Early Developmental Trajectories of Autism Symptoms in a High-Risk Infant Cohort

Background: Previous studies suggest that the initial symptoms of autism spectrum disorders (ASD) are often detected by parents by the age of 2, but that there is considerable variability in onset and developmental course. Prospective studies of high-risk infants have provided new insights about early ASD symptoms, but mainly focus on cross-sectional comparisons, with limited attention to changes over time.  Objectives: To assess whether there are distinct symptom trajectories among a longitudinal cohort of infant siblings of children with ASD (hereafter, ‘high-risk infants’) and low-risk comparison infants, and whether trajectory membership is associated with diagnostic outcomes.

Methods: Developmental trajectories of ASD symptoms from ages 6 to 18 months, indexed by the total score on the Autism Observational Scale for Infants (AOSI; higher scores indicate greater symptomatology), were identified by semi-parametric group-based modeling using SAS (PROC TRAJ) in a combined sample of high- and low-risk infants (n = 401 and 160, respectively). We then examined whether trajectory membership was associated with diagnostic outcomes among the 225 high-risk and 91 low-risk infants followed to age 3 years. ASD diagnoses were based on the ADI-R, ADOS and expert clinical judgment using DSM-IV, blind to prior study data.

Results: A 3-group solution provided optimal fit to variation in ASD symptom trajectories. One group, which included all but one of the low-risk infants and 68% of the high-risk infants, had minimal ASD symptoms from ages 6 to 18 months. A second group, who scored higher on the AOSI than the first group but had a similarly flat trajectory, included 24% of the high-risk sample: 6 of 22 diagnosed with autistic disorder (27%), 13 of 30 with other ASDs (43%) and 36 of 173 (21%) who were not diagnosed with ASD (21 with clinical concerns such as language delay, and 15 who were typically developing). One of 91 infants in the low-risk group belonged to this trajectory (the only low-risk child diagnosed with ASD). Thus, membership in this second group (moderate but stable levels of early symptoms) was associated with increased risk of ASD (χ² = 5.36, p=.021), but was non-specific and had relatively limited positive predictive value. A third group had similar levels of 6-month symptoms as the second group, but a markedly inclining trajectory. This included 12 of 52 children with ASD (10 of 22 or 46% with autistic disorder; and 2 of 30 or 7% with other ASDs), compared to 4 of 173 siblings who were not diagnosed with ASD (2.3%), 3 of whom had other clinical concerns such as language delay at age 3 (χ² = 65.2, p<.001). Overall, 12 of 16 high-risk infants (75%) in the third group were diagnosed with ASD.

Conclusions: The presence of increasing ASD symptoms between 6 and 18 months was highly predictive of autistic disorder at age 3. However, 27% of high-risk infants later diagnosed with autistic disorder and 43% of those diagnosed with other ASDs had stable moderate-level symptom trajectories to age 18 months shared by some high-risk infants not diagnosed with ASD.