Neonatal Disorders


Hyperbilirubinemia:  Also known as – Neonatal
:  This disorder is the result of hemolytic processes
in the neonate and brings elevated serum bilirubin levels and mild jaundice
(yellowness of the skin).  It can be physiologic (with jaundice the
only symptom)  it is very common and tends to more common and more
severe in certain ethnic groups whose mean peak of unconjugated bilirubin
is approximately twice that of the rest of the population.  It can
be pathologic (resulting from an underlying disease).  Physiologic
jaundice is self limiting; prognosis for pathologic jaundice varies, depending
on the cause.  Untreated, severe hyperbilirubinemia may result in
kernicterus, a neurologic syndrome resulting from deposition of unconjugated
bilirubin in the brain cells and characterized by severe neural symptoms. 
Survivors may develop cerebral palsy, epilepsy, or mental retardation,
or may have only minor sequelae, such as perceptual motor handicaps and
learning disorders.

Causes:  As erythrocytes break down at the end of their
neonatal life cycle, hemoglobin separates into globin (protein) and heme
(iron) fragments.  heme fragments form unconjugated  (indirect)
bilirubin, which binds with albumin for transport to lliver cells to conjugate
with glucuronide, forming direct bilirubin. Because unconjugated bilirubin
is fat soluble and cannot be excreted in the urine or bile, it may escape
to extravascular tissue, especially fatty tissue and the brain, resulting
in hyperbilirubinemia.

This pathophysiologic process may develop several ways.  Factors
that disrupt conjugation and usurp albumin-binding sites include drugs
such as aspirin, tranquilizers, and sulfonamides and conditions such as
hypothermia, anoxia, hypoglycemia, and hypoalbuminemia..  Decreased
hepatic function can result in reduced bilirubin conjugation.  increased
erythrocyte production or breakdown can accompany hemolytic disorders,
or Rh or ABO incompatibility.  Biliary obstruction or hepatitis may
block normal bile flow.  maternal enzymes present in breast milk can
inhibit the neonate’s glucuronyl transferase conjugation activity.


The predominant sign of hyperbilirubinemia is jaundice, which does not
become clinically apparent until serum bilirubin levels reach about 7 mg/100
ml.  Physiologic jaundice develops 24 hours after delivery in 50%
of term neonates (usually day 2 – day 3) and 48 hours after delivery in
80% of premature neonates (usually 3 – 5 days).  It generally disappears
by day 7 in term neonates and by day 9 or day 10 in premature neonates. 
Throughout physiologic jaundice, serum unconjugated bilirubin does not
exceed 12 mg/100 ml.  Pathologic jaundice may appear anytime after
the first day of life and persists beyond 7 days with serum bilirubin levels
greater than 12 mg/100 ml in a term neonate, 15 mg/100 ml in a premature
neonate, or increasing more than 5 mg/100 ml in 24 hours.


Depending on the underlying cause, treatment may include phototherapy,
exchange transfusions, albumin infusion, and possible drug therapy . 
Phototherapy is the treatment of choice for physiologic jaundice and pathologic
jaundice from erythroblastosis fetalis (after the initial exchange transfusion). 
Phototherapy uses fluorescent light to decompose bilirubin in the skin
by  oxidation and is usually discontinued after bilirubin levels fall
below 10 mg/100 ml and continue after bilirubin levels fall below 10 mg/100
ml and continue to decrease for 24 hours.

An exchange transfusion replaces the neonate’s blood with fresh blood
(less than 48 hours old), removing some of the unconjugated bilirubin in
serum.  Possible indications for exchange transfusions include hydrops
fetalis, polycythemia, erythroblastosis fetalis, marked reticulocytosis,
drug toxicity, and jaundice that develops within the first 6 hours after

For excessive bilirubin levels, treatment may include albumin administration,
which provides additional albumin for binding unconjugated bilirubin. 
This may be done 1 to 2 hours before exchange or as a substitute for a
portion of the plasma in the transfused blood.


Erythroblastosis Fetalis

Erythroblastosis Fetalis:   Hemolytic
anemia of the fetus or newborn due to transplacental transmission of maternally
formed antibody against the fetus erythrocytes, usually secondary to an
incompatibility between the mother’s Rh blood group and that of her offspring.

A hemolytic disease of the fetus and newborn, this disorder stems from
an incompatibility of fetal and maternal blood, resulting in maternal antibody
activity against fetal RBC’s.

