as well, as the trophic feeding does
not provide enough calories for growth.
4) Jaundice:The Liver is like other organs it's not mature enough in those premature babies,
especially the enzymes that are capable of degradation of the Hemoglobin, and
conjugation of bilirubin to get rid of it, and for that reason those babies are more
subjected than full term babies to having neonatal jaundice, and
hyperbilirubinimia. Also these babies may have polycythemia and born with Hb
17-22 mg/dl, with their fetal RBC life span as about 70 days which causes more
destruction, and they have immature GIT, leading to increased enterohepatic
circulation of bilirubin and bile salts.
5) Pulmonary diseases:
A) Respiratory Distress Syndrome RDS:
It is the leading cause of death in the premature infants. Lungs in those
babies are functionally not mature, during intrauterine life only 5% of the
circulation goes to their lungs, so the lung is not functioning, baby in the
uterus doesn't use his lungs for respiration, they exchange their gases
through the umbilical cord of their mothers, the lungs and the alveoli of the
lungs are filled with fluid. If the baby was born full term, usually there is
specific type of cells on the walls of the alveoli called pneumocytes type 2,
these cells produce the surfactants. Surfactants physically contain
phospholipids and proteins. The main function of the surfactant is to lower
the surface tension between water and the air, which is trying to collapse
the lungs.
The alveoli of premature babies are filled with fluid, and surfactants are not
there, so the lungs are stiff, and they tend to collapse at low lung volumes
during expiration. So they need a ventilator for their respiration
(continuous positive airway pressure CPAP), also we can give them
exogenous surfactant through endotrachial tube intubation, although
exogenous surfactant is very expensive but it will improve the compliance
of the lungs, so the lungs functionally can do gas exchange.

 There is what we call critical alveolar pressure CAP, which is the pressure
needed to open up the alveoli. In RDS It is not homogeneous in all parts of
the lungs, which means different amount of pressure is needed at different
areas to open up alveoli. Some areas of the lungs may need more pressure
than other adjacent areas, so RDS is not a homogeneous disease. It is well
known that one of the functions of the surfactant is to make CAP more
homogenized, which means that the whole lung opens and closes at a
specific CAP. Before the scientific internevtion to find ways of introducing
exogenous surfactant, such preterm infants used to be put on ventilators.
Those infants were exposed to high pressure, without taking into
consideration the difference of CAP among different parts of the lung,
ending up with pneumothorax and dying due to RDS. Death of the RDS
now is less than before, but still there.
B) Apnea of prematurity: Apnea is the cessation of breathing more than 20
seconds, or for less than 20 seconds if it is accompanied by bradycardia or
oxygen (O2) desaturation (hypoxia and cyanosis).

Bradycardia in a premature neonate is considered clinically significant when the heart rate
slows by least 30 bpm from the resting heart rate.

An O2 saturation level of more than 85% is considered pathologic in this age group, as is a
decrease in O2 saturation should it persist for 5 seconds or longer.

Short breathing pauses (5 to 10 seconds) occur frequently in premature infants and are normal,
but not prolonged (20 seconds or greater)
There are 3 types of apnea that happen in the neonate:
1. Obstructive apnea: continuation of chest wall movements (Inspiratory
efforts) present, and airway obstruction is present. Absence of noticeable
airflow. It may occur when the infant's neck is hyperflexed or conversely,
hyperextended (wrong positioning of the head of the baby). It may also
occur due to poor pharyngeal muscle tone in premature infants or to
inflammation of the soft tissues, which can block the flow of air though the
pharynx and vocal cords.
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2. Central apnea: complete cessation of airflow and Inspiratory efforts with

no chest wall movements. It can happen with any baby born less than 34
weeks of gestational age, and it's because of the immaturity of the
respiratory center.
3. Mixed apnea: a combination of these two events. It is the most frequent
type. Airway obstruction with inspiratory efforts precedes or follows
central apnea. It may begin as a brief episode of obstruction followed by a
central apnea. Alternatively, central apnea may produce upper airway
closure (passive pharyngeal hypotonia), resulting in mixed apnea.
Pathophysiology: <<<<< from emedicine

Ventilatory drive is primarily dependent on response to increased levels of carbon dioxide

(CO2) and acid in the blood. A secondary stimulus is hypoxia. Responses to these stimuli are
impaired in premature infants due to immaturity of specialized regions of the brain that sense
these changes (chemoreceptors).

