Periconceptional Folic Acid Supplementation and the Risk of Spontaneous Abortion among Women Who Prepared to Conceive: Impact of Supplementation Initiation Timing

Abstract

It is unclear whether periconceptional folic acid (FA) supplementation decreases the risk of spontaneous abortion (SA). The impact of supplementation initiation timing has not been ascertained. This cohort study aimed to investigate the association between maternal periconceptional FA supplementation and risk of SA, with due consideration of the supplementation initiation timing. Through the National Free Pre-conception Health Examination Project (NFPHEP), we identified 65,643 pregnancies on FA supplementation in Chongqing, China between 2010 and 2015. After adjusting for covariates, maternal periconceptional FA supplementation was associated with a lower risk of SA (adjusted risk ratio [aRR]: 0.52; 95% confidence interval [CI]: 0.48–0.56). Pregnant women with FA supplementation initiated at least 3 months before conception had a 10% lower risk of SA (aRR: 0.46; 95% CI: 0.42–0.50) than those with FA supplementation initiated 1–2 months before conception (aRR: 0.56; 95% CI: 0.50–0.62) or after conception (aRR: 0.56; 95% CI: 0.51–0.61). These associations might not thoroughly account for FA supplementation, and to some extent our findings confirm the role of the utilization of healthcare in preventing SAs. Women who initiated healthcare, including taking FA earlier during the periconceptional period, could have a lower risk of SA.