Pediatric Autism Spectrum Disorder Research Articles

Primary care of children with autism spectrum disorder: Applying evidence-based interventions.

Pediatric autism spectrum disorder (ASD) consists of multisystem components that primary care providers (PCPs) must address. PCPs improve health outcomes associated with ASD when they administer developmental screening tools and thoroughly assess identified concerns. Pursuing specialty health services early in childhood combined with managing comorbid conditions curtails symptom escalation and disease progression.

Primary care of children with autism spectrum disorders: Developing confident healthcare leaders.

This series of articles aims to equip primary care providers (PCPs) with the tools to become healthcare leaders managing patients with pediatric autism spectrum disorder (ASD). Individuals with ASD can experience optimal health outcomes when timely, evidence-based interventions are implemented in the primary care setting. PCPs are uniquely situated to institute changes that redirect the trajectory of ASD.

Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder

Autism spectrum disorder (ASD) is a brain disorder characterized by social impairments. ASD is currently diagnosed on the basis of behavioral criteria because no robust biomarkers have been identified. However, we recently found that cerebrospinal fluid (CSF) concentration of the "social" neuropeptide arginine vasopressin (AVP) is significantly lower in pediatric ASD cases vs. controls. As an initial step in establishing the direction of causation for this association, we capitalized upon a rare biomaterials collection of newborn CSF samples to conduct a quasi-prospective test of whether this association held before the developmental period when ASD first manifests. CSF samples had been collected in the course of medical care of 0- to 3-mo-old febrile infants (n = 913) and subsequently archived at -70 °C. We identified a subset of CSF samples from individuals later diagnosed with ASD, matched them 1:2 with appropriate controls (n = 33 total), and quantified their AVP and oxytocin (OXT) concentrations. Neonatal CSF AVP concentrations were significantly lower among ASD cases than controls and individually predicted case status, with highest precision when cases with comorbid attention-deficit/hyperactivity disorder were removed from the analysis. The associations were specific to AVP, as ASD cases and controls did not differ in neonatal CSF concentrations of the structurally related neuropeptide, OXT. These preliminary findings suggest that a neurochemical marker of ASD may be present very early in life, and if replicated in a larger, prospective study, this approach could transform how ASD is detected, both in behaviorally symptomatic children, and in infants at risk for developing it.

Identification of Pediatric Autism Spectrum Disorder Cases Using Health Administrative Data.

Administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases in epidemiological studies. However, validation studies on this mode of case ascertainment have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We report on the diagnostic accuracy of using readily available health administrative data for pediatric ASD case ascertainment. The validation cohort included almost all the ASD-positive children born in British Columbia, Canada from April 1, 2000 to December 31, 2009 and consisted of 8,670 children in total. 4,079 ASD-positive and 2,787 ASD-negative children were identified using Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) assessments done through the British Columbia Autism Assessment Network (BCAAN). An additional 1,804 ADOS/ADI-R assessed ASD-positive children were identified using Ministry of Education records. This prospectively collected clinical data (the diagnostic gold standard) was then linked to each child's physician billing and hospital discharge data. The diagnostic accuracy of 11 algorithms that used the administrative data to assign ASD case status was assessed. For all algorithms, high positive predictive values (PPVs) were observed alongside low values for other measures of diagnostic accuracy illustrating that PPVs alone are not an adequate measure of diagnostic accuracy. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders. Utilizing these data may result in misclassification bias. Methodologically sound, region-specific validation studies are needed to support the use of administrative data for ASD case ascertainment. Autism Res 2020, 13: 456-463. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Health administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases for research purposes. However, previous validation studies on this sort of case identification have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders.

Dietary and Supplement-Based Complementary and Alternative Medicine Use in Pediatric Autism Spectrum Disorder

