1. Barone R, Cirnigliaro L, Saccuzzo L, Valdese S, Pettinato F, Prato A, Bernardini L, Fichera M, Rizzo R. PARK2 microdeletion in a multiplex family with autism spectrum disorder. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 2022.

BACKGROUND: PARK2 (PRKN; MIM*602544) encodes Parkin protein, an ubiquitin-protein ligase required for proteasomal degradation and operating in the synaptic compartments. Copy number variations (CNVs) involving PARK2 have been associated with autism spectrum disorder (ASD). We report on a family with ASD (multiplex family) harbouring a microdeletion at chr. 6q26 causing PARK2 disruption. METHODS: CNV analyses were performed using CGH/SNP-array platforms, and the detected microdeletion was confirmed by real-time quantitative PCR. Standardized psychometric evaluation was used for neurobehavioral characterization. RESULTS: We found an intragenic ~157 kb microdeletion of the chromosomal region 6q26 causing PARK2 disruption in two male sibs with ASD and syndromic phenotype. They both had dysmorphic facial features with coarse faces, deeply set eyes with long horizontal palpebral fissures, long eyelashes and thick eyebrows, fleshy lips and mild skeletal problems. We found an intrafamilial clinical heterogeneity owing to different severity of the autism symptoms between the affected sibs: the younger one had minimally verbal autism and severe intellectual disability, whereas his older brother presented high-functioning autism and preserved speech. Parental analysis and real-time PCR using a PRKN fragment mapping within the deletion demonstrated that the deletion was inherited from their father having subthreshold features of ASD consisting with broad autism phenotype. CONCLUSIONS: The study corroborates the hypothesis that PARK2 aberrations may be associated with ASD and highlights correlations between CNV affecting PARK2 and ASD in a multiplex family. We show remarkable intrafamilial variability in the severity of inherited ASD associated with PARK2 microdeletion.

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2. Brisendine AE, O’Kelley SE, Sen B, Preskitt J, Wingate MS. Classifying children with ASD by service utilization and treatment type: A cluster analysis of a nationally representative United States survey. Acta psychologica. 2022; 232: 103800.

BACKGROUND: If there are patterns of the distribution of services and treatments across the population of people with ASD, these patterns should be based along clinical characteristics or other service needs and not sociodemographic characteristics unrelated to evidence-based care. We examined how individuals in a broad, nationally representative sample « grouped together » based on service utilization and services needed but not covered by insurance. By understanding various treatment patterns, clinicians, researchers, policymakers, and self-advocates and their families can better advocate for high-quality, evidence-based services to be provided equitably. METHODS: Using the 2011 Survey of Pathways to Diagnosis and Services, a cluster analysis was performed to explore patterns in this population based on medication use, private services use, school-based service use, and services not covered by insurance. Differences in clusters were then explored through multinomial logistic regression. RESULTS: Six clusters emerged, showing differences in the level of service/medication usage and insurance coverage. Differences across clusters were associated with the level of functional limitation and age at ASD diagnosis. Disparities by insurance type, functional limitation, and age at diagnosis exist among patterns of ASD service provision. CONCLUSIONS: Our analysis showed that intervention for children with ASD can be across several scales – high and low users of services (both private and school-based), high and low users of medications, and high and low levels of reported non-covered services. The differences were clustered in multiple ways. Further research should incorporate longitudinal and nationally representative data to explore these relationships further.

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3. Carlier S, Vorlet P, C SDR, Malamateniou C. Strategies, challenges and enabling factors when imaging autistic individuals in Swiss medical imaging departments. Journal of medical imaging and radiation sciences. 2022.

INTRODUCTION: Autistic individuals may require medical imaging but they can face barriers that are related to lack of adjustments in their care. This study aims to explore and understand strategies currently used by Swiss radiographers to image autistic patients and to propose recommendations for clinical practice. METHODS: The Swiss Ethics of the canton of Vaud committee approved the study. Data collection was gathered using a mixed method approach by an online survey and followed by selected interviews. Descriptive statistics and thematic analysis were used to analyse the data. RESULTS: A hundred completed responses to the survey were obtained and five individual interviews were conducted. Sixty participants reported having managed autistic patients. The main enablers identified were: the support from carers, adapting the behaviour of staff and customising communication. The main challenges were a lack of communication and the lack of knowledge about autism to appropriately manage the patient. Only five radiographers had received prior training in autism. CONCLUSION: Medical imaging departments must develop protocols to overcome the lack of communication between services, radiographers, and autistic service users. The lack of radiographer knowledge about autism can impact autistic patient management, resulting in carers playing an important role during the examination. Customised education for radiographers about autism is needed. IMPLICATION FOR PRACTICE: The development of a scheduling protocol for each imaging modality could improve communication with the patient. The organisation of the physical environment and the patient’s preparation for the examination are critical to provide adequate imaging care. It is suggested that medical imaging professionals, autistic service users, and autism organisations collaborate to develop autism related guidelines for medical imaging examinations.

