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Predicting Preeclampsia

Abnormal levels of certain molecules may signal life-threatening condition

THURSDAY, Feb. 5, 2004 (HealthDayNews) -- Abnormal levels of certain molecules in the blood may predict the development of preeclampsia in pregnant women, new research has found.

Preeclampsia is a potentially life-threatening condition that affects up to 5 percent of all pregnancies in the United States. The condition involves dangerously high blood pressure and protein in the urine.

"Preeclampsia is not uncommon, and both the mother and fetus are at risk for serious complications and even death," says Dr. Caren G. Solomon, author of a perspective article that accompanies the study in the Feb. 12 issue of the New England Journal of Medicine.

The article is being released early to coincide with a presentation Thursday at the annual meeting of the Society for Maternal-Fetal Medicine in New Orleans.

So far, any precise cause or causes of preeclampsia have eluded scientists (although some risk factors, such as obesity, are known) and, while individual symptoms can be treated, the "cure" is to deliver the baby.

Such a cure only works well if the woman is near term, however.

"If a woman gets preeclampsia and it's very early in the pregnancy, if you deliver the baby, the baby won't be able to survive," says study leader Dr. Richard J. Levine, a research medical officer in the epidemiology branch of the National Institute of Child Health and Human Development. "Even if it's a little older, it may be at risk for all kinds of problems in later life."

The hope is that these findings might one day lead to screening tests for preeclampsia and maybe even some treatment options, but it will take more research.

"These are intriguing data, but this cannot tell us that this molecule is the cause of preeclampsia," says Solomon, who is deputy editor of the journal and an associate physician at Brigham and Women's Hospital in Boston. "We don't know yet what [the role of the molecules] is going to be in identifying women who will develop preeclampsia or potentially in the development of a therapy. It's a very interesting observation and paves the way for a lot of follow-up studies that can help answer those questions."

Investigators had already zeroed in on the placenta as a central player in the onset of preeclampsia.

Study co-author S. Ananth Karumanchi had already discovered that a molecule called sFlt-1 is present in large quantities in women with preeclampsia. When injected into rats, sFlt-1 also caused an illness similar to preeclampsia. SFlt-1 is an anti-angiogenic compound, meaning it interferes with blood supply.

For this study, the investigators compared blood from 120 women who had developed preeclampsia with blood from 120 women who had had normal pregnancies. Some of the blood samples were taken before the diagnosis of preeclampsia was made.

The women who eventually developed preeclampsia had three times the blood levels of sFlt-1 as the women with normal pregnancies. At the beginning of their pregnancies, however, blood levels of sFlt-1 in both groups of women were similar. Levels began to rise steeply about five weeks before the onset of preeclampsia.

Conversely, levels of Placenta Growth Factor (PIGF) and Vascular Endothelial Growth Factor (VEGF), which both promote blood supply, were present in inverse proportions to sFlt-1.

Specifically, sFlt-1 seemed to be binding the PlGF and the VEGF, Levine says. "Both PlGF and VEGF are required to maintain the health of endothelial cells, which line blood vessels throughout the body," he says. "These cells become dysfunctional."

"The high levels of sFlt-1 are thought to interfere with appropriate blood flow in the placenta, and also might account for other abnormalities in preeclampsia, including high blood pressure and protein in the urine in the mother," Solomon explains.

One issue that remains to be resolved is whether levels of these compounds can distinguish women who will get preeclampsia from women who will get gestational hypertension, a less serious condition. Figuring that out is the next step, Levine says.

More information

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

SOURCES: Richard J. Levine, M.D., research medical officer, epidemiology branch, National Institute of Child Health and Human Development, Bethesda, Md.; Caren G. Solomon, M.D., deputy editor, New England Journal of Medicine, and associate physician, Brigham and Women's Hospital, Boston; Feb. 12, 2004, New England Journal of Medicine
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