Pre-conceptional Intake of Folic Acid Supplements is Inversely Associated with Risk of Preterm Birth and Small-for-gestational-age Birth: a Prospective Cohort Study

Abstract Associations of folic acid supplementation with risk of preterm birth (PTB) and small-for-gestational-age (SGA) birth were unclear for the Chinese populations. The aim of the present study was to investigate the associations in a large Chinese prospective cohort study: the Jiaxing Birth Cohort. In the Jiaxing Birth Cohort, 240 954 pregnant women visited local clinics or hospitals within their first trimester in Southeast China during 1999–2012. Information on anthropometric parameters, folic acid supplementation and other maternal characteristics were collected by in-person interviews during their first visit. Pregnancy outcomes were recorded during the follow-up of these participants. Multinomial logistic regression was used to examine the association of folic acid supplementation with pregnancy outcomes. The prevalence of folic acid supplementation was 24·9 % in the cohort. The prevalence of PTB and SGA birth was 3·48 and 9·2 %, respectively. Pre-conceptional folic acid supplementation was associated with 8 % lower risk of PTB (relative risk (RR) 0·92; 95 % CI 0·85, 1·00; P=0·04) and 19 % lower risk of SGA birth (RR 0·81; 95 % CI 0·70, 0·95; P=0·008), compared with non-users. Higher frequency of pre-conceptional folic acid use was associated with lower risk of PTB (P trend=0·032) and SGA birth (P trend=0·046). No significant association between post-conceptional initiation of folic acid supplementation and either outcome was observed. In conclusion, the present study suggests an association between pre-conceptional, but not post-conceptional, folic acid supplementation and lower risk of PTB and SGA birth in the Jiaxing Birth Cohort. Further research in other cohorts of large sample size is needed to replicate these findings.