Adaptive Behavior Scales Research Articles

Concordance between patient-centered and adaptive behavior outcome measures after applied behavior analysis for autism

BackgroundApplied behavior analysis (ABA) is an evidence-based approach to autism spectrum disorder that has been shown in clinical trials to improve child functional status. There is substantial focus in ABA on setting and tracking individualized goals that are patient-centered, but limited research on how to measure progress on such patient-centered outcomes.PurposeThe purpose of this investigation was to assess concordance between patient-centered and standard outcome measures of treatment progress in a real-world clinical sample of children receiving ABA for autism spectrum disorder.MethodsThis observational study used a clinical sample of children ages 3 to 16 years (N = 154) who received 24 months of ABA from an integrated health system. Concordance between three outcome measures after ABA was assessed using a correlation matrix: (1) patient-centered measures of progress on individualized treatment goals, (2) caregiver-centered measure of progress on treatment participation goals, and (3) the Vineland Adaptive Behavior Scales adaptive behavior composite.ResultsThere was limited concordance among measures at both 12 and 24 months of ABA. None of the patient-centered measures showed significant positive correlation with adaptive behavior composite difference scores at either 12 or 24 months, nor did the caregiver measure. The percentage of children achieving clinically meaningful gain on patient-centered goal measures increased between 12 and 24 months of ABA, while the percentage of children achieving clinically meaningful gains in adaptive behavior declined during the same time period.ConclusionsIn a health system implementation of ABA, there was limited concordance between patient-centered and standard measures of clinically meaningful treatment progress for children with ASD. Clinicians should have ongoing dialogue with patients and parents/caregivers to ensure that interventions for ASD are resulting in progress towards outcomes that are meaningful to patients and families.

Effects of Omega-3-6-9 fatty acid supplementation on behavior and sleep in preterm toddlers with autism symptomatology: Secondary analysis of a randomized clinical trial

BackgroundChildren born extremely preterm disproportionately experience sequelae of preterm birth compared to those born at later gestational ages, including higher prevalence of autism spectrum disorder (ASD) and associated behaviors. AimExplore effects of combined dietary docosahexaenoic acid, eicosapentaenoic acid, gamma-linolenic acid, and oleic acid (omega 3-6-9) on caregiver-reported behavior and sleep in toddlers born at ≤29 weeks' gestation who were exhibiting symptoms commonly seen with ASD. Study design90-day randomized (1:1), double blinded, placebo-controlled trial. SubjectsThirty-one children aged 18–38 months received omega 3-6-9 (n = 15) or canola oil placebo (n = 16). Outcome MeasuresMixed effects regression analyses followed intent to treat and explored treatment effects on measures of caregiver-reported behavior (Child Behavior Checklist 1.5–5, Toddler Behavior Assessment Questionnaire – Short Form, Vineland Adaptive Behavior Scales, 2nd Edition) and sleep (Children's Sleep Habits Questionnaire, Brief Infant Sleep Questionnaire). ResultsTwenty-nine of 31 (94%; ntx = 13, nplacebo = 16) children randomized had data available for at least one outcome measure, 27 (87%; ntx = 12, nplacebo = 15) had complete outcome data. Children randomized to omega 3-6-9 experienced a medium magnitude benefit of supplementation on anxious and depressed behaviors (ΔDifference = −1.27, d = −0.58, p = 0.049) and internalizing behaviors (ΔDifference = −3.41, d = −0.68, p = 0.05); and a large magnitude benefit on interpersonal relationship adaptive behaviors (ΔDifference = 7.50, d = 0.83, p = 0.01), compared to placebo. No effects were observed on other aspects of behavior or sleep. ConclusionsFindings provide preliminary support for further exploration of omega 3-6-9 during toddlerhood to improve socioemotional outcomes among children born preterm, especially for those showing early symptoms commonly seen with ASD. Results need to be replicated in a larger sample. Trial registrationRegistered with ClinicalTrials.gov: NCT01683565.

A Comparison of Adaptive Functioning Between Children With Duplication 7 Syndrome and Williams-Beuren Syndrome: A Pilot Investigation.

