Factors Associated with Confirmed and Unconfirmed Autism Spectrum Disorder Diagnosis in Children Volunteering for Research.

PURPOSE: Diagnostic accuracy of autism spectrum disorder (ASD) is crucial to track and characterize ASD, as well as to guide appropriate interventions at the individual level. However, under-diagnosis, over-diagnosis, and misdiagnosis of ASD are still prevalent. METHODS: We describe 232 children (MAge = 10.71 years; 19% female) with community-based diagnoses of ASD referred for research participation. Extensive assessment procedures were employed to confirm ASD diagnosis before study inclusion. The sample was subsequently divided into two groups with either confirmed ASD diagnoses (ASD+) or unconfirmed/inaccurate diagnoses (ASD-). Clinical characteristics differentiating the groups were further analyzed. RESULTS: 47% of children with community-based ASD diagnoses did not meet ASD criteria by expert consensus. ASD + and ASD- groups did not differ in age, gender, ethnicity, or racial make-up. The ASD + group was more likely to have a history of early language delays compared to the ASD- group; however, no group differences in current functional language use were reported by caregivers. The ASD + group scored significantly higher on ADI-R scores and on the ADOS-2 algorithm composite scores and calibrated severity scores (CSSs). The ASD- group attained higher estimated IQ scores and higher rates of psychiatric disorders, including anxiety disorder, disruptive behavior, and mood disorder diagnoses. Broadly, caregiver questionnaires (SRS-2, CCC-2) did not differentiate groups. CONCLUSION: Increased reported psychiatric disorders in the ASD- group suggests psychiatric complexity may contribute to community misdiagnosis and possible overdiagnosis of ASD. Clinician-mediated tools (ADI-R, ADOS-2) differentiated ASD + versus ASD- groups, whereas caregiver-reported questionnaires did not.

Provider perspectives on equity in use of mobile health autism screening tools.

LAY ABSTRACT: Families may find information about autism online, and health care and education providers may use online tools to screen for autism. However, we do not know if online autism screening tools are easily used by families and providers. We interviewed primary care and educational providers, asking them to review results from online tools that screen for autism. Providers had concerns about how usable and accessible these tools are for diverse families and suggested changes to make tools easier to use.

Consanguinity as a Risk Factor for Autism.

PURPOSE: Genetic and environmental risk factors associated with Autism Spectrum Disorders (ASD) continue to be a focus of research worldwide. Consanguinity, the cultural practice of marrying within a family, is common in cultures and societies of the Middle East, North Africa and parts of Asia. Consanguinity has been investigated as a risk factor for ASD in a limited number of studies, with mixed results. We employed registry and survey data from Qatar to evaluate the role of consanguinity as a risk factor for ASD. METHODS: Data were sourced from a national registry and a population-based survey of autism recently conducted in Qatar. We selected a sample of 891 children (mean age: 8.3 years) with (N = 361) or without (N = 530) ASD. Data on consanguinity and covariates were collected through questionnaires and interviews. RESULTS: The prevalence of consanguinity in the overall sample was 41.2% with no significant difference between cases and controls (42.1% vs 41.3%; p = .836). In adjusted multiple logistic regression analyses, consanguinity was not associated with risk of ASD (aOR = 1.065; 95% CI: .751-1.509; NS). CONCLUSION: Parental consanguinity was not associated with autism risk in our study. Replication in other populations with high rates of consanguineous unions is recommended.

Editorial: Is autism overdiagnosed?

After attention was drawn in the late 1960s to the poor reproducibility of psychiatric diagnosis between clinicians, methods and procedures used to diagnose psychiatric disorders were greatly improved. Sources of variance contributing to the poor reliability of psychiatric diagnosis were identified that included: information variance (how clinicians go about enquiring about symptoms), interpretation variance (how clinicians weigh the observed symptomatology towards diagnostic formulations), and criterion variance (how clinicians arrange symptom constellations to generate specific diagnoses). To improve the reliability of diagnosis, progresses were made in two major directions. First, diagnostic instruments were developed to standardize the way symptoms are elicited, evaluated, and scored. These diagnostic interviews were either highly structured for use in large-scale studies (e.g. the DIS), by lay interviewers without a clinical background, and with a style of questioning that emphasized adherence to the exact wording of probes, reliance on closed questions with simple response formats (Yes/No) and recording respondents' answers without interviewer's judgment contribution. By contrast, semi-structured interviews (e.g. the SADS) were designed to be used by clinically trained interviewers and adopted a more flexible, conversational style, using open-ended questions, utilizing all behavioral descriptions generated in the interview, and developing scoring conventions that called upon the clinical judgment of the interviewer. Second, diagnostic criteria and algorithms were introduced in nosographies in 1980 for the DSM and soon after in ICD. Algorithm-derived diagnoses could subsequently be tested for their validity using follow-up, family history, treatment response studies, or other external criteria.

