A possible association between congenital abnormalities and the use of different sulfonamides during pregnancy

ArticleinCongenital Anomalies 44(2):79-86 · July 2004with12 Reads
Impact Factor: 1.08 · DOI: 10.1111/j.1741-4520.2004.00012.x · Source: PubMed
Abstract

ABSTRACT 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.

    • "Given close to term, they have been known to cause neonatal hemolytic anemia, neonatal jaundice and theoretically , kernicterus [5,37,61]. Due to their mechanism of action, teratogenicity of sulfonamides has been suspected, and one study has linked sulfonamides specifically to ventricular septal defects and talipes [62]. In a large population-based case-control study (using data from the NBDPS) of more than 30 birth defects, the exposure to a number of antibiotics during the first 3 months of pregnancy and 1-month preconception was reported. "
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    • "After trimethoprim-sulfamethazine (co-trimoxazole) use during the second and/or third gestational month of pregnant women, a higher risk of CHD was found in their children [7,8]. A higher risk of CHD was also observed after the intake of certain sulfonamides [47]. However, the most important argument for the role of FA in the pathogenesis of CHD was that the risk of CHD after the use of FA-antagonists without concomitant use of MVs was 7.7 (95% CI: 2.8–21.7) "
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    • "[20] was found in their children. A higher risk of CVMs was also observed after the intake of certain sulfonamides (OR with 95% CI: 3.5, 1.9-6.4)[21]. However, the most important argument for the role of FA in the pathogenesis of CVMs was that the risk of CVMs after the use FA antagonists without concomitant use of MVs was 7.7 (95% CI: 2.8- 21.7) while this risk was only 1.5 (95% CI: 0.6-3.8) "
    [Show abstract] [Hide abstract] ABSTRACT: The prevention of neural tube defects with periconceptional folic acid or folic acid-containing multivitamin supplementation is accepted by the scientific community; here the possible prevention of cardiovascular malformations is discussed. The aim of this presentation is to show the main findings of trials and studies that resulted in the prevention of neural tube defects and particularly cardiovascular malformations by folic acid-containing multivitamins or folic acid supplementation in order to stimulate the incorporation of folic acid-containing multivitamins or folic acid in the prevention of cardiovascular malformations.
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