Pediatric Autism Spectrum Disorder Research Articles

Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial.

The clinical utility of Bacteroides fragilis in treating autism spectrum disorder (ASD) remains unclear. Therefore, this randomized, double-blind, placebo-controlled study aimed to explore the therapeutic effects and safety of B. fragilis BF839 in the treatment of pediatric ASD. We examined 60 children aged 2-10 years diagnosed with ASD, and participants received either BF839 powder (10 g/bar with ≥106 CFU/bar of viable bacteria, two bars/day) or placebo for 16 weeks. The primary outcomes was Autism Behavior Checklist (ABC) score. The secondary outcomes were Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Normal Development of Social Skills from Infants to Junior High School Children (S-M), Gastrointestinal Symptom Rating Scale (GSRS) scores, and fecal microbiome composition. Assessments were performed on day 0 and at weeks 8 and 16. Compared with the placebo group, the BF839 group showed significant improvement in the ABC body and object use scores at week 16, which was more pronounced in children with ASD aged <4 years. Among children with a baseline CARS score ≥30, the BF839 group showed significant improvements at week 16 in the ABC total score, ABC body and object use score, CARS score, and GSRS score compared to the placebo group. Only two patients (6.67%) in the BF839 group experienced mild diarrhea. Compared with baseline and placebo group levels, the BF839 group showed a significant post-intervention increase in abundance of bifidobacteria and change in the metabolic function of neuroactive compounds encoded by intestinal microorganisms. BF839 significantly and safely improved abnormal behavior and gastrointestinal symptoms in children with ASD.

THE USE OF CANNABIDIOL IN PEDIATRIC DENTISTRY PATIENTS WITH AUTISM SPECTRUM DISORDER: INTEGRATIVE REVIEW

This research project aims to conduct a literature review on the use of cannabidiol (CBD) in pediatric dental patients diagnosed with Autism Spectrum Disorders (ASD). The focus will be on the intersection between pediatric dentistry and ASD treatment, aiming to fill a substantial gap in the scientific and clinical understanding of the subject. The integrated approach provides a solid foundation for informed decision-making by healthcare professionals, family members, and caregivers. The central problem of the research lies in the need for substantial evidence supporting the efficacy and safety of CBD in this specific patient group. The absence of reliable data poses significant challenges for making informed decisions about the pediatric dental treatment of children with ASD, impacting the quality of life for these patients. Therefore, the adopted methodology will involve a literature search, using exclusively recently published articles from the last 5 years, available in databases such as PUBMED and SCIELO, among other relevant sources. The main objective of this literature review is to assess the efficacy of CBD in managing symptoms associated with ASD in pediatric dental contexts, considering its potential therapeutic benefits and possible side effects. The research aims to fill this gap by establishing a comprehensive investigation into the use of CBD in children with ASD, directing its attention to specific implications for oral health.

A population pharmacokinetics model of balovaptan to support dose selection in adult and pediatric populations

Balovaptan is a brain-penetrating vasopressin receptor 1a antagonist previously investigated for the core symptoms of autism spectrum disorder (ASD). A population pharmacokinetic (PK) model of balovaptan was developed, initially to assist clinical dosing for adult and pediatric ASD studies and subsequently for new clinical indications including malignant cerebral edema (MCE) and post-traumatic stress disorder. The final model incorporates one-compartment disposition and describes time- and dose-dependent non-linear PK through empirical drug binding and a gut extraction component with turnover. An age effect on clearance observed in children was modeled by an asymptotic function that predicts adult-equivalent exposures at 40% of the adult dose for children aged 2–4 years, 70% for 5–9 years, and at the full adult dose for ≥ 10 years. The model was adapted for intravenous (IV) balovaptan dosing and combined with in vitro and ex vivo pharmacodynamic data to simulate brain receptor occupancy as a guide for dosing in a phase II trial of MCE prophylaxis after acute ischemic stroke. A sequence of three stepped-dose daily infusions of 50, 25 and 15 mg over 30 or 60 min was predicted to achieve a target occupancy of ≥ 80% in ≥ 95% of patients over a 3-day period. This model predicts both oral and IV balovaptan exposure across a wide age range and will be a valuable tool to analyze and predict its PK in new indications and target populations, including pediatric patients.

