# Perinatal brain growth and autistic traits in toddlers

## TL;DR

Reduced brain volume in early infancy is linked to more autistic traits at 18 months, suggesting early brain development may influence autism risk.

## Contribution

This study identifies postnatal brain volume reductions as a novel early marker for autistic traits in toddlers.

## Key findings

- Postnatal total brain volume, cortical grey matter, and white matter volume were negatively associated with autistic traits in toddlerhood.
- The association was observed in both the dHCP and CHILD cohorts but not in prenatal brain volumes or perinatal growth rates.
- Regional analyses highlighted potential significance in the temporal lobe, warranting further investigation.

## Abstract

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 autistic children, but less is known about whether this extends to the wider spectrum of traits or to early brain development in the first 6 months of life. 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’). The results informed 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). 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, after controlling for total brain volume, showed patterns of note in the temporal lobe, which warrant further research. In conclusion, 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, to children later diagnosed with autism and how it affects the development and connectivity of specific regions, particularly in the temporal lobes.