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Prior eye-tracking studies involving autistic individuals have focused on total looking time or proportion of looking time to key regions of interest. These studies have not examined another important feature, the ability to sustain attention to stimuli. In particular, the ability to sustain attention to a dynamic social stimulus might reflect more advanced self-regulatory skills that may enhance engagement with and comprehension of social information. In a sample of 155 autistic children (2–8 years of age), we examined children’s average look duration while they viewed a complex, dynamic stimulus containing both social and nonsocial elements. After accounting for children’s age and intelligence quotient, we found that shorter average look duration was associated with increased autism spectrum disorder severity across multiple clinical measures. To calculate average look duration, we divided the length of total looking time in seconds by the total number of uninterrupted looks to the video media. Thus, the ability to sustain attention while viewing complex dynamic information could be important for comprehending dynamic social information. Lay Abstract Many studies of autism look at the differences in how autistic research participants look at certain types of images. These studies often focus on where research participants are looking within the image, but that does not tell us everything about how much they are paying attention. It could be useful to know more about how well autistic research participants can focus on an image with people in it, because those who can look at images of people for longer duration without stopping may be able to easily learn other skills that help them to interact with people. We measured how long autistic research participants watched the video without breaking their attention. The video sometimes had a person speaking, and at other times had toys moving and making sounds. We measured the typical amount of time autistic research participants could look at the video before they looked away. We found that research participants with more severe autism tended to look at the video for shorter amounts of time. The ability to focus without stopping may be related to social skills in autistic people.

Autistic children’s play provides insights into social, communication, and other skills; however, methods for measuring these observations can be labor-intensive and rely on subjective judgment. This study explored whether children’s movement and location during play measured via automated video tracking correlates with clinical features. Movement tracking metrics of 164 autistic children (27–96 months old) during free play were analyzed in relation to standard assessments of cognitive, language, social-communication, and adaptive skills. Children with higher cognitive and language abilities were more likely to spend time in the center toy region and more slowly or never approached the region without toys. Children with higher autism-related features spent less time in the center. Children with lower daily living skills spent more time near the caregiver and those with lower overall adaptive and language skills approached the caregiver more quickly. Over 90% of autistic children representing a range of ages and skills provided analyzable movement data during play and those with higher cognitive, language, and adaptive skills displayed movement tracking patterns that reflect more sustained focus on toy play and independence from the caregiver. Results suggest that automated movement tracking is a promising complementary, objective method for assessing clinical variation during autistic children’s play. Lay Abstract Play-based observations allow researchers to observe autistic children across a wide range of ages and skills. We recorded autistic children playing with toys in the center of a room and at a corner table while a caregiver remained seated off to the side and used video tracking technology to track children’s movement and location. We examined how time children spent in room regions and whether or not they approached each region during play related to their cognitive, social, communication, and adaptive skills to determine if tracking child movement and location can meaningfully demonstrate clinical variation among autistic children representing a range of ages and skills. One significant finding was that autistic children who spent more time in the toy-containing center of the room had higher cognitive and language abilities, whereas those who spent less time in the center had higher levels of autism-related behaviors. In contrast, children who spent more time in the caregiver region had lower daily living skills and those who were quicker to approach the caregiver had lower adaptive behavior and language skills. These findings support the use of movement tracking as a complementary method of measuring clinical differences among autistic children. Furthermore, over 90% of autistic children representing a range of ages and skills in this study provided analyzable play observation data, demonstrating that this method allows autistic children of all levels of support needs to participate in research and demonstrate their social, communication, and attention skills without wearing any devices.

