Possible Cause of Preeclampsia Uncovered

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June 7, 2001 -- Even experts admit they're baffled about the cause of preeclampsia, a severe complication of pregnancy that causes high blood pressure and can threaten the life of both the expectant mother and her unborn child. But a new study suggests that the condition may be caused by the body's shortage of a natural compound that causes the blood vessel walls to relax.

Preeclampsia, which occurs in about 5% of all pregnancies, is a rapidly progressive condition marked by a sudden rise in blood pressure, abnormally high weight gain, severe headaches, vision problems, presence of protein in the urine, and buildup of fluid in tissues causing swelling. Because many of these symptoms can occur in a normal pregnancy, prompt evaluation and diagnosis by a physician, followed by prompt treatment when necessary, are essential to preserve the health of the mother and the fetus.

Since preeclampsia can be serious and sometimes fatal, women are often admitted to the hospital for bed rest and close monitoring. They may be treated with fluids and high blood pressure medications until the baby can be delivered safely, which usually resolves the condition.

"It's a major cause of maternal mortality, especially in developing countries where it may account for 80% of maternal deaths," says Valerian E. Kagan, PhD, professor of obstetrics and gynecology at the University of Pittsburgh, in an interview with WebMD.

Previous studies have suggested that preeclampsia is caused by poor blood flow to the placenta, the protective sack that supplies blood and nourishment to the developing fetus.

According to the new theory, which is described in the June issue of Circulation Research, this inadequate blood supply triggers oxidative stress, a condition in which oxygen compounds released into the bloodstream cause damage to tissues and interfere with the release of the chemical nitric oxide.

Normally, nitric oxide causes the walls of blood vessels to relax, thereby easing blood pressure. So a shortage of the chemical would lead to an increase in blood pressure.

This nitric oxide shortage theory is supported by a recent small study out of the U.K. This study suggests that vitamin C, an antioxidant, may reduce the incidence of preeclampsia because it prevents oxidative stress. Similarly, other evidence suggests that women who have low blood levels of ascorbate, a form of vitamin C found in the body, may be at increased risk for preeclampsia. Although the mechanism is unknown, ascorbate does play a role in the release of nitric oxide.

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In the current study, Kagan and colleagues suggest that in pregnant women with preeclampsia, oxidative stress might cause a decrease in ascorbate levels. This decrease prevents nitric oxide from being released when needed, triggering a sharp rise in blood pressure and other symptoms.

They came to this conclusion by evaluating 21 pregnant women with preeclampsia and comparing them with 21 pregnant women with no evidence of the disorder and with 12 nonpregnant women.

They found that the women with preeclampsia had high levels of special substances in their blood that normally store nitric oxide until it is needed. Increased levels of these substances suggest nitric oxide is trapped and not being released when needed. In particular, one of these substances was significantly higher in blood samples taken from women with preeclampsia than in either of the other two groups.

"I think that the major problem now is to really further establish that ... by fixing that or doing something about it we can somehow help in preventing preeclampsia," Kagan tells WebMD. But before they can move ahead, more research is needed to confirm their results. Once confirmed, researchers will begin investigating how to stop this process and, therefore, prevent preeclampsia.

Other preeclampsia researchers, however, aren't so sure that Kagan and colleagues have made their case.

Marshall Lindheimer, MD, professor emeritus, of obstetrics and gynecology and medicine at the University of Chicagohas a problem with the groups of women used in the study. He tells WebMD that preeclampsia studies need to compare pregnant women with preeclampsia against pregnant women with high blood pressure but no preeclampsia. The findings reported by Kagan and colleagues could be common to different types of high blood pressure as well as to preeclampsia, Lindheimer says.

"It's an interesting paper; it's a descriptive paper," says Leslie Myatt, PhD, a professor of obstetrics and gynecology and maternal and fetal medicine at the University of Cincinnati who reviewed the study for WebMD, "but it poses more questions than answers, unfortunately."

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