title: Gestational vitamin D deficiency and autism-related traits: the Generation R Study.
abstract: There is intense interest in identifying modifiable risk factors associated with autism-spectrum disorders (ASD). Autism-related traits, which can be assessed in a continuous fashion, share risk factors with ASD, and thus can serve as informative phenotypes in population-based cohort studies. Based on the growing body of research linking gestational vitamin D deficiency with altered brain development, this common exposure is a candidate modifiable risk factor for ASD and autism-related traits. The association between gestational vitamin D deficiency and a continuous measure of autism-related traits at ~6 years (Social Responsiveness Scale; SRS) was determined in a large population-based cohort of mothers and their children (n=4229). 25-hydroxyvitamin D (25OHD) was assessed from maternal mid-gestation sera and from neonatal sera (collected from cord blood). Vitamin D deficiency was defined as 25OHD concentrations less than 25 nmol l-1. Compared with the 25OHD sufficient group (25OHD>50 nmol l-1), those who were 25OHD deficient had significantly higher (more abnormal) SRS scores (mid-gestation n=2866, β=0.06, P<0.001; cord blood n=1712, β=0.03, P=0.01). The findings persisted (a) when we restricted the models to offspring with European ancestry, (b) when we adjusted for sample structure using genetic data, (c) when 25OHD was entered as a continuous measure in the models and (d) when we corrected for the effect of season of blood sampling. Gestational vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny.
authors.affiliation: Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: A A E
authors.initials: AAE
authors.lastname: Vinkhuyzen
authors.affiliation: Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.|Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, Australia.
authors.forename: D W
authors.initials: DW
authors.lastname: Eyles
authors.affiliation: Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.|Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, Australia.
authors.forename: T H J
authors.initials: THJ
authors.lastname: Burne
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: L M E
authors.initials: LME
authors.lastname: Blanken
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Kruithof
authors.affiliation: Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Verhulst
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: V W
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.|Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, Australia.|National Centre for Register-Based Research, Aarhus University, Aarhus C, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: McGrath
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000209:etiology*; D002648:Child; D015331:Cohort Studies; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009035:Mothers; D009426:Netherlands; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications*
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D