When is the brain enlarged in autism? A meta-analysis of all brain size reports.

Multiple studies have reported increased brain size in autism, while others have found no difference from normal. These conflicting results may be due to a lack of accounting for age-related changes in brain enlargement, use of small sample sizes, or differences in data acquisition methods. Reports of autism head circumference (HC), magnetic resonance imaging (MRI), and post-mortem brain weight (BW) that met specific criteria were identified and analyzed. Percent difference from normal values (%Diff) and standardized mean differences (SMD) were calculated to compare brain size across studies and measurement methods. Curve fitting, analysis of variance, and heterogeneity analyses were applied to assay the effects of age and measurement type on reported brain size in autism. A fitted curve of HC and MRI %Diff values from 15 studies revealed a largely consistent pattern of brain size changes. Specifically, brain size in autism was slightly reduced at birth, dramatically increased within the first year of life, but then plateaued so that by adulthood the majority of cases were within normal range. Analysis of variance of MRI and post-mortem %Diff values by age group (young child, older child, adult) and measurement type (MRI, BW) revealed a significant main effect of both age and measurement type, with the youngest ages (2-5) showing the greatest deviation from normal. Random effects heterogeneity analysis revealed a significant effect of age on HC and MRI SMD. These findings reveal a period of pathological brain growth and arrest in autism that is largely restricted to the first years of life, before the typical age of clinical identification. Study of the older autistic brain, thus, reflects the outcome, rather than the process, of pathology. Future research focusing on this early process of brain pathology will likely be critical to elucidate the etiology of autism.