A Preliminary Investigation of Prematurity Status and Clinical Presentation In Children with Autism Spectrum Disorders

Background: Autism spectrum disorders (ASD) are highly sexually dimorphic conditions affecting males with greater frequency than females. Recent reports suggest that ex-preterm children are at an increased risk for developing ASD. Children with ASD born at term versus those born prematurely may have differences in clinical phenotype that could potentially be distinguished on the basis of clinical and/or cognitive features and/or proxy markers. ASD in ex-preterm children may be a manifestation of wide cognitive deficits and comparing these children to those with ASD born at term might help in the identification of a subgroup with specific developmental patterns and prognosis. Therefore, we hypothesize phenotype dimorphism in the clinical presentation of ASD symptoms in children born at term compared to those born preterm.

Objectives: Our objectives are three fold: 1) to determine if ASD children born at term versus those born preterm can be distinguished on the basis of clinical features; 2) to evaluate differences in ASD phenotype in children born at term and preterm using proxy markers for in utero androgen exposure; 3) to examine any head circumference differences as related to prematurity status.

Methods: Children with ASD born at term (≥37 months) and born preterm (≤36 months) between the ages of 3 and 12 years were included in this study.  ASD diagnosis was based on Autism Diagnostic Interview Revised (ADI-R), Autism Diagnostic Observations Schedule (ADOS), and expert clinical opinion. Measures included the Stanford Binet, 5th Edition, the Vineland Adaptive Behavior Scales, 2nd Edition, and the Affect Recognition and Theory of Mind subscales of the NEPSY-II. Parent report measures included the Social Responsiveness Scale (SRS), the Repetitive Behavior Scale Revised (RBS-R), and the Sensory Profile Questionnaire (SPQ). Furthermore, a toy preference task used to determine gender specific toy preference and ratio measurements of the 2^nd to 4^th digits were both used as proxy measures of exposure to in utero androgens.

Results: To date, data from 27 ASD subjects born at term and 13 ASD subjects born preterm have been collected. There were no significant differences between the two groups on the SRS, RBS-R, or SPQ. In addition, no differences between the two groups were found on 2^nd to 4^th digit ratio or head circumference measurements.

Conclusions: Findings from this preliminary investigation show no behavioral or proxy marker differences between children with ASD born preterm when compared to children born with ASD at term. These observations suggest that children with ASD born preterm and at term appear to be phenotypically similar based on the measures assessed.  However, our sample size is small and additional data are required to assess if group differences are evident in a larger sample size.