Clinicians can now use two new biomarker-based assays in combination to determine which patients admitted to the hospital for a hypertensive disorder of pregnancy are at higher risk for poor outcomes.

By Alejandro Risso

Preeclampsia is a life-threatening blood pressure disorder that can occur during pregnancy and the postpartum period. Worldwide, 76,000 women and 500,000 babies die each year from this disorder,[i] and many more mothers are at risk of medically necessary preterm delivery, intrauterine growth restriction, and other complications.

Until recently, however, the current tools available for clinical diagnosis of preeclampsia—blood pressure measurement, checking proteinuria levels, blood tests for evaluation of complications (aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet (PLT) count), and regular prenatal care—have provided ambiguous results to clinicians.[ii],[iii] Few new diagnostic options have become available to clinicians and clinical labs to help identify or predict progression to severe disease and adverse outcomes.

As is often the case in the development of new diagnostics, innovations are a direct result of clinician and clinical laboratory demand. Such is the case with preeclampsia and other new tests that can improve maternal and fetal health outcomes. This demand is leading to increased reliance on state-of-the-art analyzers that, because of their footprint and ease of use, are capable of easily slotting into existing labs as well as an expanding the menu of novel and routine assays that labs can run.

A Biomarker-Based Assay Breakthrough

Following extensive clinical research, including the recent PRAECIS study,[iv] a new preeclampsia test that uses validated biomarkers has recently been granted FDA clearance. Clinicians can now use two new biomarker-based assays in combination to determine which patients admitted to the hospital for a hypertensive disorder of pregnancy are at higher risk for poor outcomes versus those likely to remain stable.

In the PRAECIS study, clinicians were able to stratify women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks of gestation according to their risk of progressing to preeclampsia with severe features within the next two weeks. The stratification was based on a ratio of measured soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). The assays  to detect these biomarkers, Thermo Scientific B·R·A·H·M·S PlGF plus KRYPTOR and B·R·A·H·M·S sFlt-1 KRYPTOR,  received breakthrough designation and clearance for the risk assessment and clinical management of preeclampsia.

Easily Incorporated in Clinical Labs

Today, the lab serving Cedars Sinai Medical Center Los Angeles is among those already providing clinicians with the new prognostic biomarker-based assay, which is based on the sFlt-1/PLGF ratio derived from either plasma or serum samples. The test results, in conjunction with other laboratory and clinical findings, guides clinicians toward the appropriate American College of Obstetrics and Gynecology (ACOG) criteria, which includes ongoing monitoring for low-risk patients or stepped-up care for high-risk patients. 

Anders Berg, MD, PhD, who is the CLIA lab director for Cedars-Sinai Medical Center Los Angeles, is quick to point out that action is one of the most important criteria for the clinicians his lab serves: “Clinicians, hospitals, and patients want testing that informs action. Tests that are immediately actionable can save lives and reduce unnecessary costs.”

Cedars Sinai Medical Center has faced an increasing number of preeclampsia cases in recent years, and the Center’s heads of obstetrics and family medicine advocated strongly for the lab to add the new biomarker-based assay to its menu.

“Given the number of mothers who come through our doors, and the increasing incidence of preeclampsia nationwide, the decision to add this test was easy. We are thrilled to be one of the first health systems in the country to offer it to our patients. Now our clinicians have a new objective tool to help them make important care decisions affecting both a baby’s and mother’s health, including whether to immediately transfer a higher risk pregnancy to a tertiary care facility, and we believe this will lead to improved care management and better outcomes overall,” Berg added.

Like many hospitals and clinical labs, Berg and his team were deliberate in their consideration of the new test. The key criteria were impact on patients’ health outcomes, validation through FDA clearance, how affordably and efficiently the test and its analytical system can be validated by the lab, compatibility with existing workflows, and confidence in rapid turnaround times to inform actionable medical decisions.

A Case for the Future

The sFlt-1 and PlGF biomarker-based assays are designed to run on the Thermo Scientific B·R·A·H·M·S KRYPTOR compact PLUS immunoassay analyzer. The benchtop instrument uses TRACE technology, to help labs deliver results to clinicians in less than 30 minutes while offering the flexibility to quickly expand test menus as new assays receive clearance.

Speed is only part of what’s important to clinical decision makers. Berg underscores the importance of having new objective tools to assist clinicians in making major care decisions, including whether to immediately transfer a higher risk pregnancy to a tertiary care facility. He says that adding the preeclampsia assays to his lab’s testing menu was an easy decision and “it should be a priority for all laboratories and hospitals to do everything they can to address the poor maternal health outcomes associated with preeclampsia, especially the disparate impact it has across certain parts of our population.”

Labcorp, a provider of innovative and comprehensive laboratory services, is another early adopter of the preeclampsia biomarker-based assays that was able to quickly validate the test on its existing system to ensure access to its clinical customers.

