Get SET Early to Identify and Treatment Refer Autism Spectrum Disorder at 1 Year and Discover Factors That Influence Early Diagnosis.

OBJECTIVES: To examine the impact of a new approach, Get SET Early, on the rates of early autism spectrum disorder (ASD) detection and factors that influence the screen-evaluate-treat chain. STUDY DESIGN: After attending Get SET Early training, 203 pediatricians administered 57 603 total screens using the Communication and Symbolic Behavior Scales Infant-Toddler Checklist at 12-, 18-, and 24-month well-baby examinations, and parents designated presence or absence of concern. For screen-positive toddlers, pediatricians specified if the child was being referred for evaluation, and if not, why not. RESULTS: Collapsed across ages, toddlers were evaluated and referred for treatment at a median age of 19 months, and those screened at 12 months (59.4% of sample) by 15 months. Pediatricians referred one-third of screen-positive toddlers for evaluation, citing lack of confidence in the accuracy of screen-positive results as the primary reason for nonreferral. If a parent expressed concerns, referral probability doubled, and the rate of an ASD diagnosis increased by 37%. Of 897 toddlers evaluated, almost one-half were diagnosed as ASD, translating into an ASD prevalence of 1%. CONCLUSIONS: The Get SET Early model was effective at detecting ASD and initiating very early treatment. Results also underscored the need for change in early identification approaches to formally operationalize and incorporate pediatrician judgment and level of parent concern into the process.

Default mode-visual network hypoconnectivity in an autism subtype with pronounced social visual engagement difficulties.

Social visual engagement difficulties are hallmark early signs of autism (ASD) and are easily quantified using eye tracking methods. However, it is unclear how these difficulties are linked to atypical early functional brain organization in ASD. With resting state fMRI data in a large sample of ASD toddlers and other non-ASD comparison groups, we find ASD-related functional hypoconnnectivity between 'social brain' circuitry such as the default mode network (DMN) and visual and attention networks. An eye tracking-identified ASD subtype with pronounced early social visual engagement difficulties (GeoPref ASD) is characterized by marked DMN-occipito-temporal cortex (OTC) hypoconnectivity. Increased DMN-OTC hypoconnectivity is also related to increased severity of social-communication difficulties, but only in GeoPref ASD. Early and pronounced social-visual circuit hypoconnectivity is a key underlying neurobiological feature describing GeoPref ASD and may be critical for future social-communicative development and represent new treatment targets for early intervention in these individuals.

Evaluation of the Diagnostic Stability of the Early Autism Spectrum Disorder Phenotype in the General Population Starting at 12 Months.

Importance: Universal early screening for autism spectrum disorder (ASD) in primary care is becoming increasingly common and is believed to be a pivotal step toward early treatment. However, the diagnostic stability of ASD in large cohorts from the general population, particularly in those younger than 18 months, is unknown. Changes in the phenotypic expression of ASD across early development compared with toddlers with other delays are also unknown. Objectives: To examine the diagnostic stability of ASD in a large cohort of toddlers starting at 12 months of age and to compare this stability with that of toddlers with other disorders, such as developmental delay. Design, Setting, and Participants: In this prospective cohort study performed from January 1, 2006, to December 31, 2018, a total of 2241 toddlers were referred from the general population through a universal screening program in primary care or community referral. Eligible toddlers received their first diagnostic evaluation between 12 and 36 months of age and had at least 1 subsequent evaluation. Exposures: Diagnosis was denoted after each evaluation visit as ASD, ASD features, language delay, developmental delay, other developmental issue, typical sibling of an ASD proband, or typical development. Main Outcomes and Measures: Diagnostic stability coefficients were calculated within 2-month age bands, and logistic regression models were used to explore the associations of sex, age, diagnosis at first visit, and interval between first and last diagnosis with stability. Toddlers with a non-ASD diagnosis at their first visit diagnosed with ASD at their last were designated as having late-identified ASD. Results: Among the 1269 toddlers included in the study (918 [72.3%] male; median age at first evaluation, 17.6 months [interquartile range, 14.0-24.4 months]; median age at final evaluation, 36.2 months [interquartile range, 33.4-40.9 months]), the overall diagnostic stability for ASD was 0.84 (95% CI, 0.80-0.87), which was higher than any other diagnostic group. Only 7 toddlers (1.8%) initially considered to have ASD transitioned into a final diagnosis of typical development. Diagnostic stability of ASD within the youngest age band (12-13 months) was lowest at 0.50 (95% CI, 0.32-0.69) but increased to 0.79 by 14 months and 0.83 by 16 months (age bands of 12 vs 14 and 16 months; odds ratio, 4.25; 95% CI, 1.59-11.74). A total of 105 toddlers (23.8%) were not designated as having ASD at their first visit but were identified at a later visit. Conclusions and Relevance: The findings suggest that an ASD diagnosis becomes stable starting at 14 months of age and overall is more stable than other diagnostic categories, including language or developmental delay. After a toddler is identified as having ASD, there may be a low chance that he or she will test within typical levels at 3 years of age. This finding opens the opportunity to test the impact of very early-age treatment of ASD.

