The clinical syndrome of bilirubin-induced neurologic dysfunction

Semin Fetal Neonatal Med. 2015 Feb;20(1):6-13. doi: 10.1016/j.siny.2014.12.008. Epub 2015 Jan 7.


Clinicians have hypothesized a spectrum of minor neurologic manifestations, consistent with neuroanatomical reports and collectively termed as a "syndrome of bilirubin-induced neurologic dysfunction (BIND)," which can occur in the absence of classical kernicterus. The current review builds on these initial reports with a focus on clinical signs and symptoms that are assessed by standardized tools and manifest from neonatal age to childhood. These clinical manifestations are characterized by the following domains: (i) neuromotor signs; (ii) muscle tone abnormalities; (iii) hyperexcitable neonatal reflexes; (iv) variety of neurobehavior manifestations; (v) speech and language abnormalities; and (vi) evolving array of central processing abnormalities, such as sensorineural audiology and visuomotor dysfunctions. Concerns remain that the most vulnerable infants are likely to acquire BIND, either because their exposure to bilirubin is not identified as severe enough to need treatment or is prolonged but slightly below current threshold levels for intervention. Knowing that a total serum/plasma bilirubin (TB) level is not the most precise indicator of neurotoxicity, the role of expanded biomarkers or a "bilirubin panel" has yet to be validated in prospective studies. Future studies that correlate early "toxic" bilirubin exposure to long-term academic potential of children are needed to explore new insights into bilirubin's effect on the structural and functional maturation of an infant's neural network topology.

Keywords: Bilirubin; Bilirubin-induced neurologic dysfunction (BIND); Minor neurologic dysfunction; Subtle bilirubin injury.

Publication types

  • Review

MeSH terms

  • Bilirubin / blood*
  • Humans
  • Hyperbilirubinemia, Neonatal / blood
  • Hyperbilirubinemia, Neonatal / complications*
  • Infant
  • Infant, Newborn
  • Kernicterus / blood
  • Kernicterus / etiology
  • Nervous System Diseases / blood
  • Nervous System Diseases / etiology*
  • Syndrome


  • Bilirubin