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A specific imbalance of two placental proteins predicted which women were at risk of developing a severe form of preeclampsia, a life-threatening blood pressure disorder of pregnancy, in a new study by Cedars-Sinai investigators. The test involves measuring levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PIGF) in the bloodstream.

The study is published in NEJM Evidence. 

“We discovered that a blood test measuring the ratio between two proteins involved in blood vessel development in the placenta could identify which of the women would develop preterm preeclampsia with severe features,” said study co-senior author Sarah Kilpatrick, MD, PhD, chair of the department of obstetrics and gynecology at Cedars-Sinai.

“This test was significantly better than all the standard-of-care markers for preeclampsia with severe features. It predicted with over 90% accuracy whether the patient would develop preeclampsia with severe features or not, while the usual markers were accurate less than 75% of the time,” she added.

Preeclampsia is the most common hypertensive disorder associated with pregnancy. The severe form of the disease can lead to dangerously high blood pressure, organ failure, vision loss, or even stroke. It affects approximately 5% of pregnant women and is a leading cause of maternal and fetal death and serious illness. There is great interest in a better test to determine which patients are at the highest risk of this condition. Prospects include a test using RNA fragments.

This blinded, prospective study of women initially hospitalized for preterm hypertension involved 1,014 patients from 18 hospitals.

“This multicenter investigation is one of a few large studies of the risk for developing preeclampsia with severe features in the United States. The women represented a more racially diverse cohort than previous studies and included patients from both smaller community hospitals and large academic medical centers, in both cities and rural areas,” said Kilpatrick.

Investigators found that the specific protein imbalance revealed a way to quantify patients’ risk of developing severe preeclampsia.

“An sFlt-1 to PIGF ratio of 40 or greater predicted the development of serious preeclampsia, adverse outcomes, and early delivery within two weeks, two-thirds of the time,” said S. Ananth Karumanchi, MD, the co-senior author of the study.

“Conversely, if the critical ratio between the two proteins was below 40, we found the risk that the patient would progress to preeclampsia with severe features within two weeks of the blood test was less than 5%,” said Karumanchi, who is also director of nephrology at Cedars-Sinai.

Currently, the only cure for preeclampsia is delivery. A test indicating that a preterm patient, a woman who has completed less than 37 weeks of pregnancy, is likely to develop severe disease could help optimize care.

Rates of preeclampsia have been steadily on the rise, largely due to increases in obesity and hypertension in the nation. Black, American Indian, and Alaska Native women have significantly higher rates of the disease than white women, and a higher risk of death.

Investigators also hope the findings can point the way to potential drug therapies for women at risk.

“We know sFlt-1 is the protein that goes up even before any symptoms of preeclampsia occur and the ratio of sFlt-1 to PlGF predicts worsening disease,” said Karumanchi. “Further research may identify a drug mechanism that could reduce levels of sFlt-1 and be used to safely prolong pregnancy; that would be a gamechanger for very preterm preeclampsia patients.”

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