Individuals with autism spectrum disorder are more likely than typically developing individuals to experience a range of gastrointestinal abnormalities, including chronic diarrhea, constipation, food sensitivities, and abdominal pain. These gastrointestinal symptoms have been associated with higher levels of irritability and aggressive behavior, but less is known about their relationship with core autism spectrum disorder symptoms. We investigated the relationship between autism spectrum disorder and gastrointestinal symptom severity while accounting for three associated behavioral symptom domains (Irritability, Aggressiveness, and Specific Fears), in a sample of 176 children (140 males and 36 females) ages 2–7 years old with autism spectrum disorder. Most participants had at least one reported gastrointestinal symptom (93.2%) and had more than one gastrointestinal symptom (88.1%). After accounting for each associated behavioral symptom domain, repetitive behaviors and stereotypies were positively associated with gastrointestinal symptom severity. Social and communication difficulties were not significantly associated with gastrointestinal symptom severity after accounting for associated behavioral symptoms. Our findings replicate a previously described association between irritability and aggression and gastrointestinal symptoms. Furthermore, gastrointestinal symptom severity is associated with repetitive behaviors, a subset of core autism spectrum disorder symptoms. This suggests that gastrointestinal symptoms may exacerbate repetitive behaviors, or vice versa, independent from other associated behavioral symptoms. Lay Abstract Individuals with autism spectrum disorder are more likely than typically developing individuals to experience a range of gastrointestinal abnormalities, including chronic diarrhea, constipation, food sensitivities, and abdominal pain. These gastrointestinal symptoms have been associated with higher levels of irritability and aggressive behavior, but less is known about their relationship with core autism spectrum disorder symptoms. We investigated the relationship between autism spectrum disorder symptom severity and gastrointestinal symptoms while accounting for three associated behavioral symptom domains (Irritability, Aggressiveness, and Specific Fears), in a sample of 176 children (140 males and 36 females) ages 2–7 years old with autism spectrum disorder. A large majority (93.2%) of the sample had at least one reported gastrointestinal symptom, and most (88.1%) participants had more than one gastrointestinal symptom. Various types of gastrointestinal symptoms were reported; the most common symptoms reported were constipation, food limits, gas/bloating, and stomach pain. After accounting for each associated behavioral symptom domain, repetitive behaviors and stereotypies were significantly associated with gastrointestinal symptom severity. Increased severity of autism spectrum disorder symptoms was correlated with increased gastrointestinal symptom severity. Social and communication difficulties were not significantly associated with gastrointestinal symptom severity after accounting for associated behavioral symptoms. Our findings replicate a previously described association between irritability and aggression and gastrointestinal symptoms. Furthermore, we found that repetitive behaviors, but not social or communication symptoms, are associated with gastrointestinal symptom severity, even after accounting for associated behavioral symptoms. This suggests that gastrointestinal symptoms may exacerbate repetitive behaviors, or vice versa, independent from other associated behavioral symptoms.

Although it has been found that autistic children exhibit delays in executive function abilities and atypical patterns of attention, less is known about the relationship between executive function and attention abilities and social and language skills in early childhood. In this study, 180 autistic children, age 2–8 years, participated in a study examining the relationship between executive function abilities, measured by the Behavior Rating Inventory of Executive Function, and assessments of sustained attention measured via eye-tracking and several language and social communication measures. Results revealed that children with higher caregiver-reported executive function skills, specifically, working memory and planning/organization abilities, demonstrated higher levels of caregiver-reported receptive-expressive social communication abilities measured via the Pervasive Developmental Disorder Behavior Inventory. Higher executive function abilities across all domains were associated with lower levels of social pragmatic problems. Children who were able to sustain their attention for a longer duration demonstrated higher expressive language abilities. These results suggest that executive function and attention skills may play an important role in multiple domains of functioning in autistic children. It will be useful to determine whether therapies that seek to improve executive function skills in autistic individuals also positively influence their social/communication and language abilities. Lay Abstract Executive functioning describes a set of cognitive processes that affect thinking and behavior. Past research has shown that autistic individuals often have delays in the acquisition of executive function abilities. Our study explored how differences in executive function and attention abilities relate to social abilities and communication/language in 180 young autistic children. Data were gathered via caregiver report (questionnaires/interviews) and an assessment of vocabulary skills. The ability to sustain attention to a dynamic video was measured via eye tracking. We found that children with higher levels of executive function skills demonstrated lower levels of social pragmatic problems, a measure of having difficulties in social contexts. Furthermore, children who were able to sustain their attention longer to the video displayed higher levels of expressive language. Our results emphasize the importance of executive function and attention skills across multiple areas of functioning in autistic children, in particular those that involve language and social communication.

