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Pathogenesis and etiology of unconjugated hyperbilirubinemia in the newborn

Ronald J Wong, BA
Vinod K Bhutani, MD, FAAP
Section Editors
Steven A Abrams, MD
Elizabeth B Rand, MD
Deputy Editor
Melanie S Kim, MD


Almost all newborn infants develop a total serum or plasma bilirubin (TB) level greater than 1 mg/dL (17 micromol/L), which is the upper limit of normal for adults. As the TB increases, it produces neonatal jaundice, the yellowish discoloration of the skin and/or conjunctiva caused by bilirubin deposition [1]. Neonates with severe hyperbilirubinemia (defined as a TB >25 mg/dL [428 micromol/L]) are at risk for bilirubin-induced neurologic dysfunction (BIND), which occurs when bilirubin crosses the blood-brain barrier and binds to brain tissue

The pathogenesis and etiology of neonatal unconjugated hyperbilirubinemia is reviewed here. The clinical features, evaluation, prevention, and treatment of this disorder 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".)


Neonatal hyperbilirubinemia in infants ≥35 weeks gestational age (GA) is defined as total serum or plasma bilirubin (TB) >95th percentile on the hour-specific Bhutani nomogram (figure 1) [2].

Severe neonatal hyperbilirubinemia is defined as a TB >25 mg/dL (428 micromol/L). It is associated with an increased risk for bilirubin-induced neurologic dysfunction (BIND), which occurs when bilirubin crosses the blood-brain barrier and binds to brain tissue. (See "Clinical manifestations of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Clinical manifestations'.)

Acute bilirubin encephalopathy (ABE) is used to describe the acute manifestations of BIND. (See "Clinical manifestations of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Acute bilirubin encephalopathy'.)

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Literature review current through: Nov 2017. | This topic last updated: Oct 23, 2017.
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