Longitudinal White Matter Maturation in Preterm Infants: Functional Pathway-Specific Trajectories and Associations with Motor Outcomes

Background: During the first 2 years of life, human white matter (WM) undergoes rapid development, establishing a structural foundation for later neurodevelopment. Methods: We conducted a mixed-model analysis for repeated measures to investigate the developmental trajectories of functionally distinct 26 WM pathways between preterm and full-term groups during the first 2 years of life using diffusion tensor imaging (total scans = 174; preterm = 58; full-term = 23). Results: We observed significant differences between the preterm and full-term groups in the developmental trajectories associated with motor function (left corticospinal tract and left pre-primary motor cortex connection tracts), visual processing (bilateral pathway between the V1/V2 and V4, PV-MT, pathway connecting the V1/V2 and V5/MT, and optic radiation), and cognition (genu, body, and splenium of the corpus callosum). Furthermore, inter-regional correlation matrix analysis revealed stronger connectivity, specifically within motor- and visual-related pathways, in the preterm group than that for the full-term group, suggesting an adaptive mechanism that supports circuit-level resilience following preterm birth. Moreover, in the model investigating the associations between the WM individual rate of change and long-term neurodevelopmental outcomes, the middle cerebellar peduncle (MCP) tract showed the strongest associations with motor scores, suggesting that faster maturation of the MCP tract may enhance motor functions as a key compensatory mechanism following preterm birth. Conclusions: Delineating the longitudinal change rates of specific WM pathways not only deepens our understanding of the neurodevelopmental sequelae of prematurity but also highlights their potential as early biomarkers to guide timely interventions.