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.

Figure 1

Cohort flowchart. Cohort flowchart—162 neonates with SES data were included in the final analysis; 126 infants had at least one MRI scan as well as an 18‐month Bayley‐III Cognitive Composite score.

Figure 2

Subregional hippocampus segmentation at two time points. Sagittal T1‐weighted MR images showing hippocampus segmentation early‐in‐life (top row) and at term‐equivalent age (bottom row) for the same neonate. Manual segmentation of the anterior (green) and posterior (pink) hippocampus is shown in the full brain images (left), and in more detail with (A and C) and without (B and D) segmentation labels (right). The dark blue line marks the slice (*) where the hippocampus is divided (landmark structure: uncal apex), which is counted as the most posterior slice of the anterior hippocampus. Anterior, posterior, and total hippocampal volumes are calculated (V_aHC, V_pHC, and V_HC). V_aHC, volume anterior hippocampus (in mm³); V_pHC, volume posterior hippocampus (in mm³); V_HC, volume total hippocampus (in mm³).

Figure 3

Spatial maps of independent component analysis. Representative spatial maps showing the independent component analysis results of resting‐state functional MRI data on sagittal, coronal, and axial slices of the early‐in‐life (A–D) and term‐equivalent age (E–H) T2‐weighted brain template. Labeled signal of neuronal activity networks are displayed in red to yellow colors, with the color bar demonstrating the image intensity threshold (z‐scored) on the right. (A) Frontal lobe, (B) temporal lobe, (C) auricular network, (D) parietooccipital area, (E) sensorimotor area, (F) posterior cingular cortex, (G) basal ganglia, (H) default mode network.

Figure 4

Hippocampal subregional volumes (A and B) as well as hippocampal functional connectivity (C) and 18‐month cognitive outcome by maternal level of education (high school, college/undergraduate degree, and postgraduate degree). Maternal level of education modifies the association between anterior hippocampal volumes (A) and 18‐month cognitive outcome, and that between hippocampal functional connectivity (C) and 18‐month cognitive outcome. mHC, mean total hippocampus; mWB, mean whole brain.