Food, nutrition, and autism: from soil to fork.

Food and nutrition-related factors have the potential to impact development of autism spectrum disorder (ASD) and quality of life for people with ASD, but gaps in evidence exist. On 10 November 2022, Tufts University's Friedman School of Nutrition Science and Policy and Food and Nutrition Innovation Institute hosted a 1-d meeting to explore the evidence and evidence gaps regarding the relationships of food and nutrition with ASD. This meeting report summarizes the presentations and deliberations from the meeting. Topics addressed included prenatal and child dietary intake, the microbiome, obesity, food-related environmental exposures, mechanisms and biological processes linking these factors and ASD, food-related social factors, and data sources for future research. Presentations highlighted evidence for protective associations with prenatal folic acid supplementation and ASD development, increases in risk of ASD with maternal gestational obesity, and the potential for exposure to environmental contaminants in foods and food packaging to influence ASD development. The importance of the maternal and child microbiome in ASD development or ASD-related behaviors in the child was reviewed, as was the role of discrimination in leading to disparities in environmental exposures and psychosocial factors that may influence ASD. The role of child diet and high prevalence of food selectivity in children with ASD and its association with adverse outcomes were also discussed. Priority evidence gaps identified by participants include further clarifying ASD development, including biomarkers and key mechanisms; interactions among psychosocial, social, and biological determinants; interventions addressing diet, supplementation, and the microbiome to prevent and improve quality of life for people with ASD; and mechanisms of action of diet-related factors associated with ASD. Participants developed research proposals to address the priority evidence gaps. The workshop findings serve as a foundation for future prioritization of scientific research to address evidence gaps related to food, nutrition, and ASD.

Diagnostic certainty during in-person and telehealth autism evaluations.

Background: Many diagnostic evaluations abruptly shifted to telehealth during the COVID-19 pandemic; however, little is known about the impact on diagnosis patterns for children evaluated for autism spectrum disorder (ASD). The purpose of this clinical research study was to examine (1) the frequency of diagnoses evaluated beyond ASD; (2) the frequency of diagnoses made, including ASD; and (3) clinician diagnostic certainty for all diagnoses evaluated for children who received an evaluation due to primary concerns about ASD via telehealth during the pandemic compared to those evaluated in person before the pandemic at an ASD specialty clinic. Methods: The sample included 2192 children, 1-17 years (M = 6.5 years; SD = 3.9), evaluated by a physician/psychologist at an ASD specialty center. A total of 649 children were evaluated in-person September 1, 2019-March 13, 2020 (pre-pandemic) and 1543 were evaluated via telehealth March 14, 2020-July 26, 2021 (during pandemic). Upon completion of each evaluation, clinicians provided a final diagnostic determination (i.e., "Yes," "No," "Possible," or "Not Assessed") for the following DSM-5 conditions: ASD, attention-deficit/hyperactivity disorder (ADHD), intellectual developmental disorder (IDD), anxiety (ANX), depression (DEP), and behavioral disorder (BD). "Possible" indicated lower certainty and the diagnosis was not provided. "Not Assessed" indicated the disorder was not evaluated. Results: Diagnostic certainty for ASD and ADHD was lower and clinicians evaluated for and made diagnoses of IDD less often during evaluations that occurred via telehealth during the pandemic versus in person before the pandemic. DEP and BD were diagnosed more frequently, diagnostic certainty of DEP was lower, and no differences in the frequency of ANX diagnoses emerged during evaluations conducted via telehealth during the pandemic compared to those conducted in person before the pandemic. Conclusions: Differences emerged in the frequency of diagnoses evaluated and made and diagnostic certainty for evaluations conducted via telehealth during the pandemic compared to in person before the pandemic, which likely impacted patients and reflect real-word challenges. Future work should examine whether these patterns are generalizable and the mechanisms that contribute to these differences.

A pilot, single-arm feasibility study of an integrated cognitive-behavioral treatment for anxiety in young autistic children.

