Dietary Folate Intake and Fecundability in Two Preconception Cohorts

Folate is an antioxidant micronutrient present in many vegetables, fruits, whole grains, beans, and the liver. Its synthetic counterpart, folic acid, is used as a dietary supplement for fortification of wheat and other foods. An average daily intake of 250 mu g dietary folate equivalents is recommended by the European Food Safety Authority for adult women. In a 2015 cohort study of American women undergoing assisted reproductive technology, a positive association was found between total folate intake (from natural sources, fortified foods, and supplements) and implantation, clinical pregnancy, and live birth rates. This association, however, was attenuated when the exposure to folate was exclusively dietary, even though folic acid from fortified foods was included. Intake of supplemental folic acid has been associated with improved fertility, but there are few data about the relation between dietary folate and fecundability. Recommendations for dosage of preconception dietary folate and folic acid supplementation are important not only to prevent neural tube defects but also to enhance fecundability. No prior study has examined the role of dietary folate and total folate (dietary and supplemental intakes) on fecundability, the per-cycle probability of conception among couples trying to conceive naturally. The aim of this study was to determine the association of dietary folate intake and total folate intake (dietary and supplemental intakes) on fecundability in 2 similar cohorts of women trying to conceive naturally. Data were obtained from 2 internet-based prospective cohort studies of pregnancy planners: SnartForaeldre.dk (SF; n = 3755), a study from Denmark, where folic acid fortification is not performed and Pregnancy Study Online (PRESTO; n = 5804), a study from North America, where the food supply is fortified with folic acid. Menstrual cycles at risk were contributed by women until pregnancy or a censoring event, whichever came first. The association between dietary folate and total folate intake and fecundability was examined by computing fecundability ratios (FRs) and 95% confidence interval (CI) using a proportional probabilities regression model. Compared with dietary folate intake =400 mu g/d, the adjusted FRs (aFRs) for women in SF were 0.92 (95% CI, 0.85-0.99) for intake 250 to 399 mu g/d and 0.80 (95% CI, 0.68-0.94) for intake less than 250 mu g/d. The corresponding aFRs in PRESTO were similar: 0.95 (95% CI, 0.89-1.01) for intake 250 to 399 mu g/d and 0.81 (95% CI, 0.65-1.00) for intake less than 250 mu g/d. Compared with the highest level of total folate intake (diet folate =400 mu g/d plus folic acid supplementation), fecundability was lowest in both cohorts among women with the lowest dietary folate intake (