Interstitial deletions of 7q11.23 cause the well-known Williams–Beuren Syndrome (WBS), while duplication of the same region leads to duplication 7 syndrome (Dup7). Children with WBS share a distinct neurobehavioral phenotype including mild to severe intellectual disability, severely impaired visual spatial abilities, relatively preserved verbal expressive skills, anxiety problems, enhanced social motivation (i.e., hypersociable behaviors) and socio-communicative problems. Children with Dup7 syndrome exhibit some “inverted” features when compared to those of individuals with WBS, such as reduced social motivation and impairment of expressive language. Direct comparison of WBS and Dup7 represents a unique opportunity for the neurobehavioral characterization of the 7q11.23 section. However, most of the available data come from qualitative analysis between different studies. To the best of our knowledge, there are no studies directly comparing features of two matched samples of individuals with WBS and Dup7 syndromes. In this pilot study, we compare the adaptive functioning – measured with the Vineland Adaptive Behavior Scales, Second Edition – of two relatively small samples of children with molecularly confirmed diagnosis of WBS and Dup7 matched for IQ and chronological age, with a particular attention to socialization domain and expressive subdomain. Contrary to our assumption, we have not found any significant difference on socialization domain and expressive subdomains. This pilot investigation suggests that, when matched for chronological age and cognitive level, children with WBS and Dup7 share more similarities than expected. The inverted features that emerge in clinical settings on expressive language and social motivation seem not to differently interfere with the daily abilities to communicate and socialize with meaningful others during daily lives. Differences highlighted by previous undirected comparisons could be due to general and non-specific factors such as cognitive level, which is more severely impaired in individuals with WBS than Dup7. Implications for assessment and treatment are discussed.

Quantifying medical manifestations in Hurler syndrome with the infant physical symptom score: associations with long-term physical and adaptive outcomes.

A physical symptom score (PSS) for the mucopolysaccharidosis (MPS) disorders has been developed to quantitate the somatic burden of disease across multiple organ systems. Studies have demonstrated the sensitivity and its relationship to age, IQ and adaptive functioning of the PSS in older children. With the onset of newborn screening, there is an increased need to characterize the somatic symptoms in the earliest stages of life, especially for young children under 36 months of age. Consequently, a new scale, Infant Physical Symptom Score (IPSS), was developed to score physical symptoms in infants and toddlers. Part I. To create a measure to quantify somatic burden in patients with MPS disorders under 36 months of age. The IPSS assess outcomes and changes in somatic disease in individuals with MPS disorders diagnosed very early in life. Part II. To determine the relationship between IPSS and other measures to evaluate its validity and utility, a) we evaluated the relationship between the IPSS and PSS in the same patients with MPS I over time to determine if the two scales are measuring the same concepts, and b) we evaluated the association between IPSS and a functional adaptive measure over time with a focus on the age at first treatment (under 36 months) to determine if the IPSS has predictive value. Part I. The Infant Physical Symptom Score (IPSS) for the infant population in MPS disorders was established using data from 39 patients enrolled in the Lysosomal Disease Network longitudinal MPS I study (U54NS065768). All of these patients had Hurler syndrome (MPS IH) and underwent hematopoietic stem cell transplant (HSCT) at the University of Minnesota. Items for the IPSS were selected by reviewing CRFs prepared for the MPS I longitudinal study and examining medical records of these patients prior to HSCT based on the knowledge gained from the development of the PSS. Part II. Of those 39 patients, a subset of 19 were all seen 9 to 12 years post HSCT. Having retrospectively calculated their IPSS prior to HSCT, we categorized them by age at HSCT, and examined their most recent PSS along with Composite and Daily Living Skills scores on the Vineland Adaptive Behavior Scales - Second Edition (VABS-II). The total score on the IPSS collected prior to transplant differed by patient's age at transplant, as expected in this progressive condition. Those transplanted at ≤12 months of age had a mean score of 7.4, which was significantly lower, suggesting less somatic disease burden, compared to those transplanted at >12 to ≤24 months (mean 11.8) and > 24 to ≤36 months (mean 13.6). Higher IPSS reflects more evidence of somatic disease burden and lower IPSS reflects less evidence of disease burden. Nine to 12 years later, the severity level as measured by the PSS was comparable to severity on the IPSS suggesting that the two scales are measuring similar concepts. Retrospectively calculated pre-transplant IPSS were negatively associated with higher VABS-II Composite scores 9-12 years later (p value-0.015) and to a lesser extent Daily Living Skills scores (p value-0.081). We conclude that the IPSS appears to be a useful approach to quantifying the somatic disease burden of MPS IH patients under 36 months of age.