OBJECTIVE: Anxiety is prevalent in young autistic children under 7 years of age. Yet there is a paucity of empirically based interventions for this age group. DINO Strategies for Anxiety and Uncertainty Reduction (DINOSAUR) is an innovative cognitive behavioral intervention that seeks to optimize treatment response in young autistic children by targeting anxiety and the contributing mechanisms of intolerance of uncertainty and parental accommodation using a telehealth delivery model. This pilot, single-arm study examines the preliminary feasibility of DINOSAUR. METHODS: Fourteen autistic children ages 4-6 years with average language and cognitive skills and their parents received the intervention. Quantitative and qualitative data pertaining to parent satisfaction and treatment outcomes were collected. RESULTS: Attendance, retention, and parent satisfaction ratings offer preliminary support for the feasibility of the treatment model. Change in clinical severity ratings on a semi-structured parent interview of anxiety and parents' qualitative report suggests the potential to benefit young autistic children. CONCLUSIONS: Results support future study of the DINOSAUR model in a larger, randomized controlled trial.

Genetic liability for gastrointestinal inflammation disorders and association with gastrointestinal symptoms in children with and without autism.

Children with autism spectrum disorder (ASD) have a greater prevalence of gastrointestinal (GI) symptoms than children without ASD. We tested whether polygenic scores for each of three GI disorders (ulcerative colitis, inflammatory bowel disease, and Crohn's disease) were related to GI symptoms in children with and without ASD. Using genotyping data (564 ASD cases and 715 controls) and external genome-wide association study summary statistics, we computed GI polygenic scores for ulcerative colitis (UC-PGS), inflammatory bowel disease (IDB-PGS), and Crohn's disease (CD-PGS). Multivariable logistic regression models, adjusted for genetic ancestry, were used to estimate associations between each GI-PGS and (1) ASD case-control status, and (2) specific GI symptoms in neurotypical children and separately in ASD children. In children without ASD, polygenic scores for ulcerative colitis were significantly associated with experiencing any GI symptom (adjusted odds ratio (aOR) = 1.36, 95% confidence interval (CI) = 1.03-1.81, p = 0.03) and diarrhea specifically (aOR = 5.35, 95% CI = 1.77-26.20, p = 0.01). Among children without ASD, IBD-PGS, and Crohn's PGS were significantly associated with diarrhea (aOR = 3.55, 95% CI = 1.25-12.34, p = 0.02) and loose stools alternating with constipation (aOR = 2.57, 95% CI = 1.13-6.55, p = 0.03), respectively. However, the three PGS were not associated with GI symptoms in the ASD case group. Furthermore, polygenic scores for ulcerative colitis significantly interacted with ASD status on presentation of any GI symptom within a European ancestry subset (aOR = 0.42, 95% CI = 0.19-0.88, p = 0.02). Genetic risk factors for some GI symptoms differ between children with and without ASD. Furthermore, our finding that increased genetic risks for GI inflammatory disorders are associated with GI symptoms in children without ASD informs future work on the early detection of GI disorders.

Accelerometer-assessed sleep and decline in physical function in older men.

OBJECTIVES: Assess the prospective association of actigraphically measured sleep with self-report and objective measures of physical function among community-dwelling older men. METHODS: Participants were (n = 1496) men aged ≥65 years from the Osteoporotic Fractures in Men Study and ancillary sleep study who were followed up at 4 years for physical function outcomes. Sleep predictors included baseline total sleep time (<6, 6-8 hours [reference], >8 hours), sleep efficiency (<80% or ≥80% [reference]), wake after sleep onset (<90 [reference] or ≥90 minutes), and sleep onset latency (<30 [reference] or ≥30 minutes), measured by wrist actigraphy. Outcomes included self-reported difficulties in mobility and instrumental activities of daily living and objective measures of physical performance (time to complete chair stands, gait speed, grip strength, best narrow walk pace). Multivariable regression models estimated associations between the sleep predictors and change in physical function at follow-up, adjusting for demographic and health-related variables. RESULTS: Participants with short average baseline total sleep time (<6 hours) had significantly greater slowing in their walking speed from baseline to follow-up. Participants with long baseline sleep onset latency (≥30 minutes) had significant increases in mobility difficulties and time to complete chair stands. Sleep efficiency and wake after sleep onset were not significantly associated with any outcomes. No sleep predictors were associated with change in instrumental activities of daily living. CONCLUSIONS: These findings add to the body of evidence showing links between poor sleep and subsequent declines in physical function. Further experimental research is needed to understand the mechanisms at play.

