Early blood test accurately predicts preeclampsia months before symptoms

Preeclampsia risk may be measured up to 5 months before a patient presents with symptoms through a first-trimester simple blood test, according to a recent study presented at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE).¹

High accuracy of cfRNA model in predicting early-onset preeclampsia

Investigators developed a cell-free RNA (cfRNA) model for early-onset preeclampsia (EOPE) prediction. In a nested case-control analysis, the model displayed a sensitivity of 83%, specificity of 90%, and an area under the curve of 0.88. This indicated high accuracy at a mean of 18 weeks before 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 Nerea Castillo Marco, PhD, first study author. “Identifying high-risk pregnancies this early opens a crucial window for preventive treatment and closer monitoring to protect mothers and babies.”

The importance of early preeclampsia screening was highlighted by Eran Bornstein, MD, director of obstetrics and gynecology at Northwell’s Lenox Hill Hospital, in an interview with Contemporary OB/GYN.² According to Bornstein, early detection allows for effective intervention with low-dose aspirin, significantly reducing preeclampsia risk when administered after first-trimester screening.

Use of machine learning to identify predictive signatures

The model employed cfRNA liquid biopsies of maternal plasma from 216 participants.¹ These patients had blood samples collected at multiple time points, including 9 to 14 weeks’ gestation, 18 to 28 weeks’, over 28 weeks’ and at diagnosis. Across the study population, cfRNA extraction was performed in 548 plasma samples.

Sequencing was performed using Illumina technology, and cfRNA signatures linked to future preeclampsia development were identified through machine learning. This is an improvement over traditional first-trimester screening methods for preeclampsia, which miss over half of future preeclampsia cases.

These methods rely on maternal risk factors and placental biomarkers. In comparison, subtle molecular signals may be identified across multiple tissues using cfRNA, allowing for diagnosis months before symptom development. The model successfully predicted both EOPE and late-onset preeclampsia (LOPE) in this timeframe.

Differentiating EOPE and LOPE

A link to genes associated with the maternal endometrium was found for 47.2% of predictive transcripts. Specifically, they were linked to decidualization resistance, which investigators described as a failure to have the uterine lining adapt properly in early pregnancy. According to investigators, this highlights a key role of uterine dysfunction in EOPE.

Prediction of LOPE was accomplished at an average of 14.9 weeks before onset using a distinct cfRNA signature that had little overlap with EOPE. Unlike EOPE signatures, LOPE signatures had few decidualization-related transcripts. Instead, broader systemic biological signals were observed, highlighting EOPE and LOPE as biologically and temporally distinct conditions.

To expand on these findings, investigators plan on conducting research about the utility and feasibility of cfRNA screening in standard prenatal care. According to Tamara Garrido, PhD, project lead, this may lead to cfRNA-based screening be available in clinical practice within 1 year, increasing the availability of early, non-invasive identification of non-invasive pregnancies.

“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,” said Karen Sermon, MD, PhD, Chair of ESHRE.

References

1. Simple blood test detects preeclampsia risk months before symptoms appear, new study shows. European Society of Human Reproduction and Embryology. June 29, 2025. Accessed July 8, 2025. https://www.eurekalert.org/news-releases/1088640.
2. Bornstein E. Eran Bornstein, MD explains the need for first trimester preeclampsia screening. Contemporary OB/GYN. June 9, 2025. Accessed July 8, 2025. https://www.contemporaryobgyn.net/view/eran-bornstein-md-explains-the-need-for-first-trimester-preeclampsia-screening.