Neonatal

Hyperbilirubinemia
Pathophysiology

The normal newborn produces 6 to 10 mg of bilirubin/kg/day, as opposed to

the production of 3 to 4 mg/kg/day

One gram of hemoglobin produces 34 mg of bilirubin in the adult.

The normal adult serum bilirubin level is <1 mg/dL.

Adults appear jaundiced when the serum bilirubin level is >2 mg/dL

Newborns appear jaundiced when it is >7 mg/dL.

Transport

Uptake

Conjugation

Excretion

Fetal bilirubin metabolism

Drugs That Cause Significant Displacement of Bilirubin

from Albumin In vitro

Sulfonamides

Moxalactam

Fusidic acid

Radiographic contrast media for cholangiography (sodium iodipamide, sodium ipodate, iopanoic
acid, meglumine loglycamate)

Aspirin

Apazone

Tolbutamide

Rapid infusions of albumin preservatives (sodium caprylate and N-acetyltryptophan)

Rapid infusions of ampicillin

Long-chain FFAs at high molar ratios of FFA:albumin

FFA = free fatty acid.

PHYSIOLOGIC HYPERBILIRUBINEMIA
The serum UCB level of most newborn infants rises to >2 mg/dL in the first week of life.

This level usually rises in full-term infants to a peak of 6 to 8 mg/dL by 3 days of age
and then falls.

A rise to 12 mg/dL is in the physiologic range.

In premature infants, the peak may be 10 to 12 mg/dL on the fifth day of life,
possibly rising >15 mg/dL without any specific abnormality of bilirubin metabolism.

Levels <2 mg/dL may not be seen until 1 month of age in both full-term and
premature infants

PHYSIOLOGIC HYPERBILIRUBINEMIA

A. Increased bilirubin production

1. Increased RBC volume per kilogram and decreased RBC survival (90 day versus 120 day) in
infants compared with adults.

2. Increased ineffective erythropoiesis and increased turnover of nonhemoglobin heme

proteins.

B.Increased enterohepatic circulation caused by high levels of intestinal -glucuronidase,

preponderance of bilirubin monoglucuronide rather than diglucuronide, decreased intestinal
bacteria, and decreased gut motility with poor evacuation of bilirubin-laden meconium.

C. Defective uptake of bilirubin from plasma caused by decreased ligandin and binding of
ligandin by other anions.

D. Defective conjugation due to decreased UDPG-T activity.

E. Decreased hepatic excretion of bilirubin.

NONPHYSIOLOGIC HYPERBILIRUBINEMIA
1. Onset of jaundice before 24 hours of age.
2. Any elevation of serum bilirubin that requires phototherapy (see Figs.
18.2, 18.3, 18.4 and VI.D).
3. A rise in serum bilirubin levels of >0.5 mg/dL/hour.
4. Signs of underlying illness in any infant (vomiting, lethargy, poor
feeding, excessive weight loss, apnea, tachypnea, or temperature
instability).
5. Jaundice persisting after 8 days in a term infant or after 14 days in a
premature infant.

Indirect causes