An exploration of health effects of folic acid in pregnancy beyond reducing neural tube defects

Abstract

Objectives: First, to examine the biological basis of why folic acid may have health effects beyond its proven effect of reducing neural tube defects; and second, to explore current controversial policies of folic acid supplementation and food fortification.

Methods: We searched MEDLINE for English-language papers published from 1991 to 2003, using the key words "folic acid" and "folate." The literature search was restricted to human studies. Of 8986 publications identified, 65 were relevant to the objectives of this paper.

Results: Analysis of the literature revealed that a major mechanism of folic acid in improving infant health may be related to its effect in correcting maternal folate-homocysteine-methylenetetrahydrofolate reductase metabolic defects. Conversely, exposure to high levels of folic acid may have such adverse health effects as increased risk of neurologic disorders in the general population.

Conclusions: Randomized trials or well-designed prospective cohort studies are needed to assess the effects of folic acid on various pregnancy outcomes. To enable an examination of the association between folic acid and rare outcomes, such as a specific category of birth defects and fetal and neonatal deaths, it is necessary to recruit a large number of pregnant women to participate in such studies.