Daniel L. Coury

Gastrointestinal Conditions in Children With Autism Spectrum Disorder: Developing a Research Agenda

* Abbreviations: ASD — : autism spectrum disorder GI — : gastrointestinal 5-HT — : serotonin Autism spectrum disorders (ASDs) are a set of complex neurodevelopmental disorders defined behaviorally by impaired social interaction, delayed and disordered language, repetitive or stereotypic behavior, and a restricted range of interests. ASDs represent a significant public health issue with recent estimates indicating that as many as 1% of children in the United States are diagnosed with an ASD.1,2 Many individuals with ASDs have symptoms of associated medical conditions, including seizures, sleep problems, metabolic conditions, and gastrointestinal (GI) disorders, which have significant health, developmental, social, and educational impacts. Gastrointestinal complaints are a commonly reported concern for parents and may be related to problem behaviors and other medical issues such as dysregulated sleep (ATN Annual Registry Report, unpublished data, November 2009).3 Despite the magnitude of these issues, potential GI problems are not routinely considered in ASD evaluations. This likely reflects several factors, including variability in reported rates of GI disorders, controversies regarding the relationship between GI symptoms and the putative causes of autism, the limited verbal capacity of many ASD patients, and the lack of recognition by clinicians that certain behavioral manifestations in children with ASDs are indicators of GI problems (eg, pain, discomfort, or nausea).4–10 Whether GI issues in this population are directly related to the pathophysiology of autism, or are strictly a comorbid condition of ASD remains to be determined, but clinical practice and research to date indicate the important role of GI conditions in ASDs and their impact on children as well as their parents and clinicians.9 On November 15, 2009, a symposium addressing these issues was organized as an adjunct to the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. A … Address correspondence to Daniel L. Coury, MD, Professor of Pediatrics and Psychiatry, The Ohio State University, Chief, Developmental & Behavioral Pediatrics, Nationwide Childrens Hospital, 700 Childrens Dr, Timken G-350, Columbus OH 43205-2696

Use of Psychotropic Medication in Children and Adolescents With Autism Spectrum Disorders

OBJECTIVES: The goal of this study was to examine rates of psychotropic medication use and identify associated child and family characteristics among children and adolescents with autism spectrum disorder (ASD) enrolled in an autism registry maintained by the Autism Treatment Network (ATN). METHODS: The sample, derived from the ATN registry, consists of 2853 children aged 2 to 17 years with diagnoses of ASD supported by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the Autism Diagnostic Observation Schedule with available data on medication use. As part of initial enrollment in the registry, parents completed questionnaires on current psychotropic medication use, psychiatric and medical conditions, and demographics. RESULTS: Of the 2853 children, 763 (27%) were taking ≥1 psychotropic medication; 15% were prescribed 1 medication, 7.4% received 2 medications, and 4.5% received ≥3. Among children aged 3 to 5 years, 11% were taking ≥1 psychotropic medication; among 6-to 11-year-old children, 46%; and 66% of adolescents aged 12 to 17 years were taking at ≥1 psychotropic medication. A parent report of comorbid diagnosis of attention-deficit/hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder, depression, or anxiety was associated with a high rate of use, with 80% receiving ≥1 psychotropic medication. Only 15% of children with no comorbid psychiatric disorder were taking psychotropic medication. Psychotropic medication use was also related to sleep and gastrointestinal problems. CONCLUSIONS: The prescription of psychotropic medications in this registry sample is highly related to comorbid psychiatric disorder. Other factors associated with use include medical comorbidities, race, ethnicity, and older age. Pediatrics 2012;130:S69—S76.