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4. Carter Leno V, Begum-Ali J, Goodwin A, Mason L, Pasco G, Pickles A, Garg S, Green J, Charman T, Johnson MH, Jones EJH. Infant excitation/inhibition balance interacts with executive attention to predict autistic traits in childhood. Molecular autism. 2022; 13(1): 46.

BACKGROUND: Autism is proposed to be characterised by an atypical balance of cortical excitation and inhibition (E/I). However, most studies have examined E/I alterations in older autistic individuals, meaning that findings could in part reflect homeostatic compensation. To assess the directionality of effects, it is necessary to examine alterations in E/I balance early in the lifespan before symptom emergence. Recent explanatory frameworks have argued that it is also necessary to consider how early risk features interact with later developing modifier factors to predict autism outcomes. METHOD: We indexed E/I balance in early infancy by extracting the aperiodic exponent of the slope of the electroencephalogram (EEG) power spectrum (‘1/f’). To validate our index of E/I balance, we tested for differences in the aperiodic exponent in 10-month-old infants with (n = 22) and without (n = 27) neurofibromatosis type 1 (NF1), a condition thought to be characterised by alterations to cortical inhibition. We then tested for E/I alterations in a larger heterogeneous longitudinal cohort of infants with and without a family history of neurodevelopmental conditions (n = 150) who had been followed to early childhood. We tested the relevance of alterations in E/I balance and our proposed modifier, executive attention, by assessing whether associations between 10-month aperiodic slope and 36-month neurodevelopmental traits were moderated by 24-month executive attention. Analyses adjusted for age at EEG assessment, sex and number of EEG trials. RESULTS: Infants with NF1 were characterised by a higher aperiodic exponent, indicative of greater inhibition, supporting our infant measure of E/I. Longitudinal analyses showed a significant interaction between aperiodic slope and executive attention, such that higher aperiodic exponents predicted greater autistic traits in childhood, but only in infants who also had weaker executive functioning abilities. LIMITATIONS: The current study relied on parent report of infant executive functioning-type abilities; future work is required to replicate effects with objective measures of cognition. CONCLUSIONS: Results suggest alterations in E/I balance are on the developmental pathway to autism outcomes, and that higher executive functioning abilities may buffer the impact of early cortical atypicalities, consistent with proposals that stronger executive functioning abilities may modify the impact of a wide range of risk factors.

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5. Frye RE, Lane A, Worner A, Werner BA, McCarty PJ, Scheck AC, Collins HL, Adelman SJ, Quadros EV, Rossignol DA. The Soluble Folate Receptor in Autism Spectrum Disorder: Relation to Autism Severity and Leucovorin Treatment. Journal of personalized medicine. 2022; 12(12).

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with life-long consequences that affects up to 1 in 44 children. Treatment with leucovorin (folinic acid), a reduced form of folate, has been shown to improve symptoms in those with ASD and folate pathway abnormalities in controlled clinical trials. Although soluble folate binding proteins (sFBPs) have been observed in the serum of some patients with ASD, the significance of this finding has not been studied. Here, we present a cohort of ASD patients with sFBPs. These patients had severe ASD and were medically complex. Using baseline controlled open-label methodology and standardized assessments, these patients were found to improve in both core and associated ASD symptoms with leucovorin treatment. No adverse effects were related to leucovorin treatment. This is the first report of the sFBPs in ASD. This study complements ongoing controlled clinical trials and suggests that leucovorin may be effective for children with ASD who are positive for sFBPs. Further, sFBPs might be important biomarkers for treatment response to leucovorin in children with ASD. This study paves the way for further controlled studies for patients with sFBPs.

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6. Gao L, Liu XN. Status Quo and Advanced Progress in Oral Health Care and Treatment of Children with Autism Spectrum Disorder: A Literatiure Review. The Chinese journal of dental research : the official journal of the Scientific Section of the Chinese Stomatological Association (CSA). 2022; 25(4): 251-9.

