Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects in Offspring: A Meta-Analysis of Epidemiological Observational Studies

Abstract

Epidemiological studies have reported conflicting results regarding the association between maternal folic acid supplementation and the risk of congenital heart defects (CHDs). However, a meta-analysis of the association between maternal folic acid supplementation and CHDs in offspring has not been conducted. We searched the MEDLINE and EMBASE databases for articles cataloged between their inceptions and October 10, 2014 and identified relevant published studies that assessed the association between maternal folate supplementation and the risk of CHDs. Study-specific relative risk estimates were pooled using random-effects or fixed-effects models. Out of the 1,606 articles found in our initial literature searches, a total of 1 randomized controlled trial, 1 cohort study, and 16 case-control studies were included in our final meta-analysis. The overall results of this meta-analysis provide evidence that maternal folate supplementation is associated with a significantly decreased risk of CHDs (RR = 0.72, 95% CI: 0.63–0.82). Statistically significant heterogeneity was detected (Q = 82.48, P < 0.001, I2 = 79.4%). We conducted stratified and meta-regression analyses to identify the origin of the heterogeneity among the studies, and a Galbraith plot was generated to graphically assess the sources of heterogeneity. This meta-analysis provides a robust estimate of the positive association between maternal folate supplementation and a decreased risk of CHDs.

Risk factors of different congenital heart defects in Guangdong, China

“…Our findings supported the previous studies by Hernandez-Diaz et al (17) and Czeizel et al (18), which consistently demonstrated that maternal exposure to trimethoprimsulfonamide treatment during the first trimester was associated with 2-3-folds of the risk of CHD. It has been suggested that trimethoprim-sulfonamide as folate antagonists works by inhibiting dihydrofolate reductase, with a similar mode of action to that of the recognized teratogenic drug methotrexate, is suspected of inducing malformations when given during the critical period (19,20). Maternal self-reported exposure to trimethoprim-sulfonamide is very low in this study (only two in cases and zero in controls), and a couple of mothers did not report or remember the exact name of the antibiotics.…”

Noninherited Risk Factors of Congenital Heart Defects in Offspring: A Revi

“…54 A meta-analysis of the association between maternal folic acid supplementation and CHDs provide evidence that maternal folate supplementation is associated with a significantly decreased risk of CHDs (RR = 0.72, 95% CI: 0.63-0.82). 55 Homocysteine acts as folic acid antagonist and increased levels of maternal serum homocysteine are associated with increased risk of occurrence of CHDs in their offsprings as altered homocysteine metabolism may play role in CHDs. 56 Multivitamin use has been associated with lower risks for some birth defects.…”

Congenital Heart Diseases in Children: Incidence, Risk Factors, Mortality

“…Результаты исследований последних лет подтверждают, что прием фолиевой кислоты во время беременности снижает риск ВПС на 28-39% [30][31][32]. Была продемонстрирована Примечание.…”