Blood concentrations of two proteins that affect blood vessel growth appear to foretell preeclampsia, the baffling pregnancy condition that can threaten the lives of both a woman and her unborn baby. The findings from two new studies may lead scientists to develop screening tests and treatments for the disease.
Preeclampsia strikes about 5 percent of pregnancies in the United States. In these cases, during the second half of a pregnancy, women develop high blood pressure and excess protein in their urine. The condition can escalate to eclampsia, which includes potentially fatal seizures.
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Preeclampsia can be moderated, but the only known cure is delivery of the baby and removal of the placenta.
“If we could predict the development of preeclampsia, we could offer treatment before it becomes a serious problem,” says Duane Alexander, director of the National Institute of Child Health and Human Development (NICHD) in Bethesda, Md.
Both new studies examined pregnant women’s blood concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt1). In a normal pregnancy, PlGF promotes growth of placental blood vessels, whereas sFlt1 keeps that growth in check and halts it late in the third trimester.
In one study, researchers led by NICHD epidemiologist Richard J. Levine examined blood samples that had been archived throughout the pregnancies of 120 women eventually diagnosed with preeclampsia and 120 women without the disease. The work is reported in the Feb. 12 New England Journal of Medicine.
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Beginning 13 to 16 weeks into pregnancy, women who developed preeclampsia had significantly lower PlGF concentrations than the other women did. In contrast, blood concentrations of sFlt1 were similar for the two groups until the third trimester. Then, more of the women who developed the disease showed a spike in sFlt1 concentrations.
“It appears that early on, the differences in PlGF are apparent, whereas later on, differences in sFlt1 are more apparent,” says Ravi Thadhani, a nephrologist at Massachusetts General Hospital in Boston and a coauthor of the study.
Thadhani and Levine also participated in the second study, which reviewed concentrations of the two proteins during only the first trimester of pregnancy. The study included blood samples from 40 women who developed preeclampsia, 80 women who had high blood pressure or bore small babies but didn’t develop preeclampsia, and 80 women who completed normal pregnancies.
The findings were consistent with those of the first study and, in addition, suggested that PlGF and sFlt1 readings can selectively predict preeclampsia, setting the disease apart from other pregnancy problems that lead to high blood pressure or low birth weight. The findings appear in the February Journal of Clinical Endocrinology and Metabolism.
“This is exciting work that marks a new chapter in our efforts to understand and conquer a very bad and continually understudied disease,” says nephrologist Marshall D. Lindheimer of the University of Chicago.
“If sFlt1 and PlGF are good markers, we can design a test for women at high risk for preeclampsia,” says Levine. For preeclampsia treatments, he adds, “I believe that in the future, we will have people try to develop molecules that would block sFlt1.”
However, Levine calls the new papers “just a start” toward fully understanding what causes preeclampsia.