Pediatric autism spectrum disorder: Role of yoga prana vidya system as complementary medicine in accelerating patient progress

Autism spectrum disorder (ASD) is a complex formative condition, described by tenacious difficulties in social cooperation and correspondence and confined and dreary behavior. There is no solution for Autism and a few treatments are accessible as well as certain drugs to further develop life for impacted youngsters and grown-ups. This paper presents a case of a boy who was treated from the age of 8 years with Yoga Prana Vidya (YPV) healing complementarily to other therapies achieving positive progress. This study uses the case study method by going through the patient’s medical records, the healer’s records, and the patient’s mother’s feedback. YPV healing was applied as a long-term intervention spanning 3 years, complementary to home-based “Son-Rise” program therapy. Within the first 15 days of YPV healing, the boy’s improvements were noticeable, and progress began after a stagnant condition over the previous 2 years. After 3 months of YPV intervention, the boy became more receptive to faster learning. After a year of healing, the boy’s condition improved from Grade 1 to Grade 2 of the “Son-Rise” gradation. At the end of the 3rd year, the boy achieved most of the Grade 3. YPV healing is being continued further. The integrated and holistic system of YPV healing therapy was successfully applied to the autism case as a complementary therapy, achieving the patient’s faster progress, and enabling parents to overcome social stigma. Further research is recommended on the application of YPV healing therapy in the treatment of ASD.

Advancing autism spectrum disorder diagnosis through ensemble learning

Advancing autism spectrum disorder diagnosis through ensemble learning

Behavioral symptoms of Alzheimer’s disease and autism spectrum disorder: Insights to guide future non‐pharmacological interventions

AbstractBackgroundMany behavioral and psychiatric symptoms of dementia (BPSD) share similarities with those described in pediatric autism spectrum disorder (ASD), including anxiety, depression, and communication deficits. However, the possibility of late‐life onset of behaviors stereotypic of ASD in Alzheimer’s disease (AD) has been poorly explored. Findings of three studies are presented here to illustrate associations in behaviors between ASD and AD.MethodsCare partners of persons with cognitive impairment (MCI or dementia) from the University of Kentucky Alzheimer’s Disease Research Center community‐based longitudinal cohort were surveyed using the Gilliam Autism Rating Scale‐2 (GARS‐2). Analyses included t‐tests, chi‐square, analysis of variance, and linear regression models to explore frequency of ASD behaviors in this cohort, and the relationship of behaviors represented in the GARS‐2 compared to behavioral categories used in AD assessment (Neuropsychiatric Inventory‐Questionnaire; NPI‐Q). Lastly, cross‐sectional postmortem neuropathological analyses compared “Autism Possible” to “Autism Unlikely” in available cases.ResultsAnalyses included 142 GARS‐2 respondents. A substantial number of participants presented with ASD‐like behaviors, and those with high Autism Index scores had significantly younger age at onset (71.1±11.0 vs. 76.7±8.3; p = 0.034) and more severe cognitive impairment than those who scored in the “Autism Unlikely” range. ASD‐like behaviors were also significantly correlated with BPSD severity ratings (r = 0.47; p &lt; 0.001). In neuropathological analyses, the two groups differed in the frontal and temporal regions, specific to tau pathology.ConclusionThese findings suggest that ASD‐like behaviors may emerge in AD as a result of shared neurological substrates, given that such behaviors are associated with an earlier age of onset and more severe cognitive impairment. With emerging evidence linking BPSD and ASD, additional research is needed to understand shared mechanisms, as well as development of novel treatment approaches to address behavioral symptoms of AD.