Self-Report Measurement of Well-Being in Autistic Adults: Psychometric Properties of the PERMA Profiler.

Background: Studies of positive psychology and emotional well-being have broadened our understanding of mental health. However, mental health research involving autistic adults has been largely deficit-focused. Few studies have examined well-being using established positive psychological frameworks. Methods: This study examined the psychometric characteristics of the PERMA Profiler, a 23-item questionnaire that measures well-being across five subscales (Positive emotion, Engagement, Relationships, Meaning, and Accomplishment), in a sample of 517 autistic adults ages 18-84 years (M = 39.5, standard deviation [SD] = 13.3). Reliability (internal consistency), structural validity (via confirmatory factor analysis including bifactor modeling), and concurrent validity were examined. Results: The PERMA Profiler mean (SD) well-being score was 5.4 (SD = 1.7), which is notably lower than the mean of 7.0 previously found in nonautistic samples. Subscale scores were highest for Engagement (M = 6.8; SD = 1.9), followed by Accomplishment (M = 5.6; SD = 2.2), Relationships (M = 5.2; SD = 2.6), Meaning (M = 5.2; SD = 2.7), and Positive emotion (M = 5.0; SD = 2.4). Factor analyses revealed strong psychometrics (Cronbach's α = 0.93; Comparative Fit Index = 0.94; Tucker-Lewis Index = 0.97; root mean square error of approximation = 0.08; standardized root mean residual = 0.05) and superior fit of the bifactor model, supporting a general factor for conceptualizing well-being as opposed to a five-factor model. PERMA well-being and subscale scores were significantly correlated (p < 0.001) with mental health conditions and life satisfaction. Conclusion: These findings support use of an adapted version of the PERMA Profiler in mental health research to evaluate well-being among autistic adults. Similar to studies with nonautistic populations, the Engagement measure may not capture the experiences of the autistic population and further refinement is needed. Follow-up research should represent a more diverse autistic population, collaborate with autistic coinvestigators, and explore potential correlates of well-being (such as social stigma) while using the PERMA Profiler.

Why is this an important issue?: "Well-being" captures a state of comfort, health, and happiness and is more than just the absence of disease or negative feelings. Only a few studies to date have focused on the emotional well-being of autistic adults. The positive psychology-based PERMA Profiler (named after the five subscales: Positive emotions, Engagement, Relationships, Meaning, and Accomplishment) is a brief self-report measure for rating well-being using 23 questions. It has been widely used for studying well-being in nonautistic populations. However, no studies have tested how well the PERMA Profiler measures well-being among autistic adults. What was the purpose of this study?: The goal was to evaluate the PERMA Profiler using data from a group of autistic adults living in the United States. This was the first study that tested how well the PERMA Profiler measures the well-being of autistic adults, both overall and across the five subscales. What did the researchers do?: First, we collected responses to the PERMA Profiler and other questions from more than 500 autistic adults. Then, we tested whether the PERMA Profiler measures well-being consistently and if the measure performs as expected (i.e., did it measure what it is supposed to measure?). We also compared well-being scores with the mental health (anxiety and depression) and life satisfaction of the study participants. What were the results of the study?: The average overall well-being score was 5.4 out of 10, with higher values indicating experiencing well-being more often. Notably, the average well-being score was 7.0 in unrelated, previous studies of nonautistic adults). The PERMA Profiler measured well-being consistently in our sample. The overall well-being scores and each of the five subscale scores were related to mental health and life satisfaction as expected. The "Engagement" subscale did not perform as well as the others in our sample, which was consistent with the findings of studies with nonautistic adults. What do these findings add to what was already known?: This is the first study to evaluate the effectiveness of the PERMA Profile or any measure of self-reported well-being in a sample of autistic adults. These results can help future researchers determine how best to study well-being, specifically in autistic adults. These findings point to important changes that might be made to the PERMA Profiler before it is used in future research. What are potential weaknesses in the study?: Autistic adults were not involved in the development of the PERMA Profiler. Therefore, the measure may need to be changed by teams involving autistic coinvestigators before use with other samples. Second, our findings may not represent larger, more diverse groups of autistic adults because most participants were White (85%), well-educated (more than 80% completed at least some college), and did not have intellectual disability. Lastly, the study was conducted during the COVID-19 pandemic, which likely impacted the well-being of participants. How will these findings help autistic adults now or in the future?: Our study provides preliminary support for the PERMA Profiler and suggests next steps for improving it and other measures of well-being before expanding use with autistic adults. Our findings may help the field of autism research develop new measures for understanding and improving well-being. The strengths and weaknesses of the PERMA Profiler that we identified can inform future strengths-based research involving autistic adults.