Previous literature has shown that complementary and alternative medicine (CAM) is steadily increasing in autism spectrum disorder (ASD). However, little data is currently available regarding its use, safety, and efficacy in children with ASD. Thus, the purpose of this study is to describe the use of supplement-based CAM therapies in children between the ages of 4 to 17 years with ASD. This population-based, cross-sectional study evaluated children with ASD regarding supplement use. A total of 210 participants were recruited from a variety of sources including educational and physical activity programs, and social media to complete a questionnaire. Primary caregivers provided information on current supplement based CAM use. Data evaluated the proportion of children that used supplement therapies, the types of supplements used, reasons for use, perceived safety, and demographic factors associated with use (e.g., income, parental education, severity of disorder). Seventy-five percent of children with ASD consumed supplements with multivitamins (77.8%), vitamin D (44.9%), omega 3 (42.5%), probiotics (36.5%), and magnesium (28.1%) as the most prevalent. Several supplements, such as adrenal cortex extract, where product safety has not yet been demonstrated, were also reported. A gluten free diet was the most common specialty diet followed amongst those with restrictions (14.8%). Health care professionals were the most frequent information source regarding supplements; however, 33% of parents reported not disclosing all their child’s supplements to their physician. In conclusion, the use of supplement therapies in children with ASD is endemic and highlights the need for further research concerning public health education surrounding safety and efficacy.

Reduced prefrontal hemodynamic response in pediatric autism spectrum disorder measured with near-infrared spectroscopy

BackgroundFunctional neuroimaging studies suggest that prefrontal cortex dysfunction is present in people with autism spectrum disorder (ASD). Near-infrared spectroscopy is a noninvasive optical tool for examining oxygenation and hemodynamic changes in the cerebral cortex by measuring changes in oxygenated hemoglobin.MethodsTwelve drug-naïve male participants, aged 7–15 years and diagnosed with ASD according to DSM-5 criteria, and 12 age- and intelligence quotient (IQ)-matched healthy control males participated in the present study after giving informed consent. Relative concentrations of oxyhemoglobin were measured with frontal probes every 0.1 s during the Stroop color-word task, using 24-channel near-infrared spectroscopy.ResultsOxyhemoglobin changes during the Stroop color-word task in the ASD group were significantly smaller than those in the control group at channels 12 and 13, located over the dorsolateral prefrontal cortex (FDR-corrected P: 0.0021–0.0063).ConclusionThe results suggest that male children with ASD have reduced prefrontal hemodynamic responses, measured with near-infrared spectroscopy.

217. The Role of the Microbiome in Complex Phenotypes of Pediatric Autism Spectrum Disorder

217. The Role of the Microbiome in Complex Phenotypes of Pediatric Autism Spectrum Disorder

Atypical Antipsychotics for Irritability in Pediatric Autism: A Systematic Review and Network Meta-Analysis.

Irritability is common in pediatric autism spectrum disorder (ASD) patients. This can have major implications in child development, receptivity to behavioral therapy, as well as child and caregiver well-being. A systematic review and network meta-analysis were conducted to assess the efficacy and safety of atypical antipsychotics in treating irritability in these patients. Studies were identified from Medline, Embase, and PsycINFO from inception to March 2018. The clinical trials database was reviewed. Studies were included if they were a double-blind, randomized controlled trial utilizing the Aberrant Behavior Checklist Irritability (ABC-I) to measure the efficacy of atypical antipsychotic monotherapy. Data extraction was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-analyses for network meta-analysis guidelines. The main outcome was the reduction in irritability score using the ABC-I subscale from baseline. Eight trials comparing four interventions-risperidone, aripiprazole, lurasidone, and placebo in 878 patients, were included. Both risperidone and aripiprazole had significantly reduced ABC-I scores than placebo. Estimates of mean differences (95% credible intervals) were risperidone, -6.89 (-11.14, -2.54); aripiprazole, -6.62 (-10.88, -2.22); and lurasidone, -1.61 (-9.50, 6.23). Both risperidone and aripiprazole had similar safety. There were only eight studies included in the analysis, however, sample sizes were not small. Variance in reporting of adverse effects limited the quality of safety analysis. Risperidone and aripiprazole were the two best drugs, with comparable efficacy and safety in pediatric ASD patients. These two medications could be beneficial in improving irritability in these patients.

Closing Gaps in Nutrition Care: Continuing Education in Pediatric Autism Spectrum Disorder for Registered Dietitians in North Carolina

Closing Gaps in Nutrition Care: Continuing Education in Pediatric Autism Spectrum Disorder for Registered Dietitians in North Carolina

Presentation and Correlates of Hoarding Behaviors in Children with Autism Spectrum Disorders and Comorbid Anxiety or Obsessive-Compulsive Symptoms.