Episodes of both central and mixed apneic share an element of decreased respiratory center
output to the respiratory muscles

Periodic breathing is defined as periods of regular respiration for as long as 20

seconds followed by apneic periods of 10 seconds or less that occur at least 3
times in succession.

Periodic breathing may be observed for 2-6% of the breathing time in healthy term neonates
and as much as 25% of the breathing time in preterm neonates

Periodic breathing is not accompanied by a change in facial color (such as blueness around the
mouth) or a drop in heart rate.
Treatment of apnea of prematurity involves administration of oxygen (CPAP)
to hypoxic infants, transfusion of anemic infants, and physical cutaneous
stimulation for infants with mild apnea. For treatment of apnea, either we use
aminophylline or caffeine citrate to stimulate the respiratory center and
prevent apnea.

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Methylxanthines (caffeine or theophylline) are the mainstay of pharmacologic

treatment of apnea, as they stimulate the respiratory center which is inhibited by
adenosine (they are adenosine antagonists). Caffeine is the preferred drug for
treating apnea of prematurity.
C) Pneumothorax: which is the presence of air in the pleural space, it might
happen due to iatrogenic reasons because we use higher pressure than is needed
for the lung, because we don't know exactly how much pressure (CAP) we must
use, so sometimes we may end up having rupture of some of the alveoli, and the air
goes around the lung and will lead to lung collapse. And it occurs in RDS because
of difficulty in expanding the lungs because of paucity of surfactants.

If the gas is under tension, the pneumothorax shifts the mediastinum to the
opposite side of the chest, producing hypotension, hypoxia, and hypercapnia.
With decreasing venous return due to the high intrathoracic pressure, this will
decrease the cardiac output, but there will be tachycardia.

Clinical picture: dyspnea and distress, tachypnea, cyanosis, and decreased

breath sounds on the involved side

To prevent pneumothorax, infants are ventilated with the lowest pressure that
provides adequate chest movement, and satisfactory blood gases.

Infants without a continuous air leak or respiratory distress and who have no
underlying lung disease or have no need for assisted ventilation may be observed
closely without specific treatment. The pneumothorax will typically resolve in one
to two days. Infants with respiratory distress should be monitored closely. Oxygen
supplementation should be provided as needed to maintain adequate saturation.

Treatment of a symptomatic pneumothorax requires immediate insertion of a

needle (aspiration of pleural air by thoracostomy), or insertion of a pleural chest
tube connected to negative pressure or to an underwater drain. Prophylactic or
therapeutic use of exogenous surfactant has reduced the incidence of pulmonary
air leaks.
D) Pneumonia: there is an entity called ventilator-associated pneumonia, which
is a subtype of hospital-acquired pneumonia in patients being on a ventilator,
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there is higher risk of developing pneumonia, due to infection through the