As clinicians and lab directors confront an expanding menu of biomarker-based assays, the theory is that they will be able to better assess or predict whether a disease is going to develop into a medically dangerous situation. In this case, the information will be highly actionable, even if it doesn’t provide a yes/no answer. The key is having objective evidence for better decision-making, improved care, reduction of unnecessary procedures and costs, and the ability to direct the right treatment to those at greatest risk for poor outcomes.

“Labcorp is proud to partner with Thermo Fisher to offer this test, which provides clinicians early and objective information to assist in the management of preeclampsia. In line with Labcorp’s mission to improve health and improve lives, this offering is another example of our commitment to provide the most comprehensive and advanced menu of diagnostic tests, while supporting patients and providers with clinically important and meaningful information to support better outcomes for parents and their newborns,” says Marcia Eisenberg, PhD, chief scientific officer of Labcorp. 

Developing Biomaker-based Assays

As part of the FDA approval process for the new preeclampsia biomarker-based assays, researchers studied more than 1,000 pregnant women in 18 hospitals across the U.S., 31% of whom were Black. Black women are 60% more likely to develop preeclampsia,[v] and this makes the new test particularly important from a health equity standpoint. Wider availability and access to objective tests earlier in pregnancy, especially for lower income and higher risk individuals, answers an important call for health equity in this country.

According to Sarosh Rana, MD, MPH, professor of Obstetrics and Gynecology and section chief of Maternal Fetal Medicine at the University of Chicago, this new biomarker-based assay provides an important “warning sign” for Black women and others disproportionately affected by preeclampsia, and her team is among those nationwide already using the new assays in daily practice. Rana was one of the clinicians nationally pushing for better maternal care diagnostics, especially tests that ensure treatment objectivity and improve health equity.

When clinicians and their labs collaborate to expand their testing menus, they must weigh the costs against the economic and clinical consequences of not making a change. In the case of the preeclampsia biomarker-based assays, the consequences of delayed diagnosis or misdiagnosis are well documented. Offering a routine lab test during a critical point in pregnancy can not only better utilize finite healthcare resources, but it can also save lives.

The new biomarker-based assays are a significant scientific achievement and pave the way for further development around the B·R·A·H·M·S KRYPTOR compact PLUS analyzer, but the societal impact on mothers, babies, and those disproportionately affected supersedes all. Black women have higher rates of pre-existing chronic hypertension, preeclampsia-related complications, and adverse outcomes, and an objective test for preeclampsia-related complications directly benefits them. This makes the development and widespread use of an objective, accessible, and affordable test both a clinical and societal benefit.

Author Bio

Alejandro Risso is the president of the Clinical Diagnostics business at Thermo Fisher Scientific Inc. The Clinical Diagnostics Division provides customers and patients with diagnostic solutions that improve patient outcomes. Thermo Fisher Scientific’s innovation in clinical diagnostics made global headlines in 2023, when its Preeclampsia Blood Test was recognized in the “TIME Best Inventions of 2023,” a list of 200 extraordinary innovations that are changing lives around the world.  Prior to his current role, Alejandro held General Management roles of global responsibility driving specialized diagnostic businesses in Clinical Biomarkers & Immunoassay Platforms, Therapeutic Drug Monitoring, Toxicology, Quality Controls for immunoassays, and other diagnostics products and services. He has also served in other global leadership roles in the U.S. and Europe since his start in 2014.Before joining Thermo Fisher Scientific, Alejandro worked in Management Consulting in New York City, most recently with The Boston Consulting Group. 

Featured Image: The sFlt-1 and PlGF biomarker-based assays are designed to run on the Thermo Scientific B·R·A·H·M·S KRYPTOR compact PLUS immunoassay analyzer. Photo: Thermo Fisher Scientific

REFERENCES

[i] Poon, L. et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia. Int. J. Gynaecol. Obstet. 145, 1 (2019).

[ii] Zhang J, Klebanoff MA, Roberts JM. Prediction of adverse outcomes by common definitions of hypertension in pregnancy. Obstet Gynecol. 2001 Feb;97(2):261-7. doi: 10.1016/s0029-7844(00)01125-x. PMID: 11165592.

[iii] Magee, L., Nicolaides, K., and von Dadelszen, P. Preeclampsia, May 2022, The New-England Medical Review and Journal 386(19):1817-1832 DOI:10.1056/NEJMra2109523

[iv] Ravi Thadhani et al, Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy, NEJM Evidence (2022). DOI: 10.1056/EVIDoa2200161

[v] Healthcare Cost and Utilization Project (HCUP); Agency for Healthcare Research and Quality (AHRQ), “Delivery Hospitalizations Involving Preeclampsia and Eclampsia, 2005-2014,” April 2017