17033
Early Head and Body Overgrowth in Boys and Girls with ASD: Prevalence Rate and Clinical Outcomes
Brain enlargement in infancy, recently reported to occur in association with an generalized overgrowth in physical stature, is one of the best-replicated biological findings in ASD. It is not clear whether generalized overgrowth is also present in girls, what its prevalence is, and whether it is associated with clinical outcomes in childhood.
Objectives:
To examine: somatic growth in boys and girls with ASD compared to a community sample of typically developing (TD) children; prevalence of generalized overgrowthin ASD and TD infants; and predictive association between generalized overgrowth and clinical phenotype at 4 years.
Methods:
Head circumference (HC) as an indirect measure of brain size in infancy, height, and weight measurements were collected retrospectively from 200 children (161M/39F) with ASD and 147 typically-developing (TD) controls (98M/49F) between birth and 24 months of age. Growth curves for each measure were modeled using splines. The three measures were combined using principal components analysis to obtain a generalized overgrowth component (PC1). Prevalence rates of macrocephaly were estimated by the proportion of children with HC scores 2 SD above/below the TD mean; macrosomy rates were estimated similarly using PC1 scores. Extreme generalized and HC growth rates were estimated by the proportion exceeding 2 SD above the mean in change between birth and 24 months in TD group. Social, developmental, and adaptive functioning was measured at 2 and 4 years.
Results:
Generalized overgrowth was more pronounced in boys than in girls with ASD. Extreme overgrowth from birth to 2 years was present in 16% of the ASD toddlers as compared to 3.4% in TD controls (p<.001); at 2 years. Corresponding estimates were similar when only HC growth was considered: extreme HC overgrowth was noted in 15.0% of toddlers with ASD but only 3.4% of TD controls (p < .001). At 24 month 6.5% of toddlers with ASD had macrocephaly compared with 4.1% of TD controls (p= .47). Within ASD group, larger body size at birth predicted lower verbal (p=.01), nonverbal (p=.005), and adaptive communication (p=.02) skills and higher autism severity (p=.02) at 4 years. Accelerated somatic postnatal growth contributed to poorer verbal (p=.005), nonverbal (p=.01), adaptive communication (p=.007), and repetitive behavior (p=.002) scores at 4 years after controlling for body size at birth.
Conclusions:
Co-occurrence of accelerated skeletal and HC growth in ASD suggests a common mechanism, potentially constraining the search for underlying biological factors. Girls are less likely to exhibit overgrowth than boys, though factors related to such dimorphism remain unknown. Although early growth abnormalities in ASD are less common than previously thought, their presence is predictive of clinical outcome at 4 years. Future studies will elucidate pre- and postnatal factors affecting growth in ASD and determine whether the generalized overgrowth endophenotype plays a role in etiology of the disorder and reveals novel treatment targets.