Phenotypic Profiles of Children with and without An Autism Spectrum Disorder in the Study to Explore Early Development

Background: The Study to Explore Early Development (SEED) was funded by the Centers for Disease Control and Prevention to enhance knowledge of autism spectrum disorder (ASD) phenotypes and etiologies. SEED presents a unique opportunity to investigate ASD phenotypes because of its population- based ascertainment, large sample size, and comprehensive data collection, including a child developmental evaluation. 

Objectives: Our objective was to describe different phenotypes (i.e., cognitive, adaptive, social, language, behavioral, medical, psychiatric, and developmental) of children recruited and enrolled in SEED. We compared the profile of children classified as ASD with the profile of children classified as developmental delay or disorder (DD) and children in the population control (POP) group.

Methods: Children 2-5 years old were ascertained through birth certificate records and multiple education and clinic sources serving children with developmental problems. All children were screened with the Social Communication Questionnaire (SCQ) upon enrollment and all families were asked to complete the Social Responsiveness Scale (SRS). Information on co-occurring conditions was obtained by telephone interview. Children without a prior ASD diagnosis who passed the ASD screen received a limited developmental evaluation, which included the Mullen Scales of Early Learning (MSEL) only.  Children with a prior ASD diagnosis or who failed the ASD screen received a comprehensive evaluation, which included the MSEL, Vineland Adaptive Behavior Scales (VABS),  Autism Diagnostic Interview – Revised (ADI-R), and Autism Diagnostic Observation Schedule (ADOS). After the developmental evaluation, all children were classified into one of four groups:  ASD, DD with ASD symptoms, DD without ASD symptoms, or POP.  Children had to meet ASD criteria on the ADOS and ADI-R, or have discordance between the instruments resolved, in order to receive an ASD classification. DD children with ASD symptoms were those who completed a comprehensive developmental evaluation but did not meet SEED criteria for ASD and DD children without ASD symptoms were those who completed a limited developmental evaluation due to low ASD risk.

Results: 2,233 out of 3,576 children enrolled had a final study classification as of May 2011: 600 ASD, 244 DD with ASD symptoms, 591 DD without ASD symptoms, and 798 POP.  The mean age at time of clinic visit did not differ between final classification groups (M=58.65 months, SD=7.44 months). There were significant differences between all study groups on SCQ, SRS, and MSEL scores, with ASD children showing more deficit than other children. DD children with ASD symptoms had more cognitive and ASD deficit, but more adaptive abilities, than DD children without ASD symptoms.  These two groups of DD children also differed in terms of presence of co-occurring developmental and psychiatric conditions (e.g., learning disabilities and sensory integration problems).  

Conclusions: SEED ascertainment and recruitment methods yielded study groups with different phenotypic profiles. Cognitive and ASD characteristics were normally distributed in our sample. DD children with ASD symptoms were different from DD children without ASD symptoms and may represent children with sub-threshold ASD symptomotology. The unique study groups enrolled in SEED offer an ideal sample to explore phenotypic subgroups and etiologic factors associated with ASD.