Fetal cocaine exposure and neonatal bilirubinemia.
To assess the effect of fetal exposure to cocaine on neonatal serum bilirubin values, we compared 17 infants whose cocaine exposure was confirmed by urine toxicology studies, with no evidence of other drug exposure by history or urinalysis, with 31 sequentially born healthy term infants without evidence of maternal drug use. The mean (+/- SD) bilirubin concentration in control infants was 110 +/- 32 mumol/L (6.5 +/- 1.9 mg/dl) at 30.5 +/- 5.4 hours of age, compared with 55 +/- 26 mumol/L (3.2 +/- 1.5 mg/dl) at 30.8 +/- 5.3 hours in cocaine-exposed infants (p < 0.001). We also compared the abilities of cocaine and clofibrate, a known inducer of bilirubin uridine diphosphate-glucuronosyl transferase (BGT), to induce drug and bilirubin metabolizing pathways in young male Sprague-Dawley rats. Animals received drugs or saline solution for 7 days, and livers were assayed for cytochrome P-450, peroxisomal beta-oxidase, delta 5-3-ketosteroid isomerase (KSI), glutathione-S-transferase (GST), and BGT. Cocaine was a weak inducer of GST but a strong inducer of KSI, a member of the GST family of enzymes that is closely associated with bilirubin transport (ligandin) in liver, and a moderately strong inducer of BGT. Neither drug increased cytochrome P-450 levels, and only clofibrate induced peroxisomal beta-oxidase. We conclude that cocaine appears to induce bilirubin metabolizing pathways, resulting in a lower risk of neonatal hyperbilirubinemia.
Wennberg
R P
RP
Department of Pediatrics, University of California, Davis 95616.
Yin
J
J
Miller
M
M
Maynard
A
A
D000818:Animals; D001663:Bilirubin / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D002994:Clofibrate / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002994:Clofibrate; D003042:Cocaine; D001663:Bilirubin