Autism Treatment Network Research Articles

Pattern of Diagnosis and Co-occurring Symptoms in Adopted Children With Autism Spectrum Disorder.

To determine whether adopted children with autism spectrum disorder (ASD) differ from the general ASD population in terms of diagnosis, internalizing and externalizing behaviors, sleep problems, and medications. We studied 163 adoptees in the Autism Speaks Autism Treatment Network (ATN) in comparison with 5624 nonadopted ATN participants (aged 1.5-17.6 years; mean [SD] = 6.2 [3.4] years). Gender, age, race, ethnicity, IQ, and categorical Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ASD diagnosis were tested for differences by group (adopted versus nonadopted) by using independent-samples t tests for continuous variables and Fisher's exact tests for categorical variables. Logistic or linear regression models were used to examine the association between adoption status and several outcome variables, after controlling for covariates. After controlling for demographics and diagnosis, there were significant differences in group characteristics, including greater propensity for externalizing behavior (P < .001), internalizing behavior (P = .001), and sleep problems (P < .001) in the adopted population. Adoptees were also prescribed psychotropic medications (P < .001) more often than the nonadoptees. Adoptees received a diagnosis of pervasive developmental disorder-not otherwise specified significantly more frequently than controls (odds ratio = 1.8; CI = 1.3-2.5; P < .001), despite no significant difference in symptoms on standardized measures. These results suggest that the population of adopted children with ASD differs from the general ASD population both with regard to diagnostic subtype and co-occurring behavioral problems. Future research should evaluate the contributions of specific factors associated with adoption such as biological family history, pregnancy history, early childhood experience, and age at adoption.

Sleep Difficulties and Medications in Children With Autism Spectrum Disorders: A Registry Study

Sleep difficulties are common in children with autism spectrum disorders, with wide-ranging effects on the child's daytime behavior. We reviewed data within our Autism Speaks Autism Treatment Network Registry to determine the prevalence of sleep difficulties and patterns of medication use. Data from 1518 children ages 4 to 10 years were analyzed to determine the number of children documented to have sleep difficulties by parent-completed questionnaires and clinician-completed forms and how these findings related to the use of sleep medications. The Children's Sleep Habits Questionnaire total score was ≥41 (associated with clinically significant sleep problems in past research) in 71% of children. The prevalence of sleep diagnoses was less frequent (30% of children aged 4-10 years; P < .0001). Medications for sleep were prescribed in 46% of 4- to 10-year-olds given a sleep diagnosis. The most common medication used for sleep was melatonin followed by α-agonists, with a variety of other medications taken for sleep (anticonvulsants, antidepressants, atypical antipsychotics, and benzodiazepines). Children taking medications for sleep had worse daytime behavior and pediatric quality of life than children not taking sleep medications. Parent concerns about sleep may not be reflected in the information gathered during a clinic visit, supporting the need to develop screening practice pathways for sleep in autism spectrum disorders. Furthermore, many medications taken for sleep have adverse effects, supporting the need for evidence-based interventions in this population.

Irritability and Problem Behavior in Autism Spectrum Disorder: A Practice Pathway for Pediatric Primary Care.

Pediatric primary care providers (PCPs) caring for patients with autism spectrum disorder (ASD) often encounter irritability (vocal or motoric outbursts expressive of anger, frustration, or distress) and problem behavior (directed acts of aggression toward other people, self, or property). The Autism Intervention Research Network on Physical Health and Autism Speaks Autism Treatment Network charged a multidisciplinary workgroup with developing a practice pathway to assist PCPs in the evaluation and treatment of irritability and problem behavior (I/PB). The workgroup reviewed the literature on the evaluation and treatment of contributory factors for I/PB in ASD. The workgroup then achieved consensus on the content and sequence of each step in the pathway. The practice pathway is designed to help the PCP generate individualized treatment plans based on contributing factors identified in each patient. These factors may include medical conditions, which the PCP is in a key position to address; functional communication challenges that can be addressed at school or at home; psychosocial stressors that may be ameliorated; inadvertent reinforcement of I/PB; and co-occurring psychiatric conditions that can be treated. The pathway provides guidance on psychotropic medication use, when indicated, within an individualized treatment plan. In addition to guidance on assessment, referral, and initial treatment, the pathway includes monitoring of treatment response and periodic reassessment. The pediatric PCP caring for the patient with ASD is in a unique position to help generate an individualized treatment plan that targets factors contributing to I/PB and to implement this plan in collaboration with parents, schools, and other providers.

