title: Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study.
abstract: BACKGROUND
  The increased male prevalence of autism spectrum disorder (ASD) may be mirrored by the early emergence of sex differences in ASD symptoms and cognitive functioning. The female protective effect hypothesis posits that ASD recurrence and symptoms will be higher among relatives of female probands. This study examined sex differences and sex of proband differences in ASD outcome and in the development of ASD symptoms and cognitive functioning among the high-risk younger siblings of ASD probands and low-risk children.
  
  
  METHODS
  Prior to 18 months of age, 1824 infants (1241 high-risk siblings, 583 low-risk) from 15 sites were recruited. Hierarchical generalized linear model (HGLM) analyses of younger sibling and proband sex differences in ASD recurrence among high-risk siblings were followed by HGLM analyses of sex differences and group differences (high-risk ASD, high-risk non-ASD, and low-risk) on the Mullen Scales of Early Learning (MSEL) subscales (Expressive and Receptive Language, Fine Motor, and Visual Reception) at 18, 24, and 36 months and Autism Diagnostic Observation Schedule (ADOS) domain scores (social affect (SA) and restricted and repetitive behaviors (RRB)) at 24 and 36 months.
  
  
  RESULTS
  Of 1241 high-risk siblings, 252 had ASD outcomes. Male recurrence was 26.7 % and female recurrence 10.3 %, with a 3.18 odds ratio. The HR-ASD group had lower MSEL subscale scores and higher RRB and SA scores than the HR non-ASD group, which had lower MSEL subscale scores and higher RRB scores than the LR group. Regardless of group, males obtained lower MSEL subscale scores, and higher ADOS RRB scores, than females. There were, however, no significant interactions between sex and group on either the MSEL or ADOS. Proband sex did not affect ASD outcome, MSEL subscale, or ADOS domain scores.
  
  
  CONCLUSIONS
  A 3.2:1 male:female odds ratio emerged among a large sample of prospectively followed high-risk siblings. Sex differences in cognitive performance and repetitive behaviors were apparent not only in high-risk children with ASD, but also in high-risk children without ASD and in low-risk children. Sex differences in young children with ASD do not appear to be ASD-specific but instead reflect typically occurring sex differences seen in children without ASD. Results did not support a female protective effect hypothesis.
authors.affiliation: University of Miami, Coral Gables, FL USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Messinger
authors.affiliation: University of California, Davis, FL USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Young
authors.affiliation: Seattle Children's Research Institute, Seattle, WA USA ; University of Washington, Seattle, WA USA.
authors.forename: Sara Jane
authors.initials: SJ
authors.lastname: Webb
authors.affiliation: University of California, Davis, FL USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Ozonoff
authors.affiliation: Izaak Walton Killam Health Centre, Dalhousie University, Halifax, NS Canada.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bryson
authors.affiliation: University of Massachusetts, Boston, MA USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Carter
authors.affiliation: University of California, San Diego, CA USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Carver
authors.affiliation: King's College London, London, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Charman
authors.affiliation: Yale University School of Medicine, New Haven, CT USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Chawarska
authors.affiliation: University of Calgary, Calgary, AB Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Curtin
authors.affiliation: University of California, San Diego, CA USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Dobkins
authors.affiliation: University of California, Davis, FL USA.
authors.forename: Irva
authors.initials: I
authors.lastname: Hertz-Picciotto
authors.affiliation: University of California, Los Angeles, CA USA.
authors.forename: Ted
authors.initials: T
authors.lastname: Hutman
authors.affiliation: University of Pittsburgh, Pittsburgh, PA USA.
authors.forename: Jana M
authors.initials: JM
authors.lastname: Iverson
authors.affiliation: Kennedy Krieger Institute and John Hopkins School of Medicine, Baltimore, MD USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Landa
authors.affiliation: Harvard Medical School, Boston, MA USA ; Harvard Graduate School of Education, Cambridge, UK ; Boston Children's Hospital, Boston, MA USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Nelson
authors.affiliation: University of Washington, Seattle, WA USA.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Stone
authors.affiliation: Boston University, Boston, MA USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Tager-Flusberg
authors.affiliation: University of Alberta, Edmonton, AB Canada.
authors.forename: Lonnie
authors.initials: L
authors.lastname: Zwaigenbaum
keywords: Development; High-risk siblings; Longitudinal; Sex differences; Symptom severity