International Meeting for Autism Research: Early Generalized Overgrowth In Boys with Autism

Early Generalized Overgrowth In Boys with Autism

Thursday, May 12, 2011: 2:30 PM
Douglas Pavilion A (Manchester Grand Hyatt)
2:00 PM
D. Campbell1, L. Chen1, F. Shic2, A. Klin3, J. Chang1 and K. Chawarska2, (1)Department of Statistics, Yale University, New Haven, CT, (2)Yale University School of Medicine, New Haven, CT, (3)Marcus Autism Center, Children's Healthcare of Atlanta & Emory School of Medicine, Atlanta, GA
Background: Reports of atypical head circumference (HC) overgrowth in infants later diagnosed with autism resulted in concerted efforts to identify factors responsible for brain overgrowth and their association with etiology of autism.  Thus far, however, no mechanisms of HC overgrowth have been identified.  Moreover, considering several divergent reports, it is also not clear whether this phenomenon is independent of overall body growth and whether it is associated with specific social or cognitive features.

Objectives: To examine the trajectory of early HC growth from birth to 24 months in autism compared to control groups; to assess whether HC growth in autism is independent of height and weight growth during infancy; and to examine HC growth patterns in relationship to social, verbal, cognitive, and adaptive functioning levels. 

Methods: We compared growth trajectories from birth to 24 months of boys with autistic disorder (N=64), pervasive developmental disorder-not otherwise specified (PDD-NOS) (N=34); non-autistic developmental delays (DD) (N=31); and typically developing boys (TD) (N=55).  Bayesian multi-level growth curve models were used to analyze the growth measurements. The effects were modeled as low-rank thin-plate splines.  Splines were chosen as they allow for fitting diverse growth functions.  Considering that the true forms of the morphological growth functions are unknown, this controlled flexibility in modeling was preferable.  Estimated mean curves for each group were calculated along with 95% credible bands.  After models were fit for HC, height, and weight individually, principal components analysis was used to generate combinations of the three variables that could be meaningful in explaining trends seen in the sample.  Measures derived from principal component scores were modeled in the same way as HC, height, and weight. 

Results: Growth curve modeling suggests that by 4.8 months of age (p=.05), boys with autism were significantly longer than TD controls; by 9.5 months (p=.05), had larger head circumferences; and by 11.4 months (p=.05), they weighed more.  None of the other clinical groups showed a similar overgrowth pattern. In the autism group, boys who were in the top 10% of overall physical size between 6 and 12 months of age exhibited greater severity of social deficits (p=.009) and lower adaptive functioning (p=.034).

Conclusions: While boys with autism experience accelerated HC growth rate in the first year of life, this phenomenon reflects a generalized process affecting other morphological features including height and weight.  Presence of more severe symptoms and lower adaptive functioning in the boys with the most extreme overgrowth suggests a possible link between factors involved in the atypical physical growth and the severity of social impairment in autism.  When considering potential underlying mechanisms for enlarged total brain volume and acceleration of head circumference growth in autism, most researchers to date have focused on factors affecting neuronal development.  However, considering the present findings, efforts should be advanced to examine factors responsible for the entire constellation of neural and non-neural growth-related phenotypic traits as it is possible that these two phenomena share common etiology.

| More