Molecules in Blood Foretell Development of Preeclampsia

The findings appear in the September 7 New England Journal of Medicine.

Preeclampsia is a leading cause of maternal death and often occurs without warning. The condition results in high blood pressure and protein in the urine. Preeclampsia may begin with mild symptoms, then progress to severe preeclampsia and to eclampsia — dangerously high blood pressure and convulsions — which may result in disability or death. When preeclampsia is not severe, the high blood pressure it causes can usually be treated in the short term. The only cure for preeclampsia is delivery of the baby. The condition is estimated to complicate from 3 to 5 percent of all pregnancies.

When preeclampsia occurs late in a pregnancy, the baby can be delivered with relatively few ill effects. However, if preeclampsia occurs early in pregnancy, delivery of the baby would result in premature birth, which increases the risk of death, and for such lifelong complications as blindness, cerebral palsy, and learning disabilities. In such instances, physicians are forced to weigh the mother's risk of severe disease or eclampsia against the consequences of preterm birth for the baby.

In the current study, the researchers present strong evidence that an imbalance of two proteins produced by the placenta is responsible for the symptoms of preeclampsia. Abnormally high levels of these proteins appear to deprive the blood vessels of substances needed to keep the lining of the blood vessels healthy. Deprived of these essential substances, the cells lining the blood vessels begin to sicken and die. As a result, the blood pressure increases, and the blood vessels leach protein into the tissues and urine.

The first of these two proteins is known as soluble endoglin. It begins accumulating in the blood of pregnant women 2 to 3 months before they develop preeclampsia. In women who developed preterm preeclampsia, levels of soluble endoglin began to rise in the 17th to the 20th week of pregnancy. In women who developed preeclampsia at full term, soluble endoglin levels rose at the 25th to the 28th week of pregnancy.

Similarly, soluble endoglin levels also rose in the 33rd through the 36th week of pregnancy for women who later developed gestational hypertension — hypertension without protein in the urine. Levels rose still further after the onset of gestational hypertension.

The second protein involved in the chemical imbalance is called soluble fms-like tyrosine kinase 1 (sFlt1). The women in the study who had developed preeclampsia had increased levels of sFlt1. The increase in sFlt1 was accompanied by reduced levels of a substance, placental growth factor (PlGF). Both women with term preeclampsia and women with gestational hypertension had a simultaneous rise in soluble endoglin, and an increase in the ratio of sFlt1 to PlGF (high levels of sFlt1 and low levels of PlGF.)

A possible treatment for preeclampsia might involve reducing levels of sFlt1 or soluble endoglin or adding more of the molecules that they remove from the blood stream, so that more VEGF, PlGF, and TGF beta would be available for the blood vessels that need them. One company has developed the means to produce a form of VEGF. Presumably, such a drug would raise the levels of circulating VEGF in the bloodstream. The surplus VEGF would bind to the high levels of sFlt1 produced during preeclampsia, but enough free VEGF would still be available to attach to cell surface receptors to promote the health of blood vessels.

Message posted by: Rashmi Nemade