Biomarkers predicting preeclampsia risk: New study points the way to preventing death and serious illness in women with hypertensive disorders of pregnancy

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In a study of pregnant women in the United States, Cedars-Sinai researchers found that a specific imbalance of two placental proteins could predict which women were at risk of developing a severe form of preeclampsia, a life-threatening blood pressure disorder.

The study is published in the journal NEJM evidence.

“We found that a blood test that measures the relationship between two proteins involved in the development of blood vessels in the placenta could identify which of the women would develop premature 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 standard-of-care markers for preeclampsia with severe features. It predicted with greater than 90% accuracy whether or not the patient would develop preeclampsia with severe features, while the usual markers had less than 75 percent accuracy.” % of the time.”

The blinded prospective study of women initially hospitalized for premature hypertension involved 1014 patients from 18 hospitals across the country.

“This multicenter investigation is one of the few large studies of the risk of developing preeclampsia with severe features in the US. 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 cities and rural areas,” Kilpatrick said.

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 a stroke. It affects approximately 5% of pregnant women and is a leading cause of maternal and fetal death and serious illness.

The researchers found that a specific protein imbalance revealed in blood tests of hospitalized pregnant women provided a way to quantify their risk of developing severe preeclampsia. It involves levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PIGF) in the bloodstream.

“An sFlt-1 to PIGF ratio of 40 or more predicted the development of severe preeclampsia, adverse outcomes, and preterm delivery within two weeks, two-thirds of the time,” said S. Ananth Karumanchi, MD, co-senior author of the study, who holds the Medallion Chair in Vascular Biology.

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

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

“We anticipate that this blood test may eventually lead to better health outcomes for mothers and their babies,” Kilpatrick said. “It is well known that pre-eclampsia progresses in virtually all women until they give birth. But it can be very difficult to predict the optimal time for delivery. Having an accurate test would help us ensure that the mother was in the right hospital for the delivery.” managing your care and that of your premature baby.

Preeclampsia rates have been steadily rising, largely due to rising obesity and high blood pressure in the country. Black, American Indian, and Alaska Native women have significantly higher rates of disease than white women and a higher risk of death.

The researchers also hope the findings could point the way to possible drug therapies for women at risk.

“We know that sFlt-1 is the protein that increases even before any symptoms of preeclampsia occur, and the ratio of sFlt-1 to PlGF predicts worsening of the disease,” Karumanchi said. “Further research may identify a pharmacological mechanism that could lower sFlt-1 levels and be used to safely prolong pregnancy; that would be a game changer for patients with very premature preeclampsia.”

While the study involved a single blood test for two proteins, the researchers are encouraged that further research, involving large numbers of subjects, will provide better tools to thwart preeclampsia before it can seriously harm patients and their babies.

“We conducted this study to identify a simple and accurate biomarker that clinicians can use to determine who is at higher risk for preeclampsia with severe features and who would be a suitable candidate for treatments we might develop for this devastating condition,” said study co-author . lead author Ravi Thadhani, MD, MPH, professor of medicine at Harvard Medical School, academic director at Mass General Brigham in Boston, Massachusetts, and visiting faculty scientist at Cedars-Sinai. “I think we achieved this goal.”

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