Abstract
BackgroundLarge controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder.MethodsWe performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. On average, participating toddlers had >8 measurements between birth and the age of two, which enabled us to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy.ResultsThe analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first 2 years of life.ConclusionsThese negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. We believe that conflicting results reported in other studies are due to small sample sizes, use of misleading population norms, changes in the clinical definition of autism over time, and/or inclusion of individuals with syndromic autism. While abnormally large brains may be evident in some individuals with autism and more clearly visible in MRI scans, converging evidence from this and other studies suggests that enlarged HC is not a common etiology of the entire autism population. Early HC measures, therefore, offer very limited clinical utility for assessment of autism risk in the general population.
Highlights
Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism
Head circumference and autism severity We examined the potential relationships between head circumference (HC) as measured at specific ages and autism severity as quantified by the Autism Diagnostic Observation Schedule (ADOS) total score or calibrated severity score at the time of diagnosis
Our results demonstrate that toddlers diagnosed with autism in southern Israel do not exhibit early HC overgrowth during the first 2 years of life
Summary
Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. The validity of early findings that were mostly based on comparisons with CDC population norms have been questioned, because these norms have underestimated the true HC distribution in the general population [18] With this in mind, several comparisons of early HC measurements between toddlers with autism and community-matched controls did not find any significant between-group differences [19,20,21,22,23]. Several comparisons of early HC measurements between toddlers with autism and community-matched controls did not find any significant between-group differences [19,20,21,22,23] These studies demonstrate the ongoing controversy regarding the existence and clinical significance of early brain overgrowth in toddlers with autism
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