Early prediction of preeclampsia in pregnancy with cell-free RNA
- PMID: 35140405
- PMCID: PMC8971130
- DOI: 10.1038/s41586-022-04410-z
Early prediction of preeclampsia in pregnancy with cell-free RNA
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.
© 2022. The Author(s).
Conflict of interest statement
M.N.M., S.K.V., G.M.S., D.K.S. and S.R.Q. are inventors on a patent application submitted by the Chan Zuckerberg Biohub and Stanford University that covers non-invasive early prediction of preeclampsia and monitoring maternal organ health over pregnancy (USPTO application number 63/159,400 filed on 10 March 2021 and 63/276,467 filed on 5 November 2021). S.R.Q. is a founder, consultant and shareholder of Mirvie. M.N.M. is also a shareholder of Mirvie.
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