Special Report: Autism Spectrum Disorder and Inflexible Thinking—Affecting Patients Across the Lifespan

Special Report: Autism Spectrum Disorder and Inflexible Thinking—Affecting Patients Across the Lifespan

Understanding and Exploration of Traditional Chinese Medicine in Treating Pediatric Autism Spectrum Disorders

Understanding and Exploration of Traditional Chinese Medicine in Treating Pediatric Autism Spectrum Disorders

Atypical local brain connectivity in pediatric autism spectrum disorder? A coordinate-based meta-analysis of regional homogeneity studies

Despite decades of massive neuroimaging research, the comprehensive characterization of short-range functional connectivity in autism spectrum disorder (ASD) remains a major challenge for scientific advances and clinical translation. From the theoretical point of view, it has been suggested a generalized local over-connectivity that would characterize ASD. This stance is known as the general local over-connectivity theory. However, there is little empirical evidence supporting such hypothesis, especially with regard to pediatric individuals with ASD (age ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le$$\\end{document} 18 years old). To explore this issue, we performed a coordinate-based meta-analysis of regional homogeneity studies to identify significant changes of local connectivity. Our analyses revealed local functional under-connectivity patterns in the bilateral posterior cingulate cortex and superior frontal gyrus (key components of the default mode network) and in the bilateral paracentral lobule (a part of the sensorimotor network). We also performed a functional association analysis of the identified areas, whose dysfunction is clinically consistent with the well-known deficits affecting individuals with ASD. Importantly, we did not find relevant clusters of local hyper-connectivity, which is contrary to the hypothesis that ASD may be characterized by generalized local over-connectivity. If confirmed, our result will provide a valuable insight into the understanding of the complex ASD pathophysiology.

Prevalence of Pediatric Autism Spectrum Disorder in Korea Using National Statistics Including the COVID-19 Pandemic, 2011 to 2021

Purpose: Regularly analyzing the prevalence of autism spectrum disorder (ASD) is im-portant to inform policies and strategies for proper management. The present study aimed to estimate trends in ASD prevalence according to age and time in Korean chil-dren.Methods: We monitored the annual prevalence of ASD in children aged 2 to 18 years based on information from Statistics Korea and the Korean National Health Insurance Service. We estimated changes in prevalence between 2011 and 2021 after stratifying participants into three age groups. Furthermore, we analyzed the prevalence of ASD by birth year. Results: The highest level of prevalence appeared in children aged 6 years, and thereaf-ter, it declined with age. The prevalence of ASD in children aged 2 to 18 years in-creased from 0.05% in 2011 to 0.12% in 2021. During the same time, the prevalence in preschool children (2 to 5 years) remarkably increased from 0.04% in 2011 to 0.12% in 2021, while the prevalence in adolescents (13 to 18 years) increased from 0.05% in 2011 to 0.09% in 2021. The prevalence of ASD notably increased during the coronavirus dis-ease 2019 (COVID-19) pandemic (2020 to 2021). Among children born between 2011 and 2015, the prevalence of ASD was higher for children with recent birth years, espe-cially during the COVID-19 pandemic. Conclusion: The overall ASD prevalence in children and adolescents in Korea seems to be increasing, especially in preschool children during the COVID-19 pandemic. Early and more effective interventions are necessary for Korean children.

Neurobehavioral Associations with NREM and REM Sleep Architecture in Children with Autism Spectrum Disorder.