endotracheal tube.
E) Chronic lung disease: (previously known as bronchopulmonary dysplasia)
this is a disease entity specific for preterm infants treated with oxygen and
positive-pressure ventilation (PPV), and the definition of it, is oxygen
dependence at 36 weeks' corrected gestational age. And it is accompanied by
characteristic clinical and radiographic findings that correspond to anatomic
abnormalities
6) Metabolic disturbances:
Like hypoglycemia (Serum glucose concentrations less than 45 mg/dL),
hypocalcaemia (< 8 mg/dl in term infants, and < 7 mg/dl in preterm infants). Most
of the glycogen that is stored in the liver takes place in the 3rd trimester of the
pregnancy, so those infants who are born premature; they don't have enough
stored glycogen in their liver, so they are more liable to develop hypoglycemia; to
prevent hypoglycemia we calculate how much glucose input (mg/kg/min) they
need, and according to this we give them IV fluid.
Most of the calcium is transferred from the mother to the baby in the 3rd
trimester of the pregnancy, so if they are born prematurely, basically their Ca is
less than 3500mg, and they are subjected to develop hypocalcaemia, so we add
calcium in their fluid. Many causes of neonatal hypocalcemia such as abrupt
cessation of calcium from the mother at birth, decreased vitamin D levels,
increased calcitonin levels such as in perinatal asphyxia, decreased and delayed
milk intake, maternal diabetes which is associated with hypomagnesemia,
hyperphosphatemia
7) PDA (Patent Ductus Arteriosus):
As you know there are many shunting system in the fetal circulation. Fetus has 3
shunts, one is the foramen ovale between the atria, one is ductus venosus
between the umbilical vein and IVC, and the last one is through ductus arteriosus
which is between the pulmonary artery and the aorta. It prevents the blood from
going to the lungs, (because of high pulmonary vascular resistance) so it will go
back from the pulmonary artery to the aorta.
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What happens in full term baby is once they are born, because of high oxygen
tension the duct is physiologically closed, that is the formerly low oxygen
saturation of the fetus of 35% to 45%, after delivery it will be around 95% to 100%,
and this is enough to functionally close the duct in 24-48 hours. And it's
anatomically closed because of the modulation of the endothelial cells surrounding
the duct; it's usually closed within 48 hours of life, but anatomical closure may
take months, so any changes may lead to reopening of the ductus arteriosus.
In premature babies because they are subjected to hypoxia and oxygen saturation
is low, we try to control the hypoxia; those babies because we give them extra
fluid in their initial life, their duct might either not close or reopen after closure;
symptoms of the PDA usually starts on the 2nd or the 3rd day of life, the oxygen
demand of the baby increases.
A patent ductus arteriosus allows a portion of the oxygenated blood from the left heart to flow
back to the lungs by flowing from the aorta (which has higher pressure) to the pulmonary artery. If
this shunt is substantial, the neonate becomes short of breath: the additional fluid returning to the
lungs increases lung pressure to the point that the neonate has greater difficulty inflating the lungs.
This uses more calories than normal and often interferes with feeding in infancy, and leading to
falirue to thrive
It becomes evident that the infant, who starts building up CO2, becomes in need
for more oxygen. Sometimes we may see active pericordium, and we see bounding
pulsation, they also develop Gallop rhythm (An abnormal rhythm of the heart that
includes 3 or 4 sounds. It is similar to the sound of a running horse, thus its name),
and respiratory problems.
The condition may cause hepatomegaly, and if not treated, may progress to cause
heart failure, or what's called Eisenmenger Syndrome (Cyanotic Heart). A large
PDA initially causes left ventricular overload. Over time, there may be a progressive rise in
pulmonary artery pressures, which in the uncorrected patient, may lead to irreversible pulmonary
vascular changes. With sufficiently increased pulmonary vascular resistance, flow reverses to a
right-to-left shunt and over time, these patients develop cyanotic heart disease (ie, Eisenmenger
syndrome.

