Preconception Dietary Folate Intake and Risk of Spontaneous Abortion

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Abstract Objectives Previous studies suggest a beneficial effect of supplemental folic acid use and dietary folate intake on fertility, while results for fetal loss are conflicting. Most previous research on fetal loss focused on folic acid supplement use. We therefore, investigated the association between dietary folate intake and spontaneous abortion (SAB) in a Danish preconception cohort of couples trying to conceive. Methods We recruited couples who were trying to conceive and did not receive fertility treatment. Pregnancies were ascertained through bimonthly follow-up questionnaires completed up to 12 months after study entry. SABs were identified by self-report on the follow-up questionnaires and through the Danish National Patient Registry. Dietary folate intake at study entry was estimated using a validated food frequency questionnaire (FFQ). Folate intake was adjusted for total energy intake using the residual method and categorized as < 250,250–399 and > = 400µg/day. We used Cox proportional hazards regression models with gestational weeks as time scale to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for SAB, adjusting for age, partner's age, educational attainment, smoking status, anthropometry, physical activity, alcohol intake, folic acid supplement use, time-to-pregnancy, gravidity and parity. In sensitivity analyses, we stratified by folic acid supplement use, body mass index (BMI) and alcohol intake. Results Of the 2,957 women who became pregnant within 12 months of study entry and completed the FFQ, we identified 432 SABs. HRs for an SAB among women who consumed 250–399 and >= 400 µg/day of dietary folate compared with <250 µg/day were 0.83 (95% CI: 0.53; 1.29) and 0.87 (95% CI: 0.54; 1.39), respectively. Comparing intake > = 400 with <250 µg/day, the association was stronger when the analysis was restricted to folic acid supplement users, 0.74 (95% CI: 0.39; 1.40), to women with a BMI >= 25, 0.67 (95% CI: 0.31; 1.43), and to a reported alcohol intake >4 drinks/week, 0.66 (95% CI: 0.16; 2.66). Conclusions Our study may suggest that high dietary folate intake among folic acid supplement users is associated with a lower risk of SAB, although our estimates are imprecise. Funding Sources National Institute of Child Health and Human Development.