Typical Levels of Eye-Region Fixation in Toddlers With Autism Spectrum Disorder Across Multiple Contexts.

OBJECTIVE: Unusual eye contact is a common clinical feature in autism spectrum disorder (ASD), yet eye-tracking studies that quantify eye fixation report inconsistent results, possibly because of small samples, varied stimuli, and considerable heterogeneity of eye-region fixation even within typical development. Goals were to examine eye-region fixation levels in a large, very young cohort; the degree to which the presence of speech, hand gestures, and a geometric distractor influence eye-region fixation; and possible developmental changes across time. METHOD: In experiment 1, 385 toddlers (143 with ASD, 242 without ASD, 11-47 months old) watched an actress engaging in child-directed speech with hand gestures against a plain background. Ninety-one toddlers participated approximately 8 months later. In experiment 2, another 231 toddlers (74 with ASD, 157 without ASD, 12-47 months old) watched the same video, but with embedded geometric distractors. Total fixation duration on facial and body regions (eg, eyes, hands) and geometric distractor regions (experiment 2 only) while the actress was speaking or silent, with or without gesturing, was examined, as were relations with clinical traits. RESULTS: Overall, across the 2 experiments and the 2 cross-sectional and longitudinal samples, eye-region fixation duration did not differ between toddlers with and without ASD, although fixation toward the face overall was decreased in toddlers with ASD. This decrease became more apparent with the presence of geometric distractors (experiment 2) as indexed by a geometric preference score, and this score was associated with autism severity. CONCLUSION: Within the context of viewing child-friendly vignettes, decreased eye-region fixation does not reliably characterize toddlers with ASD. An index of competition between faces and external distractors might be a more robust measure.

The geometric preference subtype in ASD: identifying a consistent, early-emerging phenomenon through eye tracking.

Background: The wide range of ability and disability in ASD creates a need for tools that parse the phenotypic heterogeneity into meaningful subtypes. Using eye tracking, our past studies revealed that when presented with social and geometric images, a subset of ASD toddlers preferred viewing geometric images, and these toddlers also had greater symptom severity than ASD toddlers with greater social attention. This study tests whether this "GeoPref test" effect would generalize across different social stimuli. Methods: Two hundred and twenty-seven toddlers (76 ASD) watched a 90-s video, the Complex Social GeoPref test, of dynamic geometric images paired with social images of children interacting and moving. Proportion of visual fixation time and number of saccades per second to both images were calculated. To allow for cross-paradigm comparisons, a subset of 126 toddlers also participated in the original GeoPref test. Measures of cognitive and social functioning (MSEL, ADOS, VABS) were collected and related to eye tracking data. To examine utility as a diagnostic indicator to detect ASD toddlers, validation statistics (e.g., sensitivity, specificity, ROC, AUC) were calculated for the Complex Social GeoPref test alone and when combined with the original GeoPref test. Results: ASD toddlers spent a significantly greater amount of time viewing geometric images than any other diagnostic group. Fixation patterns from ASD toddlers who participated in both tests revealed a significant correlation, supporting the idea that these tests identify a phenotypically meaningful ASD subgroup. Combined use of both original and Complex Social GeoPref tests identified a subgroup of about 1 in 3 ASD toddlers from the "GeoPref" subtype (sensitivity 35%, specificity 94%, AUC 0.75.) Replicating our previous studies, more time looking at geometric images was associated with significantly greater ADOS symptom severity. Conclusions: Regardless of the complexity of the social images used (low in the original GeoPref test vs high in the new Complex Social GeoPref test), eye tracking of toddlers can accurately identify a specific ASD "GeoPref" subtype with elevated symptom severity. The GeoPref tests are predictive of ASD at the individual subject level and thus potentially useful for various clinical applications (e.g., early identification, prognosis, or development of subtype-specific treatments).

Rethinking the idea of late autism spectrum disorder onset.

A common theory of autism spectrum disorder (ASD) symptom onset includes toddlers who do not display symptoms until well after age 2, which are termed late-onset ASD cases. Objectives were to analyze differences in clinical phenotype between toddlers identified as ASD at initial evaluations (early diagnosed) versus those initially considered nonspectrum, then later identified as ASD (late diagnosed). Two hundred seventy-three toddlers recruited from the general population based on a failed developmental screening form or parent or physician concerns were followed longitudinally from 12 months and identified as early- and late-diagnosed cases of ASD, language delayed, or typically developing. Toddlers completed common standardized assessments and experimental eye-tracking and observational measures every 9-12 months until age 3. Longitudinal performance on standardized assessments and experimental tests from initial evaluations were compared. Delay in social communication skills was seen in both ASD groups at early-age initial assessment, including increased preference for nonsocial stimuli, increased stereotypic play, reduced exploration, and use of gestures. On standardized psychometric assessments, early-diagnosed toddlers showed more impairment initially while late-diagnosed toddlers showed a slowing in language acquisition. Similar social communication impairments were present at very early ages in both early-detected ASD and so-called late-onset ASD. Data indicate ASD is present whether detected or not by current methods, and development of more sensitive tools is needed.