Grant Bolsters Research to Address Rising Maternal Mortality Rates

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Kathryn Lindley, MD, holder of the Samuel S. Riven, MD, Directorship in Cardiology.

The United States has the highest maternal mortality rate of any industrialized nation, a trend that has been accelerating for 20 years. But nearly two out of three maternal deaths are preventable, with cardiovascular disease (CVD) being the leading cause of death, said Kathryn Lindley, MD, holder of the Samuel S. Riven, MD, Directorship in Cardiology.

To combat the trend, The National Institutes of Health (NIH) has awarded a $4.1 million grant to Vanderbilt University Medical Center and University of California, San Diego to better understand the mechanism behind the association between preeclampsia (PE) and other hypertensive disorders of pregnancy (HDP) and CVD. Though a strong association has been established, it remains unclear whether the links stem from an underlying genetic, environmental and physiologic state that precedes pregnancy or is a direct effect of PE/HDP.

The central goal of the Multi-Omics for Maternal Health after Preeclampsia (MOM-Health) Disease Study is to use multiomic analyses of biofluids (blood, saliva and urine) and placental tissue, linked with comprehensive phenotypic and environmental exposure measures, in a diverse population, to uncover mechanisms leading from PE/HDP to intervenable postpartum maternal health outcomes.

Half of pregnancy-associated maternal deaths occur in the year after delivery, Lindley said. Although maternal morbidity is increasing across all racial and ethnic groups, Black, Hispanic, and Native American women are disproportionately affected. Advancing maternal age and socioeconomic and geographic barriers to accessing care may be partly to blame.

“About 5% to 10% of pregnant women will have preeclampsia, a type of high blood pressure, many of whom will be completely healthy before pregnancy,” said Lindley, associate professor of Medicine. “We know that people who get PE are at a much higher risk of having heart problems later, such as high blood pressure, strokes, heart attacks and heart failure. If we can better screen for these factors, we can intervene medically to prevent deaths during and after pregnancy.”

The research team is comprised of a multidisciplinary effort across two institutions, with the VUMC side led by Lindley, (cardiovascular), Ravi Shah, MD, (cardiovascular), and Sarah Osmundson, MD (maternal fetal medicine).

For the five-year study, researchers will recruit 680 participants (180 high-risk and 500 low-risk) in the second trimester of pregnancy and follow them through pregnancy, yielding 200 cases with PE/HDP and 480 in the control group.

At delivery, all 680 participants will have placental tissue and cord blood samples collected. Then, for one year after delivery, researchers will follow the 200 cases with PE/HDP and a subset of 100 controls. They will collect biosamples and other measures to determine whether risks for heart issues develop, including changes in cholesterol or blood sugar levels, Lindley said.

Researchers will gather multiomic, phenotypic and environmental exposure data. The result could contribute to a better understanding of the mechanics of PE/EDP and better identifying the risk of such cardiovascular diseases in the patient population. Lindley said the results could inform the development of screening tests to better determine which women are at higher risk for heart issues and intervene earlier for better outcomes. It could result in new medical treatments and a better understanding of risk factors and lifestyle changes that could prevent them, such as weight loss and treating blood pressure.

“Understanding whether and how pregnancy impacts women’s health will help us better manage pregnancy complications and their health after pregnancy,” Osmundson said.

The study is supported by NIH grant 1U01HG013189-01.

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