Unbound (Free) Bilirubin: Improving the Paradigm for Evaluating Neonatal Jaundice

BACKGROUND: The serum or plasma total bilirubin concentration (B-T) has long been the standard clinical laboratory test for evaluating neonatal jaundice, despite studies showing that B-T correlates poorly with acute bilirubin encephalopathy (ABE) and its sequelae including death, classical kernicterus, or bilirubin-induced neurological dysfunction (BIND). The poor correlation between B-T and ABE is commonly attributed to the confounding effects of comorbidities such as hemolytic diseases, prematurity, asphyxia, or infection. Mounting evidence suggests, however, that B-T inherently performs poorly because it is the plasma non-protein-bound (unbound or free) bilirubin concentration (B-f), rather than B-T, that is more closely associated with central nervous system bilirubin concentrations and therefore ABE and its sequelae. CONTENT: This article reviews (a) the complex relationship between serum or plasma bilirubin measurements and ABE, (b) the history underlying the limited use of B-f in the clinical setting, (c) the peroxidase method for measuring B-f and technical and other issues involved in adapting the measurement to routine clinical use, (d) clinical experience using B-f in the management of newborn jaundice, and (e) the value of B-f measurements in research investigating bilirubin pathochemistry. SUMMARY: Increasing evidence from clinical studies, clinical experience, and basic research investigating bilirubin neurotoxicity supports efforts to incorporate B-f expeditiously into the routine evaluation of newborn jaundice. (C) 2009 American Association for Clinical Chemistry