Preeclampsia diagnostics and the promise of angiogenic biomarkers

Preeclampsia continues to represent one of the most serious challenges in maternal health, affecting between 2% and 8% of pregnancies worldwide¹. Despite improvements in obstetric care, it remains a leading cause of maternal and perinatal morbidity and mortality. In many cases, its onset can be sudden and unpredictable, leaving clinicians to make difficult decisions under pressure.

Blood pressure and proteinuria have been traditional biomarkers for preeclampsia diagnosis for decades. However, these parameters can be inconsistent and lack predictive accuracy. Other key indicators, such as thrombocytopenia, impaired liver or kidney function, pulmonary edema, or persistent neurological symptoms often appear only after the disease has advanced. This clinical complexity drives the need for better diagnostic tools, ones that can identify risk earlier, stratify patients more precisely, and support timely, evidence-based decisions.

During a recent educational webinar hosted by SelectScience^® and Siemens Healthineers, Dr. Michael O’Bryan, global director of medical science liaisons and a trained OB-GYN, explored how new biomarker-based diagnostic tools are reshaping risk assessment and patient management in preeclampsia.

The pathophysiology of preeclampsia

Preeclampsia is a vascular disorder characterized by damage to the endothelial lining of blood vessels, which contributes to hypertension, edema, and strain on vital organs. As a result, researchers are particularly interested in the placenta and a class of proteins known as angiogenic factors, which play a key role in regulating blood vessel growth. Two angiogenic factors are central to this discussion: placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1).

Both belong to the vascular endothelial growth factor (VEGF) family and regulate angiogenesis during pregnancy. “PlGF is necessary for placentation and the placental growth that occurs throughout most of pregnancy to support the growing fetus,” says Dr. O’Bryan. “It’s directly responsible for stimulating and maintaining cytotrophoblast invasion and supporting angiogenesis of that fetal blood supply.”

By contrast, sFlt-1 acts as a counterbalance. “The sFlt-1 is made by the placenta and is used to tightly regulate the availability of PlGF and VEGF throughout pregnancy—and here's the key here—to prevent placental overgrowth,” he shares. In healthy pregnancies, levels of these biomarkers shift gradually, PlGF increases in early pregnancy and peaks near 30 weeks, while sFlt-1 levels stay relatively stable until late gestation, when they rise naturally before delivery.

In preeclampsia, that balance is disturbed. “The concentrations of free PlGF are significantly lower in the preeclampsia cohorts,” Dr. O’Bryan notes. “The sFlt-1 was elevated in women who eventually developed preeclampsia.” When these trends are combined, the sFlt-1/PlGF ratio becomes a powerful reflection of disease biology and a measurable diagnostic tool.

sFlt-1/PlGF ratio for diagnostic confidence

Numerous clinical studies, including the landmark PROGNOSIS trial², have validated the use of the sFlt-1/PlGF ratio to help clinicians distinguish between women at low and high risk of developing preeclampsia. “If you don’t care about anything else in this study, take this away,” Dr. O’Bryan states. “The study authors were able to assign a cutoff ratio of 38 for ruling out preeclampsia within one week of testing with a very high negative predictive value. That’s the key.”

This ability to rule out preeclampsia with high confidence is critical. It helps reduce unnecessary hospital admissions and anxiety for patients whose symptoms may be unrelated to the disease. “This is about giving physicians more confidence in their decisions, avoiding unnecessary early deliveries, and extending monitoring in lower risk cases,” says Dr. O’Bryan

Higher sFlt-1/PlGF ratios, on the other hand, can serve as an early warning. “Over 85 before 34 weeks of gestation and over 110 after 34 weeks of gestation is more specific for the diagnosis of preeclampsia,” he explains. Serial measurements can also help identify progression. “Women with higher ratios delivered earlier than women who did not develop an elevated ratio,” says Dr. O’Bryan. “The ratio elevated far more rapidly and dramatically in those who required early delivery versus those who did not.”

This trend analysis offers valuable prognostic insight, supporting individualized monitoring strategies. “Something that becomes simple and repeatable is going to be extremely important here,” he says. “Because an OB-GYN is going to look at when is the last optimal date, when is the soonest latest date we have to deliver—it becomes this risk versus reward.”

