Folic acid is a crucial nutrient for pregnant women, widely recognized for its role in preventing neural tube defects in fetuses. Given the rising global prevalence of congenital heart disease (CHD), understanding the relationship between Folic acid supplementation during pregnancy and CHD risk has become increasingly important. A meta-analysis published in the Nutrition Journal in 2022 offers valuable insights into this connection.

Research Methods

To explore the association between Folic acid supplementation during pregnancy and CHD risk, researchers conducted a comprehensive review of authoritative databases, including PubMed, Web of Science, and Google Scholar. A total of 21 studies were included, covering 106,920 cases of CHD. These studies consisted of one randomized controlled trial, five cohort studies, and 15 case-control studies, spanning regions such as the United States, Europe, China, Canada, and Australia. All studies were published in English and provided data on Folic acid supplementation during the periconceptional period and CHD risk.

Heterogeneity among studies was assessed using Cochran’s Q and I² statistics, and subgroup analyses and meta-regression were employed to investigate potential influencing factors.

Results

·        Overall Association: Folic acid supplementation during pregnancy was associated with a reduced risk of CHD (odds ratio [OR] = 0.82, 95% confidence interval [CI]: 0.72–0.94). However, significant heterogeneity was observed among the studies (P < 0.001, I² = 92.7%).

·        ---This suggests that while Folic acid supplementation may generally reduce CHD risk, the effect varies widely across studies, likely due to differences in Folic acid dose, timing of supplementation, and study design.

·        Timing of Supplementation: Initiating Folic acid supplementation within one month before or after conception was associated with an increased risk of CHD (OR = 1.10, 95% CI: 0.99–1.23).

·        ---This highlights the importance of timing in Folic acid supplementation, suggesting that both preconception and early pregnancy periods are critical for optimal fetal development.

·        High-Dose Folic Acid: High doses of folic acid intake (ranging from >356 μg to ≥546.4 μg, depending on the study) were linked to an increased risk of atrial septal defect (ASD) (OR = 1.23, 95% CI: 0.64–2.34).

·        ---This finding indicates that excessive folic acid intake may have adverse effects on fetal cardiac development.

Conclusions

While the meta-analysis suggests that Folic acid supplementation is generally associated with a reduced risk of CHD, the high heterogeneity among studies underscores the complexity of this relationship. Factors such as Folic acid dose, timing of supplementation, and individual metabolic differences likely play significant roles. Importantly, high doses of synthetic folic acid may pose risks to fetal cardiac development.

Future research should focus on elucidating the underlying mechanisms and conducting more rigorous clinical trials to provide clearer guidance.

Recommendations for Pregnant Women

1.      Personalized Supplementation: Folic acid requirements can vary significantly among individuals. Consider personalized Folic acid supplementation based on your metabolic profile. For those with impaired Folic acid metabolism, active forms of Folic acid, such as 6S-5-methyltetrahydropteroic acid (MagnaFolic acid), may be more effective.

2.      Consult a Healthcare Professional: Before starting any supplementation, consult your healthcare provider to determine the appropriate dose and type of Folic acid supplement based on your health status and pregnancy needs.

3.      Avoid Excessive Intake: Be cautious of high doses of synthetic folic acid, as excessive intake may have unintended consequences, particularly for fetal cardiac development.

4.      Balanced Diet: Aim for a balanced diet rich in natural sources of Folic acid, such as leafy green vegetables, legumes, and citrus fruits. Natural Folic acid from food sources is generally safe and beneficial.

5.      Regular Prenatal Care: Regular prenatal checkups are essential to monitor fetal development and address any potential issues early.

By following these recommendations, pregnant women can optimize their Folic acid intake to support healthy fetal development while minimizing potential risks.

References

Cheng Z, Gu R, Lian Z, Gu HF. Evaluation of the association between maternal folic acid supplementation and the risk of congenital heart disease: a systematic review and meta-analysis. Nutrition Journal. 2022;21:20. doi:10.1186/s12937-022-00772-2.