PT  - JOURNAL ARTICLE
AU  - Wen, Shi Wu
AU  - Zhou, Jia
AU  - Yang, Qiuying
AU  - Fraser, William
AU  - Olatunbosun, Olufemi
AU  - Walker, Mark
TI  - Maternal exposure to folic acid antagonists and placenta-mediated adverse pregnancy outcomes
AID  - 10.1503/cmaj.080859
DP  - 2008 Dec 02
TA  - Canadian Medical Association Journal
PG  - 1263--1268
VI  - 179
IP  - 12
4099  - http://www.cmaj.ca/content/179/12/1263.short
4100  - http://www.cmaj.ca/content/179/12/1263.full
SO  - CMAJ2008 Dec 02; 179
AB  - Background: In previous studies, maternal exposure to folic acid antagonists was associated with increased risks of neural tube defects, cardiovascular defects, oral clefts and urinary tract defects. The objective of the current study was to assess the possible effects of using folic acid antagonists in pregnancy on placenta-mediated adverse outcomes of pregnancy. Methods: We used data from an administrative database to retrospectively compare the occurrence of placenta-mediated adverse pregnancy outcomes between pregnant women exposed to folic acid antagonists and women without exposure to these agents. Results: We included in the analysis a total of 14 982 women who had been exposed to folic acid antagonists and 59 825 women who had not been exposed. Sulfamethoxazole–trimethoprim was the most frequently prescribed dihydrofolate reductase inhibitor (a total of 12 546 exposures during the preconception period and all 3 trimesters), and phenobarbital was the most frequently prescribed among the other folic acid antagonists (a total of 1565 exposures). The risks of preeclampsia (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] 1.39–1.66), severe preeclampsia (OR 1.77, 95% CI 1.38–2.28), placental abruption (OR 1.32, 95% CI 1.12–1.57), fetal growth restriction defined as less than the 10th percentile (OR 1.07, 95% CI 1.01–1.13), fetal growth restriction defined as less than the 3rd percentile (OR 1.22, 95% CI 1.11–1.34) and fetal death (OR 1.35, 95% CI 1.07–1.70) were greater among mothers with exposure to folic acid antagonists. In general, the risks associated with exposure to other folic acid antagonists were higher than those associated with exposure to dihydrofolate reductase inhibitors. Supplementary analyses involving tight matching with propensity score, restriction of the analysis to women with exposure during the first and second trimesters and restriction of the analysis to specific categories of folic acid antagonists yielded similar results. Interpretation: Maternal exposure to folic acid antagonists appears to increase the risk of placenta-mediated adverse outcomes of pregnancy.