China: Maternal folic acid (FA) supplementation seems to be associated with a decreased risk of congenital heart diseases (CHD), the heterogeneity of this association, however, is significantly high, says a recent study in the Nutrition Journal. This suggests the need for further investigation of the real relationship between maternal FA supplementation and CHD with well-designed clinical studies and biological experiments.

Folic acid (FA), as a synthetic form of folate, has been used widely for dietary supplementation in pregnant women. The role of FA supplementation in preventing the occurrence and recurrence of fetal neural tube defects (NTD) is confirmed. However, the incidence of CHD has been parallelly increasing worldwide.
Against the above background, Harvest F. Gu, China Pharmaceutical University, Nanjing, China, and colleagues aimed to evaluate whether FA supplementation is associated with a decreased risk of CHD.
For this purpose, the researchers searched the literature using online databases 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. To test the heterogeneity, Cochran's Q and I2 statistics were used.
The findings of the study were as follows:

· Maternal FA supplementation was found to be associated with a decreased risk of CHD (OR = 0.82). However, the heterogeneity of the association was high.
· FA supplementation within 1 month before and after pregnancy correlated positively with CHD (OR 1.10), and high-dose FA intake is positively associated with atrial septal defect (OR 1.23).
· Pregnant women with irrational FA use may be at increased risk for CHD.
"Data from the meta-analysis suggest that the heterogeneity of the association between maternal FA supplementation and CHD is significantly high. This may be caused by the confounders such as timing and dose of FA administration," wrote the authors. "Subsequently, the outcome on the actual effect of FA supplementation on CHD may be influenced by heterogeneity."
Based on the above, it is necessary to correctly assess the association of FA supplementation with CHD, they say. "Further experiments designed to study the association between FA and CHD and its molecular mechanisms have been taken into consideration," they concluded.
Reference:
Cheng, Z., Gu, R., Lian, Z. et al. Evaluation of the association between maternal folic acid supplementation and the risk of congenital heart disease: a systematic review and meta-analysis. Nutr J 21, 20 (2022). https://doi.org/10.1186/s12937-022-00772-2