Received on December 2, 2008
Accepted on February 27, 2009

Reviews

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

¹ Division of Neonatology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA
² Division of Neonatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA
³ Gastroenterology/Hepatology Division, Department of Medicine, University of Washington School of Medicine, Seattle, WA
⁴ Centro Studi Fegato and Department of Life Sciences, University of Trieste, Trieste, Italy

^* To whom correspondence should be addressed. E-mail: Ligand{at}centurytel.net.

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 (1) the complex relationship between serum or plasma bilirubin measurements and ABE, (2) the history underlying the limited use of B_f in the clinical setting, (3) the peroxidase method for measuring B_f and technical and other issues involved in adapting the measurement to routine clinical use, (4) clinical experience using B_f in the management of newborn jaundice, and (5) 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.