Ensuring a mother has adequate amounts of folate during pregnancy is clearly beneficial for fetal development, although there may be adverse effects if taken beyond recommended dosages. Additionally, folate exposure during pregnancy may impact the infants' epigenome (gene expression), potentially influencing health in the long term.[1]
In the 1990s several large randomized controlled trials (RCTs) conducted in various countries found that folic acid supplementation was effective at lowering the risk of fetal NTDs when taken before conception.[2][3][4] In response, folic acid supplementation is now routinely recommended to women who are pregnant or trying to conceive. Because of the clear benefits of folic acid supplementation, it’s no longer ethical to perform RCTs where one group of pregnant women is given folic acid and the other is not. As a result, much of the research we have today is from decades-old RCTs or observational studies, providing an overall weaker evidence base.
Limited data from RCTs suggests that folic acid supplementation likely reduces the rate of pregnancy termination due to NTDs and may increase birth weight, although research is mixed on the latter.[5][6][7] Unfortunately, folic acid has not been found to protect against other types of congenital disorders, such as cleft lip, cleft palate, or congenital heart defects.[7].
Observational research suggests that folic acid supplementation during pregnancy may be associated with a reduced risk of certain types of childhood cancers,[8][9] and a reduced risk of autism and attention deficit hyperactivity disorder (ADHD) traits.[10]