Obesity and Autism.

Overweight and obesity are increasingly prevalent in the general pediatric population. Evidence suggests that children with autism spectrum disorders (ASDs) may be at elevated risk for unhealthy weight. We identify the prevalence of overweight and obesity in a multisite clinical sample of children with ASDs and explore concurrent associations with variables identified as risk factors for unhealthy weight in the general population. Participants were 5053 children with confirmed diagnosis of ASD in the Autism Speaks Autism Treatment Network. Measured values for weight and height were used to calculate BMI percentiles; Centers for Disease Control and Prevention criteria for BMI for gender and age were used to define overweight and obesity (≥85th and ≥95th percentiles, respectively). In children age 2 to 17 years, 33.6% were overweight and 18% were obese. Compared with a general US population sample, rates of unhealthy weight were significantly higher among children with ASDs ages 2 to 5 years and among those of non-Hispanic white origin. Multivariate analyses revealed that older age, Hispanic or Latino ethnicity, lower parent education levels, and sleep and affective problems were all significant predictors of obesity. Our results indicate that the prevalence of unhealthy weight is significantly greater among children with ASD compared with the general population, with differences present as early as ages 2 to 5 years. Because obesity is more prevalent among older children in the general population, these findings raise the question of whether there are different trajectories of weight gain among children with ASDs, possibly beginning in early childhood.

Female Autism Phenotypes Investigated at Different Levels of Language and Developmental Abilities.

This study investigated the differences in clinical symptoms between females and males with autism spectrum disorder (ASD) across three verbal ability groups (nonverbal, phrase and fluent speech), based on which Autism Diagnostic Observation Schedule module was administered to 5723 individuals in four research datasets. In the Simons Simplex Collection and Autism Treatment Network, females with ASD and phrase or fluent speech had lower cognitive, adaptive, and social abilities than males. In the Autism Genetics Resource Exchange and the Autism Consortium, females with phrase or fluent speech had similar or better adaptive and social abilities than males. Females who were nonverbal had similar cognitive, adaptive, and social abilities as males. Population-based longitudinal studies of verbally fluent females with ASD are needed.

Dietary Supplementation in Children with Autism Spectrum Disorders: Common, Insufficient, and Excessive

BackgroundLittle is known about the effect on dietary adequacy of supplements given to children with autism spectrum disorder (ASD). ObjectiveThis cross-sectional study examines dietary supplement use and micronutrient intake in children with ASD. DesignThree-day diet/supplement records and use of a gluten/casein-free diet (GFCF) were documented. Estimates of usual intake of micronutrients from food and supplements were compared with the Dietary Reference Intakes. ParticipantsChildren aged 2 to 11 years (N=288) with ASD from five Autism Treatment Network sites from 2009-2011. Main outcome measuresPercentage of children meeting or exceeding upper limits of micronutrient intake with or without supplements and relative to GFCF diet status. Statistical analysisMicronutrient intake from food and supplements was compared by Spearman rank correlation. Usual intake was estimated by the National Cancer Institute method adjusted for age, sex, supplement use, and GFCF diet. Adequacy of intake was compared between supplement use status and between food and total intake in supplement users relative to Dietary Reference Intakes limits. ResultsDietary supplements, especially multivitamin/minerals, were used by 56% of children with ASD. The most common micronutrient deficits were not corrected (vitamin D, calcium, potassium, pantothenic acid, and choline) by supplements. Almost one-third of children remained deficient for vitamin D and up to 54% for calcium. Children receiving GFCF diets had similar micronutrient intake but were more likely to use supplements (78% vs 56%; P=0.01). Supplementation led to excess vitamin A, folate, and zinc intake across the sample, vitamin C, and copper among children aged 2 to 3 years, and manganese and copper for children aged 4 to 8 years. ConclusionsFew children with ASD need most of the micronutrients they are commonly given as supplements, which often leads to excess intake. Even when supplements are used, careful attention should be given to adequacy of vitamin D and calcium intake.

