Neonatal bilirubin binding capacity discerns risk of neurological dysfunction

Pediatr Res. 2015 Feb;77(2):334-9. doi: 10.1038/pr.2014.191. Epub 2014 Nov 24.

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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Bilirubin / blood
  • Bilirubin / metabolism*
  • Bilirubin / toxicity*
  • Fluorometry / methods
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature / metabolism*
  • Logistic Models
  • Neurotoxicity Syndromes / blood*
  • Neurotoxicity Syndromes / etiology*
  • Prospective Studies
  • Protein Binding
  • Risk Assessment / methods*

Substances

  • Bilirubin