Objective: Insomnia and daytime behavioral problems are common issues in pediatric autism spectrum disorder (ASD), yet specific underlying relationships with NonRapid Eye Movement sleep (NREM) and Rapid Eye Movement (REM) sleep architecture are understudied. We hypothesize that REM sleep alterations (REM%, REM EEG power) are associated with more internalizing behaviors and NREM sleep deficits (N3%; slow wave activity (SWA) 0.5–3 Hz EEG power) are associated with increased externalizing behaviors in children with ASD vs. typical developing controls (TD). Methods: In an age- and gender-matched pediatric cohort of n = 23 ASD and n = 20 TD participants, we collected macro/micro sleep architecture with overnight home polysomnogram and daytime behavior scores with Child Behavior Checklist (CBCL) scores. Results: Controlling for non-verbal IQ and medication use, ASD and TD children have similar REM and NREM sleep architecture. Only ASD children show positive relationships between REM%, REM theta power and REM beta power with internalizing scores. Only TD participants showed an inverse relationship between NREM SWA and externalizing scores. Conclusion: REM sleep measures reflect concerning internalizing behaviours in ASD and could serve as a biomarker for mood disorders in this population. While improving deep sleep may help externalizing behaviours in TD, we do not find evidence of this relationship in ASD.

Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder

There are no approved medications for the core symptoms of autism spectrum disorder (ASD), socialization and communication difficulties. To evaluate the efficacy and safety of balovaptan, an oral selective vasopressin 1a receptor antagonist, compared with placebo in children and adolescents with ASD. The aV1ation study was a randomized, double-blind, 24-week, parallel-group, placebo-controlled phase 2 trial. Between November 22, 2016, and September 3, 2019, individuals were screened and randomly assigned to treatment groups. The primary efficacy analysis population comprised participants taking age-adjusted balovaptan equivalent to a 10-mg adult dose and participants from the concurrently randomized placebo group. This multicenter trial took place across 41 sites in the US. Participants were aged 5 to 17 years with diagnosed ASD and an IQ of 70 or greater. Data were analyzed from April 8 to November 16, 2020. Participants were randomly assigned to daily 4-mg or 10-mg adult-equivalent balovaptan or placebo, until the 4-mg group was discontinued. The primary end point was change from baseline on the Vineland-II two-domain composite (2DC; socialization and communication domains) score at week 24. Between November 2016 and September 2019, a total of 599 individuals were screened and 339 participants were randomly assigned to receive 4-mg balovaptan adult-equivalent dose (91 [26.8%]), 10-mg balovaptan adult-equivalent dose (126 [37.2%]), or placebo (122 [36.0%]). Primary analysis included 86 participants assigned to receive 10-mg balovaptan adult-equivalent dose and 81 assigned to receive placebo (mean [SD] age, 12.1 [3.4] years; 139 male participants [83.2%]). No statistically significant differences were observed between the balovaptan and placebo groups in change from baseline on the Vineland-II 2DC score at week 24 (difference in adjusted least-squares mean, -0.16; 90% CI, -2.56 to 2.23; P = .91). No improvements for balovaptan vs placebo were observed at week 24 for any secondary end points. Balovaptan was well tolerated with no emerging safety concerns. Similar proportions of participants reported adverse events (balovaptan, 66 of 86 [76.7%] vs placebo, 61 of 81 [75.3%]) and serious adverse events (balovaptan, 1 of 86 [1.2%] vs placebo, 4 of 81 [4.9%]). In this randomized clinical trial, balovaptan did not demonstrate efficacy in improvement of socialization and communication in this population with pediatric ASD. Balovaptan was well tolerated in children 5 years or older. Further development of robust, sensitive, and objective outcome measures may help to improve future studies in the assessment of therapies targeting communication and socialization in pediatric ASD. ClinicalTrials.gov Identifier: NCT02901431.

Neuroleptic Malignant Syndrome in Children with Autism Spectrum Disorder (ASD): A Case Report and Brief Review of Recent Literature

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening, idiosyncratic adverse reaction to antipsychotic drugs. Despite the increasing rates in the prescription of antipsychotics in pediatric patients with autism spectrum disorder (ASD), little is known about the occurrence and hallmarks of NMS in this specific population. NMS appears to be part of the larger catatonia domain, based on the frequent relationship between ASD and catatonia, on the shared, when not overlapping, clinical features with malignant catatonia, and on the effectiveness of catatonia treatments on the NMS/MC symptoms. The intrinsic difficulties of exploring NMS in ASD in controlled studies accounts for the subsequent lack of available information. Based on recent reports and on our case report, clinical features of NMS in the pediatric ASD population appear to be the same as the non-ASD population. Further studies are needed to confirm these results.

