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<p>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 (<i>n</i> = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene <i>PAPPA2</i> 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.</p>

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Molecular subtyping of hypertensive disorders of pregnancy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月8日

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  • 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

摘要

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.