RNA as a Roadmap to Improved Diagnosis and Treatment of Preeclampsia

Preeclampsia, a condition that causes high blood pressure and organ damage during pregnancy, is responsible for 14% of maternal deaths each year. Despite the high prevalence of preeclampsia, its causes continue to elude scientists. Even more troublingly, there are currently no tests that can consistently predict the onset of preeclampsia early on in pregnancy, and early diagnosis is critical for effectively treating the condition. A team of biologists and doctors may have hit on a marker for preeclampsia that is the ticket to achieving this earlier diagnosis.

In a study published in the journal Nature Communications, scientists at iPremom Pregnancy HealthCare Diagnostics in Spain explore a new approach to diagnosing preeclampsia. They reported that examining a specific type of RNA in blood samples can predict as early as the first trimester that someone is likely to get preeclampsia. With this, they offer a promising non-invasive method for diagnosing preeclampsia and monitoring its progression throughout pregnancy.

High magnification micrograph of hypertrophic decidual vasculopathy, as seen in pre-eclampsia. Wikimedia, 2010. Creative Commons License.

Preeclampsia is persistent high blood pressure that develops during pregnancy and is accompanied by damage to the kidneys, liver, lungs, or brain. In the worst cases, it can cause seizures and strokes. There are two types of preeclampsia: early-onset preeclampsia (EOPE), which begins before the 34th week of pregnancy, and late-onset preeclampsia (LOPE), which begins after the 34th week of pregnancy.

Both types are usually diagnosed after the 20th week of pregnancy, and the current diagnosis is made based on the patient showing symptoms of preeclampsia, such as high blood pressure, kidney or liver problems, fluid in their lungs, or seizures. Collecting information on some of these markers requires invasive testing, and basing a diagnosis on these criteria means that the diagnosis is only possible after the worst effects of preeclampsia have already begun.

According to the study in Nature Communications, all that may be required for diagnosis is a blood test. The study reports that cell-free RNA (cfRNA) from a blood sample can not only indicate if a patient is at risk for preeclampsia, but also which type of preeclampsia, EOPE or LOPE, they are at risk for. cfRNA is any RNA that is found outside of cells in bodily fluids, like blood. RNA is a messenger that tells our cells what to do based on the genes in our DNA. When organs start malfunctioning as a result of preeclampsia, it’s because the RNA brings them different information from a patient’s genes than it normally does. This means that the cfRNA from a healthy patient has a different sequence of genes than the cfRNA from a patient with preeclampsia.

The study analyzed data from 7,142 pregnant women. They drew blood from each participant once during their first trimester, once during their second trimester, and once at the time of their preeclampsia diagnosis, or after 28 weeks if they did not develop preeclampsia. They examined participants’ cfRNA to determine what organs it came from and compared the genes in the cfRNA of patients with preeclampsia to the cfRNA of healthy patients.

They found that patients with EOPE experienced tissue damage in their liver, kidneys, and placenta eight weeks before they began experiencing clinical symptoms and received their diagnosis. By the time of diagnosis, patients with EOPE were showing even more widespread organ damage, with additional disruptions to their brain, lungs, and lymphoid tissues. Conversely, patients with LOPE did not show signs of organ damage much prior to the time of their diagnosis. The study concluded that changes to cfRNA and organ damage progressively get worse for patients with EOPE, while they are more static for patients with LOPE.

Next, they created a model to predict whether or not a patient would develop preeclampsia based on cfRNA markers collected from a blood sample in the first trimester. Nearly all of their samples accurately predicted whether or not a patient would develop EOPE. However, the model was not as successful in predicting LOPE risk in the first trimester. They created an additional model to predict preeclampsia based on cfRNA collected in the second trimester. This model produced reliable predictions for EOPE and LOPE.

Whereas current diagnostic techniques are best at predicting preeclampsia only two weeks before the onset of symptoms, the models built in this study can predict preeclampsia up to 18 weeks before the onset of symptoms. The study offers a reliable, standardized method of predicting preeclampsia early on in pregnancy, which would allow for earlier interventions to treat preeclampsia and minimize its risk. Additionally, the distinctions the study found between cfRNA changes in EOPE and LOPE open up an avenue to studying the causes of each type and developing new therapeutics for them.

A large-scale study is currently underway to further assess the validity of the predictive cfRNA model. While the model has not yet been used clinically, it could fundamentally alter the way that preeclampsia is diagnosed and treated and save the lives of tens of thousands of pregnant women each year.

By Ada Fiala

References:

Castillo-Marco, N., Cordero, T., Igual, M, et al. Maternal plasma cell-free RNA as a predictor of early and late-onset preeclampsia throughout pregnancy. Nature Communications 16, 9208 (2025). https://doi.org/10.1038/s41467-025-64215-2

CD Genomics. Cell-free RNA (cfRNA) as a liquid biopsy biomarker for disease screening and diagnosis. https://rna.cd-genomics.com/resource/cfrna-biomarker.html 

Preeclampsia Foundation. What is preeclampsia? 2023. https://www.preeclampsia.org/what-is-preeclampsia