Autism spectrum disorder (ASD) has become one of the fastest growing diseases in the world, causing a great burden to ASD children’s families and society. Children with ASD face more disadvantages relating to their oral health than those without ASD. There is a positive correlation between prevalence of caries lesions and severity of ASD. Poorer oral hygiene, higher detection rates of dental calculus and far more frequent cases of gingivitis occur in children with ASD. Traumatic injuries and various types of malocclusions are more frequent in children with ASD. Poorer oral health care and treatment status are caused by multiple adverse factors. Ways of promoting effective oral health care and treatment include pretreatment counselling; improvement of the individualised treatment environment; routine behaviour guidance techniques (BGTs) including tell-show-do, distraction, role model presentation, voice control, visual education and social stories, encouragement and reinforcement; targeted BGTs including visual education, behaviour modelling, applied behaviour analysis (ABA) and systematic desensitisation; passive BGTs including protective restraint, pharmaceutically administrated sedation and general anaesthesia; oral health education for guardians; and interdisciplinary collaboration and professional dental care/treatment. Dentists, families with children with ASD and schools should cooperate to improve family-centred oral health care and treatment for ASD children not only in China, but also the whole world.

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7. Ghahari N, Yousefian F, Behzadi S, Jalilzadeh A. Rural-Urban Differences in Age at Autism Diagnosis: A Multiple Model Analysis. Iranian journal of psychiatry. 2022; 17(3): 294-303.

Objective: Early recognition of autism is important, but diagnosis age varies among children. Recent studies have aimed to identify factors affecting age of diagnosis and several studies have attempted to explore geographic variation in age at diagnosis of autism. However, there is a lack of research examining geographic variations with multiple models to find whether geographic differences can be explained by risk factors such as socioeconomic status and differences in child characteristics. This study aimed to address this gap of knowledge by comparing age at diagnosis of autism between the group of people living in the center of the province and the group of people living in the rest of the province, considering potential medical and socioeconomic confounders. Method : The study population consisted of 50 autistic children born in East Azerbaijan Province between 2004 and 2016. Initially, univariate testing by ANOVA was performed to identify family and individual factors contributing to differences in age at autism diagnosis. Following this, the association between living in the center of the province and age at diagnosis in univariate and multivariate analyses was examined. Results: Results from the initial univariate analysis indicate a significant association between living in the center of province and early diagnosis. However, inclusion of possible confounders in multiple model illustrates that these geographical disparities in age at diagnosis can be explained by differences in socioeconomic and medical status. Conclusion: Although geographic variation in age at diagnosis of autism was observed, analyses show that differences in individual and family-level factors may contribute to geographic differences. In this study, most of the observed variation was accounted for by family-level factors rather than geographic policies. Findings prove that multiple strategies are required to identify targeted interventions and strategies.

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8. Hodges AK, Hathaway KL, McMahon MXH, Volkert VM, Sharp WG. Treatment of Feeding Concerns in Children With Autism Spectrum Disorder: A Systematic Review of Behavioral Interventions With Caregiver Training. Behavior modification. 2022: 1454455221137328.

Successful feeding intervention ultimately requires generalization and adoption of treatment into the home. Treatment models, however, differ regarding how and when caregivers are integrated into care delivery process. Some treatments involve a primary model of parent training with caregivers serving as co-therapist at the onset of intervention, while others involve a complimentary model where a therapist delivers the intervention and caregiver training occurs once the child’s behavior is stable. This review systematically evaluates the evidence-base regarding behavioral feeding intervention for children with autism spectrum disorder (ASD), with a specific focus on interventions involving parent training. Results provide further evidence regarding the potential benefits of behavioral intervention to improve feeding concerns in ASD, while also highlighting growing attention to documenting and/or evaluating parent training within the treatment literature. Important questions remain regarding factors guiding the use of a primary or complimentary model of parent training.

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9. Jiang Y, Han L, Meng J, Wang Z, Zhou Y, Yuan H, Xu H, Zhang X, Zhao Y, Lu J, Xu H, Zhang C, Zhang YW. Gene therapy using human FMRP isoforms driven by the human FMR1 promoter rescues fragile X syndrome mouse deficits. Molecular therapy Methods & clinical development. 2022; 27: 246-58.

