Preconception environments shape pregnancy-related structural brain remodeling and intergenerational mental health outcomes

Pregnancy is accompanied by structural brain remodeling in networks supporting socio-emotional processing and cognitive control. However, it remains unclear whether and how modifiable preconception environments shape individual variability in pregnancy-related brain remodeling, and whether such environment-shaped brain features relate to subsequent maternal and offspring mental health. Here we leverage the Singaporean S-PRESTO preconception cohort, with brain structural MRI acquired before conception (PCV; n = 194) and at 3 months postpartum (PNV; n = 61). Age-related gray matter volume (GMV) trajectories were modeled based on PCV data to derive longitudinal region-wise deviation scores, accounting for normative age trends. Pregnancy-related GMV reductions were found in default mode, frontoparietal control, salience, and limbic networks, as well as hippocampus and caudate. We then identified a multivariate pattern linking preconception lifestyle, sociodemographic, psychological, and social-support variables to GMV within these pregnancy-vulnerable brain regions using partial least squares approach. Specifically, higher preconception brain GMV was associated with more advantaged socioeconomic status, healthier diet, better sleep, non-smoking, stronger social support, and higher conscientiousness/lower neuroticism. This environment-associated brain pattern relates to better maternal executive function, lower depression, anxiety, stress and more favorable metabolic health. Importantly, the same brain resilience pattern also predicted lower postpartum anxiety and fewer offspring internalizing symptoms at age four. Together, these findings implicate modifiable preconception environments in shaping brain structural resilience to pregnancy-related remodelling and highlight preconception as a potential window to promote maternal brain health and positive intergenerational mental health outcomes.