title: Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence.
abstract: Emerging evidence from epidemiological studies supports the notion that maternal folate status regulated by dietary and genetic factors early in pregnancy may influence the risk of autism spectrum disorders (ASD). In this review, we provide an overview of what is known about the role of folate in the aetiology of neurodevelopmental disorders; summarise relevant biological, genetic and epigenetic mechanisms; and synthesise the evidence from human observational studies and randomised controlled trials that have examined the relationship between maternal folate and ASD or related traits. Much of the existing literature on this topic is subject to limitations such as potential confounding by healthy behaviours and other dietary factors, and exposure assessed within limited exposure windows. As the existing evidence is inconclusive, further research remains to be conducted in order to verify this hypothesis. Complete assessment of maternal functional folate status through the pre- and peri-conceptional periods requires biological measurement of folate, vitamin B12 and homocysteine and genetic variants involved in one-carbon metabolism and epigenetic mechanisms. In addition to more complete assessment of maternal functional folate status, careful consideration of potential confounding is warranted.
authors.affiliation: 1Department of Epidemiology and Biostatistics,Drexel University School of Public Health,Philadelphia,PA 19104,USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: DeVilbiss
authors.affiliation: 2Department of Public Health Sciences,Division of Public Health Epidemiology,Karolinska Institutet,171 77 Stockholm,Sweden.
authors.forename: Renee M
authors.initials: RM
authors.lastname: Gardner
authors.affiliation: 1Department of Epidemiology and Biostatistics,Drexel University School of Public Health,Philadelphia,PA 19104,USA.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Newschaffer
authors.affiliation: 1Department of Epidemiology and Biostatistics,Drexel University School of Public Health,Philadelphia,PA 19104,USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Lee
mesh_terms: D002659:Child Development Disorders, Pervasive / Q000097:blood / Q000209:etiology*; D019175:DNA Methylation; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005494:Folic Acid Deficiency / Q000097:blood / Q000150:complications*; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D012307:Risk Factors; D014803:Vitamin B Complex / Q000097:blood
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid
keywords: ASD autism spectrum disorders; Autism; Epigenetics; FA folic acid; Folic acid; MTHFR methylene tetrahydrofolate reductase; Neurodevelopment; Pregnancy