A framework for measuring the cost to families of caring for children's health: the design, methodology, and study population of the r-Kids study.

BACKGROUND: All families experience financial and time costs related to caring for their children's health. Understanding the economic burden faced by families of children with chronic health conditions (CHC) is crucial for designing effective policies to support families. METHODS: In this prospective study we used electronic health records to identify children between 3 and 17 years old with autism spectrum disorder (ASD), asthma, or neither (control) from three Kaiser Permanente regions and several community health centers in the OCHIN network. We oversampled children from racial and ethnic minority groups. Parent/guardian respondents completed surveys three times, approximately four months apart. The surveys included the Family Economic Impact Inventory (measuring financial, time, and employment costs of caring for a child's health), and standardized measures of children's quality of life, behavioral problems, and symptom severity for children with ASD or asthma. We also assessed parenting stress and parent physical and mental health. All materials were provided in English and Spanish. RESULTS: Of the 1,461 families that enrolled (564 ASD, 468 asthma, 429 control), children were predominantly male (79%), with a mean age of 9.0 years, and racially and ethnically diverse (43% non-Hispanic white; 22% Hispanic; 35% Asian, Black, Native Hawaiian, or another race/ethnicity). The majority of survey respondents were female (86%), had a college degree (62%), and were married/partnered (79%). ASD group respondents were less likely to be employed (73%) than those in the asthma or control groups (both 80%; p = .023). Only 32% of the control group reported a household income ≤ $4,000/month compared with 41% of asthma and 38% of ASD families (p = .006). CONCLUSIONS: Utilizing a novel measure assessing family economic burden, we successfully collected survey responses from a large and diverse sample of families. Drawing upon the conceptual framework, survey measures, and self-report data described herein we will conduct future analyses to examine the economic burdens related to CHC and the incremental differences in these burdens between health groups. This information will help policy makers to design more equitable health and social policies that could reduce the burden on families.

Consistency and reliability of automated language measures across expressive language samples in autism.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with substantial clinical heterogeneity, especially in language and communication ability. There is a need for validated language outcome measures that show sensitivity to true change for this population. We used Natural Language Processing to analyze expressive language transcripts of 64 highly-verbal children and young adults (age: 6-23 years, mean 12.8 years; 78.1% male) with ASD to examine the validity across language sampling context and test-retest reliability of six previously validated Automated Language Measures (ALMs), including Mean Length of Utterance in Morphemes, Number of Distinct Word Roots, C-units per minute, unintelligible proportion, um rate, and repetition proportion. Three expressive language samples were collected at baseline and again 4 weeks later. These samples comprised interview tasks from the Autism Diagnostic Observation Schedule (ADOS-2) Modules 3 and 4, a conversation task, and a narration task. The influence of language sampling context on each ALM was estimated using either generalized linear mixed-effects models or generalized linear models, adjusted for age, sex, and IQ. The 4 weeks test-retest reliability was evaluated using Lin's Concordance Correlation Coefficient (CCC). The three different sampling contexts were associated with significantly (P < 0.001) different distributions for each ALM. With one exception (repetition proportion), ALMs also showed good test-retest reliability (median CCC: 0.73-0.88) when measured within the same context. Taken in conjunction with our previous work establishing their construct validity, this study demonstrates further critical psychometric properties of ALMs and their promising potential as language outcome measures for ASD research.

Mobile and online consumer tools to screen for autism do not promote equity.

LAY ABSTRACT: Many parents wonder if their child might have autism. Many parents use their smartphones to answer health questions. We asked, "How easy or hard is it for parents to use their smartphones to find 'tools' to test their child for signs of autism?" After doing pretend parent searches, we found that only one in 10 search results were tools to test children for autism. These tools were not designed for parents who have low income or other challenges such as low literacy skills, low English proficiency, or not being tech-savvy.

"Um" and "Uh" Usage Patterns in Children with Autism: Associations with Measures of Structural and Pragmatic Language Ability.

