Blood Test Detects Preeclampsia Risk Months Before Symptoms Appear

Existing screening techniques in the first trimester rely primarily on maternal risk indicators or placental biomarkers, but these methods fail to detect over half of the cases and frequently identify risk only after the condition has already begun to develop. New findings presented at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) reveal that a straightforward blood test conducted during the first trimester may accurately flag women at risk of developing preeclampsia up to five months before a clinical diagnosis is made.

Researchers from the Carlos Simon Foundation (Valencia, Spain) and iPremom (Valencia, Spain) employed a cell-free RNA (cfRNA) “liquid biopsy” of maternal plasma to carry out the study. Between September 2021 and June 2024, 9,586 pregnant individuals from 14 hospitals in Spain participated. In a nested case-control study involving 216 participants, the team was able to successfully forecast both early-onset and late-onset forms of preeclampsia well ahead of symptom manifestation. The cfRNA methodology captures nuanced molecular cues from multiple maternal sources, such as the uterus and placenta, long before symptoms develop. According to findings published in Human Reproduction, blood was drawn during three different pregnancy stages (9–14 weeks, 18–28 weeks, and beyond 28 weeks or at diagnosis). cfRNA was extracted from 548 plasma samples taken from the 216 selected individuals and analyzed using Illumina sequencing technology. Researchers applied machine learning techniques to identify cfRNA “signatures” that could forecast the later development of preeclampsia.

In the first trimester, the cfRNA-based model achieved an 83% sensitivity and 90% specificity in predicting early-onset preeclampsia (EOPE), with an average lead time of 18 weeks before diagnosis and an AUC of 0.88. Notably, 47.2% of the predictive transcripts were associated with genes related to the maternal endometrium, particularly those involved in decidualization resistance—a failure of the uterine lining to adapt properly in early pregnancy. These findings bolster the idea that uterine dysfunction is a significant contributor to EOPE. Late-onset preeclampsia (LOPE) was also forecasted using a different cfRNA signature, approximately 14.9 weeks before clinical onset, and shared minimal transcript overlap with the EOPE profile. Unlike EOPE, the LOPE markers contained few decidualization-related genes and instead reflected broader systemic biological changes. This distinction affirms that EOPE and LOPE are biologically and temporally separate disorders.

“We are currently conducting a prospective clinical study designed to validate the utility and feasibility of cfRNA screening in standard prenatal care,” said project leader Dr. Tamara Garrido. “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.”

Related Links:
Carlos Simon Foundation
iPremom