Abstract
BackgroundProspective studies of infants at high familial risk for autism spectrum disorder (ASD) have identified a number of putative early markers that are associated with ASD outcome at 3 years of age. However, some diagnostic changes occur between toddlerhood and mid-childhood, which raises the question of whether infant markers remain associated with diagnosis into mid-childhood.MethodsFirst, we tested whether infant neurocognitive markers (7-month neural response to eye gaze shifts and 14-month visual disengagement latencies) as well as an observational marker of emerging ASD behaviours (the Autism Observation Scale for Infants; AOSI) predicted ASD outcome in high-risk (HR) 7-year-olds with and without an ASD diagnosis (HR-ASD and HR-No ASD) and low risk (LR) controls. Second, we tested whether the neurocognitive markers offer predictive power over and above the AOSI.ResultsBoth neurocognitive markers distinguished children with an ASD diagnosis at 7 years of age from those in the HR-No ASD and LR groups. Exploratory analysis suggested that neurocognitive markers may further differentiate stable versus lost/late diagnosis across the 3 to 7 year period, which will need to be tested in larger samples. At both 7 and 14 months, combining the neurocognitive marker with the AOSI offered a significantly improved model fit over the AOSI alone.ConclusionsInfant neurocognitive markers relate to ASD in mid-childhood, improving predictive power over and above an early observational marker. The findings have implications for understanding the neurodevelopmental mechanisms that lead from risk to disorder and for identification of potential targets of pre-emptive intervention.
Highlights
Prospective studies of infants at high familial risk for autism spectrum disorder (ASD) have identified a number of putative early markers that are associated with ASD outcome at 3 years of age
The retained sample did not differ from the nonretained sample in 3 year levels of ASD on the Autism Diagnostic Observation Schedule—Generic (ADOS-G [29]), Social Responsiveness Scale—Second Edition (SRS-2 [30]) or Social Communication Questionnaire (SCQ), developmental level on the Mullen Scales of Early Learning (MSEL [31]), adaptive behaviour assessed with the Vineland Adaptive Behavior Scales—Second Edition (VABS-II [32]), or family income
Combining P400 with behavioural symptoms from the Autism Observation Scale for Infants (AOSI) significantly improved the model fit compared to the AOSI alone, but the joint model did not improve prediction significantly compared to P400 alone
Summary
Prospective studies of infants at high familial risk for autism spectrum disorder (ASD) have identified a number of putative early markers that are associated with ASD outcome at 3 years of age. Indices of infant behavioural and neural atypicalities, both measured through observational scales and specific infant neurocognitive markers, as well as various neuroimaging methods, have been shown to associate with a later ASD diagnosis in toddlerhood (for reviews, see [8,9,10]). The British Study for Infant Siblings (BASIS) has published on several such neurocognitive markers [10] Two of those that showed an association with 3-year-old ASD diagnosis are reduced differentiation in the neural response to eye gaze shifts towards versus away from the infant at 7 months of age, measured by the amplitude of the P400 event-related potential (ERP) component [14] and prolonged attention disengagement latency at 14 months of age, measured in a visual orienting task [13, 15, 16]
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