Pragmatic language difficulties, including unusual filler usage, are common among children with Autism Spectrum Disorder (ASD). This study investigated "um" and "uh" usage in children with ASD and typically developing (TD) controls. We analyzed transcribed Autism Diagnostic Observation Schedule (ADOS) sessions for 182 children (117 ASD, 65 TD), aged 4 to 15. Although the groups did not differ in "uh" usage, the ASD group used fewer "ums" than the TD group. This held true after controlling for age, sex, and IQ. Within ASD, social affect and pragmatic language scores did not predict filler usage; however, structural language scores predicted "um" usage. Lower "um" rates among children with ASD may reflect problems with planning or production rather than pragmatic language.

The impact of autism spectrum disorder on parent employment: Results from the r-Kids study.

Parents of children with autism spectrum disorder (ASD) and other chronic health conditions often face exceptional caregiving demands that can lead to challenges related to maintaining and succeeding in employment. Detailed information on the specific ways in which these health conditions impact parent employment could aid in designing equitable, effective policies to support families. The r-Kids study used electronic health records to identify three groups of children: those with ASD, asthma, or neither condition (control), from several health care systems. We oversampled racial and ethnic minorities and matched the asthma and control groups to the age and sex distribution of the ASD group. Parents completed three online surveys over the course of a year to measure annual employment outcomes. Surveys included the Family Economic Impact Inventory (measuring employment impacts) and measures of quality of life and symptom severity. All materials were provided in English and Spanish. The study enrolled 1461 families (564 ASD, 468 asthma, 429 control). Youth were 3-16.5 years old and predominantly male (79%). The sample was diverse (43% non-Hispanic White; 35% non-Hispanic Asian, Black, Native Hawaiian, or Other; and 21% Hispanic ethnicity). Parents of children with ASD were significantly less likely to be employed than parents of youth with asthma and control combined (OR: 14.2, p < 0.001), and were more likely to have other difficulties with employment and productivity while at work. Public and employer policies to help mitigate these impacts could aid families in managing care for youth with ASD.

Parents' Concerns Are Associated with Early Intervention Evaluation and Eligibility Outcomes.

OBJECTIVE: To test the association of parents' concerns with early intervention (EI) developmental services outcomes including evaluation, eligibility, and enrollment in services. METHOD: We collected survey data on parents' concerns and EI service use data from a sample of 428 children referred to EI from 2016 to 2018 in 6 Oregon primary care clinics serving lower-income families as part of a developmental and autism spectrum disorder screening intervention. We assessed EI service use trajectories and associations of the presence of parent concern, age of child at the time of parents' concerns, number of concerns, and type of provider concern, with EI evaluation, EI eligibility, and enrollment in EI services, using bivariate testing and multivariable logistic regression. RESULTS: Only 22.9% of children referred to EI were enrolled in services 6 months later. Children whose parents had developmental and/or behavioral concerns were more likely to receive an EI evaluation and were also more likely to be eligible for services, compared with children whose parents had no concerns. There was no association between age, number of concerns, and type of concern with EI evaluation, eligibility, or services enrollment. CONCLUSION: Although only a minority of children referred to EI enrolled in services, the presence of parent concern is strongly associated with EI services evaluation and eligibility outcomes. Study results suggest that providers should assess the presence of parent concern when deciding on EI referrals and provide more support to parents who are not concerned at all.

Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.

Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and ASD-related disability at the global level are lacking. Here, we used the Global Burden of Diseases, Injuries, and Risk Factors Study data to address this gap, focusing on changes in prevalence, incidence, and disability-adjusted life years (DALYs) of ASD across the world. From 1990 to 2019, overall age-standardized estimates remained stable globally. Both prevalence and DALYs increased in countries with high socio-demographic index (SDI). However, the age-standardized incidence decreased in some low SDI countries, indicating a need to improve awareness. The male/female ratio decreased between 1990 and 2019, possibly accounted for by increasing clinical attention to ASD in females. Our results suggest that ASD detection in low SDI countries is suboptimal, and that ASD prevention/treatment in countries with high SDI should be improved, considering the increasing prevalence of the disorder. Additionally, growing attention is being paid to ASD diagnosis in females, who might have been left behind by ASD epidemiologic and clinical research previously. ASD burden estimates are underestimated as GBD does not account for mortality in ASD.

Pragmatic Language Markers of Autism Diagnosis and Severity.

