Background:Preterm infants are at risk for white matter (WM) injury and adverse neurodevelopmental outcomes.Methods:Serial diffusion tensor magnetic resonance imaging data were obtained from very preterm infants (N = 78) born <30 wk gestation imaged up to four times from 26-42 wk postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ≥2 scans (N = 50). Sixty-five children underwent neurodevelopmental testing at 2 y of age.Results:FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum, and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with patent ductus arteriosus had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At 2 y of age, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent age. Better social-emotional competence was related to lower FA in the left cingulum bundle.Conclusion:This study demonstrates regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates.