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.
Highlights
Spontaneous abortion (SA), or miscarriage, is defined in China as fetal loss before 28 gestational weeks [1,2,3]
We excluded 230 pregnancies in which the women did not adhere to guidance on folic acid (FA) supplementation, 186 ectopic pregnancies, 29,299 pregnancies that were lost to follow-up, and 1796 pregnancies recruited in 2016 due to the high rate lost to follow-up (>80%) in 2016 (Supplementary Table S1)
We investigated the influence of the following factors on the association between FA supplementation and spontaneous abortion (SA): (1) Maternal infection including reproductive tract infection (RTI), cytomegalovirus (CMV), and toxoplasma (TOX) infection before pregnancy; (2) the present pregnancies ending with induced abortion/stillbirth; (3) missing information on covariates in the study group and subgroups of FA supplementation; and (4) loss to follow-up
Summary
Spontaneous abortion (SA), or miscarriage, is defined in China as fetal loss before 28 gestational weeks [1,2,3]. FA supplementation before or during pregnancy has been established to be beneficial for the prevention of neural tube defects (NTDs) and other birth defects [8,9,10] that confer a risk of fetal chromosomal abnormalities [11]. Pre-conception FA supplementation has been reported to be associated with a lower risk of preterm delivery than supplementation initiated after conception [17]. There is a lack of evidence on the association between the timing of FA supplementation initiation and its effect on the prevention of SA. This cohort study aimed to investigate the association between maternal periconceptional FA supplementation and SA risk and examined whether the timing of supplementation initiation affected the SA risk
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