Dataset Information

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

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.

SUBMITTER: Cheng Z

PROVIDER: S-EPMC8962131 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Cheng Zhengpei Z Gu Rui R Lian Zenglin Z Gu Harvest F HF

Nutrition journal 20220326 1

<h4>Background</h4>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.<h4>Methods</h4>We searched th ...[more]

PMID: 35346212

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Project description:BackgroundAlthough many studies shown that the risk of congenital heart disease (CHD) was closely related to genetic and environmental factors, the exact mechanism was still unclear. This study was to assess the association of maternal folic acid supplementation (FAS), the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene polymorphisms in offspring and their interaction effects with the risk of CHD and its subtypes.MethodsA case-control study was conducted on 595 children with CHD and 605 healthy child controls. The multivariate logistic regression model was used to assess the association of maternal FAS, offspring MTRR gene polymorphisms and their interaction effects with CHD and its subtypes.ResultsThis study shown that maternal FAS was significantly associated with a reduced risk of CHD (OR = 0.55, 95%CI: 0.36-0.83) and its subtypes including ASD (OR = 0.25, 95%CI: 0.14-0.45), VSD (OR = 0.42, 95%CI: 0.27-0.64), and CTD (OR = 0.23, 95%CI: 0.09-0.59) in offspring. Offspring MTRR gene polymorphisms at rs162048 (GG vs. AA: OR = 2.05, 95%CI: 1.35-3.13), rs1802059 (AA vs. GG: OR = 5.13, 95%CI: 2.15-12.23; GA vs. GG: OR = 1.81, 95%CI: 1.35-2.43), rs10380 (TT vs. CC: OR = 2.27, 95%CI: 1.20-4.31) and rs1801394 (GG vs. AA: OR = 1.58, 95%CI: 1.02-2.42) were significantly associated with the risk of CHD, and similar results were also found for three subtypes of CHD. Additionally, a statistically significant interaction effect between maternal FAS and offspring MTRR gene polymorphism at rs1802059 was observed (OR = 0.38, 95%CI: 0.15-0.94). Among children who had a variant genotype at rs1802059, the risk of CHD was significantly decreased when their mother used folate for this pregnancy compared with mothers not using folate.ConclusionsIn those of Chinese descent, maternal FAS and offspring MTRR gene polymorphisms are significantly associated with the risk of CHD and its three subtypes. Furthermore, maternal FAS may help to offset some of risks of CHD due to offspring MTRR genetic variants. However, more studies with prospective designs and larger samples are needed to confirm our findings.Trial registrationRegistration number: ChiCTR1800016635; Registration time: 14/06/2018.

Project description:BackgroundTo systematically evaluate the association of MTHFR genetic polymorphisms, maternal folic acid intake, and the time when folic acid intake was started with the risk of congenital heart disease (CHD) and investigated the role of their interaction on infant CHD risk in Chinese populations.MethodsA case-control study involving 592 CHD cases, 617 health controls, and their mothers was performed. The exposures of interest were single nucleotide polymorphisms (SNPs) of the MTHFR gene, maternal folic acid use, and the time when folic acid use was started. We applied the logistic regression model to explore the strength of association.ResultsOur findings showed that mothers lacking folic acid intake had a significantly higher risk of CHD in offspring (aOR = 2.00; 95%CI: 1.34-2.98). Mothers who started to use folic acid from the first trimester of the fetation (aOR = 1.65; 95% CI: 1.22-2.23) or from the second trimester of the fetation (aOR = 7.77; 95% CI: 2.52-23.96), compared with those starting to use folic acid from 3 months previous to the conception, were at a significantly higher risk of CHD in offspring. Genetic variants at rs2066470 (AA vs. GG: aOR = 5.09, 95%CI: 1.99-13.03), rs1801133 (AA vs. GG: aOR = 2.49, 95%CI: 1.58-3.93), and rs1801131 (TG vs. TT: aOR = 1.84, 95%CI: 1.36-2.50; GG vs. TT: aOR = 3.58, 95%CI: 1.68-7.63) were significantly associated with the risk of CHD based on the multivariate analysis. Additionally, statistically significant interactions between maternal folic acid intake and genetic variants of the MTHFR gene at rs1801133 and rs1801131 were observed.ConclusionAn association of maternal folic acid intake and the time when intake was started with the risk of CHD in offspring was found. What's more, maternal folic acid fortification may help counteract partial of the risks of CHD in offspring attributable to MTHFR genetic mutations.Registration numberhttp://www.chictr.org.cn/edit.aspx?pid=28300&htm=4, identifier: ChiCTR1800016635.

Project description:Growing evidence suggests that maternal folic acid supplementation during pregnancy may be associated with the risk of childhood asthma, but these findings remain controversial. Therefore, the purpose of this systematic review and meta-analysis was to assess the association between maternal folic acid supplementation during pregnancy and the risk of childhood asthma, and to determine the safe dose of folic acid supplementation during pregnancy based on a dose-response analysis to lower the risk of childhood asthma. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant studies published before April 2022. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of eligible studies, and a fixed-effect model was employed to calculate the odds ratio (OR) of asthma with 95% confidence intervals (CI). In addition, the generalized least-squares trend (GLST) was used to explore a nonlinear dose-response relationship. Stata 15.0 was used for the statistical analysis mentioned above. This systematic review included 18 studies (13 cohort studies, 5 case-control studies) with a total of 252,770 participants, 50,248 of whom were children with asthma. The meta-analysis showed that maternal folic acid supplementation during pregnancy was significantly associated with the risk of childhood asthma (OR = 1.07; 95% CI = 1.04-1.11). The subgroup analysis revealed a significant correlation between the risk of childhood asthma and the folic acid supplementation in the first Trimester (OR = 1.09; 95% CI = 1.05-1.12), the third Trimester (OR = 1.15; 95% CI = 1.04-1.26) and the whole pregnancy (OR = 1.13; 95% CI = 1.10-1.16). At the same time, the dose-response analysis showed a nonlinear relationship between maternal folic acid intake during pregnancy and the risk of childhood asthma. The risk of asthma in children significantly increased when maternal folic acid intake reached 581 μg/day. This meta-analysis showed that maternal folic acid supplementation during pregnancy increased the risk of asthma in children. Based on the results of the dose-response analysis, less than 580 μg folic acid per day is advised in order to effectively prevent birth defects without increasing the risk of childhood asthma. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42022332140.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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