Abnormal levels of two molecules found in the blood appear to predict the development of preeclampsia, a life- threatening complication of pregnancy, according to a study by researchers at the National Institute of Child Health and Human Development of the National Institutes of Health and the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston. The findings will appear in the February 12 issue of "The New England Journal of Medicine".

When compared to women who did not have preeclampsia, women who later developed the condition had elevated blood levels of a substance known as soluble fms-like tyrosine kinase 1 (sFlt-1), before their preeclampsia occurred. Conversely, beginning early in their pregnancies, these women had lower levels of a substance known as placental growth factor (PlGF) in the blood than did women who did not develop preeclampsia.

Women who developed preeclampsia also had lower levels of another substance, vascular endothelial growth factor (VEGF). The researchers were unable to use VEGF levels to predict the development of preeclampsia; however, VEGF appears to be important for the healthy functioning of blood vessels, and the researchers theorize that the lack of VEGF as well as PlGF contributes to the health problems resulting from preeclampsia.

Preeclampsia can occur suddenly, without warning. 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. According to the study authors, preeclampsia affects about 5 per cent of all pregnancies.

"This is the most promising lead yet in the pursuit of a life-threatening disorder that has defied all attempts to prevent or cure it," said Duane Alexander, director of the NICHD. "If we could predict the development of preeclampsia, we could offer treatment before it becomes a serious problem."

In cases where the condition does not progress to eclampsia, infants born to mothers with preeclampsia may be extremely small for their age or may be born prematurely. This may, in turn, place them at risk for a variety of other birth complications.

The Flt-1 molecule belongs to a class of molecules known as receptors, explained the study's principal investigator, Richard Levine, MD, of NICHD's Division of Epidemiology, Statistics, and Prevention Research. Flt-1 sits on the surface of the cells that line the inside of blood vessels. Like a key fits into a lock, VEGF and PlGF bind to Flt-1, and in the process trigger a chain of chemical reactions inside the cell. The Flt-1 molecule also exists in a soluble form as well, which does not sit on the cell surface but instead circulates in the bloodstream. The soluble Flt-1 (sFlt-1) binds to VEGF and PlGF, preventing them from acting on the cells that line the inside of blood vessels. Pregnant women who carry normal pregnancies to term also have sFlt-1 in their blood. In these women, however, sFlt-1 is present at much lower levels, and much later in the pregnancy -- shortly before birth. The finding builds upon earlier research led by the study's co-principal investigator, Ananth Karumanchi, MD of the Renal Division at the Beth Israel Deaconess Medical Center and Harvard Medical School in Boston. Dr Karumanchi and his coworkers had previously discovered that 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.