Evaluation of the association between maternal folic acid supplementation and the risk of congenital heart disease: a systematic review and meta-analysis

source extracted confidence: high 2026-04-09
#dietary-supplements #female #folic-acid #heart-defects-congenital #humans

Evaluation of the association between maternal folic acid supplementation and the risk of congenital heart disease: a systematic review and meta-analysis

Cheng et al., 2022 | Nutr J | Meta Analysis

Citation

Cheng Zhengpei, Gu Rui, ... Gu Harvest F. Evaluation of the association between maternal folic acid supplementation and the risk of congenital heart disease: a systematic review and meta-analysis. Nutr J. 2022-Mar-26;21(1):20. doi:10.1186/s12937-022-00772-2

Abstract

BACKGROUND: Folic acid (FA), as a synthetic form of folate, has been widely used for dietary supplementation in pregnant women. The preventive effect of FA supplementation on the occurrence and recurrence of fetal neural tube defects (NTD) has been confirmed. Incidence of congenital heart diseases (CHD), however, has been parallelly increasing worldwide. The present study aimed to evaluate whether FA supplementation is associated with a decreased risk of CHD. METHODS: We searched the literature using PubMed, Web of Science and Google Scholar, for the peer-reviewed studies which reported CHD and FA and followed with a meta-analysis. The study-specific relative risks were used as summary statistics for the association between maternal FA supplementation and CHD risk. Cochran's Q and I2 statistics were used to test for the heterogeneity. RESULTS: Maternal FA supplementation was found to be associated with a decreased risk of CHD (OR = 0.82, 95% CI: 0.72-0.94). However, the heterogeneity of the association was high (P < 0.001, I2 = 92.7%). FA supplementation within 1 month before and after pregnancy correlated positively with CHD (OR 1.10, 95%CI 0.99-1.23), and high-dose FA intake is positively associated with atrial septal defect (OR 1.23, 95%CI 0.64-2.34). Pregnant women with irrational FA use may be at increased risk for CHD. CONCLUSIONS: Data from the present study indicate that the heterogeneity of the association between maternal FA supplementation and CHD is high and suggest that the real relationship between maternal FA supplementation and CHD may need to be further investigated with well-designed clinical studies and biological experiments.

Key Findings

Maternal FA supplementation was found to be associated with a decreased risk of CHD (OR = 0.82, 95% CI: 0.72-0.94). However, the heterogeneity of the association was high (P < 0.001, I2 = 92.7%). FA supplementation within 1 month before and after pregnancy correlated positively with CHD (OR 1.10, 95%CI 0.99-1.23), and high-dose FA intake is positively associated with atrial septal defect (OR 1.23, 95%CI 0.64-2.34). Pregnant women with irrational FA use may be at increased risk for CHD.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population pregnant women
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Dietary Supplements
  • Female
  • Folic Acid
  • Heart Defects, Congenital
  • Humans
  • Neural Tube Defects
  • Pregnancy
  • Prenatal Care

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review, Research Support, Non-U.S. Gov't
  • Vertical: folate

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09