Early prediction of preeclampsia in pregnancy with cell-free RNA

Mira N. Moufarrej, Sevahn K. Vorperian, Ronald J. Wong, Ana A. Campos, Cecele C. Quaintance, Rene V. Sit, Michelle Tan, Angela M. Detweiler, Honey Mekonen, Norma F. Neff, Courtney Baruch-Gravett, James A. Litch, Maurice L. Druzin, Virginia D. Winn, Gary M. Shaw, David K. Stevenson and Stephen R. Quake ()
Additional contact information
Mira N. Moufarrej: Stanford University
Sevahn K. Vorperian: Stanford University
Ronald J. Wong: Stanford University School of Medicine
Ana A. Campos: Stanford University School of Medicine
Cecele C. Quaintance: Stanford University School of Medicine
Rene V. Sit: Chan Zuckerberg Biohub
Michelle Tan: Chan Zuckerberg Biohub
Angela M. Detweiler: Chan Zuckerberg Biohub
Honey Mekonen: Chan Zuckerberg Biohub
Norma F. Neff: Chan Zuckerberg Biohub
Courtney Baruch-Gravett: Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
James A. Litch: Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
Maurice L. Druzin: Stanford University School of Medicine
Virginia D. Winn: Stanford University School of Medicine
Gary M. Shaw: Stanford University School of Medicine
David K. Stevenson: Stanford University School of Medicine
Stephen R. Quake: Stanford University

Nature, 2022, vol. 602, issue 7898, 689-694

Abstract: Abstract Liquid biopsies that measure circulating cell-free RNA (cfRNA) offer an opportunity to study the development of pregnancy-related complications in a non-invasive manner and to bridge gaps in clinical care1–4. Here we used 404 blood samples from 199 pregnant mothers to identify and validate cfRNA transcriptomic changes that are associated with preeclampsia, a multi-organ syndrome that is the second largest cause of maternal death globally5. We find that changes in cfRNA gene expression between normotensive and preeclamptic mothers are marked and stable early in gestation, well before the onset of symptoms. These changes are enriched for genes specific to neuromuscular, endothelial and immune cell types and tissues that reflect key aspects of preeclampsia physiology6–9, suggest new hypotheses for disease progression and correlate with maternal organ health. This enabled the identification and independent validation of a panel of 18 genes that when measured between 5 and 16 weeks of gestation can form the basis of a liquid biopsy test that would identify mothers at risk of preeclampsia long before clinical symptoms manifest themselves. Tests based on these observations could help predict and manage who is at risk for preeclampsia—an important objective for obstetric care10,11.

Date: 2022
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DOI: 10.1038/s41586-022-04410-z

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