Purpose: Assessment of pragmatic language difficulties is limited with conventional tests but can be performed with informant reports. We evaluated the performance of a parent-completed language scale in differentiating autism from typical development (TD) and another neurodevelopmental disorder. Specifically, we aimed to gauge the respective values of structural and pragmatic language scores for diagnostic discrimination and for predicting severity of social impairment in autistic children. Method: 174 children aged 7 to 17 (101 with autism, 45 with ADHD, 28 with TD) were evaluated with the ADOS-2 and an abbreviated version of the WISC. Parents completed the Children's Communication Checklist, 2nd Edition (CCC-2) and the Social Responsiveness Scale. CCC-2 mean differences across diagnostic groups were tested with analysis of variance and covariance. Multiple linear regression was used to compare the structural and pragmatic CCC-2 scores in predicting autism symptom severity. Results: Both structural and pragmatic language scores discriminated between the three diagnostic groups, with stronger effects for the pragmatic scores. Pragmatic scores remained robust predictors of ADHD and ASD diagnoses even after accounting for cognitive and structural linguistic differences. Among autistic children, social impairment severity was associated with pragmatic, but not structural, language profiles. Conclusions: In order to characterize pragmatic language, easy to administer parent questionnaires such as the CCC-2 may support clinicians who are considering an autism diagnosis and needing to evaluate and monitor social communication.

Analysis of a Repetitive Language Coding System: Comparisons between Fragile X Syndrome, Autism, and Down Syndrome.

Expressive language sampling (ELS) is a frequently used tool for language analysis, as it can be used across widely ranging cognitive and language abilities. ELS can also evaluate pragmatic language, including excessive self-repetition, which is challenging to assess with traditional standardized assessments. This study explored how a well-established ELS protocol can assess three types of linguistic self-repetition in three neurodevelopmental disabilities: fragile X syndrome (FXS), autism spectrum disorder (ASD), and Down syndrome (DS). We examined its ability to differentiate between these disorders, the relationships between repetitive language and other participant characteristics, and initial construct validity. We found that the groups with FXS and ASD differed significantly on each of the three repetitive language measure, and that the group with DS differed from either ASD or FXS on two. Cognitive ability was significantly related to phrase repetition in the group with ASD. When the groups were combined, there was evidence of convergent and divergent validity. This study extends previous research on ELS and supports its use as a means to characterize pragmatic language. It also provides information about the relationships between repetitive language and other phenotypic characteristics.

Combining voice and language features improves automated autism detection.

Variability in expressive and receptive language, difficulty with pragmatic language, and prosodic difficulties are all features of autism spectrum disorder (ASD). Quantifying language and voice characteristics is an important step for measuring outcomes for autistic people, yet clinical measurement is cumbersome and costly. Using natural language processing (NLP) methods and a harmonic model of speech, we analyzed language transcripts and audio recordings to automatically classify individuals as ASD or non-ASD. One-hundred fifty-eight participants (88 ASD, 70 non-ASD) ages 7 to 17 were evaluated with the autism diagnostic observation schedule (ADOS-2), module 3. The ADOS-2 was transcribed following modified SALT guidelines. Seven automated language measures (ALMs) and 10 automated voice measures (AVMs) for each participant were generated from the transcripts and audio of one ADOS-2 task. The measures were analyzed using support vector machine (SVM; a binary classifier) and receiver operating characteristic (ROC). The AVM model resulted in an ROC area under the curve (AUC) of 0.7800, the ALM model an AUC of 0.8748, and the combined model a significantly improved AUC of 0.9205. The ALM model better detected ASD participants who were younger and had lower language skills and shorter activity time. ASD participants detected by the AVM model had better language profiles than those detected by the language model. In combination, automated measurement of language and voice characteristics successfully differentiated children with and without autism. This methodology could help design robust outcome measures for future research. LAY SUMMARY: People with autism often struggle with communication differences which traditional clinical measures and language tests cannot fully capture. Using language transcripts and audio recordings from 158 children ages 7 to 17, we showed that automated, objective language and voice measurements successfully predict the child's diagnosis. This methodology could help design improved outcome measures for research.

Global prevalence of autism: A systematic review update.

