Perinatal brain growth and autistic traits in toddlers

Background: Autism is a heterogeneous set of neurodevelopmental conditions with a significant heritable component and perinatal origins. The earliest observable behavioural traits with which a diagnosis can be made emerge at 18 months of age. Previous studies have reported increased head circumference and brain growth in children with autism, but less is known about their early brain development in the first 6 months of life – a critical period for brain development. Methods: Data from two independent cohorts, the developing Human Connectome Project (dHCP) and Cambridge Human Imaging and Longitudinal Development (CHILD), were assessed in late fetal and early infancy for brain structure with MRI. Global and regional brain volumes in the dHCP, were studied prenatally (n=106, mean age = 29.27 [SD=3.8] gestational weeks) and postnatally (n=454, mean age = 41.28 [SD=1.93] weeks post-conception) in association with later autistic traits after 18 months of age, as captured on the parent-report Quantitative Checklist for Autism in Toddlers (‘Q-CHAT’). Nominally significant findings in the dHCP were used to inform a region-of-interest analysis in the smaller independent CHILD cohort, where participants were scanned during pregnancy (mean=31.98 weeks gestation, SD=1.52) and postnatally (mean scan age=50.45, SD=2.8 weeks post-conception)(n=27). Results: After controlling for cohort covariates, such as maternal age, birth weight, sex and age post-conception at the time of scan, postnatal total brain volume, cortical grey matter volume, and white matter volume were all negatively associated with autistic traits in toddlerhood. This was found for postnatal volumes in both the dHCP and the CHILD cohort, but was not apparent when assessing prenatal brain volume or perinatal growth rates of total brain volume in the same individuals. Regional analyses in the dHCP cohort showed that postnatal white matter volume in two regions of the temporal lobe was associated with Q-CHAT scores, after controlling for total brain volume and correcting for multiple testing. Further nominal associations of regional brain volumes in the temporal lobes were noted in both the dHCP and the CHILD cohort. Conclusions: Reduced total brain volume in the first two months of life is associated with a higher number of autistic traits, as reported by parents at 18 months of life. Further research is required to understand if this extends to later ages and how it affects the development and connectivity of specific regions, particularly in the temporal lobes.