Hyperbilirubinemia in the premature infant (less than 35 weeks gestation)
- Vinod K Bhutani, MD, FAAP
Vinod K Bhutani, MD, FAAP
- Professor of Pediatrics
- Stanford University School of Medicine
- Ronald J Wong, BA
Ronald J Wong, BA
- Senior Research Scientist
- Stanford University School of Medicine
Almost all preterm infants less than 35 weeks gestational age (GA) have elevated total serum/plasma bilirubin (TB) levels, which results in neonatal jaundice, the yellowish discoloration of the skin, and/or conjunctiva caused by bilirubin deposition. The major complication of an elevated TB (hyperbilirubinemia) is bilirubin-induced neurologic dysfunction (BIND), which occurs when circulating bilirubin crosses the blood-brain barrier and binds to brain tissue. Acute bilirubin encephalopathy (ABE) is the acute and reversible form of BIND, while kernicterus is the chronic and permanent neurologic sequelae of BIND.
Therapeutic interventions (ie, phototherapy and exchange transfusion) reduce the TB levels in the blood, which is thought to prevent BIND and, hence, kernicterus. In infants at or greater than 35 weeks GA (ie, term and late preterm infants), universally-accepted guidelines based upon an age-specific, percentile-based TB nomogram are used to decide when to initiate phototherapy and exchange transfusions to prevent severe hyperbilirubinemia and BIND . (See "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants".)
However, in infants less than 35 weeks GA, similar guidelines are not available, despite observational evidence that suggest preterm infants less than 35 weeks GA are more susceptible to BIND at lower TB levels than more mature infants. Lack of an evidence-based consensus on the management of hyperbilirubinemia in the preterm infant is due to the variability of clinical manifestations and spectrum of BIND, lack of reliable and predictive measures of bilirubin neurotoxicity, and the uncertainty of the relative risks and benefits of interventions to reduce TB levels (ie, phototherapy and exchange transfusions), particularly in the extremely low birth weight (ELBW) infant (birth weight [BW] ≤1000 g).
Hyperbilirubinemia in the premature infant <35 weeks GA will be reviewed here. The diagnosis, evaluation, and management of hyperbilirubinemia in the late preterm and term infant are discussed separately. (See "Clinical manifestations of unconjugated hyperbilirubinemia in term and late preterm infants" and "Evaluation of unconjugated hyperbilirubinemia in term and late preterm infants" and "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants".)
The prevalence of kernicterus in premature infants is uncertain. A retrospective study reported a 4 percent rate of kernicterus based upon characteristic postmortem neuropathological findings (ie, bilirubin staining and neuronal necrosis) in 81 preterm infants (gestational age [GA] <34 weeks) who died after 48 hours of life .
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- Bilirubin-induced neurologic dysfunction (BIND)
- CLINICAL MANIFESTATIONS
- Neurologic findings
- - Acute
- - Kernicterus
- Laboratory testing
- - Total bilirubin (TB)
- Transcutaneous bilirubin (TcB)
- - Free bilirubin
- Unknown risk and benefit of phototherapy
- - Prophylactic phototherapy
- - Light source and devices
- Exchange transfusion
- Our approach
- Other approaches
- SUMMARY AND RECOMMENDATIONS