NIH – Community Engaged Research on Pregnancy Related and Associated Infections and Sepsis Morbidity and Mortality (UG3/UH3 Clinical Trial Optional)

January 28, 2022 by


The purpose of this FOA is to support interdisciplinary community-engaged research designed to reduce or eliminate infections and sepsis as causes of pregnancy- related or associated morbidity and mortality (PRAMM) in the United States. This FOA is to support research primarily focused on PRAMM health disparities in areas with highest maternal morbidity and mortality.

This initiative utilizes the UG3/UH3 Phased Innovation Awards Cooperative Agreement and will be rolled out in 2 phases. Awards for the One Year UG3 phase will be used to demonstrate sufficient preparation, feasibility, and capacity to meet foundational milestones specific to the work proposed. Hypothesis driven objectives will be submitted for the UH3 phase. A UG3 project that meets its milestones will be administratively considered by NICHD and prioritized for transition to the UH3 award. Applicants responding to this FOA must address objectives for both the UG3 and UH3 phases.


Remarkable advances in perinatal care over the last 25 years in the United States have led to notable improvements in neonatal morbidity and mortality. In contrast, between 1987 and 2017, pregnancy-related mortality in the United States, defined as death during pregnancy or within one year of pregnancy from any cause related to or aggravated by pregnancy, increased from 7.2 to 17.3 pregnancy-related deaths per 100,000 live births. Among the leading causes of maternal morbidity and mortality in the United States are cardiovascular disease, hypertensive disorders, thromboembolism, hemorrhage, and infections. Research into the clinical causes of maternal morbidity and mortality has led to some improvements in the care of women during the antepartum period and labor and delivery; however, evidence suggests that up to 60% of maternal deaths in the United States could be prevented. Therefore, continued research investments are needed to identify and provide safe and effective prevention and treatment options for women.

Racial and ethnic minority women face substantially higher rates of pregnancy-related complications (i.e., severe maternal morbidity) and pregnancy-related death compared to non-Hispanic White women. Specifically, non-Hispanic Black and American Indian/Alaska Native women are 2 to 4 times more likely to die from pregnancy-related causes compared to non-Hispanic White women. Moreover, African American/Black, Hispanic/Latina, Asian, Native Hawaiian and Pacific Islander, and American Indian/Alaska Native women all have higher incidence of severe maternal morbidity compared to White women. Maternal health disparities also occur based on age, with women over the age of 40 having a maternal mortality ratio almost 5 times that of the national average. Geography may also contribute to poor maternal outcomes; a recent evaluation of maternal mortality in Louisiana found that women living in maternity care deserts had a 91% increased risk of pregnancy-associated maternal death.

Researchers have made progress in understanding the epidemiology of racial and ethnic disparities in maternal mortality and morbidity. The primary contributing factors of these disparities, such as preconception health and site of care, are well-documented. However, disparities in maternal outcomes persist after controlling for patient characteristics (e.g., health behaviors, preconception health) and health care system factors (e.g., site and quality of care), suggesting that additional factors may be contributing to the high prevalence of maternal morbidity. For example, racial biases at the individual, community, institutional, and societal levels may play a role in perpetuating racial and ethnic disparities in maternal outcomes. Structural and organizational factors in the health care systems of ambulatory and hospital care and the availability of continuity of primary care in the preconception and postpartum periods may also be affecting maternal outcomes.

Between 2011 and 2016, infection or sepsis contributed to 12.5% of pregnancy-related maternal deaths. Sepsis is life-threatening organ dysfunction caused by infection and the host’s dysregulated response to infection. The main risk factors for maternal sepsis are cesarean delivery, prolonged rupture of membranes and prolonged labor. Other risk factors include obesity, diabetes, low socio-economic status, lack of access to prenatal care, poor nutrition, primiparity, anemia, and multiple gestation. The obstetric-related causes of sepsis include endometritis, wound infection after cesarean section or episiotomy, and abdominopelvic abscess. However, pregnant women are also at risk for worse outcomes from pregnancy associated bacterial and viral infections such as influenza, urinary tract infections, and now COVID-19.

Key Dates:

Open Date (Earliest Submission Date): March 18, 2022
Letter of Intent Due Date(s): 30 days prior to application receipt date
Application: April 18, 2022

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Filed Under: Funding Opportunities