We investigated the presentation and correlates of hoarding behaviors in 204 children aged 7-13 with autism spectrum disorder (ASD) and comorbid anxiety or obsessive-compulsive disorder (OCD) symptoms. Approximately 34% of the sample presented at least moderate levels, and with 7% presenting severe to extreme levels of hoarding. Child gender predicted hoarding severity. In addition, child ASD-related social difficulties together with attention-deficit and hyperactivity disorder symptom severity positively predicted hoarding controlling for child gender and restricted and repetitive behaviors. Finally, child anxiety/OCD symptoms positively predicted hoarding, controlling for all other factors. These results suggest hoarding behaviors may constitute a common feature of pediatric ASD with comorbid anxiety/OCD, particularly in girls and children with greater social difficulties and comorbid psychiatric symptom severity.

Kynurenine Pathway in Autism Spectrum Disorders in Children

Background: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. Methods: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. Results: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 μM, p = 0.020). Conclusion: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD.

Counseling the increased risk of epilepsy in Pediatric autism spectrum disorder

Counseling the increased risk of epilepsy in Pediatric autism spectrum disorder

The Efficacy and Safety of Acupuncture for the Treatment of Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

Objectives. We aimed to summarize and critically evaluate the available evidence regarding the efficacy and safety of acupuncture for children with autism spectrum disorder (ASD). Methods. We searched 13 databases for studies published up to December 2016. Randomized controlled trials (RCTs) evaluating the efficacy of acupuncture for children with ASD were included. Outcome measures were the overall scores on scales evaluating the core symptoms of ASD and the scores for each symptom, such as social communication ability and skills, stereotypies, language ability, and cognitive function. Effect sizes were presented as mean differences (MD). Results. Twenty-seven RCTs with 1736 participants were included. Acupuncture complementary to behavioral and educational intervention significantly decreased the overall scores on the Childhood Autism Rating Scale (CARS) (MD −8.10, 95% CI −12.80 to −3.40) and the Autism Behavior Checklist (MD −8.92, 95% CI −11.29 to −6.54); however, it was unclear which of the ASD symptoms improved. Acupuncture as a monotherapy also reduced the overall CARS score. The reported adverse events were acceptable. Conclusions. This review suggests that acupuncture may be effective and safe for pediatric ASD. However, it is not conclusive due to the heterogeneity of the acupuncture treatment methods used in the studies.

Extracting autism spectrum disorder data from the electronic health record.

Little is known about the health care utilization patterns of individuals with pediatric autism spectrum disorder (ASD). Electronic health record (EHR) data provide an opportunity to study medical utilization and track outcomes among children with ASD. Methods: Using a pediatric, tertiary, academic hospital's Epic EHR, search queries were built to identify individuals aged 2-18 with International Classification of Diseases, Ninth Revision (ICD-9) codes, 299.00, 299.10, and 299.80 in their records. Codes were entered in the EHR using four different workflows: (1) during an ambulatory visit, (2) abstracted by Health Information Management (HIM) for an encounter, (3) recorded on the patient problem list, or (4) added as a chief complaint during an Emergency Department visit. Once individuals were identified, demographics, scheduling, procedures, and prescribed medications were extracted for all patient-related encounters for the period October 2010 through September 2012. There were 100,000 encounters for more than 4,800 unique individuals.Individuals were most frequently identified with an HIM abstracted code (82.6%) and least likely to be identified by a chief complaint (45.8%).Categorical frequency for reported race (2 = 816.5, p < 0.001); payor type (2 = 354.1, p < 0.001); encounter type (2 = 1497.0, p < 0.001); and department (2 = 3722.8, p < 0.001) differed by search query. Challenges encountered included, locating available discrete data elements and missing data. This study identifies challenges inherent in designing inclusive algorithms for identifying individuals with ASD and demonstrates the utility of employing multiple extractions to improve the completeness and quality of EHR data when conducting research.

Gray matter abnormalities in pediatric autism spectrum disorder: a meta-analysis with signed differential mapping.

