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Blood Tests Could Warn of Pregnancy Complication

Raised levels of two proteins may predict preeclampsia, study suggests

WEDNESDAY, Sept. 6, 2006 (HealthDay News) -- High blood levels of two proteins may tip doctors off to the development of preeclampsia, a dangerous and often unpredictable complication of pregnancy, U.S. researchers report.

"In general, you need high levels of both these proteins to get severe preeclampsia," said lead researcher Dr. Richard J. Levine, a senior investigator at the National Institute of Child Health and Human Development at the National Institutes of Health.

His team published its findings in the Sept. 7 New England Journal of Medicine.

Preeclampsia affects up to 8 percent of pregnancies around the world and can lead to premature delivery and the need for a Caesarean section. The condition results in a sudden spike in high blood pressure and a rise in protein in the urine.

One of the major challenges with preeclampsia is that it has been tough for doctors to predict who might be at risk.

While the study results are preliminary, Levine and others cautioned that "there is [now] hope for developing a predictive test as well as a diagnostic one."

In the study, Levine and his colleagues compared data from five groups of women -- those with preterm preeclampsia, those with preeclampsia at term (37 weeks), those with pregnancy-associated high blood pressure, those with normal pressure who delivered infants small for gestational age, and women with normal blood pressure who delivered infants who were not small for gestation age.

Four of the groups included 120 women each, while the group with preterm preeclampsia included 72 women. All had been participants in the Calcium for Preeclampsia Prevention trial, a study conducted from 1992 to 1995 to evaluate the effects of daily calcium supplements in reducing preeclampsia (the supplements did not prove effective).

Levine's team examined blood specimens taken and stored during the study, comparing levels of two specific proteins, endoglin and sFlt1.

Comparing women who had preeclampsia to women with stable blood pressure, Levine said protein levels "started going up two or three months before they developed the disease. So that gives us reason to believe we can identify women who will subsequently develop preeclampsia."

The first protein, soluble endoglin, began to rise in the 17th to 20th week of pregnancy in women who developed preterm preeclampsia. For women who developed preeclampsia later on, at full-term, levels started to climb at weeks 25 to 28.

Those who developed high blood pressure later (but not the protein in the urine associated with preeclampsia) had their levels rise in the 33rd through the 36th week of pregnancy.

The second protein studied was soluble fms-like tyrosine kinase 1, or "sFlt1." Those who developed preeclampsia had increased levels of this protein. They also had reduced levels of another substance called placental growth factor, or PlGF. Those who got preeclampsia at term and those who had gestational high blood pressure had a rise in the soluble endoglin and an increase in their sFlt1-to-PlGF ratio.

"We haven't investigated this enough to say how often it occurs," Levine said. Nor can they yet say how much the risk of preeclampsia rises with each increase in protein levels.

The study builds on work done previously by Dr. Ananth Karumanchi, a nephrologist at Beth Israel Deaconess Medical Center, Boston, and a co-author of the current paper.

One expert praised the study.

"It's great," said Dr. Brian Brost, an associate professor of obstetrics and gynecology at Mayo Clinic, Rochester, Minn. He said science is "getting closer and closer" to understanding and predicting preeclampsia.

Earlier this year, Brost's team found an association between preeclampsia and a third protein, HtrA, which is found in placental tissues.

In an editorial accompanying the study, Drs. Marshall Lindheimer of the University of Chicago and Jason Umans of Georgetown University noted that the "authors now have strong evidence to suggest the usefulness of these proteins in predicting preeclampsia." But they said that the data was from samples stored for about 10 years. They questioned if those samples had remained stable over such a long time.

Levine said he believes the blood samples did retain their integrity, since they showed no signs of deterioration.

Until more is known about preeclampsia, however, there is not much a woman can do to minimize her risk, Brost said.

"Currently, nothing is proven to be of marked benefit," he said.

Women should be sure to adhere to their prenatal visit schedule, he said, as close monitoring can help pick up preeclampsia early.

If the condition is diagnosed early, a doctor may prescribe medicine to lower blood pressure and buy her some time. Or, the doctor might decide to deliver the baby, if the woman is nearing term.

More information

To learn more about preeclampsia, visit the U.S. National Library of Medicine.

SOURCES: Richard J. Levine, M.D., M.P.H., senior investigator, U.S. National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md.; Brian Brost, M.D., associate professor, obstetrics and gynecology, Mayo Clinic, Rochester, Minn; Sept. 7, 2006, New England Journal of Medicine
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