Unbound Bilirubin: A Better Predictor of Kernicterus?

The peroxidase method described in this paper measures non–protein-bound bilirubin by oxidation of the free fraction. The oxidation rate is slow compared with rapid dissociation of albumin-bound bilirubin. Thus, the unbound bilirubin can be estimated from the initial rate of decline in total bilirubin concentration.In the 1970s, severe neonatal hyperbilirubinemia and kernicterus were major clinical problems. Kernicterus could usually be prevented by administering an exchange transfusion to infants whose serum unconjugated bilirubin concentration reached 341 μmol/L (20 mg/dL), but the diagnostic specificity of 341 μmol/L (20 mg/dL) was quite poor. Premature infants sometimes developed encephalopathy at very low bilirubin concentrations, especially when receiving sulfonamides.While engaged in a fellowship in neonatal medicine, I was stimulated by Gerald Odell’s 1959 paper, in which he used pharmacological arguments to explain how these drugs produced kernicterus by …