Long-term effects of preterm birth on children's brain structure: an analysis of the Adolescent Brain Cognitive Development (ABCD) Study.

Approximately 10% of births are preterm (PTB; <37 weeks gestational age; GA), which confers risk for cognitive, behavioral, and mental health challenges. Using the large and relatively diverse (i.e., designed to reflect sociodemographic variation in the US population) Adolescent Brain Cognitive Development SM Study (ABCD Study ® ), we characterized the impact of PTB on brain structure in middle-late childhood (9-10 years). The ABCD sample covers the GA spectrum, and the large sample size (∼11,500) permits consideration of how associations between PTB and brain structure are impacted by GA, sex, birthweight, and analytic choices such as controlling for total brain size. We found a pattern of relative cortical thinning in temporoparietal and dorsal prefrontal regions and thickening of medial prefrontal and occipital regions in PTB compared to children born full term (≥37 weeks GA). This pattern was apparent when controlling for mean thickness and when considering moderate (>32 and <37 weeks GA) and very PTB (≤32 weeks GA) separately, relative to full term birth. Surface area and subcortical volumes showed reductions in PTB children that were largely attenuated when controlling for brain size. Effects on cortical thickness and surface area were partially mediated by birthweight. Although boys are at increased risk for adverse outcomes following PTB, there was limited evidence of sex differences of PTB effects. Finally, cortical thickness effects estimated in a 'discovery' sample (N=7528) predicted GA in a holdout 'replication' sample (N=2139). Our findings help to clarify the effects of PTB on brain structure into late childhood across the GA spectrum. Significance Preterm birth (PTB) affects ∼10% of children and increases the risk of neurodevelopmental and mental health challenges. Here we examined long-term effects of PTB on brain structure in middle-late childhood in the large and relatively diverse ABCD sample. We further assessed the influence of gestational age, sex, birthweight, controlling for brain size and data quality. Our findings replicate a pattern of occipitotemporal and dorsal prefrontal cortical thinning in PTB that was seen in both moderate preterm and very preterm relative to full-term birth. Effects were similar in males and females and partially mediated by birthweight. Our findings suggest that community-recruited children born preterm show a pattern of structural alterations on a continuum that relates to gestational age and birthweight.