Preconception Folate Status, Dietary Intake, Supplementation, and Time to Pregnancy Among Women in a Premarital...

Background/Objectives: Folate plays a key role in one-carbon metabolism and may influence reproductive function, but evidence regarding its association with fecundability remains inconsistent. This study examined the association of folic acid (FA) supplementation, dietary folate intake, and folate status with time to pregnancy (TTP) among women planning to conceive. Methods: This study is a secondary analysis of a prospective cohort study included women enrolled during premarital health examinations in two counties in Shanxi Province (2009-2012). Folate-related exposures were assessed at baseline and included FA supplementation, dietary folate intake, and red blood cell (RBC) folate concentrations. Discrete-time proportional hazards model was used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs). Results: A total of 1475 women without a history of previous pregnancy were included, among whom 24 (1.6%) reported FA supplementation at baseline. Higher intake of several food groups was associated with increased RBC folate concentrations. In separate models, only seafood intake (1-3 times per week) was significantly associated with higher fecundability (FR: 1.23, 95% CI: 1.04, 1.44). In joint models, FA supplementation was associated with higher fecundability at 6 months (FR: 2.07, 95% CI: 1.01, 3.77), 12 months (FR: 1.91, 95% CI: 1.00, 3.30), and 24 months (FR: 1.91, 95% CI: 1.00, 3.30). Conclusions: Preconception FA supplementation showed a potential positive association with fecundability when considered alongside dietary intake and folate status, although the evidence was limited by the low use of supplementation. Further studies are needed to clarify the role of folate in human fecundability.