Nitrosatable Drug Exposure during Pregnancy and Adverse Pregnancy Outcome

Abstract

Olshan A F (Department of Epidemiology, SC-36, University of Washington, Seattle, Washington 98195, USA) and Faustman E M. Nitrosatable drug exposure during pregnancy and adverse pregnancy outcome. International Journal of Epidemiology 1989, 18: 891–899. Recent investigations have suggested that drugs that are amines can undergo endogenous or exogenous nitrosation reactions to form N-nitroso compounds. These compounds have been extensively characterized in animal models as carcinogens, mutagens and teratogens. In order to examine the possible effects of exposure to nitrosatable drugs during gestation on pregnancy outcome, data were utilized from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. Pregnancy outcomes for 6061 pregnancies in which the mother ingested a drug known to undergo nitrosation were compared with 6921 randomly sampled pregnancies without such exposure. The major outcome factors of interest were birth defects, fetal, neonatal and infant death and birthweight. Our findings suggest that no significant increases in risk of fetal, neonatal and infant death or low birthweight were associated with nitrosatable drug exposure during pregnancy. However, the risk of a tumour in the offspring of exposed mothers was increased (relative risk, RR = 2.29; 95% Cl 0.99–5.26). Increases in relative risk of major malformations was also observed and this increase was greater when exposure during the first four months of pregnancy was examined separately (RR = 1.33; 1.11–1.58). There were specific individual malformations that were observed to have increased relative risks (for example: eye malformations, hydrocephaly, craniosynostosis and meningomyelocoele/meningocoele) but interpretation was difficult due to multiple comparisons and some of these observations were associated with wide confidence intervals. These types of adverse pregnancy outcomes were consistent with animal study outcomes.