Prevalence estimates of autism are essential for informing public policy, raising awareness, and developing research priorities. Using a systematic review, we synthesized estimates of the prevalence of autism worldwide. We examined factors accounting for variability in estimates and critically reviewed evidence relevant for hypotheses about biological or social determinants (viz., biological sex, sociodemographic status, ethnicity/race, and nativity) potentially modifying prevalence estimates of autism. We performed the search in November 2021 within Medline for studies estimating autism prevalence, published since our last systematic review in 2012. Data were extracted by two independent researchers. Since 2012, 99 estimates from 71 studies were published indicating a global autism prevalence that ranges within and across regions, with a median prevalence of 100/10,000 (range: 1.09/10,000 to 436.0/10,000). The median male-to-female ratio was 4.2. The median percentage of autism cases with co-occurring intellectual disability was 33.0%. Estimates varied, likely reflecting complex and dynamic interactions between patterns of community awareness, service capacity, help seeking, and sociodemographic factors. A limitation of this review is that synthesizing methodological features precludes a quality appraisal of studies. Our findings reveal an increase in measured autism prevalence globally, reflecting the combined effects of multiple factors including the increase in community awareness and public health response globally, progress in case identification and definition, and an increase in community capacity. Hypotheses linking factors that increase the likelihood of developing autism with variations in prevalence will require research with large, representative samples and comparable autism diagnostic criteria and case-finding methods in diverse world regions over time. LAY SUMMARY: We reviewed studies of the prevalence of autism worldwide, considering the impact of geographic, ethnic, and socioeconomic factors on prevalence estimates. Approximately 1/100 children are diagnosed with autism spectrum disorder around the world. Prevalence estimates increased over time and varied greatly within and across sociodemographic groups. These findings reflect changes in the definition of autism and differences in the methodology and contexts of prevalence studies.

Emotional and Behavioral Problems in Youth with Autism: High Prevalence and Impact on Functioning.

OBJECTIVE: Emotional and behavioral problems (EBPs) may co-occur with autism spectrum disorder (ASD) and impair children's functioning beyond autism symptomatology. We compared the prevalence of EBPs in youths with or without ASD and evaluated their unique contribution to impairment in ASD. METHODS: We surveyed 1267 children (79.4% boys, mean age: 9.2 years, range: 3-17) recruited at 3 sites in Kaiser Permanente and OCHIN primary care clinical networks, with confirmed International Classification of Diseases-10th ed. diagnosis of ASD (N = 564), asthma (N = 468), or neither (N = 429). Children from the 2 comparison groups were age-matched and sex-matched to the ASD group. EBPs and impairment were measured by the Strengths and Difficulties Questionnaire and autism symptomatology by the Social Responsiveness Scale in the ASD group only. RESULTS: EBPs and impairment mean scores were significantly (p < 0.001) higher in participants with ASD compared with children from the 2 comparison groups, across sexes and age groups, with no significant difference between the asthma and control groups. Among children with ASD, both EBPs and autistic symptoms were significantly correlated with impairment (r = 0.64 and r = 0.65, respectively) and explained a significant proportion of impairment variance (R2 = 0.525; p < 0.001) in multiple linear regression. In the relative importance analysis, EBPs and autistic symptoms explained comparable proportions of impairment variance (46% and 52%, respectively) with no significant difference between their relative weights (mean difference: 0.03; 95% confidence interval: -0.049 to 0.114). CONCLUSION: Among youth with ASD, high levels of EBPs impair daily functioning as much as autistic symptoms. Systematic detection and management of EBPs may improve functioning and outcomes in youth with ASD.

Clinical Profiles of Black and White Children Referred for Autism Diagnosis.

Black children with autism are diagnosed at an older age. Whether or not late detection is paralleled by differing clinical presentation is not known. We evaluated symptom profiles of 245 Black and 488 sex- and age-matched White non-Hispanic participants (82.8% male; mean age: 4.2 years) referred for ASD diagnosis. Both groups showed similar overall levels of autistic symptoms. Black children had significantly but slightly lower scores on cognitive tests and on the Vineland communication domain than White children. Groups were comparable on internalizing and externalizing co-occurring problems. Given the largely similar clinical profiles, clinical differences in initial presentation may not be a primary reason for Black/White disparities in diagnostic and services use. Limitations of a cross-sectional referred sample are acknowledged.

Validation of Autism Diagnosis and Clinical Data in the SPARK Cohort.

The SPARK cohort was established to facilitate recruitment in studies of large numbers of participants with autism spectrum disorder (ASD). Online registration requires participants to have received a lifetime professional diagnosis by health or school providers although diagnoses are not independently verified. This study was set to examine the validity of self- and caregiver-reported autism diagnoses. Electronic medical records (EMR) of 254 SPARK participants (77.6% male, age 10.7 years) were abstracted. Using two different methods, confirmation of ASD diagnosis in EMRs was obtained in 98.8% of cases. Core clinical features recorded in EMRs were typical of autism samples and showed very good agreement with SPARK cohort data, providing further evidence of the validity of clinical information in the SPARK database.