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Treatment may be medically based if infant is less than 21 days old. Medication
includes indomethacin or ibuprofen for closure of the duct. If the infant is more
than 21 days old, surgical ligation may be indicated. Spontaneous closure of the
patent ductus arteriosus (PDA) is common. If significant respiratory distress or
impaired systemic oxygen delivery is present, therapy is usually prudent. Intravenous (IV)
indomethacin (or the newer preparation of IV ibuprofen) is frequently effective in closing a patent
ductus arteriosus (PDA) if it is administered in the first 10-14 days of life. Other options are
catheter closure and surgical ligation.
8) Neurological problems:
Any baby had born less than 32 weeks or his birth weight less than 1500g are
subjected to intraventricular hemorrhage. It is a bleeding into the brain's
ventricular system, where the cerebrospinal fluid is produced and circulates
through towards the subarachnoid space.
It is a hemorrhage in the brain that begins in the periventricular subependymal
germinal matrix can progress into the ventricular system causing IVH.
If the baby born less than 32 weeks, there will be something called the germinal
matrix (meshwork of capillary network, surrounding the ventricles in the brain),
if there is swinging of their blood pressure or swinging in oxygen in those babies
that will lead to rupture of these capillaries and have bleeding inside the ventricles
[we are talking about brain ventricles not heart ventricles].
The cause of IVH in premature infants, unlike that in older infants, children or adults, is rarely
due to trauma. Instead it is thought to result from changes in perfusion of the delicate cellular
structures that are present in the growing brain, augmented by the immaturity of the cerebral
circulatory system, which is especially vulnerable to hypoxic ischemic encephalopathy. The lack of
blood flow results in cell death and subsequent breakdown of the blood vessel walls, leading to
bleeding. While this bleeding can result in further injury, it is itself a marker for injury that has
already occurred. Most intraventricular hemorrhages occur in the first 72 hours after birth
There are different stages of intraventricular hemorrhage, usually grade 1, grade 2
and grade 3, most of the time there are no consequences, as the blood will be
reabsorbed by the brain, but if they are grade 4 or the baby develops obstructive
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hydrocephalus because of the bleeding, they will run into trouble and poor
neurological outcome.
IVH is often described in four grades:
Grade I - bleeding occurs just in the germinal matrix.
Grade II - bleeding also occurs inside the ventricles, Subependymal
hemorrhage with extension into lateral ventricles without ventricular
enlargement
Grade III - ventricles are enlarged by the blood, Subependymal hemorrhage
with extension into lateral ventricles with ventricular enlargement,
Grade IV - there is bleeding into the brain tissues around the ventricles,
Intraparenchymal hemorrhage
Periventricular leukomalacia:- PVL is a disorder of the periventricular white
matter, similar to periventricular hemorrhagic infarction . It consists of
periventricular focal necrosis, with subsequent cystic formation, and more diffuse cerebral white
matter injury. PVL is the major form of brain white matter injury that affects premature infants,
and is associated with the subsequent development of cerebral palsy, intellectual impairment, and
visual disturbances.
If the baby enters hypotensive episodes or hypoxia this will lead to infraction in
the white matter of the brain, usually this infraction appears when they are
correctly full term baby, we do ultrasound before they leave the NICU, we detect
cystic changes in the white matter, if you see these cystic changes then the baby
has high chance of developing cerebral palsy (CP).
9) Susceptibility to infection:- The preterm infants are susceptible for
infection because of more than one reason:
WBC counts in these babies are normal but functionally are effected,
there is decrease in the chemotactic activity of WBC, so they are more
liable for infection
Immunoglobulins are transferred from mother to the baby in the 3rd
trimester, so if you are born premature they don't have chance to have these
immunoglobulin.

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 A lot of iatrogenic measures done for the premature infants such as

umbilical lines, percutaneous lines, the endotracheal tubes, and venous
punctures for sampling all these lead to increase susceptibility for infection.
Poor skin barrier, umbilical stump, and more traumas, also contribute to
more risk of infection
10)

GI and NEC (necrotizing enterocolitis):