When COVID-19 disrupted autism spectrum disorder research globally, many clinical trials of behavioral interventions pivoted to telehealth. Telehealth has the potential to increase geographic reach and improve racial/ethnic diversity in research. This matters because most autism spectrum disorder intervention studies have primarily included White, upper-middle-income families from North America and Europe. Participant homogeneity limits our ability to identify what types of intervention works in which context for which populations. Importantly, telehealth needs to “fit” the local context, and in particular, include strategies that factor in the “digital divide.” This short report details contextual considerations and pre-implementation pragmatic adaptations in two autism spectrum disorder clinical trials that include Early Start Denver Model–informed caregiver coaching in the United States and South Africa. By comparing and contrasting how implementation context informed the telehealth pivot in these two clinical trials in different hemispheres, we highlight equity considerations for adaption. The pandemic is an opportunity to understand how remote intervention can “fit” diverse contexts, while providing valid scientific results. It is however important that adaptations be documented and feasibility of the adapted approach be tracked. COVID-19-related telehealth adaptations of behavioral interventions could facilitate the development of new strategies with wider global impact. Lay abstract COVID-19 caused many autism spectrum disorder caregiver-coaching studies to move to telehealth. Telehealth can increase the diversity of people who take part in research. This matters because most autism spectrum disorder studies have included people who have resources, are White, and live in North America and Europe. When study participants are similar, it is hard to understand which interventions can help different types of people who live in different parts of the world. While telehealth may allow more people to take part in research, it needs to “fit” the local context and consider the “digital divide” because many people around the world have no access to computers and the Internet. This short report describes changes to two research studies that include caregiver coaching based on the Early Start Denver Model in the United States and South Africa. We describe how the local context, including technology and Internet access, guided the telehealth approach. By doing so, we highlight ways to make telehealth available to more people around the world. The pandemic can help us understand how telehealth can “fit” diverse places and support high-quality research. It is important that study changes are tracked and we assess how well the changes work. COVID-19 telehealth changes to caregiver coaching can result in new ways to reach more people around the world.

Importance Atypical eye gaze is an early-emerging symptom of autism spectrum disorder (ASD) and holds promise for autism screening. Current eye-tracking methods are expensive and require special equipment and calibration. There is a need for scalable, feasible methods for measuring eye gaze. Objective Using computational methods based on computer vision analysis, we evaluated whether an app deployed on an iPhone or iPad that displayed strategically designed brief movies could elicit and quantify differences in eye-gaze patterns of toddlers with ASD vs typical development. Design, Setting, and Participants A prospective study in pediatric primary care clinics was conducted from December 2018 to March 2020, comparing toddlers with and without ASD. Caregivers of 1564 toddlers were invited to participate during a well-child visit. A total of 993 toddlers (63%) completed study measures. Enrollment criteria were aged 16 to 38 months, healthy, English- or Spanish-speaking caregiver, and toddler able to sit and view the app. Participants were screened with the Modified Checklist for Autism in Toddlers–Revised With Follow-up during routine care. Children were referred by their pediatrician for diagnostic evaluation based on results of the checklist or if the caregiver or pediatrician was concerned. Forty toddlers subsequently were diagnosed with ASD. Exposures A mobile app displayed on a smartphone or tablet. Main Outcomes and Measures Computer vision analysis quantified eye-gaze patterns elicited by the app, which were compared between toddlers with ASD vs typical development. Results Mean age of the sample was 21.1 months (range, 17.1-36.9 months), and 50.6% were boys, 59.8% White individuals, 16.5% Black individuals, 23.7% other race, and 16.9% Hispanic/Latino individuals. Distinctive eye-gaze patterns were detected in toddlers with ASD, characterized by reduced gaze to social stimuli and to salient social moments during the movies, and previously unknown deficits in coordination of gaze with speech sounds. The area under the receiver operating characteristic curve discriminating ASD vs non-ASD using multiple gaze features was 0.90 (95% CI, 0.82-0.97). Conclusions and Relevance The app reliably measured both known and new gaze biomarkers that distinguished toddlers with ASD vs typical development. These novel results may have potential for developing scalable autism screening tools, exportable to natural settings, and enabling data sets amenable to machine learning.

