Unbound bilirubin associated with kernicterus: a historical approach.
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.


METHODS
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.


CONCLUSIONS
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.
Ahlfors
C E
CE
Department of Pediatrics, Division of Neonatology, California Pacific Medical Center, San Francisco, California 94118, USA.
D019905:Benzyl Alcohol / Q000494:pharmacology*; D001663:Bilirubin / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D007647:Kernicterus / Q000097:blood*; D013444:Sulfisoxazole / Q000494:pharmacology*
D013444:Sulfisoxazole; D019905:Benzyl Alcohol; D001663:Bilirubin