Nature Communications (Apr 2025)
Molecular subtyping of hypertensive disorders of pregnancy
- Michal A. Elovitz,
- Elaine P. S. Gee,
- Nathaniel Delaney-Busch,
- Alison B. Moe,
- Mitsu Reddy,
- Arkady Khodursky,
- Johnny La,
- Ilma Abbas,
- Kay Mekaru,
- Hunter Collins,
- Farooq Siddiqui,
- Rory Nolan,
- Rupsa C. Boelig,
- Daniel G. Kiefer,
- Pamela M. Simmons,
- George R. Saade,
- Antonio Saad,
- Ebony B. Carter,
- Thomas F. McElrath,
- Stephen R. Quake,
- Mark A. DePristo,
- Carrie Haverty,
- Manfred Lee,
- Eugeni Namsaraev,
- Vincenzo Berghella,
- Ai-ris Y. Collier,
- Antonia I. Frolova,
- Esther Park-Hwang,
- Luis D. Pacheco,
- Elizabeth F. Sutton,
- Maneesh Jain,
- Kara Rood,
- William A. Grobman,
- Joseph R. Biggio,
- Cynthia Gyamfi-Bannerman,
- Arun Jeyabalan,
- Morten Rasmussen
Affiliations
- Michal A. Elovitz
- Mirvie Inc.
- Elaine P. S. Gee
- Mirvie Inc.
- Nathaniel Delaney-Busch
- Mirvie Inc.
- Alison B. Moe
- Mirvie Inc.
- Mitsu Reddy
- Mirvie Inc.
- Arkady Khodursky
- Mirvie Inc.
- Johnny La
- Mirvie Inc.
- Ilma Abbas
- Mirvie Inc.
- Kay Mekaru
- Mirvie Inc.
- Hunter Collins
- Mirvie Inc.
- Farooq Siddiqui
- Mirvie Inc.
- Rory Nolan
- Mirvie Inc.
- Rupsa C. Boelig
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University
- Daniel G. Kiefer
- Women’s Care Florida
- Pamela M. Simmons
- Woman’s Hospital
- George R. Saade
- Eastern Virginia Medical School
- Antonio Saad
- Inova Health
- Ebony B. Carter
- University of North Carolina at Chapel Hill
- Thomas F. McElrath
- Mirvie Inc.
- Stephen R. Quake
- Department of Bioengineering, Stanford University
- Mark A. DePristo
- BigHat Biosciences Inc.
- Carrie Haverty
- Mirvie Inc.
- Manfred Lee
- Mirvie Inc.
- Eugeni Namsaraev
- Mirvie Inc.
- Vincenzo Berghella
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University
- Ai-ris Y. Collier
- Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center
- Antonia I. Frolova
- Washington University School of Medicine
- Esther Park-Hwang
- MultiCare Health System
- Luis D. Pacheco
- Univerity of Texas Medical Branch
- Elizabeth F. Sutton
- Woman’s Hospital
- Maneesh Jain
- Mirvie Inc.
- Kara Rood
- The Ohio State University
- William A. Grobman
- The Ohio State University
- Joseph R. Biggio
- Ochsner Health
- Cynthia Gyamfi-Bannerman
- University of California San Diego
- Arun Jeyabalan
- University of Pittsburgh
- Morten Rasmussen
- Mirvie Inc.
- DOI
- https://doi.org/10.1038/s41467-025-58157-y
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 14
Abstract
Abstract Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. These results reclassify HDP clinical phenotypes into two distinct molecular subtypes, placental-associated or immune-associated. Validation performance for placental-associated HDP yields an AUC of 0.88 in the advanced maternal age population without pre-existing high risk factors. Molecular subtypes create new opportunities to apply precision-based medicine in maternal health.