A practice pathway for the identification, evaluation, and management of insomnia in children and adolescents with autism spectrum disorders

OBJECTIVE This report describes the development of a practice pathway for the identification, evaluation, and management of insomnia in children and adolescents who have autism spectrum disorders (ASDs). METHODS The Sleep Committee of the Autism Treatment Network (ATN) developed a practice pathway, based on expert consensus, to capture best practices for an overarching approach to insomnia by a general pediatrician, primary care provider, or autism medical specialist, including identification, evaluation, and management. A field test at 4 ATN sites was used to evaluate the pathway. In addition, a systematic literature review and grading of evidence provided data regarding treatments of insomnia in children who have neurodevelopmental disabilities. RESULTS The literature review revealed that current treatments for insomnia in children who have ASD show promise for behavioral/educational interventions and melatonin trials. However, there is a paucity of evidence, supporting the need for additional research. Consensus among the ATN sleep medicine committee experts included: (1) all children who have ASD should be screened for insomnia; (2) screening should be done for potential contributing factors, including other medical problems; (3) the need for therapeutic intervention should be determined; (4) therapeutic interventions should begin with parent education in the use of behavioral approaches as a first-line approach; (5) pharmacologic therapy may be indicated in certain situations; and (6) there should be follow-up after any intervention to evaluate effectiveness and tolerance of the therapy. Field testing of the practice pathway by autism medical specialists allowed for refinement of the practice pathway. CONCLUSIONS The insomnia practice pathway may help health care providers to identify and manage insomnia symptoms in children and adolescents who have ASD. It may also provide a framework to evaluate the impact of contributing factors on insomnia and to test the effectiveness of nonpharmacologic and pharmacologic treatment strategies for the nighttime symptoms and daytime functioning and quality of life in ASD.

Complementary and Alternative Medicine Use in a Large Pediatric Autism Sample

BACKGROUND AND OBJECTIVE Children and adolescents with autism spectrum disorder (ASD) often use complementary and alternative medicine (CAM), usually along with other medical care. This study aimed to determine associations of ASD diagnostic category, co-existing conditions, and use of medications with use of CAM. METHODS We used the Autism Speaks Autism Treatment Network patient registry, which collects information on CAM use, medical conditions, and psychotropic medication at enrollment. CAM was categorized as special diets versus “other” CAM; ASD was defined as autism, pervasive developmental disorder (PDD), or Asperger’s. Gastrointestinal symptoms, seizure disorders, sleep problems, and medication use were determined from parent report. Child Behavior Checklist (CBCL) scores were used to measure behavioral symptoms. Logistic regression was used to determine associations of diagnostic category, other medical conditions, and medication use with CAM treatments, controlling for demographic characteristics. RESULTS Of 3413 subjects in the registry as of April 2011, 3173 had complete data on CAM use: 896 (28%) reported any use; 548 (17%), special diets; and 643 (20%), other CAM. Higher rates of CAM use were associated with gastrointestinal symptoms (odds ratio [OR] = 1.88), seizures (OR = 1.58), and CBCL total score >70 (OR = 1.29). Children with PDD (OR = 0.62), Asperger’s (OR = 0.66), or using medications (0.69) had lower rates. CONCLUSIONS Children with ASD use more CAM when they have co-existing gastrointestinal symptoms, seizure disorders, and behavior problems. This study suggests the importance of asking about CAM use in children with ASD, especially those with complex symptoms.

Attention-Deficit/Hyperactivity Disorder Symptoms, Adaptive Functioning, and Quality of Life in Children With Autism Spectrum Disorder