Microanalysis of Daily Living Skills in adolescents with Autism Spectrum Disorder without an intellectual disability.

Adolescents with autism spectrum disorder (ASD) without an intellectual disability (ID) have daily living skills (DLS) that fall below their chronological age and affect their ability to achieve successful adult outcomes, but little is known about their specific DLS challenges. Utilizing the Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3) in a sample of 151 adolescents with ASD without an ID, we explored the VABS-3 DLS domain, subdomains, interview topics, and individual items. Results indicated that Community DLS was a relative strength, followed by Domestic DLS, and then Personal DLS. Adolescents with ASD demonstrated significant challenges in many age appropriate DLS subdomain interview topics and individual items, indicating a need for interventions to increase acquisition of DLS to improve adult outcomes.

Patterns of Restricted and Repetitive Behaviors in Toddlers and Young Children with Autism Spectrum Disorder.

ObjectivesRestricted and repetitive behaviors (RRBs) are a core symptom in the diagnosis of autism spectrum disorder (ASD). The complexity of behavioral patterns has called for the creation of phenotypically homogeneous subgroups among individuals with ASD. The purpose of this study was 1) to investigate the different types of RRBs and 2) to explore whether subgroups created by RRBs would show unique levels of functioning in toddlers and young children with ASD.MethodsA total of 313 children with ASD, aged 12–42 months were included in the analysis. The Autism Diagnostic Interview-Revised was used to obtain information on the different types of RRBs by grouping 15 items into six categories. The Vineland Adaptive Behaviors Scale, a parent-reported questionnaire, was used to measure adaptive functioning. A portion of the children were analyzed separately for verbal-related RRBs based on their expressive language level. Two-step cluster analysis using RRB groups as features was used to create subgroups. Analysis of covariance while covarying for age and language was performed to explore the clinical characteristics of each cluster group.ResultsSensory-related RRBs were the most prevalent, followed by circumscribed interests, interest in objects, resistance to change, and repetitive body movements. A subset of the children was analyzed separately to explore verbal-related RRBs. Four cluster groups were created based on reported RRBs, with multiple RRBs demonstrating significant delays in adaptive functioning.ConclusionHeterogeneity of RRBs emerges at a young age. The different patterns of RRBs can be used as valuable information to determine developmental trajectories with better implications for treatment approaches.

The Development of Adaptive Behavior Scale

The Development of Adaptive Behavior Scale

Exploring predictors of adaptive behaviour of children with autism

This research determined the predictors of the adaptive behaviour of children with autism who are enrolled in special education centres using a descriptive correlational design. There were 40 children with autism whose adaptive behaviour was assessed in terms of their communication, daily living, social and motor skills using the modified Vineland Adaptive Behaviour Scales (Vineland-3) together with their profile. Data gathered were treated using descriptive and inferential statistics. The results showed that most of the children were males whose average age was 9.6 years who belonged to low-income families and were enrolled in 2 to 3 years. The children had moderately low adaptive skills in all areas of the adaptive behaviour. Moreover, the profiles of the children were not significant predictors of the four adaptive skills being assessed. Thus, it is recommended that other factors may be considered to identify the predictors of the adaptive behaviour of children with autism. Keywords: Children with autism, communication, daily living, motor, social

Trajectories of Adaptive Behaviors During Childhood in Females and Males in the General Population.