Global evidence and guideline alignment

The growing body of evidence supporting angiogenic biomarker testing has led to changes in international clinical guidelines. “We see that this diagnostic ratio is not emerging in a vacuum,” Dr. O’Bryan shares. “There are a lot of international and national guidelines that support this angiogenic biomarker in the risk assessment for preeclampsia.”

Dr. O’Bryan points to the list of organizations supporting angiogenic biomarker testing, including the National Institute for Health and Care Excellence (NICE) which recommends using the sFlt-1/PlGF ratio to rule out preeclampsia between 20 and 34 weeks of gestation. “Again, we’re trying to get to an earlier onset of getting a fuller understanding to try to prevent,” he says. “We want to have proactive, not reactive, care here.” The International Society for the Study of Hypertension in Pregnancy (ISSHP) and the International Federation of Gynecology and Obstetrics (FIGO) have also acknowledged the value of angiogenic biomarkers for risk stratification and management.

“The ISSHP acknowledges the utility of these markers, again, in risk stratification, particularly in the difficult-to-diagnose cases,” says Dr. O’Bryan. “NICE has gone a step further and FIGO highlights the importance of precision diagnostics for improving maternal outcomes.” Together, these endorsements reflect a shift toward more evidence-based, biomarker-driven approaches in maternal health.

Implementing biomarker testing with collaboration and change

Adoption of the sFlt-1/PlGF ratio test requires collaboration across departments, from obstetrics to the laboratory and hospital administration. “You have to bridge the gap and work together,” Dr. O’Bryan emphasizes. “The biggest barrier is inertia. It’s having champions. It’s forward thinking; it’s innovative thinking to make change.”

He encouraged clinicians and laboratory teams to advocate for integration within existing workflows. “If we could implement the blood sample to come in afterwards, and we can get that ratio, which means again working with that laboratory, do we have something in our current setup to be able to handle this blood sample? Yes or no? That leads to further questions with different teams in the C-suite level,” he states.

Implementation, he adds, is not about replacing existing diagnostic methods but about complementing them. “While the support of the traditional diagnostic markers like blood pressure and proteinuria can still be considered useful—the predictive value—it’s not good enough on its own,” he says. “Why can’t we take a blood test as well, use this ratio, and begin to make predictive, evidence-based value to improve early identification and early management?”

A more precise, patient-centered future

For Dr. O’Bryan, the future of preeclampsia diagnostics lies in precision, repeatability, and accessibility. “We have enough international push now, we have enough medical-based evidence to push now with this multi-marker panel,” he says. The integration of angiogenic biomarkers into electronic health records and care algorithms marks a critical step toward global adoption.

“I’m hoping that we can envision a diagnostic landscape where the clinical judgment is enhanced,” he says. “Now we have something that is repeatable; it is measurable at any point in time we want to have a simple blood test. I’m not just having to get a urine sample and hoping that something did not go wrong when I measure a blood pressure.”

He stresses that this innovation should expand access, not just accuracy. “We’re not saying that anything currently should be replaced,” he concludes. “We’re saying: ‘How about adding in a predictable tool that identifies at-risk women earlier and more accurately?’ And this ratio, I believe, is just the beginning.”

With the growing evidence base, evolving guidelines, and broadening implementation, angiogenic biomarker testing, particularly the sFlt-1/PlGF ratio, is poised to redefine how clinicians approach preeclampsia diagnostics. As healthcare moves toward data-driven, personalized care, this innovation offers a promising path toward safer pregnancies, fewer unnecessary interventions, and improved outcomes for mothers and babies worldwide.

Discover more about how laboratory innovation is redefining preeclampsia detection and risk assessment by watching the full webinar on demand.

Learn more about preeclampsia and angiogenic biomarker solutions from Siemens Healthineers.

References
1. Pre-eclampsia. World Health Organization. Available from:https://www.who.int/news-room/fact-sheets/detail/pre-eclampsia [accessed 2026 Jan 6]
2. Zeisler H, Llurba E, Chantraine F, et al. Predictive Value of the sFlt-1 PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med 2016;374:13-22.