Postnatal corpus callosum microstructural deviations are linked to neurobehavioral outcomes in preterm infants

The neonatal period surrounding term represents a critical window for corpus callosum (CC) maturation, when axonal growth, pre-myelination, and fiber organization rapidly advance to support emerging motor and cognitive functions, yet preterm birth disrupts this process with unclear mechanisms and long-term consequences. To address this gap, we employed a normative modeling framework, based on a large term-born cohort, to characterize segment-specific CC developmental trajectories and then quantify individual deviations in preterm infants at term-equivalent age (TEA). Preterm infants exhibited selective CC microstructural abnormalities—most pronounced in the genu, anterior body, and splenium—while midsagittal area remained within normative limits. Using partial least squares correlation, we examined associations with neurobehavioral outcomes during toddler period and identified a multivariate brain–behavior coupling unique to the preterm cohort. Specifically, higher gross motor and cognitive scores but lower fine motor score were linked to a coordinated CC profile of increased anisotropy, higher splenial neurite density, reduced diffusivity, and lower genu orientation dispersion. This relationship was absent in term-born controls. These findings suggest that microstructure-informed deviation mapping at TEA may be sensitive to subtle CC alterations that are not apparent on macrostructural measures and are associated with later functional outcomes. This sensitivity to subtle and outcome-related variation highlights the value of this approach as a complement to conventional imaging, and lays the groundwork for future efforts to characterize early white matter development and identify preterm infants at elevated neurodevelopmental risk.