Preeclampsia, in its severe form, is responsible for 40,000–80,000 maternal deaths annually worldwide and is associated with an increased risk of medically indicated preterm birth, stillbirth, and intrauterine growth restriction. Women with preeclampsia can be asymptomatic until they suddenly develop severe disease.
The current procedures for diagnosing preeclampsia include monitoring blood pressure; checking proteinuria levels; evaluating levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), platelet (PLT) count; and regular prenatal care. However, these standard approaches often provide ambiguous results and may be poor predictors of preeclampsia progression and adverse outcomes. This leaves clinicians with unclear guidance on how to best manage a mother’s care.
Making biomarkers actionable
The current standard of care during preterm pregnancy includes monitoring and managing complications that can harm both the mother and fetus. Among the greatest risks are developing severe hypertension, eclampsia, and/or HELLP syndrome (H: Hemolysis, EL: Elevated liver enzymes, LP: Low platelet count), along with placental abruption, fetal growth restriction, and fetal death.
These risks can be better managed—and potentially avoided altogether—with a simple test that accurately assesses a pregnant individual’s likelihood of developing these severe outcomes. A new blood test is now available to predict the prognosis of this condition, after receiving FDA clearance in May 2023.
The Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification (PRAECIS) study demonstrated that “in women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks of gestation, measurement of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) enabled clinicians to stratify participants according to their risk of progressing” to preeclampsia with severe features within the two weeks. Additional studies concur that a test to improve risk stratification can confer substantial clinical and economic benefits.
Simple test for challenging clinical decisions
The PRAECIS study identified and validated a lab-generated sFlt-1:PlGF ratio that aids clinicians triage individuals with hypertension in late pregnancy based on their short-term risk of developing preeclampsia with severe features. The sFlt-1:PlGF ratio, in conjunction with other laboratory and clinical findings, also ensures clinicians follow the American College of Gynecology (ACOG) criteria to monitor low-risk patients and step-up care for high-risk patients.
Putting tests into practice
According to Anders Berg, MD, PhD, associate professor of pathology, vice chair, CLIA and Laboratory Operations at Cedars-Sinai Medical Center, Los Angeles, CA, whose lab has adopted the new test, “clinicians, hospitals, and patients want testing that informs action. Tests that are immediately actionable can save lives and reduce unnecessary costs.” At Berg’s lab, 50 percent of pregnant individuals who are at high risk of preeclampsia with severe features, based on this test, have their preterm babies delivered within seven days of the test result.
Berg and his team considered the impact of the test on the medical management of patients and their health outcomes. Having FDA clearance for a test was critical because it provided greater confidence in the quality of the test and relieved his lab of the expensive and time-consuming clinical validation studies required for non-FDA-cleared tests per CLIA regulations—a step toward shortening the turnaround time. Per Berg, the medical impact must outweigh every lab’s budgetary pressures and test costs.
Impact of sFlt-1/PlGF test
When I think back on my 21 years of OBGYN practice, I can think of countless patients who could have benefitted from this test. One example is a 24-year-old Black woman who was 25 weeks pregnant with her first child. She arrived at the hospital complaining of a severe headache. Her blood pressure was initially elevated but returned to normal with rest and over-the-counter medication; her headache resolved too.
Routine evaluation for preeclampsia was negative and she was discharged home. Two days later, she followed up in the office with normal blood pressure and no complaints. But later that day, her headache returned and she was sent back to the hospital for evaluation: Her blood pressure was again elevated and she had a seizure shortly after.
If this patient had an sFlt-1:PlGF ratio assessment the night of her first blood pressure elevation, I would have been alerted to her imminent severe preeclampsia. She would have been transferred to a tertiary care center for intensified observation under the care of maternal–fetal medicine specialists. The outcome for both mother and baby could have been improved dramatically.
When clinicians and clinical labs collaborate to bring new tests into practice, they must weigh the costs against the economic and clinical consequences of not making a change. The consequences of delayed diagnosis or misdiagnosis of preeclampsia progression to severe features are significant: Maternal and fetal mortality.
The new sFlt-1/PIGF assays are pathbreaking, but there’s also a vital societal impact and an opportunity to address health inequity.
Black women have higher rates of preexisting chronic hypertension and preeclampsia-related complications and adverse outcomes. An objective predictive test for preeclampsia-related complications directly benefits them.
According to Sarosh Rana, MD, MPH, professor of obstetrics and gynecology and chief of the Section of Maternal–Fetal Medicine at the University of Chicago, this sFlt-1/PIGF test provides an important “warning sign” for Black women and others disproportionately affected by preeclampsia. Rana’s team is among those already using the new assays in daily practice.
The efforts of Berg, Rana, and countless other clinicians who have worked to bring these new assays to clinical practice is a victory for the field and, most importantly, women everywhere.