Fragile X syndrome (FXS) is caused by the loss of the fragile X messenger ribonucleoprotein 1 (FMRP) encoded by the FMR1 gene. Gene therapy using adeno-associated virus (AAV) to restore FMRP expression is a promising therapeutic strategy. However, so far AAV gene therapy tests for FXS only utilized rodent FMRPs driven by promoters other than the human FMR1 promoter. Restoration of human FMRP in appropriate cell types and at physiological levels, preferably driven by the human FMR1 promoter, would be more suitable for its clinical use. Herein, we generated two human FMR1 promoter subdomains that effectively drive gene expression. When AAVs expressing two different human FMRP isoforms under the control of a human FMR1 promoter subdomain were administered into bilateral ventricles of neonatal Fmr1 (-/y) and wild-type (WT) mice, both human FMRP isoforms were expressed throughout the brain in a pattern reminiscent to that of mouse FMRP. Importantly, human FMRP expression attenuated social behavior deficits and stereotyped and repetitive behavior, and reversed dysmorphological dendritic spines in Fmr1 (-/y) mice, without affecting WT mouse behaviors. Our results demonstrate that human FMR1 promoter can effectively drive human FMRP expression in the brain to attenuate Fmr1 (-/y) mouse deficits, strengthening the notion of using AAV gene therapy for FXS treatment.

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10. Keating CT, Hickman L, Leung J, Monk R, Montgomery A, Heath H, Sowden S. Autism-related language preferences of English-speaking individuals across the globe: A mixed methods investigation. Autism research : official journal of the International Society for Autism Research. 2022.

Over the past two decades, there have been increasing discussions around which terms should be used to talk about autism. Whilst these discussions have largely revolved around the suitability of identity-first language and person-first language, more recently this debate has broadened to encompass other autism-related terminology (e.g., ‘high-functioning’). To date, academic studies have not investigated the language preferences of autistic individuals outside of the United Kingdom or Australia, nor have they compared levels of endorsement across countries. Hence, the current study adopted a mixed-methods approach, employing both quantitative and qualitative techniques, to explore the linguistic preferences of 654 English-speaking autistic adults across the globe. Despite variation in levels of endorsement between countries, we found that the most popular terms were similar-the terms ‘Autism’, ‘Autistic person’, ‘Is autistic’, ‘Neurological/Brain Difference’, ‘Differences’, ‘Challenges’, ‘Difficulties’, ‘Neurotypical people’, and ‘Neurotypicals’ were consistently favored across countries. Despite relative consensus across groups, both our quantitative and qualitative data demonstrate that there is no universally accepted way to talk about autism. Our thematic analysis revealed the reasons underlying participants’ preferences, generating six core themes, and illuminated an important guiding principle-to respect personal preferences. These findings have significant implications for informing practice, research and language policy worldwide.

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11. Liu A, Cai C, Wang Z, Wang B, He J, Xie Y, Deng H, Liu S, Zeng S, Yin Z, Wang M. Inductively coupled plasma mass spectrometry based urine metallome to construct clinical decision models for autism spectrum disorder. Metallomics : integrated biometal science. 2022; 14(12).

BACKGROUND: The global prevalence of autism spectrum disorder (ASD) is on the rise, and high levels of exposure to toxic heavy metals may be associated with this increase. Urine analysis is a noninvasive method for investigating the accumulation and excretion of heavy metals. The aim of this study was to identify ASD-associated urinary metal markers. METHODS: Overall, 70 children with ASD and 71 children with typical development (TD) were enrolled in this retrospective case-control study. In this metallomics investigation, inductively coupled plasma mass spectrometry was performed to obtain the urine profile of 27 metals. RESULTS: Children with ASD could be distinguished from children with TD based on the urine metal profile, with ASD children showing an increased urine metal Shannon diversity. A metallome-wide association analysis was used to identify seven ASD-related metals in urine, with cobalt, aluminum, selenium, and lithium significantly higher, and manganese, mercury, and titanium significantly lower in the urine of children with ASD than in children with TD. The least absolute shrinkage and selection operator (LASSO) machine learning method was used to rank the seven urine metals in terms of their effect on ASD. On the basis of these seven urine metals, we constructed a LASSO regression model for ASD classification and found an area under the receiver operating characteristic curve of 0.913. We also constructed a clinical prediction model for ASD based on the seven metals that were different in the urine of children with ASD and found that the model would be useful for the clinical prediction of ASD risk. CONCLUSIONS: The study findings suggest that altered urine metal concentrations may be an important risk factor for ASD, and we recommend further exploration of the mechanisms and clinical treatment measures for such alterations.

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12. Liu Y, Di Y, Zheng Q, Qian Z, Fan J, Ren W, Wei Z, Tian Y. Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autism. Frontiers in cellular neuroscience. 2022; 16: 1057857.