Overweight and Obesity in a Sample of Children With Autism Spectrum Disorder

ObjectiveTo determine the prevalence of overweight/obese status in children with autism spectrum disorders (ASD), identify associated characteristics, and develop a model to predict weight status. MethodsThe prevalence of overweight and obesity was determined in 2769 children with ASD enrolled in the Autism Speaks Autism Treatment Network, a collaboration of 17 academic centers, and compared with a national sample matched for age, sex, and race. Associations in the ASD sample between weight status and demographic and clinical variables, such as age, race, head circumference, and adaptive functioning, were tested using ordinal logistic regression. The accuracy of a final model that predicted weight status based on early life variables was evaluated in a validation sample. ResultsThe prevalence of overweight and obesity were 33.9% and 18.2%, respectively; ASD was associated with a higher risk of obesity (but not overweight) relative to the national sample (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.05–1.28; P = .003). In the adjusted analysis, overweight/obese status was significantly associated with Hispanic ethnicity (OR, 1.99; 95% CI, 1.37–2.89), parental high school education (OR, 1.56; 95% CI, 1.09–2.21), high birth weight (OR, 1.56; 95% CI, 1.11–2.18), macrocephaly (OR, 4.01; 95% CI, 2.96–5.43), and increased somatic symptoms (OR, 1.41; 95% CI, 1.01–1.95). A prediction model designed to have high sensitivity predicted low risk of overweight/obesity accurately, but had low positive predictive value. ConclusionsThe prevalence of obesity in children with ASD was greater than a national sample. Independent associations with increased weight status included known risk factors and macrocephaly and increased level of somatic symptoms. A model based on early life variables accurately predicted low risk of overweight/obesity.

Sleep problems in children with autism spectrum disorder: examining the contributions of sensory over-responsivity and anxiety

ObjectivesChildren with autism spectrum disorder (ASD) are at high risk for sleep problems. Previous research suggests that sensory problems and anxiety may be related to the development and maintenance of sleep problems in children with ASD. However, the relationships among these co-occurring conditions have not been previously studied. The current study examined the interrelations of these symptoms in a large well-characterized sample of children and adolescents with ASD. MethodsThe current study examined the relationships among sleep problems, sensory over-responsivity, and anxiety in 1347 children enrolled in the Autism Speaks Autism Treatment Network. The primary measures included the Children's Sleep Habits Questionnaire, the Child Behavior Checklist, and the Short Sensory Profile. ResultsIn bivariate correlations and multivariate path analyses, anxiety was associated with all types of sleep problems (ie, bedtime resistance, sleep-onset delay, sleep duration, sleep anxiety, and night wakings; p < 0.01 to p < 0.001; small to medium effect sizes). Sensory over-responsivity (SOR) was correlated with all sleep problems in bivariate analyses (p < 0.01 to p < 0.001; small effect sizes). In multivariate path models, SOR remained significantly associated with all sleep problems except night awakenings for older children, while SOR was no longer significantly associated with bedtime resistance or sleep anxiety for younger children. ConclusionsChildren with ASD who have anxiety and SOR may be particularly predisposed to sleep problems. These findings suggest that some children with ASD and sleep disturbance may have difficulties with hyperarousal. Future research using physiological measures of arousal and objective measures of sleep are needed.

