Maternal plasma cell-free RNA as a predictor of early and late-onset preeclampsia throughout pregnancy

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.

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Publication Details

Journal
Nature Communications
Published
2025-10-20
DOI
https://doi.org/10.1038/s41467-025-64215-2
Citations
1
Primary Topic
Pregnancy and preeclampsia studies
Type
article
Field-Weighted Citation Impact
2.06
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article

Maternal plasma cell-free RNA as a predictor of early and late-onset preeclampsia throughout pregnancy

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Maternal plasma cell-free RNA as a predictor of early and late-onset preeclampsia throughout pregnancy

E. Gibbone, Tamara Garrido‐Gómez, Cristina Casanova Pedraz, Emilia Ferrer, Almudena Jiménez-Méndez, Cristina Andrada-Ripollés, Alfonso López‐Soto, Diana Cuenca-Gómez, Belén Santacruz, Rebeca Herrero-Serrano, Jorge Burgos, Aránzazu Martín-Arias, Beatriz Marcos-Puig, Nerea Castillo-Marco, Alicia Martín Martínez, Mar Nieto-Tous, M M Fernández Romero, Juan Carlos Melchor, Manuel Quintana, Marta Fabre, Carlos De Bonrostro Torralba, A. Del Campo, Esther Cánovas, Nieves Luisa González González, Rogelio Monfort-Ortíz, Sheila Ortega-Sanchís, Cristina Paulés, Mercedes Hernández-Suárez, Inmaculada Martínez-Rivero, M. M. Gil, W. Plasencia, D. Orós, A. Meabe, Antonio Gómez, A. Aiartzaguena, Abril Salinas, Teresa Cordero, Elena Satorres-Pérez, Laura Rubert, Alfredo Perales, M.J. Barbazán, Olivia García-Izquierdo, I Melchor Corcóstegui, Ana Lasierra-Beamonte, Eduardo Rubio González, José Manuel Campillos Maza, Àngels Vives, S. Ruiz, Irene Muñoz-Blat, Carlos Simón, Esmeralda Sanchez-Martinez, Leire Rodríguez, Ana Palacios, Juan Luis Delgado⋈, Virginia Recio, Aitor González Amezcua, Petr Volkov, Laura Hernandez-Hernandez, Taysa Benitez-Delgado, Marina Igual, Carla Gómez-Álvarez, Neus Bernat-González, Ángela Gaspar-Doménech, Érika Ortiz-Domingo, Paloma Baviera-Royo, Encarnación Pérez-Pascual, Víctor García-Sousa, S. Alonso-Menéndez, EM Arias-Valdés, AM Arnal-Burró, R. Batalla-Urrea, M. Bondía, CR Cabrera-Leon, S. De Leon-Socorro, JL Delgado-Gonzalvez, P. Diaz-Lozano, S. Florez-Perez, J. Francés-Ferré, H. Goiti, SE Gregorio-González, MA Jodar-Perez, RM Lobo-Valentín, A. Lozano-Moreno, MJ Macías-Alonso, EM Martín-Medrano, JP Martínez-Cendán, Y. Mico, M. Montesinos-Albert, A. Moreno-Reviriego, A. Orive-Boluda, E. Padrón-Pérez, SM Peña-Lobo, C. Reula-Blasco, AC Ruiz-Peña, E. Villar-Graullera
article en
1 citations

Abstract

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.

Nature CommunicationsVol. 16(1)
Universitat de Miguel Hernández d'Elx (ES), Beth Israel Deaconess Medical Center (US), Universidad de La Laguna (ES), Universitat de València (ES), Universidad Rey Juan Carlos (ES), General Electric (Spain) (ES), Universidad Francisco de Vitoria (ES), Hospital Universitario Insular de Gran Canaria (ES), Hospital Universitario de Canarias (ES), Hospital Universitario La Paz (ES), Hospital Universitari i Politècnic La Fe (ES), BioCruces Health research Institute (ES), Hospital Universitario de Torrejón (ES), Hospital Universitario Miguel Servet (ES), Hospital Universitario Reina Sofía (ES), Hospital General Universitari de Castelló (ES), Instituto de Investigación Sanitaria Aragón (ES), Hospital General Universitario de Alicante Doctor Balmis (ES), Fundación General (ES), Hospital General Universitario de Albacete (ES), Santa Lucía University General Hospital (ES), Instituto Murciano de Investigación Biosanitaria (ES), Complejo Hospitalario Universitario de Albacete (ES), Hospital Universitario Río Hortega (ES), INCLIVA Health Research Institute (ES), Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) (ES)
Openalex Percentile: Top 11%
Pregnancy and preeclampsia studies
2.06
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