NEONATAL

HYPERBILIRUBEMIA
(JAUNDICE IN NEONATES)
WHAT IS JAUNDICE??
Jaundice is a condition that makes a newborn’s skin and the white part of the
eyes look yellow.
It happens because there is too much bilirubin in the baby’s blood
(hyperbilirubinemia).
Bilirubin is a substance that is made when the body
breaks down old red blood cells.
Jaundice usually is not a problem. But in rare cases, too much
bilirubin in the blood can cause brain damage (kernicterus).
This can lead to hearing loss, mental retardation, and behavior
problems.

In healthy babies, some jaundice almost always appears by 2 to 4 days of age. It

usually gets better or goes away on its own within a week or two without causing
problems.
In breast-fed babies, mild jaundice sometimes lasts until 10 to 14 days after birth. In some
breast-fed babies, it goes away and then comes back. Jaundice may last throughout breast-
feeding. This isn't usually a problem as long as the baby gets enough milk by being fed at
regular times.
 Kernicterus
Is the major consequence of neonatal hyperbilirubinemia.
Although it is now rare, kernicterus still occurs and can nearly always be prevented.

Kernicterus is brain damage caused by unconjugated bilirubin

deposition in basal ganglia and brain stem nuclei, caused by either acute
or chronic hyperbilirubinemia. Normally, bilirubin bound to serum
albumin stays in the intravascular space.

However, bilirubin can cross the blood-brain barrier and cause kernicterus in certain
situations:
 When serum bilirubin concentration is markedly elevated
 When serum albumin concentration is markedly low (eg, in preterm infants)
 When bilirubin is displaced from albumin by competitive binders
Pathophysiology
The majority of bilirubin is produced from the breakdown of Hb into
unconjugated bilirubin (and other substances). Unconjugated
bilirubin binds to albumin in the blood for transport to the liver,
where it is taken up by hepatocytes and conjugated with glucuronic
acid by the enzyme uridine diphosphogluconurate
glucuronosyltransferase (UGT) to make it water-soluble. The
conjugated bilirubin is excreted in bile into the duodenum.
In adults, conjugated bilirubin is reduced by gut bacteria to
urobilin and excreted.

Neonates, however, have sterile digestive tracts. They do have the enzyme β-
glucuronidase, which deconjugates the conjugated bilirubin, which is then
reabsorbed by the intestines and recycled into the circulation. This is
called enterohepatic circulation of bilirubin
Mechanisms of
hyperbilirubinemia
:Hyperbilirubinemia can be caused by one or more of the
following processes:

•Increased production
•Decreased hepatic uptake
•Decreased conjugation
•Impaired excretion
•Impaired bile flow (cholestasis)
•Increased enterohepatic circulation
Etiology
There are several ways to classify and discuss causes of
hyperbilirubinemia.

Because transient jaundice is common among healthy neonates

(unlike adults, in whom jaundice always signifies a disorder),
hyperbilirubinemia can be classified as physiologic or
pathologic. It can be classified by whether the
hyperbilirubinemia is unconjugated, conjugated, or both. It
also can be classified by mechanism.
Unconjugated
Hyperbilirubinemia
Physiologic hyperbilirubinemia
Breastfeeding jaundice
Breast milk jaundice
Pathologic hyperbilirubinemia due to
hemolytic disease
Physiologic hyperbilirubinemia

This occurs in almost all neonates. Shorter neonatal

RBC life span increases bilirubin production; deficient
conjugation due to the deficiency of UGT decreases
clearance; and low bacterial levels in the intestine
combined with increased hydrolysis of conjugated
bilirubin increase enterohepatic circulation. Bilirubin
levels can rise up to 18 mg/dL by 3 to 4 days of life (7
days in Asian infants) and fall thereafter.
Breastfeeding jaundice
develops in one sixth of breastfed infants in the first
week of life. Breastfeeding increases enterohepatic
circulation of bilirubin in some infants who have
decreased milk intake and who also have dehydration
or low caloric intake. The increased enterohepatic
circulation also may result from reduced intestinal
bacteria that convert bilirubin to nonresorbed
metabolites.
Breast milk jaundice
is different from breastfeeding jaundice. It develops
after the first 5 to 7 days of life and peaks at about 2
wk. It is thought to be caused by an increased
concentration of β-glucuronidase in breast milk,
causing an increase in the deconjugation and
reabsorption of bilirubin.
Pathologic hyperbilirubinemia
in term infants is diagnosed if
 Jaundice appears in the first 24 h, after the first week of life,
or lasts > 2 wk
 Total serum bilirubin (TSB) rises by > 5 mg/dL/day
 TSB is > 18 mg/dL
 Infant shows symptoms or signs of a serious illness

Some of the most common pathologic causes are

•Immune and nonimmune hemolytic anemia
•G6PD deficiency
•Hematoma resorption
•Sepsis
•Hypothyroidism
Liver dysfunction (eg, caused by parenteral
alimentation causing cholestasis, neonatal sepsis,
neonatal hepatitis) may cause a conjugated or mixed
hyperbilirubinemia.
Causes of Neonatal Hyperbilirubinemia
Mechanism
Increased enterohepatic circulation
Overproduction
Overproduction due to hemolytic
anemia
Undersecretion due to biliary
obstruction
Undersecretion due to metabolic-
endocrine conditions
Mixed overproduction and
undersecretion
Causes
•Breast milk (breast milk jaundice)
•Breastfeeding failure (breastfeeding jaundice)
Drug-induced paralytic ileus (Mg sulfate or morphine)
•Fasting or other cause for hypoperistalsis
•Hirschsprung's disease
•Intestinal atresia or stenosis, including annular pancreas
•Meconium ileus or meconium plug syndrome
•Swallowed blood
•Breakdown of extravascular blood (eg, hematomas; petechiae; pulmonary, cerebral, or occult hemorrhage)
•Polycythemia due to maternofetal or fetofetal transfusion or delayed umbilical cord clamping
•Certain drugs and agents in neonates with G6PD deficiency (eg, acetaminophen, alcohol, antimalarials,
aspirin, bupivacaine, corticosteroids, diazepam, nitrofurantoin, oxytocin, penicillin, phenothiazine,
sulfonamides)
•Maternofetal blood group incompatibility (eg, Rh, ABO)
•RBC enzyme deficiencies (eg, of G6PD or pyruvate kinase)
•Spherocytosis
•Thalassemias (α, β–γ)
•α1-Antitrypsin deficiency Biliary atresia
•Choledochal cyst Cystic fibrosis
•Dubin-Johnson syndrome and Rotor's syndrome Parenteral nutrition
•Tumor or band
•Crigler-Najjar syndrome Drugs and hormones
•Gilbert syndrome Hypermethioninemia
•Hypopituitarism and anencephaly Hypothyroidism
•Lucey-Driscoll syndrome Maternal diabetes
•Prematurity Tyrosinosis
•Asphyxia Intrauterine infections
•Maternal diabetes Respiratory distress syndrome
•Sepsis Severe erythroblastosis fetalis
•Syphilis TORCH infections