OBJECTIVE The purpose of the current study was to evaluate the frequency of co-occurring attention-deficit/hyperactivity disorder (ADHD) symptoms in a well-defined cohort of children with autism spectrum disorders (ASDs) and to examine the relationship between ADHD symptoms and both adaptive functioning and health-related quality of life as reported by parents or other primary caregivers. METHODS T scores on 2 ADHD-related scales from the Child Behavior Checklist were used to indicate the presence of ADHD symptoms. Participants were divided into groups based on whether their parents/caregivers rated them as having clinically significant T scores on the Attention Problem and Attention Deficit Hyperactivity Problem subscales. Standard scores from the Vineland Adaptive Behavior Scales, Second Edition and raw scores from the Pediatric Quality of Life Inventory were then compared between groups with the use of multivariate analyses. RESULTS Approximately 40% of participants had 1 elevated T score, and 19% had both ADHD-related T scores elevated on the Child Behavior Checklist. The ASD + ADHD group had lower scores on the Vineland Adaptive Behavior Scales, Second Edition and the Pediatric Quality of Life Inventory in comparison with the ASD alone group. CONCLUSIONS Results suggest greater impairment in adaptive functioning and a poorer health-related quality of life for children with ASDs and clinically significant ADHD symptoms in comparison with children with ASDs and fewer ADHD symptoms. Physicians are encouraged to evaluate for the presence of ADHD symptoms in their patients with ASDs and, if present, include symptom treatment in the overall care plan.

Healthcare for children with autism: the Autism Treatment Network.

Purpose of review Autism spectrum disorders (ASDs) are a group of a neurodevelopmental disorders affecting social, communicative, and behavioral functioning. ASD is a heterogeneous group of disorders, often accompanied by associated medical issues. Thus, the development of effective treatments is a complex task requiring consideration of diverse etiologic and phenotypic characteristics. Recent attention to the diagnosis and treatment of medical conditions in ASD children has led to the formation of a new international collaboration to improve autism care, the Autism Treatment Network (ATN). Recent findings Numerous studies have highlighted the high prevalence of gastrointestinal and sleep disorders among ASD children. Problems in communication – including being nonverbal – make the diagnosis and treatment of these conditions more difficult. Although a number of studies suggest links between neurologic impairments and gastrointestinal dysfunction and disordered sleep, these relationships remain unproven. Recent work by the ATN has begun the development of clinical guidelines in these areas, based on clinical consensus, adapting the model developed by the Cystic Fibrosis Foundation. New funding has also supported the networks development of a robust clinical research program focused on improving the physical health and care of children with ASD. These efforts promise more systematic and consistent approaches to diagnosis and treatment of these conditions. Summary Improved understanding of the underlying pathology of ASD and associated conditions, and the development of a common purpose across multiple treating sites, can improve the consistent and coordinated healthcare of children with autism.

Motor adaptation in children with myelomeningocele: Comparison to children with ADHD and healthy siblings

Myelomeningocele is a common developmental malformation of the central nervous system that usually results in motor deficits. Previous studies of myelomeningocele have not examined motor adaptation, which involves changes in the control of movements that occur as a result of repeated task exposure but do not depend on conscious recall of the exposure. We studied motor adaptation in 17 children with myelomeningocele and shunted hydrocephalus, 19 children with attention deficit/hyperactivity disorder (ADHD), and 20 healthy siblings. All children were 8 to 15 years of age. They were administered 2 measures of motor adaptation known to be sensitive to subcortical abnormalities in adult neurological disorders. One task assessed the biasing in weight judgments that occurs after exposure to heavy versus light weights, and the other assessed the adaptation in reaching movements that occurs when vision is laterally displaced by prisms. Contrary to expectations, the groups did not differ in motor adaptation. Children in all 3 groups displayed significant biasing in their weight judgments and improvement in the accuracy of pointing during prism adaptation trials. Performance on the 2 motor adaptation tasks was not related to age or IQ. Weight biasing was positively related to a measure of response disinhibition. The findings suggest that myelomeningocele does not result in global impairment of motor skills, but instead in a profile of intact and impaired motor functions that potentially may be decomposed in accordance with the neuroscience of motor skills.