Age at first autism spectrum disorder diagnosis: the role of birth cohort, demographic factors, and clinical features.

This study sought to identify factors that may be associated with delays in autism spectrum disorder (ASD) diagnosis, including birth cohort, sociodemographic characteristics, and clinical features. Participants included 1716 children and adolescents with ASD enrolled in the Autism Speaks Autism Treatment Network (AS-ATN) between the years 2008 and 2011. Data were collected at enrollment using AS-ATN parent- and clinician-report forms and standardized measures of I.Q., ASD symptoms, adaptive function, and psychiatric symptoms. Age at first ASD diagnosis was positively correlated with current age, suggesting a birth cohort effect. Sociodemographic and clinical features were also associated with age at diagnosis, even after controlling for current age. Hierarchical linear regression results showed that older current age, lower socioeconomic status (SES), higher I.Q. score, and lower levels of autism symptoms were associated with later age at initial diagnosis. There was also a significant interaction between current age and I.Q., with higher functioning children being diagnosed at younger ages than in previous years. Early diagnosis of ASD is critically important for improving access to interventions; however, many children experience diagnostic delays. In this sample, children from the most recent birth cohorts were diagnosed earlier, suggesting that early signs of ASD are being increasingly recognized. However, socioeconomic barriers to diagnosis still seem to exist. Children with less severe ASD symptoms and with higher I.Q. are also diagnosed at later ages. Efforts are still needed to reduce diagnostic disparities for families of low SES and to improve early recognition of more subtle symptoms.

Predicting health utilities for children with autism spectrum disorders.

Comparative effectiveness of interventions for children with autism spectrum disorders (ASDs) that incorporates costs is lacking due to the scarcity of information on health utility scores or preference-weighted outcomes typically used for calculating quality-adjusted life years (QALYs). This study created algorithms for mapping clinical and behavioral measures for children with ASDs to health utility scores. The algorithms could be useful for estimating the value of different interventions and treatments used in the care of children with ASDs. Participants were recruited from two Autism Treatment Network sites. Health utility data based on the Health Utilities Index Mark 3 (HUI3) for the child were obtained from the primary caregiver (proxy-reported) through a survey (N = 224). During the initial clinic visit, proxy-reported measures of the Child Behavior Checklist, Vineland II Adaptive Behavior Scales, and the Pediatric Quality of Life Inventory 4.0 (start measures) were obtained and then merged with the survey data. Nine mapping algorithms were developed using the HUI3 scores as dependent variables in ordinary least squares regressions along with the start measures, the Autism Diagnostic Observation Schedule, to measure severity, child age, and cognitive ability as independent predictors. In-sample cross-validation was conducted to evaluate predictive accuracy. Multiple imputation techniques were used for missing data. The average age for children with ASDs in this study was 8.4 (standard deviation = 3.5) years. Almost half of the children (47%) had cognitive impairment (IQ ≤ 70). Total scores for all of the outcome measures were significantly associated with the HUI3 score. The algorithms can be applied to clinical studies containing start measures of children with ASDs to predict QALYs gained from interventions.

One-year course and predictors of abdominal pain in children with autism spectrum disorders: The role of anxiety and sensory over-responsivity

ObjectivesTo examine the one-year course of parent-reported abdominal pain in children with autism spectrum disorder (ASD), and to determine whether anxiety and sensory over-responsivity (SOR) contribute to the onset or remission of abdominal pain. MethodsParticipants included 225 children (ages 2–17) with ASD enrolled in the Autism Speaks Autism Treatment Network. Primary measures included the parent-reported GI Symptom Inventory Questionnaire, Child Behavior Checklist, and Short Sensory Profile. ResultsOne-fourth (25.8%) experienced chronic abdominal pain (duration ≥3 months) at baseline, persisting at one-year follow-up for 86.7%. New onset pain occurred for 23.8% of those without baseline pain. Anxiety, SOR, and chronic abdominal pain were associated at baseline. SOR significantly predicted new onset pain, but neither anxiety nor SOR were predictors of pain remission. ConclusionsAbdominal pain appears to be common and persistent among children with ASD. The relations among SOR, anxiety and abdominal pain offer information about potential underlying mechanisms.

