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Trimethoprim and Birth Defects

Trimethoprim and other compounds that inhibit folic acid metabolism have been suspected of inducing birth defects. Observational studies have shown that using supplemental folic acid during pregnancy reduces the risk for several birth defects. Now an analysis of data from a large, multicenter, case-control study of children born with birth defects has shown that trimethoprim and other dihydrofolate reductase inhibitors are associated with cardiovascular defects and oral clefts.

Use of folic acid antagonist agents during pregnancy was determined for the mothers of 3870 infants with cardiovascular defects, 1962 with oral clefts, 1100 with urinary tract infections, and 8387 with other congenital malformations not associated with disruption of folic acid metabolism. Use of the dihydrofolate reductase inhibitors trimethoprim, triamterene, or sulfasalazine was found to increase the risk for both cardiovascular defects (relative risk, 3.4; 95 percent CI, 1.8-6.4) and oral clefts (RR, 2.6; CI, 1.1-6.1). These risks, which was limited to use of these agents during the second and third months after the last menstrual period, decreased with multivitamin supplementation. Risk was also associated with use of antiepileptic folic acid antagonists. There was no increased risk for cardiovascular defects with maternal infections during the first trimester or with the use of cephalosporins, amoxicillin, or ampicillin.

Comment: These data extend existing concerns regarding the use of trimethoprim during pregnancy. Trimethoprim should be used during pregnancy only if the potential benefits outweigh the risks. If used, it should be administered in conjunction with a supplemental multivitamin.

— R Ellison

Published in Journal Watch Infectious Diseases January 11, 2001

Citation(s):

Hernandez-Diaz et al. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000 Nov 30 343 1608-1614.

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