Moderate and late preterm infants exhibit widespread brain white matter microstructure alterations at term-equivalent age relative to term-born controls.

Despite the many studies documenting cerebral white matter microstructural alterations associated with very preterm birth (<32 weeks' gestation), there is a dearth of similar research in moderate and late preterm infants (born 32-36 weeks' gestation), who experience higher rates of neurodevelopmental delays than infants born at term (≥ 37 weeks' gestation). We therefore aimed to determine whether whole brain white matter microstructure differs between moderate and late preterm infants and term-born controls at term-equivalent age, as well as to identify potential perinatal risk factors for white matter microstructural alterations in moderate and late preterm infants. Whole brain white matter microstructure was studied in 193 moderate and late preterm infants and 83 controls at term-equivalent age by performing Tract-Based Spatial Statistics analysis of diffusion tensor imaging data. Moderate and late preterm infants had lower fractional anisotropy and higher mean, axial and radial diffusivities compared with controls in nearly 70% of the brain's major white matter fiber tracts. In the moderate and late preterm group, being born small for gestational age and male sex were associated with lower fractional anisotropy, largely within the optic radiation, corpus callosum and corona radiata. In conclusion, moderate and late preterm infants exhibit widespread brain white matter microstructural alterations compared with controls at term-equivalent age, in patterns consistent with delayed or disrupted white matter microstructural development. These findings may underpin some of the neurodevelopmental delays observed in moderate and late preterm children.