Rigid–Compulsive Behaviors are Associated with Mixed Bowel Symptoms in Autism Spectrum Disorder

Based on clinical experience, we hypothesized that rigid-compulsive behaviors are associated with severe constipation and co-occurring diarrhea or underwear staining in children with autism spectrum disorder. Using data from the Autism Treatment Network, we evaluated the association between these gastrointestinal symptoms and measures of rigid compulsive behavior in children ages 2-17. Following statistical correction, four of five primary measures were significantly associated with constipation and diarrhea or underwear staining, including parental report of repetitive behavior, parental report of compulsive behavior, clinician diagnosis of obsessive-compulsive disorder, and report of rituals observed on the autism diagnostic observation schedule. This association could point to a causal connection between these symptoms or to a common biological pathway that impacts both gut and brain.

Validity of the Aberrant Behavior Checklist in Children with Autism Spectrum Disorder

The Aberrant Behavior Checklist (ABC) is a widely used measure in autism spectrum disorder (ASD) treatment studies. We conducted confirmatory and exploratory factor analyses of the ABC in 1,893 children evaluated as part of the Autism Treatment Network. The root mean square error of approximation was .086 for the standard item assignment, and in exploratory factor analysis, the large majority of items continued to load on the originally assigned factors. Correlations between the ABC subscales and multiple external variables including the Child Behavior Checklist and demographic variables supported the convergent and divergent validity of the ABC as a measure of behavior problems in ASD. Finally, we examined the impact of participant characteristics on subscale scores and present normative data.

The association between emotional and behavioral problems and gastrointestinal symptoms among children with high-functioning autism

This study investigated the association between gastrointestinal symptoms and a broad set of emotional and behavioral concerns in 95 children with high-functioning autism and IQ scores ≥ 80. Gastrointestinal symptoms were assessed via the Autism Treatment Network's Gastrointestinal Symptom Inventory, and data were gathered on autism symptom severity, adaptive behavior, and multiple internalizing and externalizing problems. The majority (61%) of children had at least one reported gastrointestinal symptom. Emotional and behavioral problems were also common but with a high degree of variability. Children with and without gastrointestinal problems did not differ in autism symptom severity, adaptive behavior, or total internalizing or externalizing problem scores. However, participants with gastrointestinal problems had significantly higher levels of affective problems. This finding is consistent with a small body of research noting a relationship between gastrointestinal problems, irritability, and mood problems in autism spectrum disorder. More research to identify the mechanisms underlying this relationship in autism spectrum disorder is warranted. Future research should include a medical assessment of gastrointestinal concerns, longitudinal design, and participants with a range of autism spectrum disorder severity in order to clarify the directionality of this relationship and to identify factors that may impact heterogeneity in the behavioral manifestation of gastrointestinal concerns.

The Autism Impact Measure (AIM): Initial Development of a New Tool for Treatment Outcome Measurement

The current study describes the development and psychometric properties of a new measure targeting sensitivity to change of core autism spectrum disorder (ASD) symptoms, the Autism Impact Measure (AIM). The AIM uses a 2-week recall period with items rated on two corresponding 5-point scales (frequency and impact). Psychometric properties were examined using a large sample (n=440) of children with ASD enrolled in the Autism Treatment Network. The exploratory factor analysis indicated four factors and resulted in a 25-item questionnaire with excellent overall model fit. Test-retest reliability, cross-informant reliability, and convergent validity with other measures of ASD symptoms and overall functioning were strong. The AIM is a reliable and valid measure of frequency and impact of core ASD symptoms.

