title: Neonatal bilirubin binding capacity discerns risk of neurological dysfunction.
abstract: BACKGROUND
  Bilirubin binding capacity (BBC) defines the dynamic relationship between an infant's level of unbound or "free" bilirubin and his/her ability to "tolerate" increasing bilirubin loads. BBC is not synonymous with albumin (Alb) levels because Alb binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors.
  
  
  METHODS
  We utilized a novel modification of a previously developed hematofluorometric method to directly assay BBC in whole blood from preterm and term neonates and then combined these data with an archived database. Total bilirubin (TB) was also measured, and multiple regression modeling was used to determine whether BBC in combination with TB measurements can assess an infant's risk for developing bilirubin-induced neurotoxicity.
  
  
  RESULTS
  TB and BBC levels ranged from 0.7-22.8 to 6.3-47.5 mg/dl, respectively. Gestational age (GA) correlated with BBC (r = 0.54; P < 0.0002) with a slope of 0.93 mg/dl/wk by logistic regression. Our calculations demonstrate that recently recommended GA-modulated TB thresholds for phototherapy and exchange transfusion correspond to 45 and 67% saturation of our observed regression line, respectively.
  
  
  CONCLUSIONS
  We speculate that the spread of BBC levels around the regression line (± 5.8 mg/dl) suggests that individualized BBC assays would provide a robust approach to gauge risk of bilirubin neurotoxicity compared with TB and GA.
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Lamola
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Bhutani
authors.affiliation: Department of Pediatrics, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Lizhong
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Martin
authors.initials: M
authors.lastname: Castillo Cuadrado
authors.affiliation: Department of Pediatrics, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wong
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
mesh_terms: D000704:Analysis of Variance; D001663:Bilirubin / Q000097:blood / Q000378:metabolism* / Q000633:toxicity*; D005470:Fluorometry / Q000379:methods; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D016015:Logistic Models; D020258:Neurotoxicity Syndromes / Q000097:blood* / Q000209:etiology*; D011446:Prospective Studies; D011485:Protein Binding; D018570:Risk Assessment / Q000379:methods*
chemical_list: D001663:Bilirubin