The gray matter abnormalities revealed by magnetic resonance imaging are inconsistent, especially in pediatric individuals with autism spectrum disorder (ASD) (age<18years old), a phenomenon possibly related to the core pathophysiology of ASD. The purpose of our meta-analysis was to identify and map the specific gray matter abnormalities in pediatric ASD individuals thereby exploring the potential effects of clinical and demographic characteristics of these gray matter changes. A systematic search was conducted to identify voxel-based morphometry studies in pediatric individuals with ASD. The effect-size signed differential mapping method was used to quantitatively estimate the regional gray matter abnormalities in pediatric ASD individuals. Meta-regression was used to examine the associations among age, gender, intelligence quotient, symptom severity and gray matter changes. Fifteen studies including 364 pediatric individuals with ASD (male=282, age=10.3±4.4years) and 377 healthy controls (male=289, age=10.5±4.2years) were included. Pediatric ASD individuals showed significant gray matter increases in the right angular gyrus, left superior and middle frontal gyrus, left precuneus, left inferior occipital gyrus and right inferior temporal gyrus, most of which involving the default mode network, and decreases in the left cerebellum and left postcentral gyrus. The meta-regression analysis showed that the repetitive behavior scores of the Autism Diagnostic Interview-Revised were positively associated with increased gray matter volumes in the right angular gyrus. Increased rather than decreased gray matter volume, especially involving the angular gyrus and prefrontal cortex may be the core pathophysiology in the early course of ASD.

Exploring the Interaction of Motor and Social Skills With Autism Severity Using the SFARI Dataset.

Social communicative deficits and stereotyped or repetitive interests or behaviors are the defining features of autism spectrum disorder (ASD). A growing body of research suggests that gross motor deficits are also present in most children with ASD. This study sought to understand how pediatric ASD severity is related to motor skills and social skills. A multivariate analysis of variance analysis of 483 children with autism ( N = 444) and ASD ( N = 39) revealed a nonsignificant difference between groups. Results suggest little difference between severity groups on gross motor and social skills within the limited age range of the participants (about 5.6 years of age).

Effect of Bilingualism in the Anterior Cingulate Cortex: A Proton Magnetic Resonance Spectroscopy Study in Two Centres

Effect of Bilingualism in the Anterior Cingulate Cortex: A Proton Magnetic Resonance Spectroscopy Study in Two Centres

ADHD severity as it relates to comorbid psychiatric symptomatology in children with Autism Spectrum Disorders (ASD)

Comorbid diagnoses identified in pediatric samples have been correlated with a range of outcomes, including greater levels of emotional, behavioral, and educational impairment and the need for more intensive treatment. Given that previous research has documented high levels of comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) in children with Autism Spectrum Disorders (ASD), this study closely examines the relationship between parent-reported ADHD symptoms (i.e., Conners' Parent Rating Scale, Revised [CPRS-R]) and the prevalence of additional comorbid psychiatric diagnoses in a pediatric ASD sample (n=99). Regression analyses revealed that greater severity of ADHD symptomatology was significantly related to a greater number of comorbid psychiatric diagnoses, as identified using the Diagnostic Interview for Children and adolescents, 4th Edition (DICA-IV). Additionally, more severe ADHD symptoms were also associated with higher levels of symptom severity on Child Behavior Checklist (CBCL) syndrome subscales. Interestingly, increasing severity of ASD symptomatology, as measured by the Autism Diagnostic Interview, Revised (ADI-R), was not associated with a higher prevalence of comorbid psychiatric diagnoses or CBCL syndrome severity. Our study concluded that higher levels of ADHD severity—not ASD severity—were associated with a higher prevalence of comorbid psychiatric symptomatology in school-age children with ASD. These findings may encourage clinicians to thoroughly assess ADHD symptomatology in ASD children to better inform treatment planning.

Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms.

Pediatric traumatic brain injury (TBI) and autism spectrum disorder (ASD) are two serious conditions that affect youth. Recent data, both preclinical and clinical, show that pediatric TBI and ASD share not only similar symptoms but also some of the same biologic mechanisms that cause these symptoms. Prominent symptoms for both disorders include gastrointestinal problems, learning difficulties, seizures, and sensory processing disruption. In this review, we highlight some of these shared mechanisms in order to discuss potential treatment options that might be applied for each condition. We discuss potential therapeutic and pharmacologic options as well as potential novel drug targets. Furthermore, we highlight advances in understanding of brain circuitry that is being propelled by improved imaging modalities. Going forward, advanced imaging will help in diagnosis and treatment planning strategies for pediatric patients. Lessons from each field can be applied to design better and more rigorous trials that can be used to improve guidelines for pediatric patients suffering from TBI or ASD.

In The News: A roundup of news and information from our community

In <i>The</i> News: A roundup of news and information from our community