A blood pressure disorder that can develop after week 20 of pregnancy has long been one of the leading causes of maternal mortality. Pre-eclampsia is characterized by high blood pressure and protein in the urine, and if left untreated, it can damage organs, leading to either death or disability. Historically, pre-eclampsia has been very difficult to diagnose because it looks very similar to other common disorders such as chronic hypertension. In recent weeks, the FDA approved the first blood test that can predict which patients are at an elevated risk for developing pre-eclampsia with severe features.
“This test helps us figure out who is at a high risk for developing some of the more severe outcomes for pre-eclampsia,” says Nandini Raghuraman, an obstetrician/gynecologist at Washington University of St. Louis’ Barnes-Jewish Hospital.
The FDA’s approval of this test is one of two promising steps that could reduce maternal mortality in the United States, which ranks highest among the world’s developed nations, and has continued to rise since the emergence of COVID-19. The approval was based on the results from a study that was published in the New England Journal of Medicine. In this study, researchers looked at the ratio of two proteins in pregnant patients who were hospitalized based on suspicions of pre-eclampsia. What the study found was that patients with a high ratio of two specific proteins were at an elevated risk for developing pre-eclampsia with severe features, which required delivering the baby within the next two weeks; patients who had a low ratio of these two proteins were at a low risk.
To help people make sense of what this new test will mean, National Geographic spoke with several experts about the current diagnosis and treatment of pre-eclampsia.
What is pre-eclampsia?
Pre-eclampsia is a blood pressure disorder that is unique to pregnancy, that is thought to develop from abnormal blood vessel development in the placenta. “When blood pressure is very elevated, it restricts blood flow to different organs,” says Angela Burgess, a maternal-fetal medicine physician with UTHealth Houston. Over time, this can result in damage to various organs, such as the heart, kidney, liver, or brain, leading to organ failures or strokes. If left untreated, pre-eclampsia can progress to eclampsia, which is seizures.
Although the cure is delivery, “pre-eclampsia doesn’t end with delivery,” says Heather Lipkind, the director of maternal fetal medicine at Weill Cornell Medicine. Some patients can develop postpartum pre-eclampsia, which can happen within six weeks of delivery. Patients are at the highest risk for developing post-partum pre-eclampsia within 72 hours to one week following birth.
How common is pre-eclampsia?
Pre-eclampsia occurs in about 1 out of every 25 pregnancies in the United States. Some people are at a higher risk than others, due to several factors, including socioeconomic status and the presence of pre-existing conditions such as high blood pressure, diabetes, or autoimmune disorders.
In the U.S., Black women are at an elevated risk for developing pre-eclampsia, a fact that was particularly evident in recent weeks, when the track star Tori Bowie died in the eighth month of her pregnancy, with eclampsia listed on her autopsy report as a possible complication contributing to her death. Two of Bowie’s teammates, Allyson Felix and Tianna Bartoletta, also developed pre-eclampsia during their pregnancies.
Why is detecting pre-eclampsia so important?
The difficulty with pre-eclampsia, compared to a condition such as chronic hypertension, is that it can progress to a life-threatening condition very quickly, with little to no warning. “The saying we have here in Texas is that it’s a snake in the grass,” says Kjersti Aagaard, a professor of obstetrics and gynecology at Baylor College of Medicine, who was involved in the NEJM study. “You just don’t know when it’s going to get up and bite you.”
Patients can develop severe complications within a matter of hours to days, and they don’t always show obvious symptoms. Complicating the matter is the fact that the only cure for pre-eclampsia is delivery. If the condition develops earlier in pregnancy, then delivery will result in a premature baby.
Why is pre-eclampsia so hard to diagnose?
“The clinical challenge is that so many disorders in pregnancy look alike,” Aagaard says. If a patient comes in with elevated blood pressure, they may have worsening chronic hypertension, which is a stable condition that can be safely treated with blood pressure medication, or they may have developed pre-eclampsia, which can get progressively worse very fast and can only be cured by delivery.
As Aagaard notes, there was a study published last year, called the CHAP trial, which found that treating women with chronic hypertension to reach a goal blood pressure of less than 140/90 resulted in better outcomes for both the mother and baby.
This new blood test for pre-eclampsia offers a way to help differentiate patients with chronic hypertension from patients who are developing pre-eclampsia, while the CHAP trial offers further guidance on what the best strategy is for managing patients with chronic hypertension. “Within a span of a year, we’ve got two new tools in our toolbox, that we desperately needed to help pregnant folks,” Aagard says.
How does this test work?
This test looks at the ratio of two proteins, called sFLT-1 and PlGF, which are involved in the formation of blood vessels connecting the placenta to the uterine wall. Patients who had a ratio of sFLT-1:PlGF that was above 40 were at a higher risk of developing pre-eclampsia with severe features within the next two weeks, while patients that had a ratio less than 40 were not.
Of the patients who had a ratio above 40, they had a 59 percent of developing pre-eclampsia with severe features, which required delivery, within two weeks. Of the patients that had a ratio of less than 40, 94 percent of them did not develop pre-eclampsia with severe features within two weeks. These results were found to be consistent in multiple hospital settings across the country, and within a diverse group of study participants. “We found a very sweet spot on this cut off of less than 40, greater than 40,” Aagaard says.
For clinicians, this test can help them better predict who will be at a high risk in the next two weeks, while it also gives them a high level of confidence as to which patients are unlikely to develop severe complications. “The most important thing that this test does is help us identify who is at a low risk,” Raghuraman says.
As experts caution, this was a study that looked at patients who were hospitalized. Clinicians still aren’t sure how this test will be used in an outpatient setting. Understanding how it can be applied in other contexts will require more follow-up research.
Who will benefit from this test?
As Aagaard notes, there are three main groups of patients that stand to benefit from this test. The first group are the patients without chronic hypertension, for whom this test can help predict if they will develop severe complications within the next two weeks.
The second group are the patients with chronic hypertension, for whom clinicians are having a hard time separating out whether they have also developed pre-eclampsia in addition to their pre-existing hypertension. If the test comes back negative, clinicians can be confident they are not at a high risk for severe complications, and “because of the CHAP trial, we know that giving them more blood pressure medicine is the right answer,” Aagard says.
The third group are the patients who tested positive on the test but did not develop severe complications from pre-eclampsia. As it turned out, of the 93 patients who fit into this category, 53 of them ended up having other complications relating to blood flow, such as growth restriction, that also precipitated an early delivery, which suggests this test may have some additional predictive abilities. “This was really, really valuable for us,” Aagaard says.