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

PLoS ONE

Nov 2017

DOI: 10.1371/journal.pone.0187996

Citations:69

Influential Citations:4

Observational Studies (Human)

Enhanced Details

Methods

Birth cohort study conducted 2010-2012 at Gansu Provincial Maternity and Child Care Hospital, Lanzhou, China. Eligible pregnant women delivering at the hospital were interviewed with a structured questionnaire; after exclusions, 10,087 singleton live births were included (94 CHD cases). CHDs were classified using ICD-10; unconditional logistic regression estimated associations between folic acid supplementation, dietary folate intake, and CHD risk.

Intervention

Folic acid supplements (folic acid alone or folic acid-containing multivitamins) taken before conception and during pregnancy; duration categories <=12 weeks or >12 weeks; data collected for four periods: before conception and during the first, second, and third trimesters.

Results

Folic acid supplementation before pregnancy was associated with reduced risk of overall CHDs (OR 0.42, 95% CI 0.21-0.86; P trend 0.025). Subtypes showed protective effects: great arteries malformations (OR 0.37, 95% CI 0.16-0.85), cardiac septa malformations (OR 0.26, 95% CI 0.10-0.68), and atrial septal defect (OR 0.34, 95% CI 0.13-0.93). Longer duration of use showed stronger protection (P trend 0.025). After adjusting for dietary folate intake, the protective effect attenuated (OR 0.64, 95% CI 0.38-1.08). No significant protection when supplements used during pregnancy. Lower dietary folate intake during pregnancy (<149.88 mcg/day) was associated with higher risk of overall CHDs (OR 1.63, 95% CI 1.01-2.62) and PDA (OR 1.85, 95% CI 1.03-3.32). Nonusers of folic acid supplements with low dietary folate had about 2-fold higher CHD risk. No significant interaction between folic acid supplementation and dietary folate intake. Conclusion: Preconception folic acid supplementation reduces CHD risk; low dietary folate during pregnancy increases CHD risk; promoting preconception folic acid use and adequate dietary folate during pregnancy could reduce CHD burden; larger studies needed to confirm subtype-specific effects.

Limitations

Hospital-based design; potential recall bias from in-person interviews at delivery; residual confounding cannot be ruled out; limited statistical power for CHD subtypes due to small case numbers; generalizability may be limited.

Abstract

Background 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. Methods 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. Results 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. Conclusions 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. show less