title: Folic acid supplementation in pregnancy: Are there devils in the detail?
abstract: Maternal folic acid (FA) supplementation is well recognised to protect against neural tube defects. Folate is a critical cofactor in one-carbon metabolism involved in the epigenetic regulation of transcription that underpins development. Thus, it is possible that maternal FA supplementation may have additional, unforeseen persistent effects in the offspring. This is supported by the modification by maternal supplementation with one-carbon donors and FA of the epigenetic regulation of offspring phenotype in mutant mice. The present article reviews studies in human subjects and experimental animals of the effect of maternal FA intake and phenotypic outcomes in the offspring. Maternal FA intake was associated with a short-term increased incidence of allergy-related respiratory impairment in children and multigenerational respiratory impairment in rats. Higher maternal folate status during pregnancy was associated positively with insulin resistance in 6-year-olds. In rats, maternal FA supplementation modified hepatic metabolism and vascular function through altered transcription, in some cases underpinned by epigenetic changes. FA supplementation in pregnant rats increased mammary tumorigenesis, but decreased colorectal cancer in the offspring. Maternal FA supplementation decreased a range of congenital cardiac defects in children. These findings support the view that maternal FA supplementation induces persistent changes in a number of phenotypic outcomes in the offspring. However, the number of studies is limited and insufficient to indicate a need to change current recommendations for FA intake in pregnancy. Nevertheless, such effects should be investigated thoroughly in order to support firm conclusions about the risk of unanticipated long-term negative effects of maternal FA supplementation in humans.
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, Institute of Developmental Sciences Building (MP887), Southampton General Hospital, University of Southampton, Tremona Road, Southampton SO16 6YD, UK. g.c.burdge@soton.ac.uk
authors.forename: Graham C
authors.initials: GC
authors.lastname: Burdge
authors.forename: Karen A
authors.initials: KA
authors.lastname: Lillycrop
mesh_terms: D000328:Adult; D000818:Animals; D002648:Child; D019587:Dietary Supplements / Q000009:adverse effects*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy
chemical_list: D005492:Folic Acid