Neural tube defects in relation to use of folic acid antagonists during pregnancy

Periconceptional folic acid supplementation reduces the risk of neural tube defects (NTDs). To determine whether periconceptional exposure to folic ac id antagonists (FAAs) might therefore increase the risk of NTDs, the author s examined data from an ongoing case-control study of birth defects (1979-1 998) in the United States and Canada. They compared data on 1,242 infants w ith NTDs (spina bifida, anencephaly, and encephalocele) with data from a co ntrol group of 6,660 infants with malformations not related to vitamin supp lementation. Mothers were interviewed within 6 months of delivery about dem ographic, reproductive, medical, and behavioral factors and about medicatio n use. The adjusted odds ratios of NTDs related to exposure to FAAs (includ ing carbamazepine, phenobarbital, phenytoin, primidone, sulfasalazine, tria mterene, and trimethoprim) during the first or second months after the last menstrual period, compared with no use in either month, were 2.8 (95% conf idence interval: 1.7, 4.6) for FAAs as a group, 4.8 (95% confidence interva l: 1.5, 16.1) for trimethoprim (based on five exposed cases), and 6.9 (95% confidence interval: 1.9, 25.7) for carbamazepine (six exposed cases). Thes e results are adjusted for region, interview year, periconceptional folic a cid supplementation, maternal age, weight, education, and infections early in pregnancy. These findings suggest that a number of FAAs may increase NTD risk, and they provide estimates of risk for selected drugs.