Eric Rubenstein

Lessons Learned While Developing, Adapting and Implementing a Pilot Parent-Mediated Behavioural Intervention for Children with Autism Spectrum Disorder in Rural Bangladesh.

Low- and middle-income countries often have limited resources, underdeveloped health systems and scarce knowledge of autism spectrum disorder. The objectives of this preliminary study were to develop and adapt intervention materials and to train a native clinician to implement a community-based parent-mediated behavioural intervention in rural Gaibandha, Bangladesh. Intervention materials to support parents’ use of behavioural strategies were developed and refined by US behavioural intervention experts and Bangladesh field experts. Study investigators trained a native child psychologist in developmental milestones and behavioural intervention techniques. The native clinician delivered a 1-day group education session attended by 10 families of children aged 7–9 years with autism spectrum disorder, followed by two one-on-one training sessions with each family to train and practice individualized strategies for targeted challenging behaviours. Preliminary qualitative results indicate the importance of materials that are culturally appropriate and at an adequate literacy level. All families expressed strong desires to have learned the behavioural strategies when their child was younger and vocalized their need for further support and tools to help their children. This study is a preliminary step to creating sustainable and low-cost autism spectrum disorder interventions in rural Bangladesh, and possibly for families in regions with similar cultural and socioeconomic status backgrounds.

Associations between parental broader autism phenotype and child autism spectrum disorder phenotype in the Study to Explore Early Development

The autism spectrum disorder phenotype varies by social and communication ability and co-occurring developmental, behavioral, and medical conditions. Etiology is also diverse, with myriad potential genetic origins and environmental risk factors. Examining the influence of parental broader autism phenotype—a set of sub-clinical characteristics of autism spectrum disorder—on child autism spectrum disorder phenotypes may help reduce heterogeneity in potential genetic predisposition for autism spectrum disorder. We assessed the associations between parental broader autism phenotype and child phenotype among children of age 30–68 months enrolled in the Study to Explore Early Development (N = 707). Child autism spectrum disorder phenotype was defined by a replication of latent classes derived from multiple developmental and behavioral measures: Mild Language Delay with Cognitive Rigidity, Mild Language and Motor Delay with Dysregulation (e.g. anxiety/depression), General Developmental Delay, and Significant Developmental Delay with Repetitive Motor Behaviors. Scores on the Social Responsiveness Scale-Adult measured parent broader autism phenotype. Broader autism phenotype in at least one parent was associated with a child having increased odds of being classified as mild language and motor delay with dysregulation compared to significant developmental delay with repetitive motor behaviors (odds ratio: 2.44; 95% confidence interval: 1.16, 5.09). Children of parents with broader autism phenotype were more likely to have a phenotype qualitatively similar to broader autism phenotype presentation; this may have implications for etiologic research.

The broader autism phenotype in mothers is associated with increased discordance between maternal-reported and clinician-observed instruments that measure child autism spectrum disorder

Autism spectrum disorder (ASD) diagnosis relies on parent-reported and clinician-observed instruments. Sometimes, results between these instruments disagree. The broader autism phenotype (BAP) in parent-reporters may be associated with discordance. Study to Explore Early Development data (N = 712) were used to address whether mothers with BAP and children with ASD or non-ASD developmental disabilities were more likely than mothers without BAP to ‘over-’ or ‘under-report’ child ASD on ASD screeners or interviews compared with clinician observation or overall impression. Maternal BAP was associated with a child meeting thresholds on a maternal-reported screener or maternal interview when clinician ASD instruments or impressions did not (risk ratios: 1.30 to 2.85). Evidence suggests acknowledging and accounting for reporting discordances may be important when diagnosing ASD.

The prevalence of gluten free diet use among preschool children with autism spectrum disorder

Our objective was to estimate prevalence of current or ever use of a gluten free diet (GFD) in children aged 30–68 months with autism spectrum disorder (ASD) and population controls (POP); and to identify characteristics associated with ever having used GFD among children with ASD. We used data from the Study to Explore Early Development (SEED), a multi‐site, case‐control study of children with ASD. Caregivers reported GFD use by their children through structured questionnaires about diet patterns, gastrointestinal (GI) issues, and ASD‐specific treatments. Prevalence was estimated and compared using log‐Poisson regression, adjusting for confounders. In children with ASD, we examined whether child or mothers GI conditions or childs phenotypic traits were associated with ever trying a GFD. In SEED, 71 children with ASD (11.1% prevalence after adjustment) were on a GFD at time of the study and 130 (20.4%) had ever used a GFD, a greater percentage than in POP children (N = 11, 0.9% current use). Of current users with ASD, 50.7% had a dietary intervention that was prescribed by a medical professional. Among children with ASD, child GI conditions and developmental regression were positively and independently associated with having ever used a GFD. Current use and ever use of a GFD were prevalent in children with ASD identified in SEED. GFD usage was associated with GI issues and child phenotype. Clinicians may consider advising parents on how best to use these diets in the context of the childs GI presentation and current scientific knowledge about effectiveness in relation to ASD symptoms. Autism Res 2018, 11: 185–193.

