Autism and Early Exposure to the Extrauterine Enviroment

Background: Children born extremely preterm (EPT) have an elevated risk for autism spectrum disorder (ASD). In this condition, MRI studies have suggested volumetric brain abnormalities. We hypothesized that such volumetric changes are present already in the neonatal brain

Objectives: To explore regional grey matter (GM) and white matter (WM) volume differences in EPT infants at term­equivalent age (TEA) with a positive screen of ASD and/or a clinical diagnosis of ASD compared to a group of unaffected EPT infants.

Methods: We included 87 children born in Stockholm between January 2004 and March 2007 with a gestational age (GA) of <27 weeks + 0 days. Infants underwent MRI at TEA. 23 children had scores above cut-off on the Social Responsiveness Scale (SRS) and/or a clinical diagnosis of ASD at 6,5 years, and out of them 11 infants had high­quality 3D MRI and no focal lesion. Comparisons were made with 22 EPT infants with a negative ASD screening. Global (atlas-based segmentation) and regional (voxel-based morphometry (VBM)) analyses were applied. Significant clusters at the corrected (p<0.05) and uncorrected (p<0.001) level are reported for VBM.

Results: Out of 87children, 26% of EPT children either screened positive for ASD and/or had a clinical diagnosis of ASD. The ASD positive group showed significantly smaller total volumes of temporal, occipital, insular and limbic cortices in the global analysis. They also had grey matter reductions, predominantly involving the left parietal and lateral occipital cortices according to the regional analysis. After including birth weight as a covariate only the regional differences remained. 

Conclusions: EPT birth resulted in high positive screens for ASD at 6,5 years. Altered brain volumes and different maturational trajectories in regions involving social communication and behavior domains were detectable already in the neonatal period.