Long-term associations between perinatal factors and white matter microstructure at 8–10 years

Background: While perinatal factors are known to influence brain development, their long-term impact on white matter microstructure remains incompletely understood. Previous studies using tract-based spatial statistics (TBSS) have shown limited associations between neonatal measures and later white matter development. Methods: We investigated associations between perinatal factors (birth weight [BW], gestational age [GA], and head circumference at birth [HC]) and white matter microstructure in 117 children aged 8-10 years from the UNC Early Brain Development Study cohort. Diffusion tensor imaging (DTI) data were analyzed using a fiber tract-based framework examining 54 major white matter tracts. Statistical analyses were performed using a functional analysis of fiber tract profiles. Results: univariate analyses revealed stronger associations with axial diffusivity (AD) compared to radial diffusivity (RD) or fractional anisotropy (FA). AD associations with BW, GA, and HC were observed in 30, 31, and 8 tracts, respectively. Conclusion: Using a fiber tract-based analysis approach, we found that GA and BW were associated with widespread patterns of differences in white matter organization at school age, whereas HC showed limited associations. Associations involving AD were most consistently observed across tracts, suggesting that these perinatal factors may be related to variation in axonal characteristics of white matter. Overall, our findings indicate that early-life biological measures are related to later white matter microstructure, although further work is needed to clarify the developmental mechanisms underlying these associations.