Background This study is part of a larger research program focused on developing objective, scalable tools for digital behavioral phenotyping. We evaluated whether a digital app delivered on a smartphone or tablet using computer vision analysis (CVA) can elicit and accurately measure one of the most common early autism symptoms, namely failure to respond to a name call. Methods During a pediatric primary care well-child visit, 910 toddlers, 17-37 months old, were administered an app on an iPhone or iPad consisting of brief movies during which the child's name was called three times by an examiner standing behind them. Thirty-seven toddlers were subsequently diagnosed with autism spectrum disorder (ASD). Name calls and children's behavior were recorded by the camera embedded in the device, and children's head turns were coded by both CVA and a human. Results CVA coding of response to name was found to be comparable to human coding. Based on CVA, children with ASD responded to their name significantly less frequently than children without ASD. CVA also revealed that children with ASD who did orient to their name exhibited a longer latency before turning their head. Combining information about both the frequency and the delay in response to name improved the ability to distinguish toddlers with and without ASD. Conclusions A digital app delivered on an iPhone or iPad in real-world settings using computer vision analysis to quantify behavior can reliably detect a key early autism symptom-failure to respond to name. Moreover, the higher resolution offered by CVA identified a delay in head turn in toddlers with ASD who did respond to their name. Digital phenotyping is a promising methodology for early assessment of ASD symptoms.

Using eye tracking, a rich body of literature has identified atypical attention to dynamic social stimuli in children with autism. What is less clear is what constitutes typical gaze as this is highly dependent on stimulus content. Instead of looking at proportions of looking time to predefined areas of interested, here we calculate mean fixations frame-by-frame in a group of typically developing children. We then determined the distance from that typical fixation point for 155 children with autism frame-by-frame. Distance from the typical scan path was assessed in relation to clinical measures of adaptive skills and autism symptomatology. Findings revealed that less typical scan paths among children with autism were associated with lower communication abilities and greater autism symptomatology.

Disparities exist in the recognition of autism spectrum disorder (ASD) and intellectual disability (ID) in racial/ethnic minorities in the United States. This study examined whether rurality, race/ethnicity, and low resource availability are associated with disparities in primary educational classifications of ASD and ID in North Carolina (NC). Descriptive maps were created. Multilevel logistic regression models examined two separate outcomes (mild ID vs. ASD; moderate/severe ID vs. ASD). For the interaction term included in the model (race/ethnicity and residence), predicted probabilities were estimated and plotted. The effects of other covariates were also estimated. Rural counties had fewer students with ASD and a greater number of students with ID compared to urban counties. The majority of students with ASD were non-Hispanic Whites, while the majority of students with ID were non-Hispanic Blacks. Compared to non-Hispanic White students, non-Hispanic Black students were overrepresented in the ID classification and underrepresented in the ASD classification across urban and rural areas. Indicators of low resource availability were also associated with higher probabilities of ID vs. ASD classification. Differences in primary educational classification based on urban-rural divide, race/ethnicity, and resource availability are important to understand as they may point to disparities that could have significant policy and service implications. Because disparities manifest through complex interactions between environmental, socioeconomic and system-level factors, reduction in these disparities will require broader approaches that address structural determinants. Future research should utilize disparity frameworks to understand differences in primary educational classifications of ASD and ID in the context of race/ethnicity and rurality. LAY SUMMARY: Rural counties in North Carolina had fewer students with ASD and a greater number of students with ID compared to urban counties. Compared to non-Hispanic White students, non-Hispanic Black students were over-represented in the ID educational classification and underrepresented in the ASD classification. Differences in classification of ASD and ID based on urban-rural divide, race/ethnicity, and resource availability may point to disparities that could have significant policy and service implications. Autism Res 2021, 14: 1046-1060. © 2021 International Society for Autism Research, Wiley Periodicals LLC.

We examined special education classifications among students aged 3-21 in North Carolina public schools, highlighting autism spectrum disorder (ASD) and intellectual disability (ID). Results revealed variability by county in ASD and ID prevalence, and in county-level ratios of ID vs. ASD classifications. Sociodemographic characteristics predicted proportion of ASD or ID within a county; correlations showed an association between race and ID, but not ASD. County's median household income predicted proportion of students classified as ASD and ID (opposite directions), controlling for number of students and gender. Variability was unlikely related to biological incidence, and more likely related to district/school practices, or differences in resources. Disparities warrant further examination to ensure that North Carolina's youth with disabilities access necessary, appropriate resources.

