A population-based case-control teratologic study of ampicillin treatment during pregnancy

OBJECTIVE: This was a study of the association between ampicillin treatment during pregnancy and prevalence of different congenital abnormalities. STUDY DESIGN: The paired analysis of case patients with congenital abnormalities and matched population control subjects was performed in the population-based Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 38,151 pregnant women who had babies without any defects (population control group), 2632 (6.9%) had been treated with ampicillin. Of 22,865 pregnant women who had offspring with congenital abnormalities (case patients), 1643 (7.2%) had been treated with ampicillin (crude odds ratio, 1.0; 95% confidence interval, 0.7-1.2). Of 812 mothers who were delivered of babies affected by Down syndrome (patient control subjects), 61 (7.5%) had ampicillin treatment, and these were also compared with the case group. RESULTS: The prevalence of ampicillin use during the second and third months of gestation, which is the critical period for most major congenital abnormalities, showed significant difference in the case-control pair analysis only for cleft palate (odds ratio, 4.2; 95% confidence interval, 1.4-16.3). This possible association was confirmed by the analysis of medically recorded ampicillin use and by the comparison of ampicillin treatment between the group with cleft palate and the patient control subjects. CONCLUSION: Treatment with ampicillin during pregnancy may pose little if any teratogenic risk in human beings. Only a higher prevalence of cleft palate was found after the ampicillin treatment during the second and third months of gestation. The lack of an experimental animal model and the lack of consistency with previous epidemiologic studies may indicate that even this apparent risk is not real and instead is a chance association; further investigation is therefore necessary.