Kernicterus, Bilirubin-Induced Neurological Dysfunction, and New Treatments for Unconjugated Hyperbilirubinemia in Neonates

Severe hyperbilirubinemia occurs worldwide and threatens neurodevelopmental outcome of many infants. Acute kernicterus is an unambiguous clinical disorder in severely jaundiced newborn infants but may also occur in preterm infants at bilirubin levels below current treatment thresholds. Bilirubin-induced neurological dysfunction (BIND) consists of more subtle, but permanent, bilirubin encephalopathy and may present with auditory dysfunction and/or mild neurologic abnormalities such as mild impairment in neurologic and/or cognitive performance. Early prevention of severe hyperbilirubinemia is key to reduction of neurological sequelae and implies knowledge of maternal, perinatal, and neonatal risk factors. Subsequent recognition of neonates with perceived bilirubin neurotoxicity risk factors, of which hemolysis and sepsis are the most important, will enable categorization of neonates into high-, moderate-, or low-risk groups, with individualized screening and appropriate treatment. Phototherapy is the cornerstone of current treatment, and – if unsuccessful – exchange transfusion can be performed. Phototherapy does not always prevent bilirubin accumulation, and concerns exist about aggressive use in ELBW infants. Exchange transfusions are invasive procedures and associated with significant morbidity. It is highly conceivable that new treatments which either decrease bilirubin production, increase hepatic clearance, or decrease enterohepatic circulation will find their way in patients suffering severe hyperbilirubinemia and imminent BIND despite conventional treatment in the foreseeable future