Little is known about the trajectory patterns and sex differences in adaptive behaviors in the general population. We examined the trajectory classes of adaptive behaviors using a representative sample and examined whether the class structure and trajectory patterns differed between females and males. We further explored sex differences in neurodevelopmental traits in each latent class. Participants (n = 994) were children in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study)—a prospective birth cohort study. Adaptive behaviors in each domain of communication, daily living skills, and socialization were evaluated at five time points when participants were 2.7, 3.5, 4.5, 6, and 9 years old using the Vineland Adaptive Behavior Scales–Second Edition. Parallel process multigroup latent class growth analysis extracted sex-specific trajectory classes. Neurodevelopmental traits of children at age 9, autistic traits, attention deficit hyperactivity disorder (ADHD) traits, and cognitive ability were examined for females and males in each identified class. A 4-class model demonstrated the best fit. Moreover, a 4-class model that allowed for differences in class probabilities and means of growth parameters between females and males provided a better fit than a model assuming no sex differences. In the communication domain, females scored higher than their male counterparts in all four classes. In the daily living skills and socialization domains, the two higher adaptive classes (Class 1: females, 18.6%; males, 17.8%; Class 2: females, 48.8%; males, 49.8%) had similar trajectories for males and females, whereas in the two lower adaptive behavior classes (Class 3: females, 27.5%; males, 29.4%; Class 4: females, 5.1%; males, 3.0%), females had higher adaptive scores than their male counterparts. In Class 4, females were more likely to have autistic and ADHD traits exceeding the cutoffs, while males were more likely to have below-average IQ. Different trajectories in females and males suggest that adaptive skills may require adjustment based on the sex of the child, when standardizing scores, in order to achieve better early detection of skill impairment.

Pre- and Postnatal Fine Particulate Matter Exposure and Childhood Cognitive and Adaptive Function.

Increasing evidence exists for an association between early life fine particulate matter (PM2.5) exposure and several neurodevelopmental outcomes, including autism spectrum disorder (ASD); however, the association between PM2.5 and adaptive and cognitive function remains poorly understood. Participants included 658 children with ASD, 771 with a non-ASD developmental disorder, and 849 population controls from the Study to Explore Early Development. Adaptive functioning was assessed in ASD cases using the Vineland Adaptive Behavior Scales (VABS); cognitive functioning was assessed in all groups using the Mullen Scales of Early Learning (MSEL). A satellite-based model was used to assign PM2.5 exposure averages during pregnancy, each trimester, and the first year of life. Linear regression was used to estimate beta coefficients and 95% confidence intervals, adjusting for maternal age, education, prenatal tobacco use, race-ethnicity, study site, and season of birth. PM2.5 exposure was associated with poorer VABS scores for several domains, including daily living skills and socialization. Associations were present between prenatal PM2.5 and lower MSEL scores for all groups combined; results were most prominent for population controls in stratified analyses. These data suggest that early life PM2.5 exposure is associated with specific aspects of cognitive and adaptive functioning in children with and without ASD.

Characterization of phenotypic range in DYRK1A haploinsufficiency syndrome using standardized behavioral measures

DYRK1A haploinsufficiency syndrome is a well-established neurodevelopmental disorder, but detailed information on the range of cognitive and behavioral issues associated with the condition is limited. We studied 24 participants with likely pathogenic or pathogenic variants in DYRK1A through the Simons Searchlight study and systematically assessed their medical history and development using standardized instruments: Vineland Adaptive Behavior Scale II (VABS-II) and Child Behavior Checklists/1.5-5 and 6-18 (CBCL/1.5-5, CBCL/6-18). All of the individuals in the cohort had neurological manifestations including intellectual disability or developmental delay, microcephaly, autism spectrum disorder, and/or seizures. The severity of the neurodevelopmental disorder was variable with a few children scoring in the moderately low range on the adaptive behavior composite score on the VABS-II. This study confirms the association of DYRK1A haploinsufficiency with neurodevelopmental disabilities, microcephaly, autism spectrum disorder, and epilepsy and quantifies the range of adaptive behaviors.