Trends in Special Education Eligibility Among Children With Autism Spectrum Disorder, 2002-2010:

Objective: Although data on publicly available special education are informative and offer a glimpse of trends in autism spectrum disorder (ASD) and use of educational services, using these data for population-based public health monitoring has drawbacks. Our objective was to evaluate trends in special education eligibility among 8-year-old children with ASD identified in the Autism and Developmental Disabilities Monitoring Network. Methods: We used data from 5 Autism and Developmental Disabilities Monitoring Network sites (Arizona, Colorado, Georgia, Maryland, and North Carolina) during 4 surveillance years (2002, 2006, 2008, and 2010) and compared trends in 12 categories of special education eligibility by sex and race/ethnicity. We used multivariable linear risk regressions to evaluate how the proportion of children with a given eligibility changed over time. Results: Of 6010 children with ASD, more than 36% did not receive an autism eligibility in special education in each surveillance year. From surveillance year 2002 to surveillance year 2010, autism eligibility increased by 3.6 percentage points (P = .09), and intellectual disability eligibility decreased by 4.6 percentage points (P < .001). A greater proportion of boys than girls had an autism eligibility in 2002 (56.3% vs 48.8%). Compared with other racial/ethnic groups, Hispanic children had the largest increase in proportion with autism eligibility from 2002 to 2010 (15.4%, P = .005) and the largest decrease in proportion with intellectual disability (–14.3%, P = .004). Conclusion: Although most children with ASD had autism eligibility, many received special education services under other categories, and racial/ethnic disparities persisted. To monitor trends in ASD prevalence, public health officials need access to comprehensive data collected systematically, not just special education eligibility.

Broader Autism Phenotype in Parents of Children with Autism: A Systematic Review of Percentage Estimates

The broader autism phenotype (BAP) is a collection of sub-diagnostic autistic traits more common in families of individuals with autism spectrum disorder (ASD) than in the general population. BAP is a latent construct that can be defined using different domains, measured using multiple instruments, and reported using different techniques. Therefore, estimates of BAP may vary greatly across studies. Our objective was to systematically review studies that reported occurrence of BAP in parents of children with ASD in order to quantify and describe heterogeneity in estimates. We systematically searched PubMed and Scopus using PRISMA guidelines for studies quantifying percentage of parents of children with ASD who had BAP. We identified 41 studies that measured BAP in parents of children with ASD. These studies used eight different instruments, four different forms of data collection, and had a wide range of sample sizes (N = 4 to N = 3299). Percentage with BAP ranged from 2.6% to 80%. BAP was more prevalent in fathers than mothers. Parental BAP may be an important tool for parsing heterogeneity in ASD etiology and for developing parent-mediated ASD interventions. However, the variety in measurement instruments and variability in study samples limits our ability to synthesize estimates. To improve measurement of BAP and increase consistency across studies, universal methods should be accepted and adopted across studies. A more consistent approach to BAP measurement may enable efficient etiologic research that can be meta-analyzed and may allow for a larger evidence base that can be used to account for BAP when developing parent-mediated interventions.

Relationship of Weight Outcomes, Co-Occurring Conditions, and Severity of Autism Spectrum Disorder in the Study to Explore Early Development

Objective To assess contributing factors to increased obesity risk, by comparing children with autism spectrum disorder (ASD), developmental delays/disorders, and general population controls in weight status, and to examine associations between weight status and presence of co‐occurring medical, behavioral, developmental, or psychiatric conditions across groups and ASD severity among children with ASD. Study design The Study to Explore Early Development is a multisite cross‐sectional study of children, 2‐5 years of age, classified as children with ASD (n = 668), children with developmental delays/disorders (n = 914), or general population controls (n = 884). Using an observational cohort design, we compared the 3 groups. Childrens heights and weights were measured during a clinical visit. Co‐occurring conditions (medical, behavioral, developmental/psychiatric) were derived from medical records, interviews, and questionnaires. ASD severity was measured by the Ohio State University Global Severity Scale for Autism. Results The odds of overweight/obesity were 1.57 times (95% CI 1.24‐2.00) higher in children with ASD than general population controls and 1.38 times (95% CI 1.10‐1.72) higher in children with developmental delays/disorders than general population controls. The aORs were elevated for children with ASD after controlling for child co‐occurring conditions (ASD vs general population controls: aOR = 1.51; 95% CI 1.14‐2.00). Among children with ASD, those with severe ASD symptoms were 1.7 times (95% CI 1.1‐2.8) more likely to be classified as overweight/obese compared with children with mild ASD symptoms. Conclusions Prevention of excess weight gain in children with ASD, especially those with severe symptoms, and in children with developmental delays/disorders represents an important target for intervention.