Alcohol Use Patterns Among Underage Autistic and Non-Autistic Youth.

PURPOSE: We explored factors predicting repeated or hazardous alcohol use among autistic and non-autistic U.S. youth ages 16 to 20 years. METHODS: Autistic (n = 94) and non-autistic (n = 92) youth completed an online survey. By design, half of each group reported past-year alcohol use. We compared drinking patterns for autistic and non-autistic youth, and within each group between abstinent or infrequent drinkers (0-1 drinking episodes in past year) versus those who drank 2 + times in past year. RESULTS: Autistic (vs. non-autistic) youth who drank did so less frequently and consumed fewer drinks per occasion. However, 15% of autistic youth who drank in the past year reported heavy episodic drinking and 9.3% screened positive for AUDIT-C hazardous drinking. For autistic youth only, a diagnosis of depression, bullying or exclusion histories were positively associated with drinking 2 + times in the past year. Autistic youth who put more effort into masking autistic traits were less likely to report drinking 2 + times in the past year. As compared to non-autistic youth, autistic participants were less likely to drink for social reasons, to conform, or to enhance experiences, but drank to cope at similar rates. CONCLUSION: Repeated and hazardous underage alcohol occur among autistic youth. Targeted prevention programs designed to address the specific drinking profiles of autistic youth are needed.

Gastrointestinal Dysfunction in Genetically Defined Neurodevelopmental Disorders.

Gastrointestinal symptoms are common in most forms of neurodevelopment disorders (NDDs) such as in autism spectrum disorders (ASD). The current patient-reported outcome measures with validated questionnaires used in the general population of children without NDDS cannot be used in the autistic individuals. We explore here the multifactorial pathophysiology of ASD and the role of genetics and the environment in this disease spectrum and focus instead on possible diagnostics that could provide future objective insight into the connection of the gut-brain-microbiome in this disease entity. We provide our own data from both humans and a zebrafish model of ASD called Phelan-McDermid Syndrome. We hope that this review highlights the gaps in our current knowledge on many of these profound NDDs and that it provides a future framework upon which clinicians and researchers can build and network with other interested multidisciplinary specialties.

Prevalence of gastrointestinal symptoms among autistic individuals, with and without co-occurring intellectual disability.

