Filtering a protein from a pregnant person’s blood may help alleviate a dangerous pregnancy complication.
In a study of 16 women with early-onset preeclampsia, removing a particular protein from their blood slightly lowered blood pressure and prolonged certain pregnancies, researchers report April 27 in Natural medicine. If larger trials confirm the results, the technique could one day be a treatment for the sometimes fatal disease.
Preeclampsia affects 3 to 8 percent of people who give birth worldwide. “It spares no race or ethnicity, and while some populations are at increased risk, for the most part it really affects every woman in the world,” says Ravi Thadhani, a nephrologist at Cedars-Sinai Health System in Los Angeles.
The exact causes are not known, but evidence collected by Thadhani and colleagues indicates a protein called soluble Flt-1produced naturally by the placenta. Flt-1 helps control the growth of placental blood vessels and, at some point, slows placental growth so that the baby can grow.
In people with preeclampsia, Flt-1 levels can reach five times the usual level at this stage of pregnancy. Some cells lining the kidney blood vessels swell, leading to high blood pressure and protein in the urine, both hallmarks of preeclampsia. Liver damage and brain swelling may also occur. The growth of fetuses may slow and they may receive too little oxygen if the the placenta is not functioning properly.
Previously, Thadhani and his 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 symptoms of preeclampsia will develop a more severe form of the disease. It is often used in Europe but is not widely available in the United States or elsewhere. Both researchers have financial interests in companies carrying out the tests and developing treatments.
For the new study, Thadhani, Karumanchi and their colleagues designed a way to extract some of the excess Flt-1 from people’s blood. The team made an antibody that captures 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 on baboons and a handful of healthy non-pregnant people, the team tested it on 16 women suffering from early-onset preeclampsia that threatened to lead to premature birth.
Each treatment reduced Flt-1 in the women’s blood by about 17 percent and slightly lowered blood pressure and protein in the urine. In some women, symptoms have stabilized enough that delivery — the only standard treatment for preeclampsia — is delayed, giving fetuses time to grow. One woman developed severe illness and gave birth within two days of admission. Overall, treated pregnancies continued for a median duration of 10 days, and one pregnancy lasted an additional 19 days.
These extra days in the womb could help avoid some complications related to premature birth.
The babies were born at a median age of 31 weeks, still premature. But when pregnancies lasted longer, fetal growth continued. “If they are growing, that necessarily means they are healthy and getting the nutrition and oxygen they need,” says Thadhani.
Without a control group, researchers can’t say how much time the treatment added, although they estimate it may have doubled delivery time after hospitalization.
The study could mark an innovation in a field that hasn’t seen improvement in decades, says Thomas McElrath, a specialist in maternal-fetal medicine at Mass General Brigham in Boston and Harvard University.
The idea of taking down the Flt-1 has been around for a while, but no one knew if it would be safe, McElrath says. Researchers wonder why Flt-1 increases, he says, and whether suppressing it might harm by disrupting some protective balance. However, “no harm was caused to either the mother or the fetus,” he said. “This piece is encouraging.”
There have been side effects including false labor, chest discomfort, headaches, and liver enzyme problems. It’s difficult to know whether these were caused by the treatment or by a worsening of the preeclampsia, says Mark Santillan, an obstetrician who studies preeclampsia at the University of Iowa’s Carver College of Medicine in Iowa City.
Due to the small size of the study, it cannot fully address safety concerns, Santillan says. Larger studies with control groups will be needed to measure the safety and effectiveness of the treatment. Such studies should also monitor long-term health outcomes for mothers and babies.
