Growth Dysregulation in Boys with Autism Spectrum Disorder

Background:  Head circumference growth in individuals with an Autism Spectrum Disorder (ASD) has been well characterised in the first two to three years of life, and reflects a period of acceleration followed by a period of deceleration when compared to typically developing (TD) peers.  While this altered growth trajectory has been consistently found for head circumference, it is less clear if an abnormal growth trajectory also exists across measures of height and weight.

Objectives:  The current study aimed to confirm the hypothesis that physical growth overallis dysregulated in ASD.  Two explanatory hypotheses were tested: 1) a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates growth hormones; and 2) a connective tissue disorder, which is frequently associated with increased height and disproportionate body ratios. 

Methods:  The current study investigated growth patterns in 168 boys with an ASD and 875 TD boys from birth through 16 years of age using a mixed-longitudinal design.

Results:  Although male infants with ASD were found to be smaller in size at birth compared to TD male infants, they grew at a significantly faster rate throughout infancy and toddlerhood.  Once boys with ASD reached 4 years of age, they were significantly larger than TD boys, and remained so throughout childhood and adolescence, despite no longer differing in their rate of growth.  There were significantly more boys with ASD who displayed extreme general overgrowth (measures in the 90^thpercentile for their age in height, weight, and HC) compared to TD boys. 

Boys with ASD had longer limb to body ratios than TD boys; this, coupled with the increased height in the ASD group indicates possible involvement of the connective tissue in general growth dysregulation.  There was a trend for the ASD group to have a lower 2^nd to 4^thdigit ratio (an index of prenatal testosterone levels), indicating possible dysregulation of the HPA axis.  Moreover, severity of ASD was highly correlated with an increase in the cortisol awakening response (CAR), an indicator of HPA axis function; however, there was no association between the CAR and specific growth patterns. 

The boys with ASD who exhibited extreme general overgrowth did not differ from the other boys with ASD in any way to indicate the presence of a connective tissue disorder or HPA axis dysregulation in this small subgroup. However, they were significantly more affected as indicated by increased ASD severity in the extreme overgrowth group.

Conclusions:  These findings implicate a general growth dysregulation in ASD from birth through adolescence, which may be due, in part, to a connective tissue disorder.   Thus, an increased growth rate in early development may serve as a biomarker for a form of ASD.  The discovery of a specific growth anomaly and its possible determinant(s) in ASD contributes to understanding the underlying mechanisms involved in the development of these related disorders, and warrants further investigation, especially of those children with ASD who exhibit extreme general overgrowth.