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Simple blood test may be able to predict risk of preeclampsia

BOSTON — April 4, 2002 — A simple blood test conducted during the first trimester of pregnancy may be able to identify women at risk for preeclampsia, a common and dangerous complication of late pregnancy, say researchers from the Massachusetts General Hospital (MGH). The prospective study found that women who eventually developed preeclampsia, which is also called toxemia, were more likely to have had reduced blood levels of a protein called SHBG, a known marker for insulin resistance, early in pregnancy. The report appears in the April issue of The Journal of Clinical Endocrinology and Metabolism.

"This study showed that a risk factor that can be detected many weeks before symptoms appear may be able to predict who will develop preeclampsia," says Myles Wolf, MD, of the MGH Renal Unit, the paper's first author. "Our study raises the possibility of developing new approaches to diagnosis and intervention, which eventually could lead to preventive treatments."

"Preeclampsia can be devastating, and unfortunately we do not have a way to treat women with this condition," says author Ravi Thadhani, MD, MPH, of the MGH Renal Unit, the study's senior author. "Finding a way to predict who will develop preeclampsia is a necessary first step to testing new therapies."

Preeclampsia is a condition in which a pregnant woman develops high blood pressure and other metabolic abnormalities. If not appropriately managed, a woman with preeclampsia can proceed to eclampsia - characterized by seizures - or liver or kidney failure, complications that can prove fatal. Preeclampsia increases the risk of premature delivery or emergency cesarean, since delivery is the only real cure for the condition. In such instances, the baby faces the numerous risks associated with prematurity.

It is estimated that preeclampsia occurs in 5 to 7 percent of pregnancies (more than 200,000 women in the U.S. every year) and is more common in women having their first pregnancy. While preexisting diabetes and high blood pressure have been identified as risk factors, standard treatments for those conditions have not been effective in reducing the risk.

The current study is part of the MGH Obstetrical Maternal Study, a prospective study of more than 4,500 women that seeks to identify risk factors for hypertensive disorders of pregnancy. As part of that larger study, blood samples are taken from participants during the first trimester. The current report's investigators reviewed information from study participants who delivered single children in their first pregnancy and identified 45 cases of preeclampsia. They compared data on those women with information from 90 study participants randomly selected from those who had normal pregnancies, with particular attention to factors known to be associated with insulin resistance syndrome. Several of the symptoms of insulin resistance - including obesity and hypertension - are also associated with preeclampsia.

Those women who went on to develop preeclampsia were found to have had reduced levels of the protein SHBG (sex hormone binding globulin) in their first-trimester blood tests much more frequently than were women who had normal pregnancies. The researchers also found that the association of reduced SHBG levels with the risk of preeclampsia remained no matter whether women were lean or overweight.

"We know that obese women are at higher risk for preeclampsia and tend to have insulin resistance," Wolf says. "The fact that the association of preeclampsia with reduced first-trimester SHBG is also seen in lean women suggests that insulin resistance may be the true risk factor. It also may provide the only clue that a lean woman is at elevated risk."

Wolf adds that the possibility of being able to identify at-risk women earlier in their pregnancies could lead to advances in the search for preventive therapies. "One reason why the studies of possible treatments have failed could be that we can't predict who might develop preeclampsia until symptoms begin, which can be 20 to 25 weeks into pregnancy. There might be a window of opportunity in the first trimester when preventive treatment could be successful, but until now we did not have a simple way to identify high-risk women."

Along with Thadhani, who is principal investigator of the MGH Obstetrical Maternal Study, Wolf's coauthors are Laura Sandler, Kristine Munoz and Karen Hsu of the MGH Renal Unit, and Jeffrey Ecker, MD, of the MGH/Vincent Obstetrics and Gynecology Service. The study was supported by grants from the National Institutes of Health.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $300 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine.

In 1994, the MGH joined with Brigham and Women's Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.



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