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Study Links Protein to Preeclampsia

Finding could lead to test for potentially risky pregnancy complication

TUESDAY, Jan. 4, 2005 (HealthDayNews) -- Researchers have identified a compound in urine that might lead to a simple test to predict which women will develop preeclampsia, a potentially dangerous complication of pregnancy.

The compound may also play a role in causing the condition, the researchers said.

"This research finding is very exciting," said Dr. Cathy Spong, chief of the pregnancy and perinatology branch at the National Institute of Child Health and Human Development (NICHD). "If you could predict who might get preeclampsia, you could monitor them closely and perhaps give them something to prevent it."

Preeclampsia, in which the expectant mother develops dangerously high blood pressure, is believed to occur in about 5 percent of all pregnancies, affecting 200,000 American women each year. The condition can prevent the placenta, which supplies air and food to the fetus, from getting enough blood. If the placenta doesn't get sufficient blood, the baby is at risk of low birth weight and other health problems.

The only cure for preeclampsia is delivering the baby, a tricky proposition if the baby is not full term.

The condition more commonly occurs during a first pregnancy and more often in women with certain health problems, such as diabetes and chronic high blood pressure. It usually develops after the 20th week of pregnancy and can appear suddenly without warning.

"Preeclampsia is a major complication in pregnancy, something that we as obstetricians don't have a wonderful handle on why it occurs or what we can do to prevent it," Spong said. "We understand some of what happens, but we cannot clearly identify who is going to develop it."

The NICHD provided most of the funding for the new study, which appears in the Jan. 5 issue of the Journal of the American Medical Association. Spong was not involved with the research.

Previous research had shown that women with preeclampsia had high levels of a toxic molecule called sFlt-1 circulating in the blood. sFlt-1 depletes levels of two growth factors, placental growth factor (PIGF) and vascular endothelial growth factor (VEGF), which are especially needed at the time of pregnancy to help get oxygen and nutrients to the fetus via the blood supply, the researchers explained.

It seems the sFlt-1 molecule binds to PIGF and VEGF so they can't perform their role.

The new research analyzed urine samples of 120 women who developed preeclampsia and compared them to urine samples from 118 women who did not develop the condition. The urine samples were collected as part of a separate NICHD study on calcium supplements.

Women who developed preeclampsia had significantly lower levels of PIGF than women who did not develop the condition. Not only were the lower levels apparent at the time of preeclampsia's onset, they were lacking six to eight weeks later. Unlike sFlt-1, PIGF molecules are small enough to enter urine.

"Instead of measuring it in blood, we can actually look at it in urine and say the same thing," said study senior author Dr. Ananth Karumanchi, an assistant professor of medicine and obstetrics and gynecology at Harvard Medical School. "If these findings can be reproduced by other groups, this obviously makes screening in pregnant women a lot easier -- a urine test once a month during pregnancy. It's a lot easier than poking for blood."

Karumanchi and co-author Dr. Vikas Sukhatme are named as co-inventors on a patent filed for the use of these proteins to diagnose and treat preeclampsia.

While there's no cure -- other than delivery -- for preeclampsia and few treatments, Karumanchi said knowing who is at risk would be a great help to doctors.

"A lot of times preeclampsia happens out of the blue and it can rapidly spiral out of control," he said. "If you knew this was going to happen, you could have a closer follow-up." Patients in rural areas, for instance, could be transferred to a specialized care hospital.

Karumanchi said he was working on developing a protein to block the toxic molecule. "If that works out then this kind of test gets more exciting because we could start treating before symptoms appear," he said.

But such a treatment is years away, Karumanchi said. And the test to predict preeclampsia is about two or three years away, he added.

More information

For more on preeclampsia, visit the American Academy of Family Physicians.

SOURCES: Ananth Karumanchi, M.D., assistant professor, medicine and obstetrics and gynecology, Harvard Medical School, Boston; Cathy Spong, M.D., chief, pregnancy and perinatology branch, National Institute of Child Health and Human Development, Bethesda, Md.; Jan. 5, 2005, Journal of the American Medical Association
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