Socioeconomic status moderates associations between hippocampal development and cognition in preterms

Abstract Objective The hippocampus plays a critical role in cognitive networks. The anterior hippocampus is vulnerable to early‐life stress and socioeconomic status (SES) with alterations persisting beyond childhood. How SES modifies the relationship between early hippocampal development and cognition remains poorly understood. This study examined associations between SES, structural and functional development of neonatal hippocampus, and 18‐month cognition in very preterm neonates. Methods In total, 179 preterm neonates were followed prospectively. Structural and resting‐state functional MRI were obtained early‐in‐life and at term‐equivalent age (median 32.9 and 41.1 weeks post‐menstrual age) to calculate anterior and posterior hippocampal volumes and hippocampal functional connectivity strength. Eighteen‐month cognition was assessed via Bayley‐III. Longitudinal statistical analysis using generalized estimating equations, accounting for birth gestational age, post‐menstrual age at scan, sex, and motion, was performed. Results SES, measured as maternal education level, modified associations between anterior but not posterior hippocampal volumes and 18‐month cognition (interaction term p = 0.005), and between hippocampal connectivity and cognition (interaction term p = 0.05). Greater anterior hippocampal volumes and hippocampal connectivity were associated with higher cognitive scores only in the lowest SES group. Maternal education alone did not predict neonatal hippocampal volume from early‐in‐life and term. Interpretation SES modified the relationship between neonatal hippocampal development and 18‐month cognition in very preterm neonates. The lack of direct association between maternal education and neonatal hippocampal volumes indicates that socio‐environmental factors beyond the neonatal period contribute to modifying the relationship between hippocampal development and cognition. These findings point toward opportunities to more equitably promote optimal neurodevelopmental outcomes in very preterm infants.