Folate supplementation for prevention of congenital heart defects and low birth weight: an update

Rima Obeid, Wolfgang Holzgreve, Klaus Pietrzik


Women planning a pregnancy and pregnant women in the first trimester are recommended to use folate-containing supplements in order to prevent neural tube defects. The prevention of many cases of neural tube defects with folic acid is evident from meta-analysis, randomized controlled trials (RCTs), observational studies in humans and experimental evidence in animals. However, folate supplementation in pregnant women or a higher maternal folate status has been shown to be protective against other adverse birth outcomes such as congenital heart defects, low birth weight, and preterm birth. Additionally, infants and children with congenital heart defects often show disorders in folate metabolism (low folate, higher homocysteine, or low vitamin B12). Maternal genotype for several folate metabolizing genes has shown associations with the risk of having a child with congenital heart defect. There is some evidence that folate supplementation could have differential effects on sub-types of congenital heart defects, but it is not clear whether the prevention time window is the same as for neural tube defects. Some studies proposed a high dose of folic acid (in mg/d) to prevent congenital heart defects in women with a high global risk (such as those with diabetes or obesity). There are currently no RCTs to support that doses of folic acid in mg range are more effective than the currently recommended 400–800 µg/d taken at least 2–3 months before conception until the end of the first trimester.