Pregnancy induces transient brain and epigenetic aging followed by postpartum rejuvenation.

Does pregnancy age or rejuvenate the brain? Although some studies have examined changes in brain aging following childbirth and decades later, the full trajectory of brain aging across gestation and the postpartum period remains uncharacterized. Here, we leverage two unique longitudinal brain imaging datasets to map brain-age trajectories in mothers across their first pregnancy and postpartum. The first one-the largest maternal brain database to date-includes up to 340 gestational mothers scanned at six time points from pre-conception through 16 months postpartum. The second dataset consists of a dense-sampling study of three women scanned up to 27 time points from pre-conception, through pregnancy and up to 2 years postpartum. Hierarchical generalized additive models of T1w anatomical images revealed that brain age gap estimates (signed difference between predicted brain age and chronological age) increased by ~3 years during pregnancy and decreased throughout the postpartum period. By 16 months postpartum, the brain appears rejuvenated, reflected by a negative brain age gap relative to pre-conception levels. These changes were specific to gestational mothers, with no comparable trajectories observed in non-gestational mothers or nulliparous controls, and were robust across four independent brain-age prediction algorithms and replicated across two unique datasets. Additionally, in one densely-sampled participant, brain aging estimates tracked closely with multiple DNA methylation-based epigenetic clocks, signaling concordance between brain and peripheral aging markers. Our findings support the idea that pregnancy induces a transient, multi-system aging-like process, followed by a postpartum rebound that exceeds pre-conception levels.