Autism spectrum disorders (ASD) represent a group of neurodevelopmental defects characterized by social deficits and repetitive behaviors. Alteration in Glycosylation patterns could influence the nervous system development and contribute to the molecular mechanism of ASD. Interaction of environmental factors with susceptible genes may affect expressions of glycosylation-related genes and thus result in abnormal glycosylation patterns. Here, we used an environmental factor-induced model of autism by a single intraperitoneal injection of 400 mg/kg valproic acid (VPA) to female rats at day 12.5 post-conception. Following confirmation of reduced sociability and increased self-grooming behaviors in VPA-treated offspring, we analyzed the alterations in the expression profile of glycan patterns and glycan-related genes by lectin microarrays and RNA-seq, respectively. Lectin microarrays detected 14 significantly regulated lectins in VPA rats, with an up-regulation of high-mannose with antennary and down-regulation of Siaα2-3 Gal/GalNAc. Based on the KEGG and CAZy resources, we assembled a comprehensive list of 961 glycan-related genes to focus our analysis on specific genes. Of those, transcription results revealed that there were 107 differentially expressed glycan-related genes (DEGGs) after VPA treatment. Functional analysis of DEGGs encoding anabolic enzymes revealed that the process trimming to form core structure and glycan extension from core structure primarily changed, which is consistent with the changes in glycan patterns. In addition, the DEGGs encoding glycoconjugates were mainly related to extracellular matrix and axon guidance. This study provides insights into the underlying molecular mechanism of aberrant glycosylation after prenatal VPA exposure, which may serve as potential biomarkers for the autism diagnosis.

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13. Parellada M, Andreu-Bernabeu Á, Burdeus M, San José Cáceres A, Urbiola E, Carpenter LL, Kraguljac NV, McDonald WM, Nemeroff CB, Rodriguez CI, Widge AS, State MW, Sanders SJ. In Search of Biomarkers to Guide Interventions in Autism Spectrum Disorder: A Systematic Review. The American journal of psychiatry. 2022: appiajp21100992.

OBJECTIVE: The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials. METHODS: A systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included. RESULTS: A total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a « replication crisis. » CONCLUSIONS: There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic « big data » analyses of multiple potential biomarkers could accelerate discovery.

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14. Park SB, Ju Y, Kwon H, Youm H, Kim MJ, Chung J. Effect of a Cognitive Function and Social Skills-Based Digital Exercise Therapy Using IoT on Motor Coordination in Children with Intellectual and Developmental Disability. International journal of environmental research and public health. 2022; 19(24).

This study aimed to determine the effects of a virtual reality exercise program based on cognitive function and social skills on motor coordination in children with intellectual and developmental disabilities (IDD). Thirty-five children with IDD were randomly assigned to either the cognitive function and social skills-based virtual reality exercise system (CS-VR) group or the conventional virtual reality exercise system (C-VR) group. Before and after the intervention, each participant was tested for motor coordination (extended horizontal jump, hop, stationary dribble, overarm throw) and exercise performance (standing long jump, YMCA step test). Compared with the C-VR group, the CS-VR group showed significant improvements in motor coordination in terms of extended horizontal jump, hop, and overarm throw (p < 0.01, p < 0.05, and p < 0.01, respectively). In addition, compared with the C-VR group, the CS-VR group showed a significant increase in standing long jump (p < 0.01), although no significant between-group variation was found in stationary dribble and recovery heart rate (RHR) as part of the YMCA step test (p > 0.05, and p > 0.05, respectively). These results suggest that for the development of motor skills in children with IDD, it is essential to develop an exercise program that reflects the levels of cognitive functions and social skills of these children.

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15. Perkovich E, Sun L, Mire S, Laakman A, Sakhuja U, Yoshida H. What children with and without ASD see: Similar visual experiences with different pathways through parental attention strategies. Autism & developmental language impairments. 2022; 7: 23969415221137293.

