PREMOM ConsortiumAlonso-Menéndez, S.2025-12-182025-12-182025-10-20PREMOM Consortium & Alonso-Menéndez, S 2025, 'Maternal plasma cell-free RNA as a predictor of early and late-onset preeclampsia throughout pregnancy', Nature Communications, vol. 16, no. 1, 9208. https://doi.org/10.1038/s41467-025-64215-22041-1723PubMedCentral: PMC12537965unpaywall: 10.1038/s41467-025-64215-2https://hdl.handle.net/10641/6694Publisher Copyright: © The Author(s) 2025.Early- and late-onset preeclampsia (EOPE and LOPE) pose serious maternal-fetal risks, yet non-invasive early prediction remains challenging. In a prospective cohort of 9,586 pregnancies, we analyze trimester-specific plasma cell-free RNA (cfRNA) profiles from 42 EOPE and 43 LOPE cases versus 131 normotensive controls. Organ-specific transcriptomic shifts distinguish EOPE from LOPE. Predictive models based on cfRNA signatures identify EOPE up to 18.0 weeks before clinical onset in the first-trimester (T1) (AUC = 0.88), and 8.5 weeks in the second trimester (T2) (AUC = 0.89). LOPE is predicted 14.9 weeks in advance using T2 data (AUC = 0.90), while T1 performance is lower (AUC = 0.68). External validation confirms robust EOPE prediction (AUC = 0.87 at T1; 0.81 at T2) and acceptable LOPE performance (AUC = 0.63 at T1; AUC = 0.77 at T2). EOPE models are enriched for decidual transcripts, suggesting early maternal involvement; LOPE models reflect broader tissue contributions. These findings offer a path to early, non-invasive, subtype-specific preeclampsia risk stratification and prevention.142679274enghttp://creativecommons.org/licenses/by-nc-nd/4.0/General ChemistryGeneral Biochemistry, Genetics and Molecular BiologyGeneralGeneral Physics and AstronomyJournal ArticleYesyesjournal articleopen access10.1038/s41467-025-64215-2https://www.scopus.com/pages/publications/105019629645https://www.scopus.com/pages/publications/105019629645#tab=citedBy