Assessing the utility of electronic measures as a proxy for cognitive ability

AbstractLarge‐scale genomic studies have identified over 100 genes associated with autism spectrum disorder (ASD); however, important phenotypic variables are captured inconsistently. In many cases, the resources required for comprehensive characterization hinder the feasibility of collecting critical information, such as intellectual ability. Thus, electronic collection of important phenotypes would greatly facilitate large‐scale data collection efforts. This study assessed the utility of two electronic assessments as a proxy of cognitive ability relative to clinician‐administered cognitive assessments. Ninety‐two participants completed the study, including individuals with ASD (probands, n = 19), parents of probands (n = 46), and siblings without ASD (n = 27). Participants were administered the electronic‐Peabody Picture Vocabulary Test, Fourth Edition (e‐PPVT‐4), an electronic visual reasoning (VR) test, and a clinician‐administered Wechsler Abbreviated Scales of Intelligence, Second Edition (WASI‐II). Probands also completed a full, in‐person, cognitive assessment and Vineland Adaptive Behavior Scales, 2nd Edition. Correlations between scores on electronic and clinician‐administered measures were examined. Classification accuracy of individual scores based on 95% confidence intervals and score range (below average, average, above average) were also assessed. Moderate to strong correlations were identified between both electronic measures and the clinician‐administered WASI‐II (ρ = 0.606–0.712). Mean difference between standard scores ranged from 10.7 to 14.8 for the cohort. Classification accuracy based on WASI‐II 95% confidence interval was consistently low (27.5%–47.3%). Classification accuracy by score range (below average, average, above average) was variable, ranging from 33% to 86% for probands. All participants unable to complete the electronic assessments met DSM‐5 criteria for intellectual disability. e‐PPVT‐4 and VR scores were strongly correlated with scores on the WASI‐II full‐scale IQ (ρ = 0.630, 0.712), indicating utility of these measures at the group level in large‐scale genomic studies. However, the poor precision of measurement across both measures suggests that the e‐PPVT‐4 and VR are not useful alternatives to in‐person testing for the purpose of clinical assessment of an individual's IQ score.Lay SummaryLarge‐scale studies designed to identify genes associated with autism have been successful in identifying over 100 genes. However, important clinical information about participants with autism and their family members is often missed—including cognitive functioning. Cognitive testing requires in‐person administration by a trained clinician and therefore can be burdensome and often reduces feasibility of diverse samples. Here, we assessed whether electronic assessments could take the place of in‐person cognitive testing. We found that at the group level, for large‐scale studies, electronic measures added valuable information; however, they were not accurate enough to be used on an individual level (i.e., to offer feedback about an individual's predicted IQ score).

Safety of sibling cord blood cell infusion for children with cerebral palsy

Cerebral palsy (CP) is a nonprogressive neurological disorder and the most common physical disability of childhood. There is no cure for CP, but stem cells have the potential to improve brain injury and hence function. This phase 1 clinical trial investigated the safety of the intravenous infusion of full-matched sibling cord blood cells for children with CP aged 1 to 16 years. Preliminary efficacy outcomes were also investigated. Twelve participants received 12/12 HLA-matched sibling cord blood cell infusions. One treatable serious adverse reaction to cryoprotectant was observed, and no adverse reactions occurred beyond 24 h after infusion. Gross motor function measure (GMFM-66) scores did not improve compared with baseline beyond what could be expected from developmental levels, and participants had varied changes in the Quality of Upper Extremity Skills Test (QUEST) and Vineland Adaptive Behavior Scales (VABS-II) scores. In conclusion, matched sibling cord blood cell infusion for children with CP is relatively safe when conducted in an appropriate facility. Australian and New Zealand Clinical Trials Registry (ACTRN12616000403437) and Clinicaltrials.gov (NCT03087110).

