Placenta-to-heart multi-omics in preeclampsia and peripartum cardiomyopathy: A systematic review and integrative pathway synthesis of shared mechanisms and postpartum cardiovascular risk

ABSTRACT

Preeclampsia and peripartum cardiomyopathy (PPCM) are traditionally approached as distinct obstetric and cardiac disorders, yet clinical experience and epidemiologic data increasingly suggest that they reflect intersecting biological processes rather than coincidental coexistence. Both conditions are associated with excess maternal morbidity and appear to confer cardiovascular (CV) vulnerability that extends well beyond delivery. At the center of this overlap lies the placenta, an organ long viewed as transient, but now recognized as a potent regulator of maternal vascular, metabolic, and inflammatory states. Over the past decade, advances in placental multi-omics have generated a rapidly expanding and conceptually fragmented literature that has yet to be synthesized within a unified placenta–heart framework. We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines to integrate clinical, epidemiologic, translational, and omics-based studies examining mechanistic links between preeclampsia, PPCM, and subsequent maternal CV risk. Electronic databases and supplementary sources were searched, studies were screened and assessed in duplicate, and risk of bias was evaluated using established approaches. Thirty-six studies met inclusion criteria and were synthesized using a deliberately mechanism-oriented, pathway-focused strategy, allowing iterative integration of emerging multi-omics evidence. Across heterogeneous study designs and platforms, several core shared pathways consistently emerged, including placental senescence and oxidative stress, angiogenic imbalance driven by excess soluble fms-like tyrosine kinase-1, endothelial dysfunction, immune activation, and metabolic reprogramming. In contrast, other mechanisms – most notably prolactin cleavage – appeared to function as disease-dominant modifiers shaping the PPCM phenotype rather than representing universal drivers. These placental and circulating signals closely mirror molecular features described in myocardial dysfunction and plausibly persist into the postpartum period, providing a mechanistic bridge to later CV disease. To our knowledge, this is the first systematic review to integrate placental multi-omics with PPCM mechanisms into a single placenta–heart conceptual framework. Together, the findings recast pregnancy as a biologically revealing window into lifelong maternal CV health, with implications for earlier risk stratification, surveillance, and prevention.