Studying preeclampsia helps scientists better understand blood pressure and kidney function in women and men.
Historically, the findings from basic medical research conducted on male subjects have been used to develop potential treatments for both men and women. But in the study of pregnancy, this leap becomes much more challenging.
“A lot of what people have tried to extrapolate to pregnant women has come from non-pregnant men,” says Jason Umans, MD, PhD, associate professor of medicine and obstetrics/gynecology at Georgetown. “And that’s comical.”
Around half of the population can potentially become pregnant, yet there isn’t a lot of research on what a healthy pregnancy looks like. Pregnancy is challenging to study because it is a complex physiological state, says Crystal A. West, PhD, assistant professor in the department of medicine at Georgetown. “Adaptations that are required for a normal, healthy pregnancy would be pathological if they were to occur in a non-pregnant individual,” West says. “We know what normal physiology looks like, but pregnancy just flips everything on its head.”
In lectures to first-year medical students, Umans demonstrates this “flip” by showing the students blood chemistry values from a pregnant patient. While the values displayed would be a cause for concern in a nonpregnant woman, they’re all in the normal range for pregnancy. “I hope that gives our students a certain sense of understanding and insight—but also humility and caring —for pregnant women and the ability to understand what’s going on,” he says. “And how much we still have to learn.”
The paucity of research on normal pregnancy makes it more challenging to study complications of pregnancy. “In order to fully understand the disease state and to treat the disease state, you have to know what the baseline for normal physiology is,” West says. “And a lot of times, that gets ignored.”
The role of blood volume
One major complication of pregnancy is preeclampsia, a condition that is characterized by high blood pressure and evidence of damage to another organ system, usually after 20 weeks of pregnancy. Preeclampsia affects 4-6 percent of pregnancies and about 10 million pregnant women worldwide every year.
In a healthy pregnancy, a woman’s blood volume increases by a whopping 40 percent and her blood vessels dilate, accommodating the increase. In fact, healthy pregnant women typically experience a decrease in blood pressure due to the dilation of blood vessels. In many pregnant women with preeclampsia, this vasodilation fails and can be converted to vasoconstriction, causing the blood pressure to increase.
Preeclampsia can develop quickly. In addition to high blood pressure and protein in the urine, symptoms can include severe headaches, changes in vision, and upper abdominal pain, all indications of potentially life-threatening organ damage. Sudden weight gain and swelling in the hands and face are associated with preeclampsia but they also occur during healthy pregnancies, making them less reliable symptoms.
The consequences of preeclampsia can be devastating. For the mother, they can include seizures, organ damage and increased risk of developing cardiovascular disease. For the fetus, preeclampsia is associated with growth restriction, low birth weight, and prematurity. In the developing world, preeclampsia is a leading cause of maternal mortality, with approximately 80,000 women and 500,000 babies dying each year from causes related to preeclampsia.
Discovering new answers to an old problem
The research landscape for preeclampsia has changed dramatically over the last 20 years as scientists have developed a deeper understanding of its underlying mechanisms. “We understand more at a molecular level about preeclampsia than we ever had before,” Umans says. “Does that mean we know the answer? No. But we know some answers and we’re getting better at asking more sophisticated questions because of what we have learned.
“For a scientist, that makes it an exciting time because here’s a grand problem with major public health implications for us to solve during this generation instead of just reading about it,” Umans adds. “From my patient care point of view, I’d rather read about it and have it solved, of course, but intellectually, it’s cool to see it unfold at such a quickening pace.”
As a renal physiologist, West’s research focuses on how the kidney works and how the kidney adapts during pregnancy. In a normal pregnancy, the kidney retains sodium which allows for blood volume expansion—without increasing the mother’s blood pressure, because the blood vessels dilate. Last fall, West received a grant from Georgetown University Medical Center’s Partners in Research to study the mechanism of blood volume and blood pressure regulation in pregnancy.
Receiving funding from Partners in Research, a program that connects researchers with donors who are interested in supporting their work, was a rewarding experience for West. “It was neat to have people in your community involved and getting a say in what they wanted to study,” she says. “And it was really cool for me because I study women’s health and I’m talking to a group of mostly women, and they get it. That was a special experience that I don’t think I could have gotten anywhere but at Georgetown.”
In her research, West found that when a protein of interest called PAR2 was activated, it decreased blood pressure and increased renal sodium retention—two necessary responses to accommodate the maternal blood volume expansion which, in preeclampsia, becomes compromised.
West’s research may have applications for researchers studying non-gestational hypertension, notes Kathryn Sandberg, PhD, professor of medicine and director of the Center for the Study of Sex Difference in Health, Aging, and Disease. “If you can understand how the female kidney does something so amazing that the male kidney can’t, then you may find a drug target that might be able to be used in both males and females,” she said.
But West remains focused on helping pregnant women. “The long-term goal of this research is to find new therapeutic options for women with preeclampsia,” she said. “This could ultimately result in decreased maternal and fetal deaths, and reduce the long-term cognitive and cardiovascular burden to children by improving fetal nutrition.”
