Veronica Hackethal, MD
March 20, 2019
Researchers have developed a simple, noninvasive, point-of-care paper test that measures misfolded proteins in a woman's urine and looks set to improve the diagnosis of preeclampsia.
The Congo Red Dot (CRD) Paper Test is designed to be affordable and gives results in just 3 minutes.
The pilot study is the first to evaluate the diagnostic accuracy of the new test. Results were published online March 1 in E-Clinical Medicine, which is published by The Lancet.
The findings suggest that the CRD test is highly accurate for preeclampsia, and outperforms other previously proposed serum and urine immunoassay tests for diagnosis of the condition. The latter have turned out to be too expensive and impractical for bedside use.
"This is the first clinical study using the point-of-care, paper-based Congo Red Dot diagnostic test, and the mechanism proved superior in establishing or ruling out a diagnosis of preeclampsia," first author Kara Rood, MD, of Ohio State University Wexler Medical Center, Columbus, said in a press release from her institution.
"Our findings will have a huge impact on the health of women and children," she emphasized.
Preeclampsia: Leading Cause of Maternal Death and Premature Birth
Eclampsia ranks among the top five causes of death in pregnant women worldwide, accounting for about 14% of maternal deaths in low-resource countries and around 18% in the United States.
Preeclampsia is also the leading cause of premature birth because there is no treatment for it other than delivery. When faced with uncertainty in the diagnosis, physicians often err on the side of caution and deliver the newborn early. But premature birth carries its own risks for the child, including learning disabilities, cerebral palsy, and blindness.
"In the United States there are increased numbers of premature deliveries because of the uncertainty of preeclampsia. By decreasing the uncertainty of the physician in making the diagnosis that's a major advantage of the CRD test," senior author Irina Buhimschi, MD, of the University of Illinois at Chicago College of Medicine, told Medscape Medical News.
Preeclampsia is currently diagnosed when a woman suffers a combination of high blood pressure and proteinuria after 20 weeks of gestation. In the absence of proteinuria, physicians rely on other symptoms to make the diagnosis, such as headache, visual disturbances, and pain in the right upper quadrant of the abdomen.
But the diagnosis can be tricky. The main problem is that the symptoms of preeclampsia are nonspecific and occur in a variety of other medical conditions, Buhimschi explained.
And in developed countries like the United States, where women are having children later in life, they may have developed other conditions such as obesity, chronic hypertension, or kidney disease, the symptoms of which can overlap with those of preeclampsia.
A point of care test like the CRD test could vastly improve diagnosis by more accurately weeding out those who do not have preeclampsia from those who do, Buhimschi explained. That, in turn, could potentially reduce unnecessary preterm deliveries without putting mothers' lives at risk.
The test also has the potential to improve diagnosis at prenatal appointments, decrease wait times in triage areas, avoid unnecessary admissions, and decrease healthcare costs.
Test Is Being Commercially Developed to Be Affordable
The current results are from a pilot study at a single site that tested the first prototype of the CRD paper test developed over 10 years ago.
Since then, a second generation test has been developed and tested in a variety of settings, including Bangladesh, South Africa, and Mexico. Those studies are now complete. Although results have yet to be published, they suggest the test is easy to use by healthcare workers around the world, according to Buhimschi.
Currently, the test is under commercial development by GestVision, which is conducting clinical studies for US Food and Drug Administration approval. The test is also being designed for use in resource-poor settings.
"Both the CEOs of the company and myself have a vision that this should be affordable. The goal is that every woman should be able to afford this test," Buhimschi stressed.
In the pilot study, the prototype CRD test was used on fresh urine samples of 346 pregnant women evaluated for preeclampsia at the Ohio State University Wexler Medical Center.
Patients and clinical teams were blinded to the test results. Two experts in maternal-fetal medicine, also blinded to the results, independently adjudicated diagnosis for each woman.
During the study, 32% (112/346) of women received a clinical diagnosis of preeclampsia on their first triage visit. But many more (63%, 217/346) were admitted to the hospital for uncertain diagnosis or delivery.
Overall, the CRD test was positive in 25% of women. In contrast, experts diagnosed 28% (96/346) of women with preeclampsia.
The CRD Paper Test showed 80.2% sensitivity, 89.2% specificity, 92.1% negative predictive value, and 86.7% accuracy to correctly diagnose preeclampsia.
CRD Test Correctly Identified Preeclampsia in One of Every 1.4 Women
In other words, the CRD test correctly identified preeclampsia in one out of every 1.4 women. And the test correctly ruled out preeclampsia in virtually all women who did not have it (one out of 1.1 women).
The CRD test was also more accurate than other assays proposed to improve the diagnosis of preeclampsia, including urine and serum placental growth factor (accuracy: 67.3% and 60.7%, respectively), as well as urine and serum soluble fms-like tyrosine kinase-1 (accuracy: 75.8% and 72.4%, respectively).
The test offers speedy diagnosis improving wait times in obstetrical triage areas, avoidance of unnecessary admissions, and lowers costs. In addition, "our findings have potential to improve accurate timing of patients' transfers to higher-acuity hospitals, and more targeted steroids and magnesium sulfate treatment in patients at risk of indicated preterm delivery from preeclampsia," the authors stress.
"Further multicenter studies are warranted in high- and low-income countries where the CRD Paper Test has the potential to save thousands of lives," they conclude.
The study was funded by USAID, the Bill & Melinda Gates Foundation, Government of Norway, Government of Canada, United Kingdom's Department for International Development, National Institutes of Health (NIH), and Eunice Kennedy Shriver National Institute of Child Health and Human Development. Authors Irina and Catalin Buhimschi have patent applications for the use of protein misfolding for diagnostic and treatment purposes of preeclampsia and have received royalties from Yale University . Commercial development of the CRD Paper Test has been licensed by Yale University to GestVision. Irina and Catalin Buhimschi have received stock in GestVision.