Development and Replication of Objective Measurements of Social Visual Engagement to Aid in Early Diagnosis and Assessment of Autism.

Importance: Autism spectrum disorder is a common and early-emerging neurodevelopmental condition. While 80% of parents report having had concerns for their child's development before age 2 years, many children are not diagnosed until ages 4 to 5 years or later. Objective: To develop an objective performance-based tool to aid in early diagnosis and assessment of autism in children younger than 3 years. Design, Setting, and Participants: In 2 prospective, consecutively enrolled, broad-spectrum, double-blind studies, we developed an objective eye-tracking-based index test for children aged 16 to 30 months, compared its performance with best-practice reference standard diagnosis of autism (discovery study), and then replicated findings in an independent sample (replication study). Discovery and replication studies were conducted in specialty centers for autism diagnosis and treatment. Reference standard diagnoses were made using best-practice standardized protocols by specialists blind to eye-tracking results. Eye-tracking tests were administered by staff blind to clinical results. Children were enrolled from April 27, 2013, until September 26, 2017. Data were analyzed from March 28, 2018, to January 3, 2019. Main Outcomes and Measures: Prespecified primary end points were the sensitivity and specificity of the eye-tracking-based index test compared with the reference standard. Prespecified secondary end points measured convergent validity between eye-tracking-based indices and reference standard assessments of social disability, verbal ability, and nonverbal ability. Results: Data were collected from 1089 children: 719 children (mean [SD] age, 22.4 [3.6] months) in the discovery study, and 370 children (mean [SD] age, 25.4 [6.0] months) in the replication study. In discovery, 224 (31.2%) were female and 495 (68.8%) male; in replication, 120 (32.4%) were female and 250 (67.6%) male. Based on reference standard expert clinical diagnosis, there were 386 participants (53.7%) with nonautism diagnoses and 333 (46.3%) with autism diagnoses in discovery, and 184 participants (49.7%) with nonautism diagnoses and 186 (50.3%) with autism diagnoses in replication. In the discovery study, the area under the receiver operating characteristic curve was 0.90 (95% CI, 0.88-0.92), sensitivity was 81.9% (95% CI, 77.3%-85.7%), and specificity was 89.9% (95% CI, 86.4%-92.5%). In the replication study, the area under the receiver operating characteristic curve was 0.89 (95% CI, 0.86-0.93), sensitivity was 80.6% (95% CI, 74.1%-85.7%), and specificity was 82.3% (95% CI, 76.1%-87.2%). Eye-tracking test results correlated with expert clinical assessments of children's individual levels of ability, explaining 68.6% (95% CI, 58.3%-78.6%), 63.4% (95% CI, 47.9%-79.2%), and 49.0% (95% CI, 33.8%-65.4%) of variance in reference standard assessments of social disability, verbal ability, and nonverbal cognitive ability, respectively. Conclusions and Relevance: In two diagnostic studies of children younger than 3 years, objective eye-tracking-based measurements of social visual engagement quantified diagnostic status as well as individual levels of social disability, verbal ability, and nonverbal ability in autism. These findings suggest that objective measurements of social visual engagement can be used to aid in autism diagnosis and assessment.

Screening for Autism Spectrum Disorder: Profiles of Children Who Are Missed.

OBJECTIVE: To characterize children presenting with concerns for autism spectrum disorder (ASD) missed by parent-report screeners and to examine benefits of a combined screening approach with the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) and the Ages and Stages Questionnaire, Third Edition (ASQ-3). METHODS: Participants included were 154 children aged 16 to 42 months presenting for an evaluation at an autism center. Caregivers completed the M-CHAT-R, ASQ-3, and a demographic questionnaire. Children participated in an autism diagnostic evaluation consisting of the Mullen Scales of Early Learning (Mullen) and Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). RESULTS: A total of 124 children (81%) were diagnosed with ASD. The M-CHAT-R identified 85% (n = 105) of these children. Children with ASD missed by the M-CHAT-R had significantly higher scores on the Mullen and significantly lower scores on the ADOS-2. Of the ASQ-3 domains, the majority (n = 102, 82%) of children with ASD failed the communication domain; missed cases showed similar patterns of higher Mullen scores and lower ADOS-2 scores. When adopting a combined screening approach, using a failed screen from either the M-CHAT-R or ASQ-3 communication domain, 93% of children were identified. Parent-reported concerns on an open-ended questionnaire revealed ASD red flags for many missed cases. CONCLUSION: Children with ASD missed by screeners had higher scores on developmental testing and lower scores on the ADOS-2; however, children still performed below average on developmental tests. Our findings suggest that a combined screening approach was most effective for identifying children with ASD from a sample group referred for an ASD evaluation.