The Early Start Denver Model (ESDM; Rogers and Dawson in The Early Start Denver Model for Young Children with Autism: Promoting Language, Learning, and Engagement. Guilford Press, New York, 2010) is an evidence-based early intervention designed to promote developmental and social communication skills in young children with autism spectrum disorder between the ages of 12 and 60 months. The ESDM is characterized as a Naturalistic Developmental Behavioral Intervention (NDBI; Schreibman et al. in Naturalistic Developmental Behavioral Interventions: Empirically validated treatments for autism spectrum disorder. J Autism Dev Disord 45(8):2411–2428, 2015), indicating that it shares commonalities with a number of similar types of early interventions including delivery in natural contexts, shared control between the child and clinician, and use of behavioral principles/natural contingencies. The ESDM is particularly well suited for an interdisciplinary approach to care for young children on the autism spectrum given that it promotes the development of an interdisciplinary treatment team, benefits from collaboration across disciplines, and values the input of varied perspectives. Several other ways in which the ESDM approach provides a range of opportunities to collaborate and coordinate interdisciplinary care are described throughout the chapter.

Ongoing neuroinflammation may contribute to symptoms of autism spectrum disorder (ASD) in at least a portion of affected individuals. Mesenchymal stromal cells (MSCs) have demonstrated the capacity to modulate neuroinflammation, but safety and feasibility of MSC administration in children with ASD have not been well established. In this open‐label, phase I study, 12 children with ASD between 4 and 9 years of age were treated with intravenous (IV) infusions of human cord tissue mesenchymal stromal cells (hCT‐MSCs), a third‐party MSC product manufactured from unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 106 cells per kilogram at 2‐month intervals. Clinical and laboratory evaluations were performed in person at baseline and 6 months and remotely at 12 months after the final infusion. Aside from agitation during the IV placement and infusion in some participants, hCT‐MSCs were well tolerated. Five participants developed new class I anti‐human leukocyte antigen (HLA) antibodies, associated with a specific lot of hCT‐MSCs or with a partial HLA match between donor and recipient. These antibodies were clinically silent and not associated with any clinical manifestations to date. Six of 12 participants demonstrated improvement in at least two ASD‐specific measures. Manufacturing and administration of hCT‐MSCs appear to be safe and feasible in young children with ASD. Efficacy will be evaluated in a subsequent phase II randomized, placebo‐controlled clinical trial., In this phase I study, intravenous infusion of human cord tissue mesenchymal stromal cell was safe and feasible in young children with autism. Autism symptoms improved in half of children, and 40% developed clinically silent but detectable anti‐human leukocyte antigen antibodies post‐infusion.

Objective To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD). Study design This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion. Results CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power. Conclusions Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.

This review describes and evaluates measures aimed at assessing treatment response in parent-mediated early interventions targeting autism spectrum disorder (ASD). In order to be able to evaluate the relative utility of different interventions, it is critical to have access to tools that identify treatment effects. Measures across domains of child outcomes, parent or family outcomes, and parent-child interaction outcomes are evaluated by summarizing their roles in previous studies, and describing the consistency of treatment effects. In particular, some variables included in parent-child interaction outcomes generated relatively consistent treatment effects. Considerations for future research are discussed, including cultural considerations, challenges associated with the current set of outcome measures, and an emphasis on enhancing ecological validity.

In their recent paper, “Caregiver descriptions of joint activity routines with young children with autism spectrum disorder in South Africa”, Ramseur and colleagues examined the applicability of an early intervention model for children with autism spectrum disorder (ASD), which was developed and validated in more highly resourced settings, to the diverse cultural context of South Africa (1). They highlighted the importance of this work by noting the dearth of ASD research on the African continent; for example, Africa is yet to see an ASD prevalence study, and as of 2017, a scoping review identified only 53 peer-reviewed publications on ASD published in sub-Saharan Africa (2). Moreover, none of the publications focused on early intervention in Africa. Thus, Ramseur et al .’s study represents an important step forward in addressing the needs of children with ASD in South Africa.