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

HIGHLIGHTS: Associations between FA supplementation in pregnancy and effects on offspring's NTDs, allergy/respiratory problems, cancer and behaviour problems as been studied.There is growing concern about the effects of excessive FA supplementation, whether in terms of doses or times of exposure.FA supplementation in the periconceptional period is protective against NTDs while in later periods it could be deleterious.A daily dose of 0.4 mg FA in the periconceptional period seems to be effective and safe. ABSTRACT: 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. Copyright 2017 PBJ-Associação Porto Biomedical/Porto Biomedical Society.