The association between folic acid supplementation and congenital heart defects: Systematic review and meta-analysis

Abstract

Introduction: Various trial and epidemiological studies consistently documented the association between maternal folic acid supplementations and neural tube defects. However, existing literatures revealed inconclusive findings about maternal periconceptional folic acid supplementations and the risk of congenital heart defects. Thus, the current systematic review and meta-analysis was aimed to estimate the pooled association between maternal periconceptional folic acid supplementations and congenital heart defects. Methods: Electronic searches of PubMed, Web of Science/Scopus, Cochrane library and Google Scholar databases were conducted to access the required studies published up to March 2021. Predetermined eligibility criteria were used for study selections. Data extraction were independently done on excel. STATA version 14 software was used to calculate the pooled effect size with 95% confidence intervals (95% CI) of maternal periconceptional folic acid supplementations on congenital heart defects using the DerSimonian and Laird random effects meta-analysis (random effects model). Statistical heterogeneity was checked using the Cochran Q test (chi-squared statistic), I2 statistic, and by visual inspection of the funnel plot. Results: A total of 37 studies of case–control, cohort and randomized controlled trial in nature were included in the review. The finding of the present systematic review and meta-analysis indicated that periconceptional folic acid supplementation significantly decreases the risk of congenital heart defects (risk ratio (RR), 0.79; CI, 0.71, 0.89). Both Cochrane Q test statistic (χ2 = 19.33, p = 0.962) and I2 test statistic (I2 = 0.0%, p = 0.962) did not reveal statistically significant heterogeneity among included studies. In this meta-analysis, traditional funnel plot, Begg’s funnel plot, Egger’s weighted regression (p = 0.13) as well as Begg’s rank correlation statistic (p = 0.676) revealed no evidence of publication bias. Conclusion: The present systematic review and meta-analysis found that maternal periconception folic acid supplementation was significantly associated with the risk of congenital heart defects. The risk of congenital heart defects was significantly reduced by 21% among those children of mothers who use periconceptional folic acid supplementations in high-income countries. We recommend that a large prospective study be conducted to investigate the association between maternal periconceptional folic acid supplementation and occurrence of congenital heart defect of various types, especially in the developing countries.

Structural congenital anomalies in resource limited setting, 2023: A systematic review and meta-analysis

“…This study showed that clients who had never taken folic acid tablet were more likely to develop congenital anomalies, or clients who had taken folic acid tablet were less likely to develop congenital anomalies compared to those who haven't taken folic acid. Similarly a study states that maternal preconception folic acid supplementation was significantly associated with the risk of congenital anomalies [55]. A study shows a robust estimate of the positive association between maternal folate supplementation and a decreased risk of congenital anomalies [56].…”

Women's Nutrition: Folate/Folic Acid

“…Folic acid has been linked with a reduction in the risk for neural tube defects (NTD) (Czeizel 1998;Wolff et al 2009;van Gool et al 2018) and other birth defects such as congenital heart issues Erickson 2000, 2003;Czeizel, Vereczkey, and Szabo 2015;Jahanbin et al 2018;van Beynum et al 2010;Wondemagegn and Afework 2022).…”

Association of maternal weight gain in early pregnancy with congenital heart disease in offspring: a China birth cohort study

“…Whether maternal periconceptional FA supplementation could reduce the risk for CHD in the offspring remains controversial. 40 41 Wang et al 42 found that maternal periconceptional supplementation with FA or multiple micronutrients containing FA seems to decrease the risk for CHD in offspring by analysing 63 969 cases drawn from two standardised network information systems. A published article 43 using data from the CBCS suggested that there is no effect of FA and/or multivitamin supplementation on the fetal risk of CHD.…”