Maternal Heart Health Starts at Home (MomHeart): Targeting Place-Based Social Determinants to Improve Pregnancy and Postpartum Cardiovascular - ABSTRACT Adverse cardiovascular health (CVH) is the leading cause of pregnancy-related deaths in the US, which have increased 140% over the past three decades. Adverse CVH disproportionately affects pregnant individuals who experience adverse social determinants of health (SDOH) and directly contributes to marked disparities in maternal CVH. SDOH should be understood as a multi-dimensional construct to be measured and intervened upon at multiple-levels, including both individual- and neighborhood-level SDOH (iSDOH, nSDOH). An individual’s lived experience, which are shaped by experiences of both iSDOH and nSDOH, directly impacts CVH across the lifespan, including during pregnancy and the postpartum. Yet, during this important moment in a woman’s life, the relationship of SDOH factors with adverse CVH, including clinical factors, adverse pregnancy outcmes (APOs), and ultimately, cardiovascular disease (CVD) remains uncertain. In addition, nSDOH remain poorly characterized and understood during pregnancy and the postpartum. Healthy People 2030, professional recommendations, and NHLBI’s Strategic Vision Implementation Plan emphasize that effective population-level structural interventions and policies to improve CVH requires a mechanistic, holistic and integrated understanding of SDOH factors. Efforts to quantify the influence of SDOH factors on CVH have largely failed because the causal pathways are numerous, interconnected, and complex. A promising approach to test the inter-relationships of multiple SDOH factors over time is a polysocial risk score. We will harness the prospective, nuMoM2b nulliparous pregnancy cohort (nuMoM2b) and the ongoing postpartum follow-up nuMoM2b Heart Health Study (HHS). This contemporary, generalizable, and deeply phenotyped population includes >10,000 individuals during their first birth experience from across eight US centers. We will employ contemporary theoretical frameworks, machine learning, advanced Bayesian methods, and participant- engaged data walks to construct concepts, identify relationships, and shape future policy and multi-level interventions addressing SDOH and maternal CVH. Our premise in MomHeart is that maternal CVH is spatially patterned by multiple, intersecting socially-mediated factors in the peripartum period. We will accomplish three complementary specific aims: 1: Determine associations of individual iSDOH and nSDOH with maternal CVH (clinical factors, APOs, composite CVH, and predicted CVD risk), cross-sectionally and longitudinally; 2: Examine the intersectionality of iSDOH and nSDOH through a polysocial risk score and examine the associations between a polysocial risk score and maternal CVH; and 3: Conduct qualitative interviews with active nuMoM2b-HHS participants with lived experience to elucidate perspectives on how SDOH patterns discerned have had relevance to their own CVH and could serve as intervention points to improve maternal CVH. MomHeart will shape the future of precise and targeted multi-level interventions and public health policies to enhance the CVH of the highest risk pregnant and postpartum indivduals.