Importance Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders.
Objective To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder–not otherwise specified [PDD-NOS]) in children.
Design, Setting, and Patients The study sample of 85 176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity.
Main Outcome Measure Specialist-confirmed diagnosis of ASDs.
Results At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61 042) had autistic disorder, compared with 0.21% (50/24 134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use.
Conclusions and Relevance Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.
JAMA. 2013;309(6):570-577. doi:10.1001/jama.2012.155925.
Norwegian Institute of Public Health, Oslo (Drs Surén, Haugen, Lie, Magnus, Reichborn-Kjennerud, Øyen, and Stoltenberg and Mss Roth and Schjølberg); Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, United Kingdom (Dr Surén); Mailman School of Public Health, Columbia University, New York, New York (Drs Bresnahan, Hornig, Lipkin, and Susser and Ms Roth); New York State Psychiatric Institute, New York (Drs Bresnahan and Susser); National Institute of Neurological Disorders and Stroke, Bethesda, Maryland (Dr Hirtz); Institute of Psychiatry, University of Oslo, Oslo (Dr Reichborn-Kjennerud); MRC Centre for Causal Analysis in Translational Epidemiology, University of Bristol, Bristol, United Kingdom (Dr Davey Smith); Nic Waals Institute, Lovisenberg Hospital, Oslo (Dr Øyen); and Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway (Dr Stoltenberg).