Severe neonatal hyperbilirubinemia and the brain: the old but still evolving story
Sri Jayanti, Jean‐François Ghersi‐Egea, Nathalie Strazielle, Claudio Tiribelli, Silvia Gazzin
Abstract
Abstract: The immature hepatic metabolism of bilirubin at birth is responsible for neonatal hyperbilirubinemia, present in more than 60% of otherwise healthy infants. Icterus (or jaundice), the most apparent features of the increased bilirubin level in the serum, testifies the entry of the pigment in the tissues and organs, brain included. The sensitivity of the central nervous system (CNS) to bilirubin toxicity is responsible for the potential neurologic damage, and even death. The symptoms in affected neonates suggest that selected brain areas are more specifically targeted by bilirubin, a hypothesis longer explained by the deposition of bilirubin in those areas, the “kern-icterus”. Most recently, a more complex picture and alternative explanations to the variability of the symptoms recapped by the terms bilirubin induced neurological dysfunction (BIND) or kernicterus spectrum disorder (KSD) are emerging, with pre-term neonates representing a new challenge. Here we will review what is known of the disease, from the dogma of the “kern-icterus” to the most recent findings bringing into play the stage of brain development at the time of bilirubin insult. Special emphasis will be given to the emerging population of pre-term neonates, especially sensitive to bilirubin toxicity.