5.1 SYSTEMATIC REVIEW: TRANSCRANIAL MAGNETIC STIMULATION IN THE MANAGEMENT AND DIAGNOSIS OF AUTISM SPECTRUM DISORDER IN INTELLECTUALLY CAPABLE YOUTH

At present, there are no FDA-approved treatments for the core features of autism spectrum disorder (ASD) without intellectual impairment (ASD–) or well-defined biomarkers to aid in its diagnosis. Recent literature suggests that the use of transcranial magnetic stimulation (TMS) may aid in both domains. Additionally, interest has arisen investigating TMS in pediatric cases of ASD– due to the neurodevelopmental nature of the disorder, the possibility of greater clinical response due to the high degree of cortical plasticity in early life, and the opportunity for early diagnosis and initiation of treatment. Given these clinical possibilities, a systematic review of the literature investigating the use of TMS in cases of pediatric ASD– is warranted. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review of literature published through February 1, 2021 that examined control trials and crossover studies investigating TMS as a therapeutic and diagnostic tool in the management of pediatric ASD–. A total of 484 articles were screened, and 14 articles were included for final qualitative synthesis. Heterogeneity between studies was found including study design, clinical outcomes measures, diagnostic variables investigated, and TMS parameters and modalities. Notably, inhibitory TMS modalities were the most commonly utilized therapeutic intervention based on the hypothesis of delayed inhibitory neuronal development of ASD. Multiple studies demonstrated positive clinical outcomes in the domains of executive functioning, mood regulation, repetitive behaviors, and social withdrawal. Overall, no serious adverse effects were noted regardless of age, gender, TMS modality, or parameters. TMS is a safe option for the diagnosis and treatment of pediatric ASD–. However, findings are limited by variability between protocols and modalities. Future studies should include the development of standardized TMS parameters and modalities to enable larger multisite studies and to create standardized clinical protocols.

A retrospective analysis of memantine use in a pediatric neurology clinic

BackgroundMemantine is an N-methyl-D-aspartate receptor (NMDA-R) antagonist, approved for dementia, but also studied in pediatric autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). MethodsWe reviewed children treated with memantine in a single-centre pediatric neurology clinic. Clinical data extracted included age, sex, weight, clinical history, reason for memantine prescription, period of treatment trial and dosage, treatment response, side effects, and concomitant medications. ResultsEight patients met inclusion criteria with diagnoses including developmental and epileptic encephalopathy, focal epilepsy, ASD, ADHD. Four reported clear cognitive improvement, though two of these started other concurrent treatments at the time of memantine initiation. One of three patients with poorly-controlled epilepsy, a girl with a GRIN2A variant of uncertain significance, had a clear reduction in seizure frequency. No serious adverse events were noted. ConclusionsMemantine is generally well-tolerated in children, and may have potential benefit for a broad range of pediatric neurodevelopmental disorders.

The Feasibility of Magnetic Resonance Imaging in a Non-Selective Comprehensive Clinical Trial in Pediatric Autism Spectrum Disorder

There is an increasing interest in using magnetic resonance imaging (MRI) as a tool for precision medicine in autism spectrum disorder (ASD). This study investigated the feasibility of MRI scanning in a large comprehensive, inclusive and test heavy clinical trial for children (aged 3-12years) with ASD, without functioning constraints for participation. Of the 71 participants enrolled who consented to the MRI, 24 participants (38%) successfully completed an MRI scan at baseline along with other assessments. This scanning followed a familiarization procedure at two preceding visits. At post-treatment, 21 participants successfully completed the MRI scan. This study highlights the challenge of completing MRI assessments in ASD populations when conducted as one of a number of tests in a clinical trial.