Italian Diagnostic Adaptive Behavior Scale: Reliability and diagnostic accuracy compared with the Vineland-II

BackgroundThe Diagnostic Adaptive Behavior Scale (DABS) is a short scale with excellent properties to assess the conceptual, social, and practical adaptive behavior domains for the diagnosis of intellectual disability (ID) in individuals aged 4–21 years. AimsInvestigate the test-retest and inter-respondent reliability of the Italian adaptation of the DABS, verify its diagnostic accuracy in identifying individuals with ID and excluding individuals with typical development (TD), and compare its psychometric properties to those of the Vineland-II. MethodsTest-retest reliability: The same respondent completed the Italian DABS for the same assessed person at two separate times (n = 71). Inter-respondent reliability: Two respondents for the same assessed person completed the Italian DABS independently (n = 57). Diagnostic accuracy: The same respondent completed the Italian DABS and Vineland-II for the same assessed person (n = 378; 50 % ID, 50 % TD). ResultsItalian DABS test-retest and inter-respondent correlation coefficients were excellent. Italian DABS sensitivity was 86 % and specificity was 99 %, Italian DABS Areas Under the ROC Curves were excellent (or good, practical skill domain), and comparable to the results reported for the Vineland-II. ConclusionsThe Italian DABS is an excellent measure to evaluate the adaptive behavior for ID diagnosis; it is comparable to the Vineland-II but being shorter, the Italian DABS requires less time to administer.

Cognitive, Behavioral, and Sensory Profile of Pallister-Killian Syndrome: A Prospective Study of 22 Individuals.

Background: Developmental delay and intellectual disability are two pivotal elements of the phenotype of Pallister–Killian Syndrome (PKS). Our study aims to define the cognitive, adaptive, behavioral, and sensory profile of these patients and to evaluate possible correlations between the different aspects investigated and with the main clinical and demographic variables. Methods: Individuals of any age with genetically confirmed PKS were recruited. Those ≤ 42 months were administered the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III), and those > 42 months the Vineland Adaptive Behavior Scales—Second Edition (Vineland-II). Stereotyped behaviors (Stereotypy Severity Scale, SSS) and aggressive behaviors (Behavior Problems Inventory—Short Version, BPIs) were assessed in all subjects > 1 year; sensory profile (Child Sensory Profile 2, C-SP2) in all aged 2–18 years. Results: Twenty-two subjects were enrolled (11 F/11 M; age 9 months to 28 years). All subjects ≤ 42 months had psychomotor developmental delay. Of the subjects > 42 months, 15 had low IQ deviation, and 1 in the normal range. Stereotypies were frequent (median SSS-total score 25/68). Lower Vineland-II values corresponded to greater intensity and frequency of stereotypies (p = 0.004 and p = 0.003), and self-injurious behaviors (p = 0.002 and p = 0.002). Patients with severe low vision had greater interference of stereotypies (p = 0.027), and frequency and severity of aggressive behaviors (p = 0.026; p = 0.032). The C-SP2, while not homogeneous across subjects, showed prevalence of low registration and sensory seeking profiles and hypersensitivity to tactile and auditory stimuli. Lower Vineland-II scores correlated with higher Registration scores (p = 0.041), while stereotypies were more frequent and severe in case of high auditory sensitivity (p = 0.019; p = 0.007). Finally, greater sleep impairment correlated with stereotypies and self-injurious behaviors, and lower Vineland-II scores. Conclusions: The present study provides a further step in the investigation of the etiopathogenesis of the syndrome. Furthermore, these aspects could guide rehabilitation therapy through the identification of targeted protocols.

A randomized, double-blind, placebo-controlled phase II trial to explore the effects of a GABAA-\u03b15 NAM (basmisanil) on intellectual disability associated with Down syndrome

