Transient Elevation and Subsequent Normalization of Brain Age Gap During the Postpartum Period

The postpartum period involves substantial brain changes, but whether these represent pathological aging or adaptive plasticity remains unclear. We applied machine learning-based brain age prediction to quantify postpartum brain aging trajectories in a controlled longitudinal study. Brain age gap, the difference between MRI-predicted and chronological age, was assessed in 55 women (25 postpartum and 30 nulliparous controls). Postpartum women were assessed at approximately 3 and 12 months postpartum; controls were assessed at matched intervals. Postpartum women showed elevated brain age gap at 3 months (2.5 ± 2.7 years) compared with controls (0.3 ± 3.6 years; p = 0.01, Cohen's d = 0.69), which normalized by 12 months. Within-group analysis revealed significant brain age gap decrease in postpartum women (-3.3 ± 3.5 years; p = 0.008), while controls showed minimal change; the between-group difference in longitudinal change did not reach statistical significance (p = 0.12, Cohen's d = -0.58). Across all participants, brain age gap correlated with working memory performance (ρ = -0.30; p = 0.03), depressive symptoms (ρ = 0.38; p = 0.004), and subjective cognitive complaints (ρ = 0.28; p = 0.04) at baseline, providing preliminary evidence of clinical relevance. Explainability analysis using Shapley additive explanations identified subcortical structures as the network most selectively associated with the postpartum elevation in brain age gap at 3 months (p = 0.006, Cohen's d = 0.82), with normalization by 12 months. Together, these findings indicate transient brain age gap elevation in postpartum women without statistical confirmation of a trajectory differing from controls. With brain age gap providing a quantitative index of postpartum brain structural change, these preliminary findings are consistent with adaptive neuroplasticity, suggesting that such change may be temporary rather than reflecting permanent impairment.