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


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Czeizel
A E
AE
Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary. czeizel@mail.interware.hu
Rockenbauer
M
M
Sørensen
H T
HT
Olsen
J
J
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000328:Adult; D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects*; D016022:Case-Control Studies; D004338:Drug Combinations; D005260:Female; D005865:Gestational Age; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D007231:Infant, Newborn; D011159:Population Surveillance; D011247:Pregnancy; D011256:Pregnancy Outcome; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013418:Sulfamethazine / Q000009:adverse effects*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects*
D000892:Anti-Infective Agents, Urinary; D004338:Drug Combinations; D013418:Sulfamethazine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination