Pathogenesis and etiology of unconjugated hyperbilirubinemia in the newborn

INTRODUCTION—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].Hyperbilirubinemia in infants≥ 35 weeks gestation is defined as a TB> 95 percentile on the hour-specific Bhutani nomogram [2]. Hyperbilirubinemia with a TB> 25 to 30 mg/dL (428 to 513 micromol/L) is associated with an increased risk for bilirubininduced neurologic dysfunction (BIND), which occurs when bilirubin crosses the blood-brain barrier and binds to brain tissue. The term" acute bilirubin encephalopathy"(ABE) is used to describe the acute manifestations of BIND. The term" kernicterus" is used to describe the chronic and permanent sequelae of BIND. Appropriate intervention is important to consider in every infant with severe hyperbilirubinemia. However, even if these infants are adequately treated, long-term neurologic sequelae (kernicterus) can sometimes develop.