The preterm infants because of lack of primitive reflex, we start feeding them
gradually through nasogatric tube or orogastric tube and one of the complications
of this process is necrotizing enterocolitis (NEC).
Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI)
medical/surgical emergency occurring in neonates.
Necrotizing enterocolitis represents a significant clinical problem and affects close to 10% of
infants who weigh less than 1500 g, with mortality rates of 50% or more depending on severity.
Although it is more common in premature infants, it can also be observed in term and near-term
babies. NEC is infrequent in term infants (<10% of affected infants).
Most cases of NEC occur in premature infants born before 34 weeks' gestation who have been fed
enterally. Prematurity is associated with immaturity of the gastrointestinal tract, including
decreased integrity of the intestinal mucosal barrier, depressed mucosal enzymes, suppressed
gastrointestinal hormones, suppressed intestinal host defense system, decreased coordination of
intestinal motility, and differences in blood flow autoregulation, which is thought to play a
significant role in the pathogenesis of NEC. More than 90% of infants diagnosed with NEC have
been fed enterally; however, NEC has been reported in infants who have never been fed. Feeding
with human milk has shown a beneficial role in reducing the incidence of NEC. <<<< NELSON
ESSENTIALS
What happen in the preterm infants because they are subjected to hypoxia and
swinging blood pressure once they are born, they develop what is called the diving
reflex. When someone is going to dive, his blood is distributed to major organs like
brain, heart, kidney and adrenal glands, because of this there will be less amount of
blood going to the intestine, so the intestine because of hypoxia become more
friable in their mucosa.
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Once we introduce the feeding to the premature infants because of hypoxia when
the mucosa are friable because of its immaturity there will be injury to the mucosa
and bacterial overgrowth and bacterial translocation, this will lead to more and
more swelling and congestion of the Intestine, this may further increase the
venous compression and then arterial pressure, to end up in ischemia and
perforation. The presentation shows mild symptoms like feeding intolerance,
abdominal distention, increased gastric residuals, bloody diarrhea and bleeding
per rectum, and severe cases may present with perforation.
11) Ophthalmic problems:
Retinopathy of prematurity (ROP): It is caused by disorganized growth of
retinal blood vessels. It is caused by the acute and chronic effects of oxygen
toxicity on the developing blood vessels of the premature infant's retina.
An initial injury caused by factors such as hypotension, hypoxia, or hyperoxia, with free radical
formation, injures newly developing blood vessels and disrupts normal angiogenesis. Following
this disruption, vessels either resume normal growth or new vessels grow abnormally out from the
retina into the vitreous. Increased permeability of these abnormal new vessels
(neovascularization) can result in retinal edema and hemorrhage. <<<<UPTODATE
Babies less than 32 weeks, less than 1500 g because of prematurity of retina and
the presence of certain factors like endothelin-1, use of high oxygen tension, all of
those will lead to a new vascular formation in the retina and the premature babies
if you don't screen it in them they will end up being blind. Usually the screening
will be 34-36 weeks of GA, and if there are any signs we start treating them by
laser or cryotherapy (the use of cold in the treatment of disease).
Myopia:
Usually happens around one year of age, so we screen these babies in this age.
12) Hematological problems:
Anemia of prematurity:
Most of the preterm infants are anemic and the most common cause is iatrogenic
cause. Although their anemia is multifactorial, repeated blood sampling and
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reduced erythropoiesis with extremely low serum levels of erythropoietin (EPO)

are major determining factors.
The three basic mechanisms for the development of anemia of prematurity (AOP)
include (1) inadequate RBC production, (2) shortened RBC life span, and (3)
blood loss.
The transition from a relatively hypoxic state in utero to a relatively hyperoxic
state with increased tissue oxygenation after birth leads to a decline in
erythropoietin (EPO) concentration
After the delivery of the baby, the amount of the blood in his circulation is around
85 cc per kg (average is 70-80ml/kg, and higher in the premature), if the baby is 1
kg the amount of the blood in his circulation will be 80 cc only, so if we keep
drawing blood for our investigation that leads for those patients to become
anemic. Again a lot of destruction of RBC happens early in life, so mostly those
infants have multiple blood transfusions with all complications of blood
transfusion.
13) Renal problems
The premature infants kidneys are not mature enough, so they can't concentrate
their urine and they lose a lot of fluids, so we need to be careful in the amount of
fluids that we are giving to those babies, and also they have inability to
concentrate sodium and potassium, so we need to be very careful about amount of
electrolytes that we add to their fluids.
A premature baby's kidneys may have difficulty:
filtering wastes from the blood so that substances like potassium, urea, and creatinine
(among others) are kept in proper balance;
concentrating urine -that is, getting rid of wastes from the body without excreting excess
fluids; and
producing urine -this can be a problem if the kidneys were damaged during delivery or if
the baby was without oxygen for a prolonged period of time
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Done By Ahmad Shyoukh
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