Hyperbilirubinemia: subcortical mechanisms of cognitive and behavioral dysfunction.

Although development of the full syndrome of kernicterus is relatively rare, neonatal jaundice continues to occur frequently. Controversy remains concerning whether or not infants with moderate elevations in bilirubin are at risk for neurodevelopmental disorders in later childhood. Sites of brain pathology associated with bilirubin neurotoxicity are identified and well established. Based on these regions of brain involvement, we apply neuroscientific principles of brain-behavior relationships to predict types of cognitive features that may accompany hyperbilirubinemia. We address a range of neurodevelopmental abnormalities that can arise as a function of elevated neonatal bilirubin levels affecting these brain regions, even in the absence of full kernicterus syndrome. Moreover, we explain the neuropathologic mechanisms that would drive these abnormalities. We thus attempt to establish a blueprint for future investigations of these conditions, to improve neurodevelopmental outcomes.