Send to

Choose Destination
PLoS One. 2017 Nov 16;12(11):e0187996. doi: 10.1371/journal.pone.0187996. eCollection 2017.

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

Author information

Gansu Provincial Maternity and Child Care Hospital, Qilihe District, Lanzhou, Gansu Province, China.
Yale University School of Public Health, New Haven, Connecticut, United States of America.



It 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.


A 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.


Compared 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.


Our 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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center