BackgroundThere are currently no pharmacological therapies to address the intellectual disability associated with Down syndrome. Excitatory/inhibitory imbalance has been hypothesized to contribute to impairments in cognitive functioning in Down syndrome. Negative modulation of the GABAA-α5 receptor is proposed as a mechanism to attenuate GABAergic function and restore the excitatory/inhibitory balance.MethodsBasmisanil, a selective GABAA-α5 negative allosteric modulator, was evaluated at 120 mg or 240 mg BID (80 or 160 mg for 12–13 years) in a 6-month, randomized, double-blind, placebo-controlled phase II trial (Clematis) for efficacy and safety in adolescents and young adults with Down syndrome. The primary endpoint was based on a composite analysis of working memory (Repeatable Battery for the Assessment of Neuropsychological Scale [RBANS]) and independent functioning and adaptive behavior (Vineland Adaptive Behavior Scales [VABS-II] or the Clinical Global Impression-Improvement [CGI-I]). Secondary measures included the Behavior Rating Inventory of Executive Functioning-Preschool (BRIEF-P), Clinical Evaluation of Language Fundamentals (CELF-4), and Pediatric Quality of Life Inventory (Peds-QL). EEG was conducted for safety monitoring and quantitatively analyzed in adolescents.ResultsBasmisanil was safe and well-tolerated; the frequency and nature of adverse events were similar in basmisanil and placebo arms. EEG revealed treatment-related changes in spectral power (increase in low ~ 4-Hz and decrease in high ~ 20-Hz frequencies) providing evidence of functional target engagement. All treatment arms had a similar proportion of participants showing above-threshold improvement on the primary composite endpoint, evaluating concomitant responses in cognition and independent functioning (29% in placebo, 20% in low dose, and 25% in high dose). Further analysis of the individual measures contributing to the primary endpoint revealed no difference between placebo and basmisanil-treated groups in either adolescents or adults. There were also no differences across the secondary endpoints assessing changes in executive function, language, or quality of life.ConclusionsBasmisanil did not meet the primary efficacy objective of concomitant improvement on cognition and adaptive functioning after 6 months of treatment, despite evidence for target engagement. This study provides key learnings for future clinical trials in Down syndrome.Trial registrationThe study was registered on December 31, 2013, at clinicaltrials.gov as NCT02024789.

Acceptance of Telehealth Therapy to Replace In-Person Therapy for Autism Treatment During COVID-19 Pandemic: An Assessment of Patient Variables.

Importance: Children with autism achieve improved behavioral outcomes with applied behavior analytic (ABA) interventions. Typically, ABA is delivered in a participant's home or in a clinic setting. At the onset of COVID-19, treatment in these environments was not available due to health exposure concerns. A large social service organization in California rapidly pivoted to the delivery of ABA intervention through telehealth. Access disparity for telehealth has been a historical concern in health care delivery, particularly for disenfranchised populations within the autistic participant population. Objective: This study evaluated the demographic and behavioral variables associated with the acceptance or declination of telehealth by the pediatric participants' caregivers at the onset of the pandemic. Design, Setting, Participants: A non-experimental design was used, and archival data were compared for a random sample of 100 participants with autism who accepted telehealth interventions with 100 participants who declined it. Main Outcomes and Measures: Socioeconomic data, gender, age, ethnicity, language, and household size were compared. Clinical data were compared for treatment dosage, standardized Vineland Adaptive Behavior Scales scores, and Verbal Behavior Milestones Assessment and Placement Program scores. Results: None of the demographic variables were statistically significant in a participant's acceptance or declination of telehealth, but there were moderate differences in treatment dosage across the groups. Conclusions: It is concerning that a large portion of participants initially declined intervention via telehealth, resulting in these participants experiencing a gap in intervention during the pandemic. As intervention is imperative for pediatric autism participants, it is untenable that ∼40% of the population initially declined telehealth at the start of the pandemic.

An observational, prospective, multicenter, natural history study of patients with mucopolysaccharidosis type IIIA.

Mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome) is a rare genetic lysosomal storage disease characterized by early and progressive neurodegeneration resulting in a rapid decline in cognitive function affecting speech and language, adaptive behavior, and motor skills. We carried out a prospective observational study to assess the natural history of patients with MPS IIIA, using both standardized tests and patient-centric measures to determine the course of disease progression over a 2-year period. A cohort of 23 patients (7 girls, 16 boys; mean age 28-105months at baseline) with a confirmed diagnosis of MPS IIIA were assessed and followed up at intervals of 3-6months; cognitive function was measured using Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III) to derive cognitive development quotients (DQ). Daily living, speech/language development and motor skills were measured using the Vineland Adaptive Behavior Scale (VABS-II). Sleep-wake patterns, behavior and quality-of-life questionnaires were also reported at each visit using parent/caregiver reported outcome tools. All patients had early onset severe MPS IIIA, were diagnosed before 74months of age, and had cognitive scores below normal developmental levels at baseline. Patients less than 40months of age at baseline were more likely to continue developing new skills over the first 6-12months of follow-up. There was a high variability in cognitive developmental age (DA) in patients between 40 and 70months of age; two-thirds of these patients already had profound cognitive decline, with a DA ≤10months. The highest cognitive DA achieved in the full study cohort was 34months. Post hoc, patients were divided into two groups based on baseline cognitive DQ (DQ ≥50 or<50). Cognitive DQ decreased linearly over time, with a decrease from baseline of 30.1 and 9.0 points in patients with cognitive DQ ≥50 at baseline and cognitive DQ <50 at baseline, respectively. Over the 2-year study, VABS-II language scores declined progressively. Motor skills, including walking, declined over time, although significantly later than cognitive decline. No clear pattern of sleep disturbance was observed, but night waking was common in younger patients. Pain scores, as measured on the quality-of-life questionnaire, increased over the study period. The findings of this study strengthen the natural history data on cognitive decline in MPS IIIA and importantly provide additional data on endpoints, validated by the patient community as important to treat, that may form the basis of a multidomain endpoint capturing the disease complexity.

Early Intensive Behavioral Intervention Program for Children With Autism in Syria

In this study, we evaluated the effect of the Future Center Early Intensive Behavioral Intervention program on children’s skills longitudinally by sex, age, and diagnoses as dependent variables. Sixty-seven children ages 1–6 years and diagnosed with autism spectrum disorder were followed up for 2 years in Syria. They were assessed twice across the 2-year program: at their first visit and at the end of the program. Assessments included the Autism Behavior Checklist, Childhood Autism Rating Scale, and Adaptive Behavioral Scale–Arabic version. Results showed that the changes in participants’ scores from pre- to post-test were statistically significant, and the treatment group showed significantly larger gains on all scales. No significant differences were found by sex and age between the pre- and post-test on all scales, while there were significant differences regarding diagnoses. The limitations of this study and suggestions for future research are described.

Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine.

Gastrointestinal (GI) disorders are common in children with neurodevelopmental disorders such as autism spectrum disorder (ASD). A limited understanding of the biologic factors that predispose this population to GI disorders has prevented development of individualized therapies to address this important medical issue. The goal of the current study was to determine if elements of the salivary micro-transcriptome could provide insight into the biologic perturbations unique to children with ASD-related GI disturbance. This cohort study included 898 children (ages 18–73 months) with ASD, non-ASD developmental delay (DD), or typical development (TD). The saliva micro-transcriptome of each child was assessed with RNA-seq. Outputs were aligned to microbial and human databases. A Kruskal Wallis analysis of variance (ANOVA) was used to compare levels of 1821 micro-transcriptome features across neurodevelopmental status (ASD, DD, or TD) and GI presence or absence. An ANOVA was also used to compare micro-transcriptome levels among GI sub-groups (constipation, reflux, food intolerance, other GI condition, no GI condition), and to identify RNAs that differed among children taking three common GI medications (probiotics, reflux medication, or laxatives). Relationships between features identified in ANOVA testing were examined for associations with scores on the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) and the Vineland Adaptive Behavior Scales. GI disturbance rates were higher among children with ASD than peers with TD but were similar to those with DD. Five piwi-interacting RNAs and three microbial RNAs displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI sub-groups–with microRNA differences between food intolerance and reflux groups being most common. Twelve microRNAs displayed an effect of GI disturbance and showed association with GI medication uses and measures of behavior. These 12 microRNAs displayed enrichment for 13 physiologic pathways, including metabolism/digestion long-term depression, and neurobiology of addiction. This study identifies salivary micro-transcriptome features with differential expression among children with ASD-related GI disturbance. A subset of the RNAs displays relationships with treatment modality and are associated with autistic behaviors. The pathobiologic targets of the micro-transcriptome markers may serve as targets for individualized therapeutic interventions aimed at easing pain and behavioral difficulties seen in ASD-related GI disturbance.