Behavioral dimensions and white matter organization in early childhood following preterm birth

Background: Children born preterm are at increased risk for attentional, social and emotional challenges, collectively referred to as the preterm behavioral phenotype. While white matter alterations have been linked to individual behavioral domains following preterm birth, it remains unclear whether distinct dimensions of behavioral variability are associated with specific patterns of white matter organization. Understanding neurobiological risk markers for preterm phenotypic traits may help identify children at greatest risk. Objective: We investigated the extent to which these behavioral traits covary across the gestational age spectrum and whether latent behavioral dimensions are associated with white matter micro- and macro-structure in young children born preterm. Methods: We collected behavioral and diffusion MRI data from 58 children born preterm (29 females; mean age = 5.64 ± 0.99 years; GA range = 24-36 weeks) and 85 full-term children aged 4-8 years (44 females; mean age = 5.91 ± 0.95 years; mean GA = 39.26 ± 1.24 weeks). Principal component analyses were performed separately in preterm, full-term, and combined groups to characterize latent behavioral dimensions spanning autism-related traits, ADHD symptoms, and emotional functioning. Fixel-based analysis was then used to examine associations between behavioral dimensions and fiber density and fiber cross-section, adjusting for demographic and perinatal factors.Results: In the preterm sample, autism- and ADHD-related behaviors emerged as relatively distinct dimensions, whereas behavioral variance in the full-term sample was captured by a broad neurodevelopmental dimension. In children born preterm, higher scores on the ADHD-related behavioral dimension were associated with reduced fiber cross-section in the splenium of the corpus callosum. No significant associations were found for fiber density in the preterm or full-term samples. Conclusions: These findings suggest that prematurity influences not only behavioral outcomes, but also how those outcomes relate to white matter organization, highlighting the importance of considering behavioral heterogeneity when investigating brain-behavior relationships in preterm populations.