Preconception folate status and reproductive outcomes among a prospective cohort of folate-replete women.

BACKGROUND: Most studies of folate metabolism and reproduction have been conducted after pregnancy and in folate-deficient populations. However, measurement of maternal folate status preconceptionally may be most relevant to certain folate-linked early processes preceding a successful pregnancy, and there has been a major increase in folate concentrations in women of childbearing age in high resource settings.

OBJECTIVE: To examine associations between preconceptional biomarkers of maternal folate status (folate and homocysteine) and reproductive outcomes in folate-replete women.

STUDY DESIGN: Cohort nested within the Effects of Aspirin in Gestation and Reproduction trial, a block-randomized, double-blind, placebo-controlled trial whereby women were randomized to daily low-dose aspirin (81 mg/day) or placebo and all women received folic acid (400 μg/day). In total, 1228 women with 1-2 previous pregnancy losses and no documented infertility were recruited from 4 clinical sites in the United States (2006-2012) and were attempting pregnancy for up to 6 menstrual cycles. Log-binomial regression models were used to estimate relative risks and 95% confidence intervals between preconception serum folate and plasma homocysteine for anovulation, pregnancy, and pregnancy loss.

RESULTS: Greater plasma homocysteine was nonlinearly associated with greater risks of pregnancy loss only among women with 2 previous losses: a relative risk of 1.43 (95% confidence interval, 1.08-1.89) was found for plasma homocysteine concentrations at the study median of 8.0 μmol/L compared with a US population median of 6.0 μmol/L. No meaningful relationships were found between serum folate and any reproductive outcome or between plasma homocysteine and anovulation or becoming pregnant.

CONCLUSION: These data justify further study of the role of folate and homocysteine metabolism in normal and abnormal early pregnancy.