From Placental Dysfunction to Lifelong Cardiovascular–Renal Disease: A Systematic Review of Multiomics Biomarkers and Postpartum Risk Stratification after Preeclampsia and Fetal Growth Restriction
Wiku Andonotopo, Muhammad Adrianes Bachnas, Mochammad Besari Adi Pramono, Julian Dewantiningrum, I. Nyoman Hariyasa Sanjaya, Dudy Aldiansyah, Arief Setiawan, Aloysius Suryawan, Ridwan Abdullah Putra, Theresia Monica Rahardjo, Rizna Tyrani Rumanti, Roland Frederik Lengkey, Julia Windi Gunadi, Waskita Ekamaheswara Kasumba AndanaputraAbstract
Placental dysfunction has traditionally been regarded as a pregnancy-specific disorder; however, growing evidence suggests its implications extend well beyond the perinatal period. This systematic review aimed to synthesize current evidence linking preeclampsia and fetal growth restriction to long-term maternal cardiovascular and renal outcomes, and to examine the potential contribution of emerging biomarkers and multiomics approaches to risk assessment. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 principles. A comprehensive search of PubMed/MEDLINE, PubMed Central, Embase, Scopus, Web of Science, and the Cochrane Library identified 42 eligible studies published between 2000 and 2025. Included studies encompassed systematic reviews, meta-analyses, nationwide cohort studies, diagnostic investigations, and molecular profiling research. The evidence consistently demonstrated that placental dysfunction is associated with persistent cardiovascular and renal vulnerability after pregnancy. Women with a history of preeclampsia or fetal growth restriction showed increased risks of hypertension, coronary artery disease, stroke, heart failure, chronic kidney disease, and end-stage kidney disease during long-term follow-up. Mechanistically, abnormal placentation was linked to angiogenic imbalance, endothelial dysfunction, inflammation, and oxidative stress, providing a biological basis for these associations. Emerging multiomics platforms, including transcriptomics, metabolomics, proteomics, and cell-free RNA profiling, further revealed molecular heterogeneity and showed promise for earlier identification of women at increased risk. The findings support a life-course perspective in which placental dysfunction functions as an early indicator of future cardiovascular and renal disease rather than a complication confined to pregnancy. Integration of clinical characteristics with validated biomarker and multiomics data may enhance postpartum risk stratification and support more individualized preventive strategies.