Lonnie Zwaigenbaum, MD1, Wendy L. Stone, PhD2, Karen Dobkins, PhD3, Richard Urbano, PhD4, Warren Lambert, PhD4, Susan Bryson, PhD5, Katarzyna Chawarska, PhD6, John N. Constantino, MD7, Geraldine Dawson, PhD8, Ami Klin, PhD9, Rebecca Landa, Ph.D., CCC-SLP10, Sally Ozonoff, PhD11, Sally J. Rogers, PhD12, Marian Sigman, PhD13, and the Baby Sibs Research Consortium (BSRC)14. (1) Department of Pediatrics, University of Alberta, Autism Research Centre, Glenrose Rehabitation Hospital, Edmonton, AB T5B 0B7, Canada, (2) Pediatrics and Psychology & Human Development, Vanderbilt University, Nashville, TN 37203, (3) Psychology, UC San Diego, Psychology Dept. Mail Code 0109, UC San Diego, La Jolla, CA 92093, (4) Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Peabody Box 0040, 230 Appleton Place, Nashville, TN, (5) Autism Research Centre, Dalhousie University/IWK Health Centre, Halifax, ON, Canada, (6) Child Study Center, Yale University School of Medicine, New Haven, CT 06510, (7) Psychiatry, Washington University School of Medicine, (8) University of Washington, Center on Human Development and Disability, Seattle, WA 98195, (9) Yale Child Study Center, Yale School of Medicine, 40 Temple St. Suite 6B, New Haven, CT 06510, (10) Center for Autism and Related Disorders, Kennedy Krieger Institute, Johns Hopkins Medical School, 3901 Greenspring Ave, Baltimore, MD 21211, (11) Psychiatry, University of California at Davis, 2805 50th St, Sacramento, 95817, (12) Psychiatry, University of California at Davis MIND Institute, 2805 50th St, Sacramento, CA 95817, (13) Depts. of Psychiatry and Psychology, UCLA, 760 Westwood Plaza, Los Angeles, CA 90024, (14) Autism Speaks/NICHD
Background: Increased head circumference is the most consistently replicated biological marker of autism since the disorder was first described by Kanner in 1943. Recent analyses of data from medical records have suggested that accelerated head growth has an onset during the first year of life, although the apparent timing of this phenomenon varies between studies. To date, there are no
prospective data on whether atypical trajectories of head growth are predictive of ASD.
Objectives: To assess prospectively whether children with ASD identified from a cohort of high-risk infants (siblings of children with ASD) exhibit accelerated head growth relative to non-diagnosed high-risk infants and low-risk comparison infants (no family history of ASD).
Methods: Head circumference (HC) was measured prospectively on a total of 761 high-risk and 400 low-risk infants from 11 sites across North America and supplemented by data from health records (25% of total dataset). Analyses compared head growth between high-risk infants diagnosed with ASD at age 24 months (DSM-IV clinical best estimate based on developmental history and symptoms observed on the ADOS) to non-diagnosed high-risk and low risk infants. Growth trajectories were assessed using mixed longitudinal models, assessing change in HC as a function of time (linear growth) and time-squared (acceleration/deceleration), including sex as a fixed covariate, and height as a time-varying covariate.
Results: Mean HC at birth (model-based estimates) did not differ significantly between the three groups (p=0.08). However, there were significant differences between the ASD and both non-ASD groups in HC growth rate (growth rate 0.06 cm/month faster in ASD group compared to non-diagnosed high-risk and low-risk infants; p=.021 and p=.017, respectively), and in deceleration rate (deceleration rate 0.002 cm/month higher in ASD group; p=.018 and p=.021, respectively).
Conclusions: Prospectively measured head growth rates differentiate infants subsequently diagnosed with ASD from non-diagnosed high-risk and low-risk infants.