The impact of folic acid supplementation on gestational and long term health: critical temporal windows, benefits and risks

Maternal folic acid (FA) supplementation is one of the most popular nutritional interventions during pregnancy for its protective effect against neural tube defects (NTDs). The purposes of this review are: (a) to gather the current evidence regarding supplementation of maternal diet with FA and (b) to problematize the available literature in terms of dosages, critical temporal windows, and its potential benefits and risks. The expression (pregnancy OR fetus OR offspring OR mother) AND (“folic acid” AND supplementation) was searched on PubMed database, filtering for articles published from 2005 to 2014. Publications referring to FA supplementation during the periconceptional period or pregnancy in which there was a conclusion about the effects of isolated FA supplementation on pregnant woman, pregnancy or offspring were included. Of the initial 1182 papers, 109 fulfilled the inclusion criteria. The majority of the publications reported FA supplementation outcomes on offspring's health, with emphasis in NTDs, allergy/respiratory problems, cancer and behaviour problems. Some inconsistency is observed on the impact of FA supplementation on different outcomes, except for NTDs. It is also visible an increased concern about the impact of excessive supplementation, either in terms of doses or exposure's duration. In conclusion, there is a growing interest in FA supplementation issues. The protective effect of FA supplementation over NTDs has been confirmed, being the periconceptional period a critical window, and it is frequently suggested that allergy/respiratory outcomes arise from (excessive) FA supplementation particularly later in pregnancy. Further research on critical doses and time of exposure should be conducted.