title: Toward understanding kernicterus: a challenge to improve the management of jaundiced newborns.
abstract: OBJECTIVE
  We sought to evaluate the sensitivity and specificity of total serum bilirubin concentration (TSB) and free (unbound) bilirubin concentration (Bf) as predictors of risk for bilirubin toxicity and kernicterus and to examine consistency between these findings and proposed mechanisms of bilirubin transport and brain uptake.
  
  
  METHODS
  A review of literature was undertaken to define basic principles of bilirubin transport and brain uptake leading to neurotoxicity. We then reviewed experimental and clinical evidence that relate TSB or Bf to risk for bilirubin toxicity and kernicterus.
  
  
  RESULTS
  There are insufficient published data to precisely define sensitivity and specificity of either TSB or Bf in determining risk for acute bilirubin neurotoxicity or chronic sequelae (kernicterus). However, available laboratory and clinical evidence indicate that Bf is better than TSB in discriminating risk for bilirubin toxicity in patients with severe hyperbilirubinemia. These findings are consistent with basic pharmacokinetic principles involved in bilirubin transport and tissue uptake.
  
  
  CONCLUSIONS
  Experimental and clinical data strongly suggest that measurement of Bf in newborns with hyperbilirubinemia will improve risk assessment for neurotoxicity, which emphasizes the need for additional clinical evaluation relating Bf and TSB to acute bilirubin toxicity and long-term outcome. We speculate that establishing risk thresholds for neurotoxicity by using newer methods for measuring Bf in minimally diluted serum samples will improve the sensitivity and specificity of serum indicators for treating hyperbilirubinemia, thus reducing unnecessary aggressive intervention and associated cost and morbidity.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Washington, Box 356320, Seattle, WA 98195, USA. rpwennberg@hotmail.com
authors.forename: Richard P
authors.initials: RP
authors.lastname: Wennberg
authors.forename: Charles E
authors.initials: CE
authors.lastname: Ahlfors
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Bhutani
authors.forename: Lois H
authors.initials: LH
authors.lastname: Johnson
authors.forename: Steven M
authors.initials: SM
authors.lastname: Shapiro
mesh_terms: D001663:Bilirubin / Q000097:blood* / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000150:complications / Q000175:diagnosis; D007647:Kernicterus / Q000097:blood / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000032:analysis
chemical_list: D012709:Serum Albumin; D001663:Bilirubin