Developmental Differences At 6 and 12 Months Associated with ASD Outcomes in a High-Risk Infant Cohort

Background: Prospective studies of high-risk infants have yielded important insights into early developmental trajectories associated with a later diagnosis of ASD. Most previous studies have reported that differences in early cognitive and social-communication skills associated with ASD emerge at 12 months or later.

Objectives: To examine early development of cognitive and adaptive skills and behavioral risk markers of ASD using longitudinal data from a high-risk cohort, and with a focus on differences at 6 versus 12 months.

Methods: Data were drawn from an ongoing, multisite, longitudinal study of brain and behavioral development in ASD (Infant Brain Imaging Study; IBIS). Participants included 113 high-risk infants (HR; younger siblings of children with ASD) and 35 low-risk comparison infants (LR) followed to 24 months of age. Early behavioral risk markers were assessed using the Autism Observation Scale for Infants (AOSI) at 6 and 12 months. Cognitive skills were assessed using the Mullen Scales of Early Learning (MSEL) and adaptive skills using the Vineland Adaptive Behavioral Scales – II (VABS-II) at 6, 12 and 24 months. We compared HR infants meeting 24-month Autism Diagnostic Observation Schedule (ADOS) criteria for ASD (HR+; n=32), HR infants scoring below the ASD range (HR-; n=81) and LR infants (n=35) using mixed model ANOVAs, co-varying for study site and maternal education level.

Results: Significant group differences were found on MSEL and VABS-II composite scores at 6, 12 and 24 months, with post-hoc analyses revealing less advanced cognitive and adaptive skills in HR+ compared to HR- and LR groups at all 3 time points. Subscales indicating delays in HR+ compared to HR- and LR infants at 6 months included Gross Motor and Expressive Language on the MSEL, and all VABS-II subscales. HR+ infants scored lower than HR- and LR infants on all MSEL and VABS subscales at 12 months.  Mean AOSI total scores were higher in HR+ infants compared to both HR- and LR infants at 6 and 12 months (all p<.05). To further explore differences in behavioral profiles associated with ASD at 6 vs. 12 months, AOSI items were divided into two categories, the first indexing social communication and affective behaviors (‘Social Affective’), and the second, composed of items indexing other domains (‘Other’). The HR+ group had elevated scores on the AOSI-Other item group at 6 months (p< .004, mainly ‘motor control’ and ‘atypical motor behavior‘ items) and not AOSI-Social Affective (p=.1), whereas findings at 12 months were due to differences in AOSI-Social Affective ratings (p<.001) and not AOSI-Other (p=.2). To limit age variations within visits, sensitivity analysis allowing a tight optimal visit window revealed similar results.

Conclusions: Important differences during the first year were identified in this HR sample later assessed for ASD at 24 months.  Delays in cognitive and adaptive skills and qualitative differences in motor behavior emerged at 6 months, whereas manifestations of more defining features (i.e., social affective atypicalities) were detectable at 12 months. These findings will be discussed in relation to volumetric and white matter findings from ongoing neuroimaging studies of the same sample.