Research questions:
1.Are higher parity and adverse pregnancy outcomes (miscarriage, preterm birth, preeclampsia, fetal growth restriction) associated with greater long-term risk/burden of cardiovascular disease (CVD) and dementia?
2.Does physical activity (PA) intensity and volume during and around pregnancy attenuate this excess risk, and is there a dose-response or threshold?
3.Through which pathways (cardiometabolic, inflammatory, neurovascular) are any benefits mediated, and who benefits most (by BMI, SES, genetic risk such as APOE/CVD PRS)?
Objectives:
i) Quantify the association of pregnancy burden with incident CVD and dementia.
ii) Test effect-modification by PA intensity/volume and define the minimal effective dose.
iii) Decompose effects via mediation by blood pressure, adiposity, lipids, HbA1c and CRP.
iv) Triangulate causality with genetic instruments for habitual PA/fitness.
v) Identify high-risk subgroups to inform targeted antenatal and postpartum prevention.
Scientific rationale: Pregnancy imposes substantial cardiometabolic and neurovascular stress; adverse outcomes are early sentinels of later CVD and dementia. PA is low-cost, scalable, and biologically plausible to counter endothelial dysfunction, insulin resistance, inflammation and postpartum weight retention, yet intensity-specific guidance for women with high pregnancy burden is lacking. Clarifying whether-and how much-PA can offset this risk addresses a major evidence gap with immediate clinical relevance.