Management of Constipation in Children and Adolescents With Autism Spectrum Disorders

OBJECTIVES To develop a practical, readily applied algorithm for primary health care providers to identify, evaluate, and manage constipation in children with autism spectrum disorders (ASDs). METHODS The Gastroenterology Committee of the Autism Speaks Autism Treatment Network (ATN), a multisite consortium of centers dedicated to improving standards of medical care for children with ASDs, guided the development of the constipation algorithm through expert opinion and literature review. The algorithm was finalized based on results of field testing by nongastrointestinal, ATN autism medical specialists at 4 ATN sites. A systematic review and grading of the literature pertaining to constipation and children with ASDs was also performed. RESULTS Consensus among the ATN Gastroenterology Committee identified that in children with ASDs, (1) subtle or atypical symptoms might indicate the presence of constipation; (2) screening, identification, and treatment through a deliberate approach for underlying causes of constipation is appropriate; (3) diagnostic-therapeutic intervention can be provided when constipation is documented; and (4) careful follow-up after any intervention be performed to evaluate effectiveness and tolerance of the therapy. Literature review revealed limited evidence for the clinical evaluation or treatment strategies of children with ASD and constipation. CONCLUSIONS Constipation and its underlying etiology have the potential to be effectively identified and managed using a systematic approach. Lack of evidence on this topic in the literature emphasizes the need for research.

Resident Training in Developmental/Behavioral Pediatrics: Where Do We Stand?

Approximately 25% to 30% of all complaints to a general pediatrician are developmental or behavioral in origin. Despite this, residency education in developmental/behavioral pediatrics has consistently been rated poorly. Changes were set forth in 1997 to include a mandatory 1-month block rotation in developmental/behavioral pediatrics. This study was a nationwide, cross-sectional, self-administered, mailed survey of pediatricians who completed residency either before or after these changes went into effect. Overall, pediatricians’ comfort level in developmental/behavioral pediatrics was unchanged in the 2 groups. Certain areas (behavior problems, learning disabilities, sleep, and depression/anxiety) of developmental/behavioral pediatrics had lower comfort scores. Our data provide direction for the ongoing refinement of pediatric education that is based on feedback from currently practicing pediatricians.

Safety and immunogenicity of a measles, mumps, rubella and varicella vaccine given with combined Haemophilus influenzae type b conjugate/hepatitis B vaccines and combined diphtheria-tetanus-acellular pertussis vaccines.

Background: A study was conducted to assess administration of a combination measles, mumps, rubella and varicella vaccine (MMRV) with other childhood vaccines. Methods: In this open, multicenter trial, 1915 healthy children ages 12–15 months were randomized into 3 groups: group 1, MMRV, combined Haemophilus influenzae type b conjugate-hepatitis B vaccines (Hib/HepB) and combined diphtheria-tetanus-acellular pertussis vaccines (DTaP) concomitantly; group 2, MMRV followed by Hib/HepB and DTaP 42 days later; group 3, MMR and varicella vaccine followed by Hib/HepB and DTaP 42 days later. Results: Antibody responses to measles, mumps, rubella, varicella, Hib, HepB, diphtheria and tetanus were similar between groups 1 and 2 (all >95%, except varicella, 89.7% in group 1 and 90.9% in group 2). Pertussis toxin and filamentous hemagglutinin responses were significantly lower in group 1 than in group 2 (group 1, 74.1 and 67.1%; group 2, 90.4 and 86.8%, respectively). An exploratory analysis suggested that the difference in and pertussis toxin and filamentous hemagglutinin responses was likely the result of study design rather than interference among vaccine components because the groups differed in age of receipt of DTaP (group 1, ∼12 months; group 2, ∼13.5 months). When the groups were matched for age, sample size was sufficient for comparison only in children ≥13.5 months old. Pertussis toxin and filamentous hemagglutinin responses were similar in these children. The safety profiles for each vaccination regimen were comparable. Conclusions: The immunogenicity data support concomitant administration of MMRV with Hib/HepB. Limited data from an exploratory analysis indicate that MMRV can be administered concomitantly with DTaP. Concomitant administration of MMRV, Hib/HepB and DTaP is well-tolerated.