The FNIH Announces Results of a New Study Published in The New England Journal of Medicine Showing a Single Dose of Azithromycin Reduced Maternal Sepsis by 35%

• Low-Cost Antibiotic Could Prevent Sepsis in up to 2 Million Women Per Year
• Research Presented at the Society for Maternal-Fetal Medicine's 43^rd Annual Pregnancy Meeting
• Study Made Possible through Partnership between the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NICHD Global Network for Women's and Children's Health Research, the Bill & Melinda Gates Foundation and the Foundation for the National Institutes of Health

NORTH BETHESDA, Md., Feb. 9, 2023 /PRNewswire/ -- The Foundation for the National Institutes of Health (FNIH) today announced that The New England Journal of Medicine (NEJM) has published the results of a study of antibiotic treatment to protect maternal health in resource-limited settings that could benefit up to 2 million women per year.¹ The study, called the Azithromycin Prophylaxis in Labor Use Study (A-PLUS), found that one dose of azithromycin, a low-cost, generic, oral antibiotic, given during labor to women planning to deliver vaginally in low- and middle-income countries, can prevent life-threatening sepsis.

"The A-PLUS study has remarkable potential to protect maternal health and represents a significant advancement, especially for women who cannot access modern obstetrical care," said Dr. Julie Gerberding, CEO of the Foundation for the National Institutes of Health (FNIH). "This multinational study is an exemplar of what can be accomplished through team science — connecting academic researchers around the world with NIH experts and private foundations, like the Bill & Melinda Gates Foundation, to advance global health breakthroughs. We thank the thousands of women and their care providers in seven countries who agreed to participate in the study even in the midst of a pandemic."

Sepsis is a life-threatening condition caused by the body's extreme response to infection and can lead to organ failure and death. The World Health Organization (WHO) estimates sepsis due to obstetric infection is the third most common cause of maternal mortality globally.² This randomized, placebo-controlled study found that a single dose of azithromycin reduces the occurrence of maternal sepsis by approximately 35%. When a combination of sepsis and death was analyzed, there was a 33% reduction. Given the nearly 6 million cases of maternal sepsis per year,³ the A-PLUS study results suggest that up to 2 million cases of maternal sepsis per year could be prevented with this readily available, affordable medicine.

The study was designed to include 34,000 women in seven low- and middle-income countries who received a single dose of azithromycin or placebo during childbirth. However, an interim analysis found the treatment had a significant beneficial effect, and enrollment was halted early for maternal effectiveness after approximately 29,000 women were studied.

"Sepsis is one of the leading causes of maternal death worldwide and there is urgent need for low-cost, effective interventions," said Prof. Dr. Antoinette Tshefu Kitoto, Professor of Public Health at Kinshasa School of Public Health and International Principal Investigator of the UNC-Democratic Republic of the Congo site. "We saw such a significant reduction in the incidence of sepsis with azithromycin that we stopped enrolling new participants early to ensure that as many women as possible could benefit from our findings as soon as possible."

In addition to a reduction in sepsis, the study found a lower risk of maternal endometritis (uterine infection), hospital readmission and unscheduled medical visits among women who received azithromycin. Azithromycin is an inexpensive, generic antibiotic available in tablet form and suitable for room-temperature storage.

The study included women at study sites located in Bangladesh, the Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia. Consequently, the results are likely to be useful for informing national health policy and obstetrical practice in similar settings around the world.

Investigators also examined the use of azithromycin to prevent sepsis or death in newborns. The intervention had no effect in this population. The drug also had no adverse newborn effects.

In addition to publication in The New England Journal of Medicine, the study results were presented simultaneously at the Society for Maternal-Fetal Medicine's 43^rd Annual Pregnancy Meeting in San Francisco, Calif. As a result of the study's positive findings, A-PLUS investigators will provide the World Health Organization (WHO) and other professional organizations with the results to inform their guidelines.

This groundbreaking multi-site study was conducted by NICHD's Global Network for Women's and Children's Health Research and was co-funded by NICHD and the FNIH, with support to the FNIH provided by a grant from the Bill & Melinda Gates Foundation.

Funding partners:

• Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health
• Bill & Melinda Gates Foundation

Implementing partners:

• RTI International
• Boston University in conjunction with Lata Medical Research Foundation (Nagpur, India)
• Columbia University in conjunction with Aga Khan University (Pakistan)
• Indiana University School of Medicine in conjunction with Moi University (Kenya)
• Thomas Jefferson University in conjunction with Jawaharlal Nehru Medical College (Belagavi, India)
• University of Alabama at Birmingham in conjunction with University of Zambia (Zambia)
• University of Colorado, Denver in conjunction with the Institute of Nutrition of Central America and Panama (Guatemala)
• University of North Carolina at Chapel Hill in conjunction with the Kinshasa School of Public Health (Democratic Republic of Congo)
• University of Virginia in conjunction with the International Center for Diarrheal Disease Research (Bangladesh)

Additional information and a short video about the A-PLUS study are available on the FNIH website.

About the A-PLUS Study: The Azithromycin Prophylaxis in Labor Use Study (A-PLUS) analyzed the safety and effectiveness of a single intrapartum oral dose of azithromycin compared to placebo, in reducing the risk of neonatal and maternal sepsis or death in laboring women. Single-dose azithromycin is a low-cost, accessible intervention, which was found to improve maternal health. The study was led by Drs. Alan T. N. Tita and Waldemar A. Carlo, from the University of Alabama at Birmingham, and Dr. Elizabeth M. McClure, of RTI International. It was conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Global Network for Women's and Children's Health Research. The study was funded by NICHD and through a grant from the Bill & Melinda Gates Foundation to the FNIH.

About the Foundation for the National Institutes of Health: The Foundation for the National Institutes of Health (FNIH) connects the world's leading public and private organizations to accelerate biomedical breakthroughs for patients, regardless of who they are, where they live or what disease they have. Together with leading scientists and problem-solvers, and a successful track record of navigating complex problems, the FNIH accelerates new therapies, diagnostics, and potential cures; advances global health and equity in care; and celebrates and trains the next generation of scientists. Established by Congress in 1990 to support the mission of the NIH, the FNIH is a not-for-profit 501(c)(3) charitable organization. For more information about the FNIH, please visit fnih.org.

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Contact:
Melanie Doupé Gaiser
Ruder Finn, on behalf of FNIH
212.593.6459
[email protected]

References:

1. Tita A, Carlo W, McClure E, et al. Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth. N Engl J Med. 2023;388:xxx-xxx. www.nejm.org/doi/full/10.1056/NEJMoa2212111
2. Maternal infections in Health Facilities. World Health Organization. https://www.who.int/news/item/27-04-2020-maternal-infections-in-health-facilities. Published April 27, 2020. Accessed January 11, 2023.
3. Rudd KE, Johnson SC, Agesa KM, et al. Global, Regional, and National Sepsis Incidence and Mortality, 1990-2017: Analysis for the Global Burden of Disease Study. The Lancet. 2020; 395(10219):200-211.

SOURCE Foundation for the National Institutes of Health