Maternal folic acid supplementation and dietary folate intake and congenital heart defects.

Baohong Mao,Wei Dai,Nan Zhao,Zhongfeng Tang,Sijuan Xu,Weitao Qiu,Huang Huang,Xiaojuan Lin,Jie Qiu,Xiaochun He,Hongmei Cui,Yawei Zhang,Xiaoying Xu,Qing Liu,Min Zhou,Yawen Shao,Ling Lv,Katariina Laine

doi:10.1371/journal.pone.0187996

Baohong Mao, Wei Dai + Show 16 more

Open Access

https://doi.org/10.1371/journal.pone.0187996

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Abstract

BackgroundIt has been reported that folic acid supplementation before and/or during pregnancy could reduce the risk of congenital heart defects (CHDs). However, the results from limited epidemiologic studies have been inconclusive. We investigated the associations between maternal folic acid supplementation, dietary folate intake, and the risk of CHDs.MethodsA birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity & Child Care Hospital in Lanzhou, China. After exclusion of stillbirths and multiple births, a total of 94 births were identified with congenital heart defects, and 9,993 births without any birth defects. Unconditional logistic regression was used to estimate the associations.ResultsCompared to non-users, folic acid supplement users before pregnancy had a reduced risk of overall CHDs (OR: 0.42, 95% CI: 0.21–0.86, Ptrend = 0.025) after adjusted for potential confounders. A protective effect was observed for certain subtypes of CHDs (OR: 0.37, 95% CI: 0.16–0.85 for malformation of great arteries; 0.26, 0.10–0.68 for malformation of cardiac septa; 0.34, 0.13–0.93 for Atrial septal defect). A similar protective effect was also seen for multiple CHDs (OR: 0.49, 95% CI: 0.26–0.93, Ptrend = 0.004). Compared with the middle quartiles of dietary folate intake, lower dietary folate intake (<149.88 μg/day) during pregnancy were associated with increased risk of overall CHDs (OR: 1.63, 95% CI: 1.01–2.62) and patent ductus arteriosus (OR: 1.85, 95% CI: 1.03–3.32). Women who were non-user folic acid supplement and lower dietary folate intake have almost 2-fold increased CHDs risk in their offspring.ConclusionsOur study suggested that folic acid supplementation before pregnancy was associated with a reduced risk of CHDs, lower dietary folate intake during pregnancy was associated with increased risk. The observed associations varied by CHD subtypes. A synergistic effect of dietary folate intake and folic acid supplementation was also observed.

Highlights

Congenital heart defects (CHDs) are among the major birth defects in newborns and affect approximately 4 to 10 per 1,000 live births [1,2,3]
A protective effect was observed for certain subtypes of CHDs (OR: 0.37, 95% confidence intervals (CI): 0.16–0.85 for malformation of great arteries; 0.26, 0.10–0.68 for malformation of cardiac septa; 0.34, 0.13–0.93 for Atrial septal defect)
A similar protective effect was seen for multiple CHDs (OR: 0.49, 95% CI: 0.26–0.93, Ptrend = 0.004)

Summary

Introduction

Congenital heart defects (CHDs) are among the major birth defects in newborns and affect approximately 4 to 10 per 1,000 live births [1,2,3]. Two recent studies reported a reduced rate of CHDs in Quebec (Canada) and Atlanta (USA) over the past years and suggested that folic acid fortification of grain products might play a role [6, 7]. Epidemiological studies that investigated the association between folic acid intake and the risk of CHDs have reached conflicting results. Three studies investigated dietary folate intake and risk of CHDs and found no association [27,28,29]. It has been reported that folic acid supplementation before and/or during pregnancy could reduce the risk of congenital heart defects (CHDs). We investigated the associations between maternal folic acid supplementation, dietary folate intake, and the risk of CHDs

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Conclusion