Recent findings in preeclampsia research have shown that preeclampsia likely has at least two variants – an early onset and a late onset variant. Early onset is typically defined as before 34 weeks gestation and late onset is after 34 weeks gestation. While both may include severe features, research suggests that the early onset variant has unique biomarkers that are related to how the placenta grows and functions. Two of these markers, placenta growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 receptor (sFlt-1) have helped to create helpful risk stratification tools for providers to use in telling what patient may go on to develop severe disease. (See our guide on preeclampsia tests.) However, not all cases of preeclampsia may have differences in these placental markers, especially those with later onset. Late-onset preeclampsia is a significant challenge in obstetrics because it can happen without warning and still be extremely severe. For that reason, researchers continue to look at other promising risk marker candidates to answer the question: how do we tell who is at risk for late-onset preeclampsia?

In this study, researchers looked at ~7000 protein markers across 673 samples from 89 patients who had late onset preeclampsia and 91 controls who did not have any form of hypertensive disorder of pregnancy (HDP). Proteomics is the large-scale, comprehensive study of the proteome—the entire set of proteins produced or modified by an organism, system, or cell at a specific time. In this case, researchers looked at proteins created by the placenta that circulate through the blood stream during pregnancy. The samples were taken at three different points during the pregnancy: 15-22 weeks, 22-30 weeks, and 30-42 weeks. There were slight differences between the affected population and the controls. Those with late-onset preeclampsia (LOPE) were more likely to have a higher BMI and more likely to be first-time pregnant patients (nulliparity). About 810 proteins were different between those with LOPE and the controls, especially during the last point of measurement (30-42 weeks). It suggests that factors that contribute to the aging of the placenta, issues with how the placenta implants, and inflammation may all have a role to play in why some patients develop late onset preeclampsia. 

Take Home Nessage: this research is still very early-stage for identifying a group of proteins that might make a good predictive test for late-onset preeclampsia. However, it represents a beginning of understanding how we may one day have better tools to predict and/or rule out late-onset preeclampsia more fully and even possibly, to find ways to intervene to prolong pregnancy during the third trimester. The study also further supports the growing theory that preeclampsia may be two or more distinct diseases that manifest in similar ways. Patients: remember to watch out for signs and symptoms of preeclampsia during pregnancy and for six weeks after birth and tell your doctor right away. This helps you get the care you need as soon as possible.

Citation: Andresen, IJ, Romero, R, et al. Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia, 2026. J Hypertension. doi:10.1161/HYPERTENSIONAHA.125.25189

Link: https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.125.25189 

About Research Roundup:

Each quarter, our team of science writers reviews the most current research studies related to hypertensive disorders of pregnancy and summarizes those studies of greatest interest and potential impact to our community, including research studies related to risk assessment, diagnosis, prevention, and treatment. Special thanks to our volunteer research team including Dr. Sig-Linda Jacobson, Dr. Jennifer Mitchell, Dr. Julie Reynolds, Amanda Yang, and Simren Gupta who make Research Roundup possible, and to our Patient Advisory Council, who reviews these materials from the patient perspective.