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Unbound bilirubin associated with kernicterus: a historical approach
1Department of Pediatrics, Division of Neonatology, California Pacific Medical Center, San Francisco, California 94118, USA.
Objective:
To determine the unbound bilirubin concentration (UBC) associated with kernicterus with the use of clinical data from clusters of kernicterus after sulfisoxazole and benzyl alcohol administration.
Design:
Sulfisoxazole at 12 mg/dL and benzoate at 10 mmol/L are associated with kernicterus at total bilirubins near 12 and 10 mg/dL, respectively. The concurrent UBC was estimated by first measuring the drug-induced increases in UBC in plasma and artificial sera (peroxidase-diazo method). The increases were then applied to baseline UBC, determined by linear regression analysis of binding data (peroxidase method) from 86 newborns, at total bilirubins of 12 mg/dL for sulfisoxazole and 10 mg/dL for benzoate. Sensitivity and specificity were determined with existing data.
Results:
Sulfisoxazole and benzoate increased UBC in artificial sera 2.1-fold and 4.1-fold, respectively, and in plasma (sulfisoxazole) 2.4-fold. Benzoate would increase baseline UBC from 0.29 to 1.19 microg/dL and sulfisoxazole from 0.36 to 0.86 microg/dL. The sensitivity and specificity of a UBC of 0.86 microg/dL for predicting kernicterus are 79% and 92% and for 1.19 microg/dL, 50% and 98%, respectively.
Conclusion:
Historic data predict that the unbound bilirubin above which kernicterus becomes likely lies between 0.86 and 1.19 microg/dL, in good agreement with existing information.