Preeclampsia, a syndrome that can affect pregnant women, has been called mysterious in both popular and scientific literature. It is characterized by high blood pressure and often protein in the urine. Symptoms vary, ranging from headaches to seizures and life-threatening complications. What causes preeclampsia, which occurs in an estimated five to eight percent of all pregnancies, is not well understood, so there isn’t a way to determine who will develop it. The only established treatment is clinically induced delivery, which sometimes leads to premature birth.
“Currently there’s no clinically useful way to predict which women will develop preeclampsia,” says College of Public Health epidemiologist Brandie DePaoli Taylor.
Hoping to discover new connections that could shine some light on preeclampsia’s origins and inform future research or treatment, Taylor is leading a new five-year study funded by the National Institutes of Health. The study will include hundreds of women with and without preeclampsia and will analyze blood samples taken early in pregnancy. The researchers will look for biological markers in the blood that might correlate with cases of preeclampsia as well as severe symptoms.
“There’s still a lot we don’t understand about the syndrome,” Taylor says. “There’s no clinical test that tells physicians which women have the highest chance of developing preeclampsia, and of those women which will require early intervention to avoid progression to the most severe preeclampsia-related outcomes.”
The study will work with pregnancy data and biological samples taken as part of a multi-year national study called Screening for Obstetric and Pregnancy Endpoints, or SCOPE. More than 5,000 women participated in the recent study, whose purpose was to identify predictors of preeclampsia and prematurity, while creating a large bank of data and biological specimens.
Taylor’s team is exploring whether elevated levels of syncytiotrophoblast extracellular vesicles (STBEVs)—microvesicles shed from the outer layer of the placenta into the maternal bloodstream—are associated with increased risk of preeclampsia.
“We hypothesize that STBEVs may be triggering an innate immune response early in pregnancy that could result in the development of preeclampsia,” Taylor says.
In their analysis, the researchers will compare biomarkers between 280 women within the SCOPE study who experienced preeclampsia with 560 women who did not. Researchers at the University of Pittsburgh, a partner in the Temple study, will analyze the blood samples of those subjects, and Taylor’s team will crunch the numbers.
Preeclampsia currently is diagnosed after 20 weeks of pregnancy, if physicians detect new high blood pressure and protein in urine or evidence of organ dysfunction. SCOPE blood samples were taken as early as 16-18 weeks, so the researchers will be able to measure biological markers before preeclampsia is diagnosed. Knowing whether biological pathways are altered prior to disease diagnosis could help researchers better understand the origins of preeclampsia.
That could eventually improve clinical management and influence early-delivery decisions, Taylor says. Currently, in certain situations, there are women with preeclampsia who are induced for delivery early who might not have progressed to severe disease, and that puts the baby at risk, she says. There may also be women who are not induced and progress to severe symptoms that can lead to various morbidities or even maternal death.
“Eventually, research into the origins of preeclampsia, or prediction of severe symptoms, could improve clinical management. As research progresses, physicians may be able to identify women who truly need to be delivered early, versus women with preeclampsia who can be monitored as outpatients," she says. "We need better ways of not only predicting preeclampsia but combining biological and clinical data to understand severe subtypes of the disease.”
Future research into the biology of preeclampsia could lead to treatments, “if we understand more about why STBEV levels are elevated in preeclampsia and what biological impact they have," Taylor adds. "There might be some way to suppress these actions. However, we first need to determine if there is a relationship between STBEVs and preeclampsia and that is what our team is trying to accomplish.”
The overall goal of the grant, Taylor says, is to find a better way to describe the disease and the forms it takes—to unravel some of the mystery and rethink what preeclampsia is. “We will combine the biological data with the existing clinical data to see if we can develop an algorithm that can help identify subtypes of the syndrome and perhaps in the future provide enough knowledge to redefine the syndrome,” she says.