Maternal Age Shapes Gestational Brain Plasticity: A Longitudinal Study of Cortical Gray Matter Volume

The U-shaped trajectory of global cortical gray matter volume (GMV) in pregnancy is a unified representation of the structural changes pertaining to gestation and postpartum recovery. The source of the substantial interindividual variability in this established trajectory of GMV remains unknown. The present study examines whether maternal age moderates the global perinatal GMV trajectory and whether there is age-related variability in estrogen dynamics that mediates these effects. Linear mixed-effects models were used to analyze longitudinal MRI data acquired from first-time mothers (N = 219) from preconception to 6 months postpartum. Older maternal age was associated with a flatter global U-shape trajectory (β = −123.45, p < .001). Phase-locking the global trajectory into decline and recovery slopes allowed us to elucidate that the observed age-based attenuation was driven by reduced GMV decline during pregnancy (β = 406, p < .001). Postpartum recovery slopes, however, were not...Show moreThe U-shaped trajectory of global cortical gray matter volume (GMV) in pregnancy is a unified representation of the structural changes pertaining to gestation and postpartum recovery. The source of the substantial interindividual variability in this established trajectory of GMV remains unknown. The present study examines whether maternal age moderates the global perinatal GMV trajectory and whether there is age-related variability in estrogen dynamics that mediates these effects. Linear mixed-effects models were used to analyze longitudinal MRI data acquired from first-time mothers (N = 219) from preconception to 6 months postpartum. Older maternal age was associated with a flatter global U-shape trajectory (β = −123.45, p < .001). Phase-locking the global trajectory into decline and recovery slopes allowed us to elucidate that the observed age-based attenuation was driven by reduced GMV decline during pregnancy (β = 406, p < .001). Postpartum recovery slopes, however, were not moderated by age (χ²(1) = 2.23, p = .14). Exploratory mediation analyses tested whether differences in cumulative exposure to key estrogen metabolites that in turn mediated the association between maternal age and gestational GMV decline. Area-under-the-curve (AUC) metrics for estrone sulfate, estriol sulfate, and a principal component indexing pregnancy estrogen were examined as mediators in separate models. Indirect effects were not supported across all models (all ps ≥ .303). Although AUC values for all mediators were associated with the magnitude of gestational GMV decline (E1-S: β = 0.372, p = .040; E3-3S: β = 0.713, p < .001; PC1: β = −0.249, p < .001), maternal age was not associated with any mediator metrics (E1-S: β = 0.001, p = .948; E3-3S: β = 0.008, p = .276; PC1: β = −0.019, p = .434). Follow-up variance partitioning analyses indicated that maternal age accounted for a larger proportion of explained variance in GMV decline relative to cumulative estrogen exposure. Maternal age plays an important role in the structural changes women undergo in pregnancy but appears less influential postpartum. These differences in GMV decline appear to arise through mechanisms separate from cumulative estrogen exposure. Future research should situate these structural changes within a broader reproductive lifespan framework and integrate ecologically valid behavioral assessment to better link reproductive transitions to both adult neuroplasticity in women and key well- being outcomes.Show less

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Maternal Age Shapes Gestational Brain Plasticity: A Longitudinal Study of Cortical Gray Matter Volume