Use of Prospective Longitudinal Gaze Measurements in Defining Regression

Background: Prospective studies of infants at risk for ASD provide an objective measurement of symptom onset that is not subject to limitations like recall bias. Such studies suggest that declining development in children later diagnosed with ASD may be more common than estimates based on retrospective methods. Prospective studies analyzing coded social-communication behavior and ratings of social engagement, including gaze to faces, have found that infants later diagnosed with ASD exhibit a pattern of decline over the first years of life (Ozonoff et al., 2010), with a majority—over 80%—exhibiting such patterns of regression (Ozonoff et al., 2018). Examining developmental trajectories of subtle social-communicative behaviors like gaze may be an especially helpful method of defining onset patterns.

Objectives: To investigate developmental trajectories of gaze to an examiner’s face in two independent samples of infants with and without an older sibling with ASD.

Methods: Participants were assessed at up to 7 ages (6, 9, 12, 15, 18, 24, and 36 months). They were classified into one of three groups based on diagnostic assessment at 36 months: Typically Developing (TD), Non-TD (i.e., lower Mullen Scales of Early Learning [MSEL] or elevated ADOS scores), or ASD. Gaze to faces was examined in two contexts: in Cohort 1 (TD n=80, Non-TD n=55, ASD n=20) during administration of the MSEL and Cohort 2 (TD n=66, Non-TD n=34, ASD n=26) during play interaction with an examiner. Infant gaze was coded during the first 6 minutes of the Mullen Visual Reception subtest (Cohort 1) and during the 3-minute play interaction (Cohort 2). Frequency of gaze to examiner’s face was coded following procedures in Ozonoff et al. (2010) and divided by the total duration coded to create rates per minute in each context. Statistical analyses were conducted using log10 transformed rates.

Results: Mixed-effects linear models (Laird & Ware, 1982) were used to examine developmental trajectories. For each cohort, we fit a model with fixed effects for outcome group, linear, quadratic, cubic, and quartic effects of time (months), and interactions between the effects of time and group, as well as random intercept and slopes, to account for within-person correlations. Terms that did not add significantly to the model were sequentially removed. In Cohort 1, the ASD group exhibited significantly lower levels of gaze at 6 months, and gaze levels decreased over time, compared to the TD group. In Cohort 2, the ASD group exhibited significantly lower levels of gaze by 12 months, and gaze levels decreased over time, compared to the TD group. See Table 1 for parameter estimates.

Conclusions: Using prospective methods, children who developed ASD exhibited declines in gaze to an adult’s face, with differences evident by 12 months. These findings replicate declines previously reported by Ozonoff et al. (2010, 2018) in two independent samples, across two interactive contexts, strengthening the conclusions that 1) behavioral signs of ASD emerge over the first two years of life and 2) declining trajectories, consistent with regression, are common in samples of children developing ASD when prospective methods are used.