Gastrointestinal symptoms (GI) are very common among individuals on the autism spectrum. Prior research reports mixed findings regarding whether individuals with autism and co-occurring intellectual disability (ID) have elevated risk of gastrointestinal symptoms relative to individuals with autism alone. GI symptoms can be challenging to assess in individuals with autism spectrum disorder (ASD) and/or ID given challenges with language, communication, and interoception. Prior research has tended to only include individuals with documented presence or absence of GI symptoms or conditions, that is, to exclude observations in which there is uncertainty regarding presence of GI symptoms. Therefore, none of the prior autism studies reported the association between ID and the certainty regarding presence or absence of GI symptoms. The objective of this study was to examine differences in parental certainty and odds of reporting gastrointestinal signs and symptoms among children on the autism spectrum, with and without intellectual disability. Participants were 308 children (36% ID) with a clinical diagnosis of autism spectrum disorder (6-17 years). Parents endorsed whether their child had experienced or displayed a range of signs or symptoms related to GI problems in the past 3 months. Parents of autistic children with ID were less certain about the presence of more subjective symptoms, including abdominal pain, nausea, and bloating. Conversely, certainty regarding more objective signs (e.g., constipation, diarrhea, spitting up, etc.) was not significantly different. More accurate measures for GI signs/symptoms are needed for this population.

Association of common infections with cognitive performance in the Baltimore Epidemiologic Catchment Area study follow-up.

INTRODUCTION: Growing evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections. METHODS: We investigated the cross-sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and Toxoplasma gondii (TOX) with Mini-Mental State Examination (MMSE) and delayed verbal recall performance in 575 adults aged 41-97 from the Baltimore Epidemiologic Catchment Area Study. RESULTS: In multivariable-adjusted zero-inflated Poisson (ZIP) regression models, positive antibody tests for CMV (p = .011) and herpes simplex virus (p = .018) were individually associated with poorer MMSE performance (p = .011). A greater number of positive antibody tests among the five tested was associated with worse MMSE performance (p = .001). DISCUSSION: CMV, herpes simplex virus, and the global burden of multiple common infections were independently associated with poorer cognitive performance. Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer's disease biomarker changes is needed to confirm these findings.

Influences of the Immune System and Microbiome on the Etiology of ASD and GI Symptomology of Autistic Individuals.

Autism Spectrum Disorder is a developmental condition associated with impairments in communication and social interactions, and repetitive and restricted behavior or interests. Autistic individuals are more likely to experience gastrointestinal (GI) symptoms than neurotypical individuals. This may be partially due to dysbiosis of the gut microbiome. In this article, we describe the interaction of the microbiome and immune system on autism etiology. We also summarize the links between the microbiome and gastrointestinal and related symptoms among autistic individuals. We report that microbial interventions, including diet, probiotics, antibiotics, and fecal transplants, and immune-modulating therapies such as cytokine blockade during the preconception, pregnancy, and postnatal period may impact the neurodevelopment, behavior, and gastrointestinal health of autistic individuals.

Exploring the Symptom Profiles of Intolerance of Uncertainty in Autistic Children.

Intolerance of uncertainty (IU) is a multidimensional construct involving maladaptive responses to uncertainty. IU is strongly associated with autism and anxiety, yet no studies have examined its symptom profile in autistic children. This study compares IU symptom profiles in autistic and NT children and in autistic children with and without anxiety using the Intolerance of Uncertainty Scale for Children. Compared to NT peers, autistic children exhibited heightened IU symptoms in all domains, affective, behavioral, and cognitive; affective symptoms had the highest association with autism. Autistic children with anxiety also exhibited elevated IU symptoms in all domains compared to those without anxiety; behavioral IU symptoms had the highest association with anxiety. IU symptom profiles should be considered in assessment and treatment.

Replication study for ADOS-2 cut-offs to assist evaluation of autism spectrum disorder.