Correlates and Risk Markers for Sleep Disturbance in Participants of the Autism Treatment Network

We explored possible cognitive, behavioral, emotional, and physiological risk markers for sleep disturbance in children with autism spectrum disorders. Data from 1,583 children in the Autism Treatment Network were analyzed. Approximately 45 potential predictors were analyzed using hierarchical regression modeling. As medication could confound findings, it was included in the analyses as a covariate. Results revealed that anxiety, autism symptom severity, sensory sensitivities, and GI problems were associated with sleep disturbance. IQ positively predicted sleep disturbance, and children with Asperger's Disorder were more vulnerable than others. The amount of variance in sleep outcomes explained by predictor variables was modest (i.e., R (2) from .104 to .201). Predictor variables were evaluated in the context of a bidirectional theoretical framework.

Managing insomnia in children with autism spectrum disorder

Managing insomnia in children with autism spectrum disorder

Physical aggression in children and adolescents with autism spectrum disorders

Aggression is a clinically significant problem for many children and adolescents with autism spectrum disorders (ASD). However, there have been few large-scale studies addressing this issue. The current study examined the prevalence and correlates of physical aggression in a sample of 1584 children and adolescents with ASD enrolled in the Autism Treatment Network. The prevalence of aggression was 53%, with highest prevalence among young children. Aggression was significantly associated with a number of clinical features, including self-injury, sleep problems, sensory problems, GI problems, communication and social functioning. In multivariate models, self-injury, sleep problems, and sensory problems were most strongly associated with aggression. The results indicate that aggression is markedly prevalent, and clinical implications and directions for future research are discussed.

Management of Constipation in Children and Adolescents With Autism Spectrum Disorders

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). 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. 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. 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.

The Autism Treatment Network and Autism Intervention Research Network on Physical Health: Future Directions

* Abbreviations: AIR-P — : Autism Intervention Research Network on Physical Health ASD — : autism spectrum disorder ATN — : Autism Treatment Network CER — : comparative effectiveness research CTSAs — : Clinical Translational Science programs Autism spectrum disorders (ASDs) represent complex neurodevelopmental disorders with multiple etiologies.1 The resulting variability of behavioral, medical, and developmental concerns that affect individuals with ASDs has made it extremely difficult to predict which treatments work best for which individuals. Developing effective treatments and improving care for individuals with ASDs throughout the life span remain urgent priorities. Comprehensive coordinated care for individuals with ASDs will require further advances in our knowledge of medical and behavioral interventions and a health care system that can deliver them consistently. Over the past 7 years, the Autism Speaks Autism Treatment Network (ATN) and more recently the Autism Intervention Research Network on Physical Health (AIR-P) have significantly increased understanding of the prevalence, nature, and treatment of medical conditions in children with ASDs, such as gastrointestinal conditions, sleep disorders, metabolic disorders, and seizures. The network has pioneered in standardizing the clinical evaluation of children with ASDs, based on a comprehensive, multidisciplinary model of care. The network has also developed key partnerships that have helped the field move from limited consensus toward evidence-based autism-specific guidelines in key areas of medical concern, and has acquired the infrastructure and expertise to develop more targeted treatment studies that can help move the most effective therapies through the research pipeline and into the hands of consumers. The ATN has led in the application of quality improvement methods to autism care and in systematic efforts to bring the experience and lessons of the network to broader communities of professionals and parents. This effort, led by Autism Speaks, has allowed strong synergy among research, clinical, and family communities. Key areas of continued growth for the research activities of network include (1) on-going enhancement of research infrastructure, including increased availability of biological samples; (2) expansion of the research agenda to include more focused research … Address correspondence to James M. Perrin, MD, Department of Pediatrics, Harvard Medical School, MassGeneral Hospital for Children, 100 Cambridge St, #1542, Boston, MA 02114. E-mail: jperrin{at}partners.org