Human preterm birth leads to individually heterogeneous, spatially variable cortical thickness deviations that are lasting, glial cell-mediated, and relevant for adult IQ

Human brain development is affected by very preterm (VP) birth. For example, cortical thickness (CT) is aberrant on average in groups of VP neonates, children, and adults. However, distinct postmortem findings of severely impacted preterm neonates, diverse behavioral outcomes of preterm survivors, and the spatially widespread nature of hypoxia-driven pathomechanisms after VP birth imply a regionally variable and individually heterogenous impact of VP birth on brain development. We hypothesized that CT follows this pattern, from birth to adulthood, mediated by the same cell types, and relevant for cognitive performance. Regional CT deviation scores were determined from T1-weighted magnetic resonance imaging (MRI) of 95/92 VP 26-year-old adults/neonates as well as 107/375 full-term adult/neonate controls and a pre-trained large-scale normative model representing CT across the lifespan. Established gene expression data were used to estimate adult interregional distributions of seven cerebral cell types. CT deviations after preterm birth are variable and heterogenous in both neonates and adults. There was a significant association between regional patterns of CT deviations and astrocytes, oligodendrocyte precursor cells, and oligodendrocytes with gestational age in adults. This indicates a mediation of CT deviations by cell types also found affected postmortem in VP neonates. Furthermore, CT deviations in preterm adults were associated with IQ, implying a functional relevance of this pattern. This multiscale analysis of transcriptomic, behavioral, and brain phenotypic data suggests lasting CT heterogeneity and variability after VP birth, mediated by glial cells and relevant for adult cognitive outcome.