Two proteins tied to preeclampsia

Two proteins secreted by the placenta may be responsible for virtually all cases of preeclampsia, a complication of pregnancy that can kill mother or baby, researchers report.

Abnormally high levels of the proteins could be used to predict the development of the disorder weeks before symptoms occur, experts said, and the findings suggest new ways to treat the problem.

A World Health Organization (WHO) team is beginning to organize a test of the proteins' predictive value among pregnant women in the Third World, and Fremont, Calif., biotech company Scios is looking for funding to test a potential treatment.

"This finding appears to be an important step in developing a cure for preeclampsia," said Dr. Elias Zerhouni, director of the National Institutes of Health.

Researchers had identified one of the proteins in 2003 and shown that injecting it into rodents could mimic many, but not all, symptoms of the disorder. But injecting both proteins together produces the full spectrum of symptoms, yielding confidence that the two are at the root of the problem.

"There could be other things that also have a role, but these are the major players," said Dr. Richard Levine of the National Institute of Child Health and Human Development, who led the study in today's New England Journal of Medicine.

More than 6 million women around the world and 270,000 in the United States have preeclampsia during pregnancy each year. The disorder, once known as toxemia, affects up to 8 percent of all pregnancies.

Usually diagnosed late in pregnancy, the disorder is characterized by sharp increases in blood pressure, swelling and proteins in the urine.

It can progress to eclampsia, which produces seizures and often fatal complications of the liver, kidneys, lungs, blood and nervous system. Eclampsia causes 15 percent of maternal deaths during pregnancy in the United States.

Mild cases can be helped by bed rest, but there is no effective treatment other than delivery of the infant and removal of the placenta.

Premature birth associated with preeclampsia is considered one of the major sources of neurodevelopmental disorders in children.

In 2003, Dr. S. Ananth Karumanchi of the Beth Israel Deaconess Medical Center in Boston and his colleagues reported finding high levels of a protein called soluble fms-like tyrosine kinase 1 in the blood of women with preeclampsia.

The team then found the second protein, endoglin, present in abnormally high levels in women with the disorder.

Evidence suggests the disorder is triggered when the fetus is not able to absorb sufficient amounts of oxygen from the placental blood supply. In response, the placenta releases the two proteins into the bloodstream.