Intrauterine transfusions can save 40% of fetuses with erythroblastosis. 
However, in severe, untreated erythroblastosis fetalis, prognosis is poor,
especially if kernicterus (a condition with severe neural symptoms associated
with high bilirubin in the blood) develops.

Causes:  Although more than 60 RBC antigens can stimulate
antibody formation, erythroblastosis fetalis usually results from Rh isoimmunization
– a condition that develops in approximately 7% of all pregnancies in the
US.  Before the development of Rh (D) immune globulin (human), this
condition was a major cause of kernicterus and neonatal death.

During her first pregnancy, an Rh-negative female becomes sensitized
by exposure to Rh-positive fetal blood antigens inherited from the father.
A female may also become sensitized from receiving blood transfusions with
alien Rh antigens, causing agglutinins to develop; from inadequate doses
of Rh(D); or from failure to receive Rh (D) after significant fetal maternal
leakage from abruptio placentae.  Subsequent pregnancy with an Rh-positive
fetus provokes increasing amounts of maternal agglutinating antibodies
to cross the placental barrier, attach to Rh-positive cells in the fetus,
and cause hemolysis and anemia.  To compensate for this, the fetus
steps up the production of RBC’s, and erythroblast, (immature RBC’s) appear
in the fetal circulation.  Extensive hemolysis results in the release
of large amounts of unconjugated bilirubin, which the liver is unable to
conjugate and excrete, causing hyperbilirubinemia and hemolytic anemia.


Jaundice usually isn’t present at birth but may appear as soon as 30
minutes later or within 24 hours.  The mildly affected neonate shows
mild to moderate hepatosplenomegaly and pallor.  In severely affected
neonates who survive birth, erythroblastosis fetalis usually produces pallor,
edema, petechiae, hepatosplenomegaly, grunting respiration’s, crackles,
poor muscle tone, neurologic unresponsiveness, possible heart murmurs,
a bile stained umbilical cord, and yellow or meconium stained amniotic
fluid.  Untreated neonates may develop kernicterus from hemolytic
disease and show signs such as anemia, lethargy, poor sucking ability,
retracted head, stiff extremities, squinting, a high pitched cry, and convulsions.

Hydrops fetalis causes extreme hemolysis, fetal hypoxia, heart failure
(with possible pericardial effusion and circulatory collapse), edema, peritoneal
and pleural effusions, and green or brown tinged amniotic fluid (usually
indication a stillbirth).

Other symptoms of the neonate with hydrops fetalis include: enlarged
placenta, marked pallor, hepatosplenomegaly, cardiomegaly, and ascites.


Treatment depends on the degree of maternal sensitization and the effects
of hemolytic disease on the fetus or neonate.

Intrauterine intraperitoneal transfusion is performed when amniotic
fluid analysis suggests the fetus is severely affected, and delivery is
inappropriate because of fetal immaturity.  A transabdominal puncture
under fluoroscopy into the fetal peritoneal cavity allows infusion of group
O, Rh-negative blood.

Planned delivery, usually 2 to 4 weeks before term date, depends on
maternal history, serologic tests, and amniocentesis; labor may be induced
from the 34th to 38th week of gestation.  During labor, the fetus
should be monitored electronically; capillary blood scalp sampling determines
acid base balance.  Any indication of fetal distress necessitates
immediate cesarean delivery.

phenobarbital administered during the last 5 to 6 weeks of pregnancy
may lower serum bilirubin levels in the neonate.  An exchange transfusion
removes antibody coated RBC’s and prevents hyperbilirubinemia through removal
of the neonate’s blood and replacements with fresh group O, Rh-negative
blood.  Albumin infusion helps to bind bilirubin, reducing the chances
of hyperbilirubinemia.  Phototherapy by exposure to ultraviolet light
also reduces bilirubin levels.

Neonatal therapy for hydrops fetalis consists of maintaining ventilation
by intubation, oxygenation, and mechanical assistance, when necessary;
and removal of excess fluid to relieve severe ascites and respiratory distress. 
Other appropriate measures include an exchange transfusion and maintenance
of the neonate’s body temperature.

Gamma globulin that contains anti-Rh-positive antibody (Rh (O) can provide
passive immunization, which prevents maternal Rh isoimmunization in Rh-negative
females.  However, it is ineffective if sensitization has already
resulted from a previous pregnancy, abortion, or transfusion.