期刊
REPRODUCTIVE TOXICOLOGY
卷 15, 期 6, 页码 637-646出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0890-6238(01)00178-2
关键词
cotrimoxazole; trimethoprim-sulfamethoxazole; trimethoprim-sulfamethazine; teratogenic risk; multiple congenital abnormalities; congenital cardiovascular malformations
Objective: To study human teratogenic potential of two trimethoprim-sulfonamide combinations: trimethoprim-sulfaiiiethoxazole (cotrimoxazole) and trimethoprim-sulfamethazine during pregnancy. These agents have antifolate effects and other antifolate agents can induce multiple congenital abnormalities, neural-tube defects, cardiovascular, and other malformations in animal experiments and in humans. Design: Pair analysis of cases with congenital abnormalities and matched healthy controls in the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Participants: 38,151 pregnant women who had newborn infants without any congenital abnormalities (control group) and 22,865 case pregnant women who had newborns or fetuses with congenital abnormalities. Main Outcome: Prevalence of drug use in matched case-control pairs to study the possible association with congenital abnormalities. Results: In the case group 351 (1.5%) and in the control group 443 (1.2%) pregnant women were treated with cotrimoxazole (crude OR 1.3 with 95% CI 1.1-1.5). In addition 45 (0.2%) case and 39 (0.1%) control pregnant women had trimethoprim-sulfamethazine treatment (crude OR 1.9 with 95% CI 1.3-3.0). A higher rate of multiple congenital abnormalities (including mainly urinary tract and cardiovascular abnormalities) was found in case infants born to mothers with cotrimoxazole treatment during the second-third months of pregnancy. In addition, a higher rate of cardiovascular malformations occurred in cases born to mothers with cotrimoxazole treatment and trimethoprim-sulfamethazine treatment during the second-third months of pregnancy, respectively. Conclusion: Treatment with cotrimoxazole during pregnancy may increase the risk of cardiovascular malformations, and particularly multiple congenital abnormalities including defects of the urinary tract and cardiovascular system. A higher rate of cardiovascular malformations was also found after treatment with trimethoprim-sulfamethazine the second-third months of pregnancy. (C) 2001 Elsevier Science Inc. All rights reserved.
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