A substance found in the urine of pregnant women can be measured to predict the later development of preeclampsia, according to research from the National Institute of Child Health and Human Development of the National Institutes of Health.

The researchers found women were highly likely to develop preeclampsia if they had low levels of a substance known as placental growth factor (PlGF) in their urine. PlGF works in combination with a substance called vascular endothelial growth factor (VEGF). Together, the two substances foster the growth of new blood vessels, and maintain the health of cells that line the inside of blood vessels, including those in the placenta that support the developing fetus.

The researchers believe that the high blood pressure and other symptoms characteristic of preeclampsia result from low levels of PlGF and VEGF.
Researchers are making plans to refine the finding into an accurate clinical test.

"We may have reached a turning point in the extensive federal research investigation of this frequent, life-threatening complication of pregnancy," Duane Alexander, director of the NICHD said adding, "This finding sets the stage for the development of a test to screen women for high risk of preeclampsia. Once these women are identified through such a test, we can target studies to find effective ways to prevent its progression or to keep the most dangerous complications from occurring."

A few women - such as those pregnant with more than one baby or with long-term high blood pressure - are known to be at high risk for preeclampsia, explained the study's first author, Richard Levine of NICHD's Division of Epidemiology, Statistics, and Prevention Research. However, the vast majority of cases strike without warning, in first-time mothers. Usually, a pregnant woman with preeclampsia develops dangerously high blood pressure and begins excreting protein in the urine. In some cases, the condition may progress to eclampsia, a series of potentially fatal seizures. Although the high blood pressure and seizures can be treated, the only cure for preeclampsia is delivery of the baby. Combined estimates of preeclampsia and other hypertension disorders during pregnancy range from 5.9 to 8 per cent of all pregnancies in the United States.

In cases where the condition does not progress to eclampsia, infants born to mothers with preeclampsia may be extremely small for their gestational age or may be born prematurely. These conditions, in turn, place the infants at risk for a variety of other birth complications, among them blindness, cerebral palsy, or mental retardation.

This study builds upon earlier findings by the last author, S. Ananth Karumanchi of the Renal Division at the Beth Israel Deaconess Medical Centre and Harvard Medical School in Boston. Dr. Karumanchi and his co-workers had previously discovered that a substance called soluble fms- like tyrosine kinase 1 (sFlt-1) circulates in large quantities in the bloodstreams of women with preeclampsia and that sFlt-1 injected into the bloodstream of pregnant rats caused a preeclampsia-like illness.

Last year, Drs. Levine, Karumanchi and their coworkers reported that high levels of sFlt-1 likely influenced the development of preeclampsia, by binding to PlGF and VEGF. Because they were bound to sFlt-1, the two substances could not be used by the blood vessel cells that required them.

The study appears in the January 5 "Journal of the American Medical Association".