Background: Autism spectrum disorders are more common in males than females, but the relative risk of ASD among high-risk siblings (younger siblings of ASD probands) requires large-scale characterization. It is also currently not clear whether there are sex differences in symptom presentation and cognitive functioning among children with ASD; nor is it clear whether potential sex differences are unique to ASD or characterize high-risk siblings without ASD and low-risk children. Finally, there has been little opportunity to investigate the longitudinal development of symptom presentation and cognitive functioning for children with and without ASD.
Objectives:
Obj1. Compare the relative risk of ASD outcomes for males and female high-risk siblings.
Obj2. Examine sex differences in the longitudinal development of ASD symptom presentation and cognitive functioning among high-risk siblings with and without an ASD outcome and among low-risk children.
Methods: Participants were 1,830 infants (1,241 high-risk siblings, 583 low-risk) from 15 consortium-contributing sites who were recruited prior to 18 months of age (M=7.28, SD=3.36) with outcome diagnosis at 33 months or older. ASD at outcome involved both outcome diagnosis and meeting ASD cut-off criteria on the ADOS. Hierarchical generalized linear models (HGLM) in which site was included as a random variable were used to determine factors affecting ASD incidence among high-risk siblings (Obj 1) and factors affecting Mullen Scales of Early Learning (MSEL) subtest and ADOS domain scores longitudinally among high-risk ASD, high-risk non-ASD, and low-risk children (Obj 2).
Results:
Obj. 1.
Of 1,241 high-risk siblings, 252 had ASD outcomes. The sex effect was significant (X2=55.35, df=1, p<.001) with a 3.18 odds ratio (95% CI = 2.31 to 4.39) of male to female recurrence. Male recurrence was 26.7% and female recurrence 10.3%.
Obj. 2.
MSEL (see Figure 1). All main and interaction effects of Group (High-risk ASD, High-Risk Non-ASD, Low-Risk Non-ASD), Age (18, 24, & 36 months) and MSEL Subtest (a repeated measure: Expressive & Receptive, Fine Motor, Visual Reception) on MSEL scores were significant (p<.001). There was no main effect of Sex (p=.20) and Sex did not interact with Group either alone (p=.23) or in combination with other variables (p>.69). There was a Sex by Subtest interaction (p<.001).
ADOS (see Figure 2). Group (High-risk ASD, High-Risk Non-ASD, Low-Risk Non-ASD), Domain (Restricted & Repetitive Behaviors, RRB, and Social Affect, SA) and their interaction were significant (p<.001). Age (24, & 36 months) was not significant (p=.41). Sex was not significant (p=.41), nor were its interactions with any variables (p>.07), except Domain (p<.05).
Conclusions: In prospectively followed high-risk siblings, males had a 3.18-fold greater chance of ASD outcomes. However, we found no ASD-specific sex differences in symptoms and cognitive functioning. Sex differences in repetitive behaviors and social affect were apparent in children with ASD, but also in high-risk and low-risk children without ASD,. Likewise, sex differences in particular areas of cognitive performance (e.g., language and visual reception) characterized the total sample and were not unique to ASD. Sex differences that appear in children with ASD may not be ASD-specific.
