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18-Month Predictors of Later Outcomes in Younger Siblings of Children with Autism Spectrum Disorder: A Bsrc Study

Thursday, May 14, 2015: 5:30 PM-7:00 PM
Imperial Ballroom (Grand America Hotel)
K. Chawarska1, F. Shic2, S. Macari1, D. J. Campbell3, J. A. Brian4, R. J. Landa5, T. Hutman6, C. A. Nelson7, S. Ozonoff8, H. Tager-Flusberg9, G. S. Young10, I. L. Cohen11, T. Charman12, D. S. Messinger13, S. Johnson14, L. Zwaigenbaum15, A. Klin16 and S. E. Bryson17, (1)Child Study Center, Yale University School of Medicine, New Haven, CT, (2)Yale Child Study Center, Yale University School of Medicine, New Haven, CT, (3)Amgen, Inc., Thousand Oaks, CA, (4)150 Kilgour Rd., Holland Bloorview Kids Rehabilitation Hospital/ U of Toronto, Toronto, ON, Canada, (5)Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, (6)Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, (7)Division of Developmental Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, (8)MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, CA, (9)Boston University, Boston, MA, (10)MIND Institute, University California Davis, Sacramento, CA, (11)Psychology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, (12)Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom, (13)University of Miami, Coral Gables, FL, (14)University of California Los Angeles, Los Angeles, CA, (15)University of Alberta, Edmonton, AB, Canada, (16)Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, (17)Autism Research Centre, Dalhousie/IWK Health Centre, Halifax, NS, Canada
Background:  Younger siblings of children with Autism Spectrum Disorder (ASD) are at high risk (HR) for developing ASD, as well as features of the broader autism phenotype. While this complicates early diagnostic considerations in this cohort, it also provides an opportunity to examine patterns of behavior associated specifically with ASD as compared to other developmental outcomes. 

Objectives:  We examined (1) combinations of behavioral features at 18 months that are associated with ASD diagnosis at 3 years, and (2) the factors that affect accurate identification at 18 months of HR siblings who receive a diagnosis of ASD at 3 years of age. 

Methods:  We applied a nonparametric decision-tree learning algorithm, Classification and Regression Trees (CART) analysis, to individual items of the Module 1 Autism Diagnostic Observation Schedule in 719 HR siblings to identify behavioral features at 18 months that are predictive of diagnostic outcomes at 36 months.  CART analysis allows for selection of the most predictive features from a multiplicity of behavioral symptoms and their interactions, resulting in a parsimonious mapping of different sets of predictors of later outcomes. 

Results:  Three combinations of features at 18 months were predictive of ASD outcome: 1) poor eye contact and lack of communicative gestures and giving; 2) poor eye contact and a lack of imitative or spontaneous imaginative play; and 3) lack of giving and presence of repetitive stereotyped behaviors despite intact eye contact (Figure 1). These behavioral profiles predicted ASD versus non-ASD status at 36 months with 82.7% accuracy in the initial test sample and 77.3% accuracy in a validation sample. Clinical features at age 3 years among children with ASD varied as a function of their 18-month symptom profiles (Figure 2). Cases with ASD who were missed at 18 months were higher functioning and their autism symptoms increased over time.

Conclusions:  A large minority of HR siblings with ASD display marked symptoms at 18 months, whereas in others, symptoms become pronounced after 18 months, suggesting at least two windows of opportunity for identification of the affected cases in clinical settings.  Several combinations of clinical features at 18 months were predictive of ASD outcome, each associated with a different developmental course and clinical profile by the 3 years of age. Combined, these findings suggest the presence of different developmental pathways to the common diagnostic ASD outcome, pathways characterized by distinct combinations of early markers, reinforcing the need for repeated screening in the first three years of life to identify individual cases of ASD as their behavioral symptoms appear.