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

Cheng, Zhengpei; Gu, Rui; Lian, Zenglin; Gu, Harvest F.

doi:10.1186/s12937-022-00772-2

Cited by 20 publications

(11 citation statements)

References 60 publications

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“…The adjusted odds ratios (aOR) for CHD and ASD were 0.51 (95%CI: 0.34–0.77) and 0.33 (95%CI: 0.19–0.58), respectively, indicating a potential reduction in disease risk with maternal FAS. These results were consistent with similar studies, suggesting that maternal FAS decreases the risk of CHD and its subtypes [ 35 , 36 , 37 ]. The mechanism behind this effect may involve potent antioxidant and antithrombotic properties, improvement of endothelial dysfunction [ 38 ], or prevention of low maternal folic acid levels, which can lead to homocysteine accumulation and interfere with normal cardiac neural crest development [ 39 ].…”

Section: Discussionsupporting

confidence: 93%

Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease

Liu

Chen

et al. 2023

Nutrients

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Existing evidence supported that congenital heart defect (CHD) was associated with a combination of environmental and genetic factors. Based on this, this study aimed at assessing the association of maternal folic acid supplementation (FAS), genetic variations in offspring methylenetetrahydrofolate dehydrogenase (MTHFD)1 and MTHFD2 genes, and their interactions with CHD and its subtypes. A hospital-based case–control study, including 620 cases with CHD and 620 healthy children, was conducted. This study showed that the absence of FAS was significantly associated with an increased risk of total CHD and its subtypes, such as atrial septal defect (ASD). FAS during the first and second trimesters was associated with a significantly higher risk of CHD in offspring compared to FAS during the three months prior to conception. The polymorphisms of offspring MTHFD1 and MTHFD2 genes at rs2236222, rs11849530, and rs828858 were significantly associated with the risk of CHD. Additionally, a significantly positive interaction between maternal FAS and genetic variation at rs828858 was observed for the risk of CHD. These findings suggested that pregnant women should carefully consider the timing of FAS, and individuals with higher genetic risk may benefit from targeted folic acid supplementation as a preventive measure against CHD.

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Section: Discussionsupporting

confidence: 93%

Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease

Liu

Chen

et al. 2023

Nutrients

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“…As mentioned earlier, supplementation deficiencies associated with various substances may translate into abnormal fetal development. Among other supplements, folic acid and iron deficiencies in a pregnant patient’s diet may be related to the occurrence of congenital heart defects (CHDs) [ 189 , 190 , 191 ]. Congenital heart diseases, caused by abnormal development of the heart during pregnancy, are among the most common birth defects worldwide [ 191 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Genome Modifications during Pregnancy: The Impact of Essential Nutritional Supplements on DNA Methylation

Socha,

Flis,

Wartęga

2024

Nutrients

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Pregnancy is an extremely stressful period in a pregnant woman’s life. Currently, women’s awareness of the proper course of pregnancy and its possible complications is constantly growing. Therefore, a significant percentage of women increasingly reach for various dietary supplements during gestation. Some of the most popular substances included in multi-ingredient supplements are folic acid and choline. Those substances are associated with positive effects on fetal intrauterine development and fewer possible pregnancy-associated complications. Recently, more and more attention has been paid to the impacts of specific environmental factors, such as diet, stress, physical activity, etc., on epigenetic modifications, understood as changes occurring in gene expression without the direct alteration of DNA sequences. Substances such as folic acid and choline may participate in epigenetic modifications by acting via a one-carbon cycle, leading to the methyl-group donor formation. Those nutrients may indirectly impact genome phenotype by influencing the process of DNA methylation. This review article presents the current state of knowledge on the use of folic acid and choline supplementation during pregnancy, taking into account their impacts on the maternal–fetal unit and possible pregnancy outcomes, and determining possible mechanisms of action, with particular emphasis on their possible impacts on epigenetic modifications.

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“…Although the exact mechanisms of the majority of congenital malformations remain unknown, some specific congenital anomalies could be prevented by periconceptional intervention, such as folic acid (FA) supplementation to protect against neural tube defects (NTDs) [ 3 ]. In addition to protection against NTDs, FA supplementation is associated with a lower risk of the cardiac, urinary tract, and limb defects [ 4 – 6 ]. Based on these primary prevention effects, periconceptional FA use has been recommended by the US government and the World Health Organization for all women of childbearing age since 1992 [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Initiation and duration of folic acid supplementation in preventing congenital malformations

Dong

Yin

Deng

et al. 2023

BMC Med

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Background Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. Methods A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. Results Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44–1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21–1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08–5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33–0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36–0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. Conclusions The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. Trial registration Chictr.org.cn identifier: ChiCTR-SOC-17010976.

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

Cited by 20 publications

References 60 publications

Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease

Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease

Epigenetic Genome Modifications during Pregnancy: The Impact of Essential Nutritional Supplements on DNA Methylation

Initiation and duration of folic acid supplementation in preventing congenital malformations

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