Integrated Analysis of Preterm Birth and Socioeconomic Status with Neonatal Brain Structure

Importance: Preterm birth and socioeconomic status (SES) are associated with brain structure in childhood, but the relative contributions of each during the neonatal period are unknown. Objective: To investigate associations of gestational age (GA) and SES with neonatal brain morphology, by testing 3 hypotheses: GA and SES are associated with brain morphology; associations between SES and brain morphology vary across the GA range, and; associations between SES and brain structure/morphology depend on how SES is operationalized. Design: Cohort study, recruited 2016-2021. Setting: Single center, UK. Participants: 170 preterm infants and 91 term infants with median (range) birth GA 30+0 (22+1-32+6) and 39+4 (36+3-42+1) weeks, respectively. Exclusion criteria: major congenital malformation, chromosomal abnormality, congenital infection, cystic periventricular leukomalacia, hemorrhagic parenchymal infarction, post-hemorrhagic ventricular dilatation. Exposures: Using linear ridge regression models, we investigated associations of GA and SES, operationalized at the neighborhood-level (Scottish Index of Multiple Deprivation), family-level (parental education and occupation) and subjectively (WHO Quality of Life), with regional brain volumes and cortical morphology. Main outcomes/measures: Brain volume (85 parcels) and 5 whole-brain cortical morphology measures (gyrification index, thickness, sulcal depth, curvature, surface area) at term-equivalent age. Results: In fully adjusted models, GA associated with a higher proportion of brain volumes (22/85 [26%], {beta} range |-0.13| to |0.22|) than neighborhood SES (1/85 [1%], {beta}=0.17). GA associated with cortical surface area ({beta}=0.10 [95% confidence interval (CI) 0.02-0.18]) and gyrification index ({beta}=0.16 [95% CI 0.07-0.25]); neighborhood SES did not. Family-level SES associated with the volumes of more parcels than neighborhood SES, but it did not have as extensive associations with brain structure as GA. There were interactions between GA and both family- and subjective-level SES measures on brain structure. Conclusions/relevance: In a UK cohort, GA and SES impact neonatal brain morphology, but low GA has more widely distributed effects on neonatal brain structure than neighborhood-level, family-level and subjective measures of SES. Further work is warranted to elucidate the mechanisms embedding GA and level-specific SES in early brain development.