Pregnancy is often described as a time of excitement and anticipation, but it also comes with its share of challenges and uncertainties. Most of the time, these challenges are routine—morning sickness, cravings, and the endless cycle of check-ups. But doctors also keep an eye out for conditions that can complicate pregnancy, one of the most significant being preeclampsia. Preeclampsia is a condition marked by high blood pressure and signs of stress on organs like the liver and kidneys, and in serious cases it can require early delivery to protect both mother and baby. It affects about 1 in 20 pregnant women but can impact many pregnancies when there are 140 million live births annually world-wide. And when it does appear, it requires careful management. The tricky part is that it usually shows up later in pregnancy, when there’s little warning.
A recently published paper in Nature Medicine takes on a question that has been frustrating doctors for decades: is there a way to spot preeclampsia sooner? Instead of inventing a brand-new test, Dr. Gavin Ha, an associate professor at Fred Hutch Cancer Center, and his mentee Mohamed Adil, teamed up with Dr. Swati Shree, associate professor and OBGYN in the Division Maternal Fetal Medicine at UW, and Dr. Tina Lockwood, professor in the Department of Laboratory Medicine at UW to look at routine prenatal cell-free DNA Screening for signals of preeclampsia. This is the blood test that pregnant women often have done in the first trimester around 10 or 12 weeks, mainly to check for chromosomal abnormalities such as downs syndrome in the baby. It works by reading little fragments of DNA that come from both the mother and the placenta, floating in the mother’s bloodstream. What the researchers realized is that these fragments might be telling us more than just whether chromosomes look normal. They might also be giving us an early peek into how a fetal tissue is doing.
To explore that idea, graduate student Mohamed Adil built a tool they called PEARL (preeclampsia early assessment of risk from liquid biopsy). Instead of looking for genetic mutations, PEARL examines how DNA fragments floating in the mother’s blood are revealing deeper epigenetic information. DNA doesn’t just drift around randomly—it’s wrapped around proteins called nucleosomes, and those patterns leave behind a kind of fingerprint that is unique to each cell type. By mapping these nucleosome “footprints” against reference patterns from different tissues, the researchers could estimate how much of the circulating DNA came from various tissues, including placenta, the immune system, and the endothelial lining of blood vessels. A reduction in placental DNA and an increase in endothelial DNA pointed to early dysfunction. Because preeclampsia is driven by a stressed placenta and damaged blood vessels, these subtle signals in the DNA fragments turned out to be meaningful.
When they tested PEARL on blood samples from almost two thousand pregnancies, they found something striking. Women who later developed preeclampsia consistently showed weaker signals from the placenta and stronger signals from their blood vessels. In other words, the DNA was already whispering that the mother’s body was under stress—even though outwardly everything seemed fine. What’s remarkable is how early this could be seen. PEARL was able to predict risk as early as 12 weeks into pregnancy, months before preeclampsia usually appears.
The accuracy was impressive too. When applied to a large, real-world group of pregnant women, the model correctly distinguishes between positive and negative cases about 85% of the time. For a condition that has long been thought of as unpredictable this early in pregnancy, that number is hard to ignore. And the best part is that it didn’t require a new blood draw or a complicated new test. All this information came from data that was already being collected during standard prenatal care.
The implications are powerful. If doctors can know early on which women are at high risk, they can take simple but meaningful steps. Something as straightforward as starting low-dose aspirin early in pregnancy can lower risk, but doctors need to know who actually needs it. Women flagged by the test could also be monitored more closely, giving doctors a chance to step in before things become dangerous. For families, this knowledge could mean fewer frightening surprises, fewer emergency early deliveries, and more chances for healthy outcomes.
Of course, there are limits. This study mostly included women in places where cell-free DNA testing is already common, which often means wealthier countries. In parts of the world where preeclampsia is most deadly, this kind of testing is harder to access. Bringing a tool like PEARL to those settings will take work—making it cheaper, simpler, and more widely available. However, PEARL demonstrates that it is possible to predict preeclampsia in the first trimester, giving hope that further innovation could make the test affordable and accessible, especially in low- and middle-income countries.
For so long, preeclampsia has been like a hidden trap in pregnancy care, one that even experienced doctors couldn’t see coming. This research shows that the signs are there, just hidden in plain sight in the DNA floating in an expectant mother’s blood. By rethinking how we use a test that’s already part of routine care, the researchers have opened up the possibility of catching this condition early and improving outcomes for mothers and babies.
This research was supported by the National Institutes of Health, the Washington Entrepreneurial Research Evaluation and Commercialization Hub (WE-REACH), and the National Heart, Lung, and Blood Institute.
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium members Dr. Colin Pritchard and Gavin Ha contributed to this research.
Adil, M., Kolarova, T. R., Doebley, A. L., Chen, L. A., Tobey, C. L., Galipeau, P., Rosen, S., Yang, M., Colbert, B., Patton, R. D., Persse, T. W., Kawelo, E., Reichel, J. B., Pritchard, C. C., Akilesh, S., Lockwood, C. M., Ha, G., & Shree, R. (2025). Preeclampsia risk prediction from prenatal cell-free DNA screening. Nature medicine, 31(4), 1312–1318.
Science Spotlight writer Darya Moosavi is a postdoctoral research fellow within Johanna Lampe's research group at Fred Hutch. Darya studies the nuanced connections between diet, gut epithelium, and gut microbiome in relation to colorectal cancer using high-dimensional approaches.
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