A population-based case-control teratologic study of promethazine use during pregnancy.

Objective of the study was to investigate the teratogenic effect of oral promethazine, a phenothiazine derivate in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities during the years 1980-1996. Of 22,843 cases with 25 congenital abnormalities, 3648 (16.0%) were born to mothers treated orally with promethazine during pregnancy. Of 38,151 matched population controls without congenital abnormalities, 6025 (15.8%) had mothers with promethazine treatment during the study pregnancy. Of 834 malformed controls (Down syndrome), 142 (17.0%) had mothers with treatment of promethazine in the study pregnancy. The case-all matched population controls analysis showed a higher rate of cleft lip+/-cleft palate (adjusted OR with 95% CI: 1.5, 1.1-2.0) and poly/syndactyly (OR with 95% CI: 1.3, 1.0-1.8) after promethazine treatment during the 2nd and 3rd months of gestation. However, these risks were explained by recall bias, because these associations were not confirmed after the evaluation of only medically recorded promethazine uses. The comparison of promethazine treatment between 25 congenital abnormality groups and malformed controls did also not show any risk. Thus, the overall evidence from analysis presented did not suggest that clinical doses of promethazine increased the rate of congenital abnormalities in humans.