Impacts of perinatal factors on white matter outcome at 8 to 10 years by diffusion tensor imaging

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 [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 analysis was performed using a functional analysis of fiber tract profiles. Results GA and BW showed widespread significant associations with white matter microstructure (38 and 36 out of 54 tracts, respectively), while HC showed limited associations (3 out of 54 tracts). Post-hoc univariate analysis revealed stronger associations with axial diffusivity (AD) compared to radial diffusivity (RD) or fractional anisotropy (FA). AD associations with BW, GA, and HC were found in 30, 31, and 8 tracts, respectively. Conclusions Using a fiber tract-based analysis approach, we demonstrated that GA and BW are strongly predictive of white matter organization at school age, while HC showed limited predictive power. The predominant associations with AD suggest these perinatal factors primarily influence axonal organization rather than myelination. These findings enhance our understanding of how early life factors impact long-term brain development.