Early prediction of preeclampsia in pregnancy with cell-free RNA

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 care(1-4). 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 globally(5). 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 physiology(6-9), 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 care(10,11).

Automated summary

Liquid biopsies that measure circulating cell-free RNA can be used to study the development of pregnancy-related complications. This study identified and validated cfRNA transcriptomic changes associated with preeclampsia, and found that these changes are marked and stable early in gestation. Genes specific to neuromuscular, endothelial, and immune cell types and tissues are enriched in these changes, suggesting their relevance to preeclampsia physiology and providing new hypotheses for disease progression. Based on these findings, a panel of 18 genes was identified that can form the basis of a liquid biopsy test to identify mothers at risk of preeclampsia long before symptoms occur.