The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) has been widely used for ASD assessment. While prior studies investigated sensitivity and specificity of ADOS-2 Modules 1-3, there has been limited research addressing algorithm cut-off scores to optimize ADOS-2 classification. The goal of this study was to assess algorithm cut-off scores for diagnosing ASD with Modules 1-3, and to evaluate alignment of the ADOS-2 classification with the best estimate clinical diagnosis. Participants included 3144 children aged 31 months or older who received ADOS-2 Modules 1-3, as well as the best estimate clinical diagnosis. Five classification statistics were reported for each module: sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (i.e., Receiver Operator Classification Statistic), and these statistics were calculated for the optimal cut-off score. Frequency tables were used to compare ADOS-2 classification and the best estimate clinical diagnosis. Half of the sample received Module 3, 21% received Module 2, and 29% received Module 1. The overall prevalence of ASD was 60%; the male-to-female ratio was 4:1, and half of the sample was non-White. Across all modules, the autism spectrum cut-off score from the ADOS-2 manual resulted in high sensitivity (95%+) and low specificity (63%-73%). The autism cut-off score resulted in better specificity (76%-86%) with favorable sensitivity (81%-94%). The optimal cut-off scores for all modules based on the current sample were within the autism spectrum classification range except Module 2 Algorithm 2. In the No ASD group, 29% had false positives (ADOS-2 autism spectrum classification or autism classification). The ADOS-2 autism spectrum classification did not indicate directionality for diagnostic outcome (ASD 56% vs. No ASD 44%). While cut-off scores of ADOS-2 Modules 1-3 in the manual yielded good clinical utility in ASD assessment, false positives and low predictability of the autism spectrum classification remain challenging for clinicians.

Profiles and correlates of language and social communication differences among young autistic children.

Delays in early language development are characteristic of young autistic children, and one of the most recognizable first concerns that motivate parents to seek a diagnostic evaluation for their child. Although early language abilities are one of the strongest predictors of long-term outcomes, there is still much to be understood about the role of language impairment in the heterogeneous phenotypic presentation of autism. Using a person-centered, Latent Profile Analysis, we first aimed to identify distinct patterns of language and social communication ability in a clinic-based sample of 498 autistic children, ranging in age from 18 to 60 months (M = 33 mo, SD = 12 mo). Next, a multinomial logistic regression analysis was implemented to examine sociodemographic and child-based developmental differences among the identified language and social communication profiles. Three clinically meaningful profiles were identified from parent-rated and clinician-administered measures: Profile 1 (48% of the sample) "Relatively Low Language and Social Communication Abilities," Profile 2 (34% of the sample) "Relatively Elevated Language and Social Communication Abilities," and Profile 3 (18% of the sample) "Informant Discrepant Language and Relatively Elevated Social Communication Abilities." Overall, young autistic children from the lowest-resource households exhibited the lowest language and social communication abilities, and the lowest non-verbal problem-solving and fine-motor skills, along with more features of attention-deficit/hyperactivity disorder and atypical auditory processing. These findings highlight the need for effective community-based implementation strategies for young autistic children from low-resource households and underrepresented communities to improve access to individualized quality care.

Sex Hormones, Sleep, and Memory: Interrelationships Across the Adult Female Lifespan.

As the population of older adults grows, so will the prevalence of aging-related conditions, including memory impairments and sleep disturbances, both of which are more common among women. Compared to older men, older women are up to twice as likely to experience sleep disturbances and are at a higher risk of cognitive decline and Alzheimer's disease and related dementias (ADRD). These sex differences may be attributed in part to fluctuations in levels of female sex hormones (i.e., estrogen and progesterone) that occur across the adult female lifespan. Though women tend to experience the most significant sleep and memory problems during the peri-menopausal period, changes in memory and sleep have also been observed across the menstrual cycle and during pregnancy. Here, we review current knowledge on the interrelationships among female sex hormones, sleep, and memory across the female lifespan, propose possible mediating and moderating mechanisms linking these variables and describe implications for ADRD risk in later life.

Sluggish cognitive tempo profiles in survivors of childhood cancer as compared to children with attention-deficit/hyperactivity disorder.

