Investigating brain structural maturation in children and adolescents born very preterm using the brain age framework

Very preterm (VP) birth is associated with an increased risk for later neurodevelopmental and behavioural challenges. Although the neurobiological underpinnings of such challenges continue to be explored, previous studies have reported brain volume and morphology alterations in children and adolescents born VP compared with full-term (FT)-born controls. How these alterations relate to the trajectory of brain maturation, with potential implications for later brain ageing, remains unclear. In this longitudinal study, we investigate the relationship between VP birth and brain development during childhood and adolescence. We construct a normative 'brain age' model to predict age over childhood and adolescence based on measures of brain cortical and subcortical volumes and cortical morphology from structural MRI of a dataset of typically developing children aged 3-21 years (n = 768). Using this model, we examined deviations from normative brain development in a separate dataset of children and adolescents born VP (<30 weeks' gestation) at two timepoints (ages 7 and 13 years) compared with FT-born controls (120 VP and 29 FT children at age 7 years; 140 VP and 47 FT children at age 13 years). Brain age delta (brain-predicted age minus chronological age) was, on average, higher in the VP group at both timepoints compared with controls, however this difference had a small to medium effect size and was not statistically significant. Variance in brain age delta was higher in the VP group compared with controls; this difference was significant at the 13-year timepoint. Within the VP group, there was little evidence of associations between brain age delta and perinatal risk factors or cognitive and motor outcomes. Under the brain age framework, our results may suggest that children and adolescents born VP have similar brain structural developmental trajectories to term-born peers between 7 and 13 years of age.