Preterm birth, socioeconomic status, and white matter development across childhood

Preterm birth and socioeconomic status (SES) are associated with brain development in early life, but the contribution of each over time is uncertain. We examined the effects of gestational age (GA) and SES on white matter microstructure in the neonatal period and at five years. Participants included preterm and term children. Diffusion MRI was collected at term-equivalent age (n = 153 preterm, n = 90 term [127/243 female]) and from a subset at five years (n = 26 preterm, n = 32 term [22/58 female]). We assessed linear associations of GA, SES (Scottish Index of Multiple Deprivation [SIMD] and maternal education), and GA×SES interactions on fractional anisotropy (FA) using tract-based spatial statistics. We compared the proportion of voxels with significant associations between timepoints. In preterm neonates, higher GA and higher maternal education, but not SIMD, were associated with higher FA (p corrected for family-wise error rate, p_FWER < 0.05). GA-FA associations depended on maternal education and SIMD (β =|0.001-0.005|, p < 0.001). At five years, the strength and direction of GA-FA associations depended on SIMD (β =|0.013-0.028|, p < 0.001), but not maternal education. In term infants, lower SES was associated with higher FA at the neonatal timepoint only (p_FWER < 0.05). Preterm birth and SES both shape brain development at birth and continue to do so at five years. The SES measure most strongly associated with FA in preterm infants switches from a family-level (i.e. maternal education) to neighborhood-level (i.e. SIMD) measure between birth and five years, which suggests strategies to mitigate adverse effects of social inequalities on development may require adaptation as children grow.