PURPOSE: Neurocognitive late effects including problems with attention have been reported in pediatric oncology survivors. While some researchers have characterized these late effects as similar to symptoms of attention-deficit/hyperactivity disorder, inattentive presentation (ADHD-I), there remains some controversy as to whether these concerns in oncology patients are best conceptualized according to an ADHD-I or sluggish cognitive tempo (SCT) framework. The aim of this study was to describe SCT symptoms in children with ADHD-I or oncology diagnoses; identify groups of SCT symptoms among children with brain tumors (BT), acute lymphoblastic leukemia (ALL), or ADHD-I; and identify whether specific SCT profiles are associated with these diagnoses. METHODS: The sample was comprised of 364 youth (146 BT, 149 ADHD-I, 69 ALL) referred for a neuropsychological evaluation at an academic medical center. Caregivers completed the SCT scale as part of the clinical evaluation. RESULTS: Groups differed on mean scores for the SCT scales (Total, Sleepy/sluggish, Low initiation, and Daydreamy) by diagnosis (all p < 0.05), with the ADHD-I group having higher SCT symptoms on all scales. Latent profile analysis showed significant differences between latent SCT classes according to ADHD-I versus cancer diagnosis. The ADHD-I group was significantly more likely to be in the high SCT class compared to the oncology groups. CONCLUSION: Findings add to the understanding of SCT symptoms in pediatric oncology survivors. There is utility in applying the SCT framework to the oncology population; however, pediatric survivors are likely to be rated differently than youth with ADHD-I. Implications and future directions are discussed.

Analysis of Race and Sex Bias in the Autism Diagnostic Observation Schedule (ADOS-2).

Importance: There are long-standing disparities in the prevalence of autism spectrum disorder (ASD) across race and sex. Surprisingly, few studies have examined whether these disparities arise partially out of systematic biases in the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), the reference standard measure of ASD. Objective: To examine differential item functioning (DIF) of ADOS-2 items across sex and race. Design, Setting, and Participants: This is a cross-sectional study of children who were evaluated for ASD between 2014 and 2020 at a specialty outpatient clinic located in the Mid-Atlantic region of the US. Data were analyzed from July 2021 to February 2022. Exposures: Child race (Black/African American vs White) and sex (female vs male). Main Outcomes and Measures: Item-level biases across ADOS-2 harmonized algorithm items, including social affect (SA; 10 items) and repetitive/restricted behaviors (RRBs; 4 items), were evaluated across 3 modules. Measurement bias was identified by examining DIF and differential test functioning (DTF), within a graded response, item response theory framework. Statistical significance was determined by a likelihood ratio χ2 test, and a series of metrics was used to examine the magnitude of DIF and DTF. Results: A total of 6269 children (mean [SD] age, 6.77 [3.27] years; 1619 Black/African American [25.9%], 3151 White [50.3%], and 4970 male [79.4%]), were included in this study. Overall, 16 of 140 ADOS-2 diagnostic items (11%) had a significant DIF. For race, 8 items had a significant DIF, 6 of which involved SA. No single item showed DIF consistently across all modules. Most items with DIF had greater difficulty and poorer discrimination in Black/African American children compared with White children. For sex, 5 items showed significant DIF. DIF was split across SA and RRB. However, hand mannerisms evidenced DIF across all 5 algorithms, with generally greater difficulty. The magnitude of DIF was only moderate to large for 2 items: hand mannerisms (among female children) and repetitive interests (among Black/African American children). The overall estimated effect of DIF on total DTF was not large. Conclusions and Relevance: These findings suggest that the ADOS-2 does not have widespread systematic measurement bias across race or sex. However, the findings raise some concerns around underdetection that warrant further research.

Diagnostic Stability and Phenotypic Differences Among School-Age Children Diagnosed With ASD Before Age 2.

Given the importance of early detection, it is critical to understand the non-linearity in manifestation of ASD before age 24 months, when ASD symptoms are beginning to consolidate, through the age of 36 months when stability of ASD diagnosis is reportedly high into school-age when increased demands may challenge previously successful compensatory processes and permit first ASD detection. We employed a prospective, longitudinal design focused on children with an older sibling with ASD (n = 210) who received diagnostic evaluations at mean ages of 15.4 months (Time 1), 36.6 months (Time 2), and 5.7 years (Time 3) to examine: (1) diagnostic stability, (2) developmental trajectories associated with different patterns of ASD vs. non-ASD classifications, and (3) predictors of classification group over time. Clinical best estimate (CBE) diagnosis of ASD or non-ASD was made at each time point. Linear mixed-effects models were implemented to examine differences in developmental trajectories of stable and dynamic diagnostic groups. Multinomial logistic regression analyses were used to examine predictors of the likelihood of belonging to each CBE diagnostic classification group. Results revealed that sensitivity and stability of an ASD diagnosis significantly increased from Time 1 (sensitivity: 52%; stability: 63%) to Time 2 (sensitivity: 86%; stability: 68%). Different developmental trajectories of autism symptom severity and non-verbal and verbal IQ were observed across groups, with differences first observed at Time 1 and becoming more pronounced through Time 3. Presence of restricted and repetitive behaviors as well as limitations in initiation of joint attention and expressive language skills differentially predicted the likelihood of belonging to the different CBE diagnostic classification groups. Results suggest that ASD symptoms may emerge or attenuate over time, with some children meeting diagnosis at follow-up, and other children no longer meeting diagnostic criteria. From a systems perspective, diagnostic non-linearity may be viewed as a dynamic developmental process, where emergent properties arising from various biological, genetic, and experiential factors interact, culminating in phenotypic phenomena that change over time. Clinical implications include extending universal ASD and social communication screening into school-age, supporting families' understanding of diagnostic shifts, and ensuring unbiased diagnostic decision-making when following children with ASD.

Characteristics of the autism spectrum disorder gastrointestinal and related behaviors inventory in children.

Gastrointestinal (GI) symptoms are one of the prevalent co-occurring issues in autism spectrum disorder (ASD), though the range of symptom frequency estimates varies dramatically across studies, which can limit the further research of GI issues in ASD as well as potential treatment strategies. The wide range of prevalence estimates is partly due to the lack of standardized, validated measures of GI symptoms among people with ASD. The goal of this study was to (1) develop a measure, which included non-verbal and mealtime behaviors, to assess for GI symptoms and (2) evaluate its psychometric characteristics. This was accomplished by drawing on two existing tools, Autism Treatment Network Gastrointestinal Inventory and the Brief Autism Mealtime Behavior Inventory, and deriving new items, to create the "ASD Gastrointestinal and Related Behaviors Inventory" (ASD-GIRBI). The ASD-GIRBI was piloted in an online registry of families with a child with ASD. A psychometric analysis was carried out in a sample of 334 children aged 6-17 years with ASD, resulting in a 36-item tool. The Cronbach's alpha for the overall scale was 0.88. Exploratory factor analysis identified a seven-factor model (1. Bowel movement pain; 2. Aggressive or disruptive during mealtimes; 3. Particular with foods; 4. Abdominal pain and upset stomach; 5. Refusing food; 6. Constipation and encopresis; 7. Motor or other behaviors). Following validation in an independent sample with clinical evaluation of GI symptoms, this tool will be helpful for both research and clinical purposes.

Understanding educators' perspectives and experiences of COVID-19 in schools serving children with intellectual/developmental disabilities.

The COVID-19 pandemic has significantly impacted educators, both personally and professionally. However, very little is known about the extent of these impacts among educators' serving children with intellectual and developmental disabilities (IDD). The present study surveyed 230 educators (teachers, staff, and administrators) to assess their wellbeing, concerns during the pandemic, and perceived importance of various COVID-19 school mitigation strategies. Data were gathered May/June of 2021 from two separate school districts, one in the Midwest and the other in the Mid-Atlantic, serving children with IDD. Nearly half of all survey respondents reported poor wellbeing. Almost all educators reported health of themselves, students, and family members was their greatest concern when compared to pandemic-related disruption of their duties or benefits (e.g., not having enough sick time). Most educators felt disinfecting routines, vaccinations, and daily health checks were the most helpful in preventing the spread of COVID-19 in schools, while in-school mask mandates and weekly testing of students and staff were perceived as less helpful. Our findings suggest that efforts are needed to support the wellbeing of educators during these challenging times. When pandemic-related policies and procedures are decided by administrators, our data suggest educators will review decisions within the framework of health and safety of themselves, their students, and families. Understanding this framework may be particularly valuable when considering implementation of COVID-19 policies, like masking and COVID-19 testing, that are less preferred.