Filtering a protein out of a pregnant person’s blood may help ease a dangerous complication of pregnancy.
In a study of 16 women with early preeclampsia, pulling a particular protein from their blood slightly lowered blood pressure and extended some pregnancies, researchers report April 27 in Nature Medicine. If larger trials confirm the results, the technique may one day be a treatment for the sometimes-fatal condition.
Preeclampsia affects 3 to 8 percent of people who give birth worldwide. “It doesn’t spare any races or ethnicities, and while there are some populations that are increased risk, for the most part, it affects really all women around the world,” says Ravi Thadhani, a nephrologist at Cedars-Sinai Health System in Los Angeles.
The exact causes aren’t known, but evidence collected by Thadhani and colleagues point to a protein called soluble Flt-1, made naturally by the placenta. Flt-1 helps control growth of placental blood vessels and, at some point, slows placental growth so the baby can grow.
In people with preeclampsia, levels of Flt-1 may reach five times the usual amount for that stage in pregnancy. Certain cells lining kidney blood vessels swell, leading to high blood pressure and protein in the urine — both hallmarks of preeclampsia. Liver damage and brain swelling can also happen. Fetuses’ growth may slow, and they may get too little oxygen if the placenta isn’t working correctly.
Previously, Thadhani and Cedars-Sinai colleague S. Ananth Karumanchi helped develop a test based on the ratio of Flt-1 to another protein called placental growth factor. The test, approved by the U.S. Food and Drug Administration, can predict whether women with preeclampsia symptoms will develop a more serious form of the condition. It is used often in Europe but is not widely available in the United States or elsewhere. Both researchers have financial interests in companies making the test and developing treatments.
For the new study, Thadhani, Karumanchi and their colleagues devised a way to pull some of the excess Flt-1 from people’s blood. The team made an antibody that grabs the protein, then added it to a filter. A machine routes a patient’s blood through the filter and returns blood with lower Flt-1 levels. After testing the technique in baboons and a handful of healthy nonpregnant people, the team tried it in 16 women with early preeclampsia that threatened to lead to preterm birth.
Each treatment reduced Flt-1 in the women’s blood by about 17 percent and slightly decreased blood pressure and protein in the urine. In some women, symptoms stabilized enough that delivery — the only standard treatment for preeclampsia — was delayed, giving fetuses time to grow. One woman developed a severe form of the condition and delivered within two days of admission. Overall, treated pregnancies continued for a median of 10 days, and one lasted 19 additional days.
Those extra days in the womb might help stave off some complications of premature birth.
The babies were delivered at a median of 31 weeks, still preterm. But when pregnancies lasted longer, fetal growth continued. “If they’re growing, that means necessarily they’re healthy and getting the nutrition and oxygen they need,” Thadhani says.
Without a control group, the researchers can’t say how much time the treatment added, though they estimate it may have doubled the time to delivery after hospitalization.
The study could mark innovation in a field that hasn’t had improvements for decades, says Thomas McElrath, a maternal and fetal medicine specialist at Mass General Brigham in Boston and Harvard University.
The idea to remove Flt-1 has been around for a while, but no one knew whether it would be safe, McElrath says. Researchers have wondered why Flt-1 increases, he says, and whether removing it might cause harm by disrupting some protective balance. Still, “no harms stood out to either the mother or the fetus,” he says. “That piece is encouraging.”
There were side effects, including a false labor, chest discomfort, headaches and liver enzyme issues. It’s hard to know if those were caused by the treatment or by worsening preeclampsia, says Mark Santillan, an obstetrician who studies preeclampsia at the University of Iowa Carver College of Medicine in Iowa City.
Because of the study’s small size, it can’t fully address safety concerns, Santillan says. Larger studies with control groups will be needed to measure the treatment’s safety and effectiveness. Such studies should also monitor long-term health outcomes for mothers and babies.
