(Paris, France, Monday, 30 June 2025) A simple blood test taken in the first trimester of pregnancy could accurately identify women at risk of developing preeclampsia five months before clinical diagnosis, according to new research presented today at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE).[1]
Using a cell-free RNA (cfRNA) "liquid biopsy" of maternal plasma, researchers at the Carlos Simon Foundation and iPremom enrolled 9,586 pregnant women from 14 hospitals across Spain between September 2021 and June 2024. In a nested case-control analysis of 216 participants, they successfully predicted both early-onset and late-onset preeclampsia well before the onset of symptoms.
Preeclampsia, a complication marked by high blood pressure and organ damage in pregnancy, is a leading cause of maternal and infant illness worldwide.[2] Current first-trimester screening methods rely on maternal risk factors or placental biomarkers but miss over half of impending cases and often detect risk only after the disorder is already developing. By contrast, the cfRNA approach can capture subtle molecular signals from multiple maternal tissues, including the uterus and placenta, months before symptoms appear.
Blood samples were collected at multiple timepoints during pregnancy (9–14 weeks, 18–28 weeks, and >28 weeks or at diagnosis). cfRNA was extracted from 548 plasma samples across the 216 selected participants and sequenced using Illumina technology. Using machine learning, researchers identified cfRNA "signatures" that signalled future development of preeclampsia.
In the first trimester, a cfRNA model predicted early-onset preeclampsia (EOPE) with 83% sensitivity, 90% specificity, and an AUC of 0.88, on average 18 weeks prior to diagnosis.
"For the first time, we've shown that a routine blood sample in the first trimester can give an early warning for preeclampsia with high accuracy, well before symptoms appear", said biomedical researcher Dr. Nerea Castillo Marco, first author of the study. "Identifying high-risk pregnancies this early opens a crucial window for preventive treatment and closer monitoring to protect mothers and babies."
Notably, 47.2% of the predictive transcripts were linked to genes associated with the maternal endometrium, specifically decidualisation resistance, a failure of the uterine lining to properly adapt in early pregnancy. This supports the theory that uterine dysfunction plays a key role in EOPE.[3]
Late-onset preeclampsia (LOPE) was also predicted, on average 14.9 weeks before onset, using a distinct cfRNA signature with minimal overlap to that of EOPE. In contrast to EOPE, LOPE signatures included few decidualisation-related transcripts and instead reflected broader systemic biological signals. These findings confirm that EOPE and LOPE are biologically and temporally distinct conditions.
"Our transcriptomic analyses showed that EOPE involves widespread molecular changes across organs, including liver, kidney, placenta, brain, and lungs", explained Dr. Castillo Marco. "In contrast, LOPE displayed later-onset and more localised patterns, particularly in immune and hepatic pathways."
Looking ahead, the project leader Dr. Tamara Garrido said, "We are currently conducting a prospective clinical study designed to validate the utility and feasibility of cfRNA screening in standard prenatal care. With validation and regulatory efforts already underway, we anticipate that cfRNA-based screening could become available in clinical practice within the next year, offering an unprecedented opportunity for early, non-invasive identification of high-risk pregnancies and timely intervention."
Commenting on the study, Prof. Dr. Karen Sermon, Chair of ESHRE, said, "Besides offering a major breakthrough in preventive prenatal care for a common and often dangerous condition during pregnancy, this research increases our understanding at a molecular level of a complex pathology that remains poorly understood.
The study abstract will be published today in Human Reproduction, one of the world's leading reproductive medicine journals.