Interagency Collaboration for Pediatric Autism Spectrum Disorder: Perspectives of Community-Based Providers.

Interagency collaboration between community and school settings is one mechanism to serve the complex needs of pediatric patients with autism spectrum disorder (ASD). We surveyed a national sample of community-based providers to examine their perspectives on interagency collaboration with school-based providers when serving pediatric patients with ASD. Medical and behavioral/mental health professionals practicing in community settings were recruited. Participants (N = 116) completed an online survey about their interagency collaboration experiences with schools. The majority of the sample reported engaging in interagency collaboration with school-based providers; however, the frequency was limited and was associated with the number of years working in the field. Community-based providers wanted more didactic and hands-on experiences in collaboration. Barriers and facilitators were related to schools' administration, school personnels' training in ASD, information exchange, and delineating between identification systems. Our findings highlight the importance of leadership support and the need for innovative training experiences to support school-community interagency collaboration.

Developing a Culturally Sensitive ICF-Based Tool to Describe Functioning of Children with Autism Spectrum Disorder: TEA-CIFunciona Version 1.0 Pilot Study.

Background: Autism spectrum disorder (ASD) affects the daily functioning of children and their families; however, in Argentina, there are no standardized tools to guide the description, evaluation, and follow-up of functioning and disability of children with ASD. To fill this gap, the overarching purpose of this study was to create a novel tool guided by the International Classification of Functioning, Disability, and Health (ICF) Core Sets for ASD for clinical practice. Methods: A multistep methodology was used to identify the most relevant ICF categories for an Argentinian clinical setting. The content of this ICF-based shortlist was piloted and revised according to the results. Subsequently, a toolbox of measures was proposed to operationalize each ICF category. Finally, profiles of the functioning of 100 children with ASD were created. Results: An ICF-based tool called TEA-CIFunciona was created, consisting of 32 ICF categories (10 body functions, 15 activities and participation, 7 environmental factors categories). The application of TEA-CIFunciona incorporated a family-centered approach in ASD evaluations and helped identify functional needs. Conclusions: TEA-CIFunciona is the first ICF-based instrument that guides the description of functioning of children with ASD in Argentina. TEA-CIFunciona standardizes collaborative assessments in pediatric ASD populations in Latin American contexts.

A Taxonomy of Reported Harms in Pediatric Autism Spectrum Disorder Screening: Provider and Parent Perspectives.

The U.S. Preventive Services Task Force (USPSTF) report on screening for Autism Spectrum Disorder (ASD) highlighted the need for research that examines the harms potentially associated with screening so as to assess the overall net benefit of universal screening. In response, this study engages qualitative, semi-structured interviews to generate a taxonomy outlining potential harms reported by parents and providers (pediatricians and Early Intervention providers) with experience in screening young children for ASD. Potential harms emerged including: physical, psychological, social, logistical/financial, opportunity cost, attrition, and exacerbation of non-targeted disparities. Respondents reported harms being experienced by the toddlers, parents, and providers. The harms reported highlight opportunities for providers to offer resources that mitigate the potential for these unintended consequences.

Healthcare Costs of Pediatric Autism Spectrum Disorder in the United States, 2003-2015.

Published healthcare cost estimates for children with autism spectrum disorder (ASD) vary widely. One possible contributor is different methods of case ascertainment. In this study, ASD case status was determined using two sources of parent reports among 45,944 children ages 3-17years in the Medical Expenditure Panel Survey (MEPS) linked to the National Health Interview Survey (NHIS) Sample Child Core questionnaire. In a two-part regression model, the incremental annual per-child cost of ASD relative to no ASD diagnosis was $3930 (2018 US dollars) using ASD case status from the NHIS Child Core and $5621 using current-year ASD case status from MEPS. Both estimates are lower than some published estimates but still represent substantial costs to the US healthcare system.