Molecular subtyping of hypertensive disorders of pregnancy

Molecular subtyping of hypertensive disorders of pregnancy

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 stud...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58157-y
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Summary: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.
ISSN:2041-1723

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