The objective of the study presented here was to check the debated human teratogenic potential of
sulfonamide drugs. Five different
sulfonamides such as
sulfamethazine,
sulfathiourea,
sulfamethoxypyridazine,
sulfamethoxydiazine and the combination of
sulfamethazine-
sulfathiourea-
sulfamethoxypyridazine were differentiated. Cases with
congenital abnormalities were compared with their matched controls without
congenital abnormalities in the population-based large data set of the Hungarian Case-Control Surveillance of
Congenital Abnormalities between 1980 and 1996. Of 38,151 newborn infants without any
congenital abnormalities (control group), 163 (0.4%) had mothers who were treated with the
sulfonamides studied during pregnancy, while of 22,843 cases with
congenital abnormalities, 140 (0.6%) had mothers who were treated with the
sulfonamides studied during pregnancy. The analysis of cases and matched controls indicated a higher rate of cardiovascular malformation (adjusted prevalence odds ratios [POR] with 95% CI: 3.5, 1.9-6.4) and
clubfoot (adjusted POR with 95% CI: 2.6, 1.1-6.2) in infants born to mothers with
sulfonamide treatment in the second and third months of pregnancy. The detailed analysis of different
sulfonamides showed a possible association between cardiovascular malformations (adjusted POR with 95%; CI: 6.5, 2.6-15.9), particularly
ventricular septal defect (17.1, 1.3-141.1) and
sulfamethoxydiazine during the second and third months of pregnancy. In addition, a possible association was found between
clubfoot and
sulfathiourea, both during the entire pregnancy (adjusted POR with 95% CI: 2.3, 1.2-4.3) and in the second and third months of gestation (3.9, 1.1-13.8). Thus, maternal treatment of
sulfamethoxydiazine may cause
ventricular septal defect, while
sulfathiourea may induce
clubfoot; however, further studies are needed to verify or reject these associations.