Trends in documented co-occurring conditions in children with autism spectrum disorder, 2002–2010

BACKGROUND Autism spectrumdisorder (ASD) commonly presents with co-occurring medical conditions (CoCs). Little is known about patterns in CoCs in a time of rising ASD prevalence. AIMS To describe trends in number and type of documented CoCs in 8-year-old children with ASD. METHODS We used Autism and Developmental Disabilities Monitoring Network (ADDM) data, a multi-source active surveillance system monitoring ASD prevalence among 8-year-old children across the US. Data from surveillance years 2002, 2006, 2008, and 2010 were used to describe trends in count, categories, and individual CoCs. RESULTS Mean number of CoCs increased from 0.94 CoCs in 2002 to 1.06 CoCs in 2010 (p < 0.001). The percentage of children with ASD with any CoC increased from 44.5% to 56.4% (p < 0.001). CoCs with the greatest increases were in general developmental disability (10.4% to 14.5%), language disorder (18.9% to 23.6%), and motor developmental disability (10.5% to 15.6%). Sex modified the relationship between developmental (P = 0.02) and psychiatric (P < 0.001) CoCs and surveillance year. Race/ethnicity modified the relationship between neurological conditions (P = 0.04) and surveillance year. CONCLUSIONS The increase in the percentage of children with ASD and CoCs may suggest the ASD phenotype has changed over time or clinicians are more likely to diagnose CoCs.

A Phenotype of Childhood Autism Is Associated with Preexisting Maternal Anxiety and Depression

This study explored whether ASD phenotypes in the child were associated with a history of anxiety or depression in the mother. We hypothesized that an ASD profile in children characterized by mild delays and increased rates of dysregulation would be associated with preexisting maternal anxiety or depression. Participants were 672 preschool children with ASD and their mothers. Children were classified as ASD after a comprehensive developmental evaluation. Mothers reported whether a healthcare provider ever diagnosed them with anxiety or depression before the birth of their child. Four child ASD phenotypes were derived from latent class analysis: Mild Language Delay with Cognitive Rigidity (Type 1), Significant Developmental Delay with Repetitive Motor Behaviors (Type 2), General Developmental Delay (Type 3), and Mild Language and Motor Delay with Dysregulation (i.e., aggression, anxiety, depression, emotional reactivity, inattention, somatic complaints, and sleep problems) (Type 4). Type 2 ASD served as the referent category in statistical analyses. Results showed that 22.6% of mothers reported a diagnosis of anxiety or depression before the birth of their child. Maternal anxiety or depression was associated with 2.7 times the odds (95% confidence interval: 1.4, 5.3) of Type 4 or Dysregulated ASD in the child; maternal anxiety and depression was associated with 4.4 times the odds (95% confidence interval: 1.4, 14.0) of Type 4 or Dysregulated ASD in the child. Our findings suggest an association between Dysregulated ASD in the child and anxiety and depression in the mother. These findings can enhance screening methods and inform future research efforts.

A Matter of Time: The Necessity of Temporal Language in Research on Health Conditions that Present with Autism Spectrum Disorder: Rubenstein and Bishop-Fitzpatrick/Temporal Language

Relatively consistent findings from recent studies using population‐level data identify heightened physical and psychiatric morbidity in autistic people compared to the general population. Health problems that commonly present with autism spectrum disorder (ASD) are generally discussed in the literature as “co‐occurring” or “comorbid” regardless of their known or hypothesized causal mechanisms. In this commentary, we introduce a new temporally focused terminology to describe health conditions that present with ASD. Emphasizing the temporal development of health conditions in research will help the field understand whether conditions are (1) “truly co‐occurring” (share an etiologic origin with ASD in utero and are a defining characteristic of a subphenotype), (2) “resulting” (caused by ASD related disparity or the health effect of behaviors developed to cope with ASD symptoms), or (3) “associated” (conditions more common in individuals with ASD with etiology not yet known or hypothesized, or an artifact of diagnostic process or trends). Whether a health condition is “truly co‐occurring”, “resulting”, or “associated” has implications for how we design interventions to prevent and treat health conditions in people on the autism spectrum. Ultimately, we think that using clear and temporally focused language can set us on a path to better deduce etiology and develop effective prevention and intervention efforts for health conditions that impact the lives of autistic individuals. We hope that this approach to temporal language to describe health conditions that present with ASD promotes thought and discussion in research, advocate, and autistic communities. Autism Research 2019, 12: 20–25.