BACKGROUND AND AIMS: Although young children’s gaze behaviors in experimental task contexts have been shown to be potential biobehavioral markers relevant to autism spectrum disorder (ASD), we know little about their everyday gaze behaviors. The present study aims (1) to document early gaze behaviors that occur within a live, social interactive context among children with and without ASD and their parents, and (2) to examine how children’s and parents’ gaze behaviors are related for ASD and typically developing (TD) groups. A head-mounted eye-tracking system was used to record the frequency and duration of a set of gaze behaviors (such as sustained attention [SA] and joint attention [JA]) that are relevant to early cognitive and language development. METHODS: Twenty-six parent-child dyads (ASD group = 13, TD group = 13) participated. Children were between the ages of 3 and 8 years old. We placed head-mounted eye trackers on parents and children to record their parent- and child-centered views, and we also recorded their interactive parent-child object play scene from both a wall- and ceiling-mounted camera. We then annotated the frequency and duration of gaze behaviors (saccades, fixation, SA, and JA) for different regions of interest (object, face, and hands), and attention shifting. Independent group t-tests and ANOVAs were used to observe group comparisons, and linear regression was used to test the predictiveness of parent gaze behaviors for JA. RESULTS: The present study found no differences in visual experiences between children with and without ASD. Interestingly, however, significant group differences were found for parent gaze behaviors. Compared to parents of ASD children, parents of TD children focused on objects and shifted their attention between objects and their children’s faces more. In contrast, parents of ASD children were more likely to shift their attention between their own hands and their children. JA experiences were also predicted differently, depending on the group: among parents of TD children, attention to objects predicted JA, but among parents of ASD children, attention to their children predicted JA. CONCLUSION: Although no differences were found between gaze behaviors of autistic and TD children in this study, there were significant group differences in parents’ looking behaviors. This suggests potentially differential pathways for the scaffolding effect of parental gaze for ASD children compared with TD children. IMPLICATIONS: The present study revealed the impact of everyday life, social interactive context on early visual experiences, and point to potentially different pathways by which parental looking behaviors guide the looking behaviors of children with and without ASD. Identifying parental social input relevant to early attention development (e.g., JA) among autistic children has implications for mechanisms that could support socially mediated attention behaviors that have been documented to facilitate early cognitive and language development and implications for the development of parent-mediated interventions for young children with or at risk for ASD.Note: This paper uses a combination of person-first and identity-first language, an intentional decision aligning with comments put forth by Vivanti (Vivanti, 2020), recognizing the complexities of known and unknown preferences of those in the larger autism community.

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16. Samadi SA. Overview of Services for Autism Spectrum Disorders (ASD) in Low- and Middle-Income Countries (LMICs) and among Immigrants and Minority Groups in High-Income Countries (HICs). Brain sciences. 2022; 12(12).

Autism spectrum disorder (ASD) prevalence is rising […].

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17. Snijder MIJ, Dietz C, van Andel M, Ruiter ELM, Buitelaar JK, Oosterling IJ. Social COmmunication Program supported by E-health (SCOPE) for infants and toddlers at elevated likelihood of autism spectrum disorder: study design of a cluster randomized controlled trial. BMC psychiatry. 2022; 22(1): 772.

BACKGROUND: Although the importance of early detection and early intervention of autism spectrum disorders (ASD) is widely recognized, multiple barriers exist in accessing early intervention services. As an alternative to these barriers, the SCOPE project presents a new, easy accessible and blended intervention called BEAR (Blended E-health for children at eArly Risk). This paper describes this BEAR intervention and study design of an ongoing two arm cluster randomized controlled trial (RCT). METHODS: BEAR (Blended E-health for children at eArly Risk) is a blended e-health intervention, based on evidence-based naturalistic developmental behavioral interventions (NDBI’s) and can be offered to parents and infants/toddlers at high likelihood for ASD. During the ongoing RCT, N = 88 high risk infants and toddlers will be cluster randomized over the BEAR intervention and care-as-usual (CAU) conditions. The finalized version of the intervention protocol and study design are presented in this paper. The primary outcome measure is joint engagement measured by the Joint Engagement Rating Inventory (JERI) during videotaped parent-child interaction. Secondary outcome measures include severity of ASD symptoms, global level of adaptive functioning, parental well-being, parental skills and satisfaction with healthcare. Also, costs will be estimated from society’s perspective. Assessments take place at the start of the study (T1), after eight weeks (T2) and after six months (T3) and include behavioral home observations and parental questionnaires. DISCUSSION: The SCOPE project aims to contribute to improved early identification and timely start of suitable interventions for infants and toddlers at elevated likelihood for ASD. This ongoing RCT will offer insight in the feasibility, short-term and six months effects of the innovative BEAR intervention. It is estimated that inclusion for the trial (N = 88) is completed in spring 2023. TRIAL REGISTRATION: Dutch Trial Register, NTR7695. Registered at December 17(th), 2018, www.trialregister.nl .

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