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Meta-Analysis
. 2022 Mar 26;21(1):20.
doi: 10.1186/s12937-022-00772-2.

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

Zhengpei Cheng  1   2 , Rui Gu  3 , Zenglin Lian  4 , Harvest F Gu  5
Affiliations
Meta-Analysis

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

Zhengpei Cheng et al. Nutr J. .

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.

Keywords: Association; Atrial septal defect; Congenital heart disease; Folic acid; Heterogeneity.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
A flow chart of identification and selection of the studies in the current meta-analysis
Fig. 2
Fig. 2
Possible association between maternal FA supplementation and CHD. FA: folic acid; CHD: congenital heart disease; A. Odd ratio (OR) estimates for the overall association of maternal FA supplementation with the risk of CHD; B. OR estimates for the association between maternal FA supplement intake and CHD; C. OR estimates for the association between the initiation of FA supplementation on CHDs; D. Estimated OR of the association between FA supplementation time and CHD
Fig. 3
Fig. 3
Possible association between maternal FA supplementation and ASD. FA: folic acid; ASD: atrial septal defects; A. Odd ratio (OR) estimates for the overall association of maternal FA supplementation with the risk of ASD; B. OR estimates for the association between Maternal folic acid supplement intake and ASD; C. OR estimates for the association between the initiation of folic acid supplementation on ASD; D. Estimated OR of the association between folic acid supplementation time and ASD
Fig. 4
Fig. 4
Begg’s test for possible association between FA supplementation and CHD/ASD. FA: folic acid; CHD: congenital heart disease; ASD: atrial septal defects; A. Begg's test of studies examining the association between maternal folate supplementation and the risk of CHD; B. Begg's test of studies examining the association between maternal folate supplementation and the risk of ASD
See this image and copyright information in PMC

References

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