Long-Term Effects of Preterm Birth on Children’s Brain Structure: An Analysis of the Adolescent Brain Cognitive Development (ABCD) Study

Abstract

Approximately 10% of births are preterm [PTB; <37 weeks gestational age (GA)], which confers risk for cognitive, be-havioral, and mental health challenges. Using the large and relatively diverse (i.e., designed to reflect sociodemo-graphic variation in the United States population) Adolescent Brain Cognitive Development 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 with 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 (SA) and subcortical volumes showed reductions in PTB children that were largely attenuated when controlling for brain size. Effects on cortical thickness (CT) 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.