The teratogenic risk of trimethoprim-sulfonamides: A population based case-control study

E. Czeizel, M. Rockenbauer, H. T. Sørensen, J. Olsen

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Objective: To study human teratogenic potential of two trimethoprim-sulfonamide combinations: trimethoprim-sulfamethoxazole (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 trimethoprimsulfamethazine 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 in the second-third months of pregnancy.

Original languageEnglish
Pages (from-to)637-646
Number of pages10
JournalReproductive Toxicology
Volume15
Issue number6
DOIs
Publication statusPublished - 2001

Fingerprint

Trimethoprim
Sulfonamides
Sulfamethoxazole Drug Combination Trimethoprim
Case-Control Studies
Sulfamethazine
Multiple Abnormalities
Population
Folic Acid Antagonists
Pregnant Women
Pregnancy
Urinary Tract
Cardiovascular system
Defects
Therapeutics
Mothers
Newborn Infant
Cardiovascular Abnormalities
Control Groups
Neural Tube Defects
Animals

Keywords

  • Congenital cardiovascular malformations
  • Cotrimoxazole
  • Multiple congenital abnormalities
  • Teratogenic risk
  • Trimethoprim- sulfamethazine
  • Trimethoprim-sulfamethoxazole

ASJC Scopus subject areas

  • Toxicology

Cite this

The teratogenic risk of trimethoprim-sulfonamides : A population based case-control study. / Czeizel, E.; Rockenbauer, M.; Sørensen, H. T.; Olsen, J.

In: Reproductive Toxicology, Vol. 15, No. 6, 2001, p. 637-646.

Research output: Contribution to journalArticle

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abstract = "Objective: To study human teratogenic potential of two trimethoprim-sulfonamide combinations: trimethoprim-sulfamethoxazole (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 trimethoprimsulfamethazine 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 in the second-third months of pregnancy.",
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T1 - The teratogenic risk of trimethoprim-sulfonamides

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AU - Sørensen, H. T.

AU - Olsen, J.

PY - 2001

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N2 - Objective: To study human teratogenic potential of two trimethoprim-sulfonamide combinations: trimethoprim-sulfamethoxazole (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 trimethoprimsulfamethazine 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 in the second-third months of pregnancy.

AB - Objective: To study human teratogenic potential of two trimethoprim-sulfonamide combinations: trimethoprim-sulfamethoxazole (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 trimethoprimsulfamethazine 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 in the second-third months of pregnancy.

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KW - Teratogenic risk

KW - Trimethoprim- sulfamethazine

KW - Trimethoprim-sulfamethoxazole

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