A sweeping new international study has found that a single dose of the antibiotic azithromycin can help protect mothers from dangerous sepsis infections and death during vaginal childbirth. Published in the New England Journal of Medicine, the study was conducted by a UVA Health scientist and his collaborators.
Azithromycin, also known as Z-Pak, has already been shown to benefit women delivering by cesarean section. But the new findings reveal that the common antibiotic reduces mortality for women delivering vaginally and cuts their risk of developing sepsis, a potentially fatal full-body infection.
Infections, particularly sepsis, are responsible for 10% of maternal deaths shortly before, during, and after childbirth, putting such infections in the top five causes of maternal mortality worldwide.
“A single dose of the antibiotic azithromycin decreased sepsis and death by half in women in labor,” said researcher William A. Petri Jr., MD, PhD, of the University of Virginia School of Medicine’s Division of Infectious Diseases and International Health. “The simplicity of this intervention should allow its institution around the globe to protect mothers during childbirth.”
Petri is part of the Azithromycin Prophylaxis in Labor Use Study (A-PLUS) Trial Group, an international coalition of researchers that set out to determine if giving the antibiotic during childbirth would benefit either mothers or their children. More than 29,000 women in low- and middle-income countries volunteered to take part in the randomized trial; half were given azithromycin and half were given a harmless placebo.
Among the 14,637 women who received the placebo, 2.4% developed sepsis or died within six weeks. That’s compared with only 1.6% of the 14,526 women who received azithromycin. The difference was clear enough that the researchers stopped the trial early.
The antibiotic did not provide similar benefits for the babies, the researchers found. However, they say that benefits for the mothers, combined with the lack of harmful side effects, makes azithromycin an important new tool for keeping moms safe before, during, and after delivery. (The antibiotic is already recommended for caesarian births in the United States and elsewhere.)
UVA is one of seven universities participating in the Global Network for Women’s and Children’s Health, which is supported by a grant from the National Institute of Child Health and Human Development. Network research supports and conducts clinical trials in resource-limited countries by pairing foreign and U.S. investigators, with the goal of evaluating low-cost, sustainable interventions to improve maternal and child health and simultaneously building local research capacity and infrastructure.
The network team at UVA includes Petri, Drs. Chris Chisholm (Obstetrics/Gynecology), Rob Sinkin (Pediatrics), Chelsea Braun (Medicine/Infectious Diseases) and Program Manager Lauren Swindell and in Bangladesh Drs. Rashidul Haque and Masum Billah of the icddr,b research center, and Ruth Lennox of the LAMB Hospital.
Petri noted that the findings result from an important collaboration of scientists around the world working together to improve care for pregnant women and help them deliver their babies more safely.
“All of us engaged in the work of the network here in Charlottesville are enjoying the opportunity to collaborate across disciplines, each of us enriched by the perspectives of obstetricians, pediatricians, and infectious-diseases specialists,” Petri said. “The network is open to all to propose new multi-site international studies in maternal and child health, and I hope that innovative ideas and ultimately clinical trials will originate here at UVA.”
The researchers have published their findings in the prestigious New England Journal of Medicine. A full list of the authors and their affiliations is included in the paper.
Reference: “Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth” by Alan T.N. Tita, M.D., Ph.D., Waldemar A. Carlo, M.D., Elizabeth M. McClure, Ph.D., Musaku Mwenechanya, M.D., Elwyn Chomba, M.B., Ch.B., Jennifer J. Hemingway-Foday, M.P.H., Avinash Kavi, M.D., Mrityunjay C. Metgud, M.D., Shivaprasad S. Goudar, M.D., Richard Derman, M.D., M.P.H., Adrien Lokangaka, M.D., M.P.H., Antoinette Tshefu, M.D., Ph.D., M.P.H., Melissa Bauserman, M.D., M.P.H., Carl Bose, M.D., Poonam Shivkumar, M.D., Manju Waikar, M.D., Archana Patel, M.D., Ph.D., Patricia L. Hibberd, M.D., Ph.D., Paul Nyongesa, M.D., Fabian Esamai, M.B., Ch.B., M.P.H., Ph.D., Osayame A. Ekhaguere, M.B., B.S., M.P.H., Sherri Bucher, Ph.D., Saleem Jessani, M.B., B.S., Shiyam S. Tikmani, M.B., B.S., Sarah Saleem, M.B., B.S., Robert L. Goldenberg, M.D., Sk M. Billah, M.P.H., Ruth Lennox, M.B., Ch.B., Rashidul Haque, M.D., William Petri, M.D., Lester Figueroa, M.D., Manolo Mazariegos, M.D., M.P.H., Nancy F. Krebs, M.D., Janet L. Moore, M.S., Tracy L. Nolen, D.Ph. and Marion Koso-Thomas, M.D., M.P.H. for the A-PLUS Trial Group, 9 February 2023, New England Journal of Medicine.
The research was supported by The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the Foundation for the National Institutes of Health through the Maternal, Newborn & Child Health Discovery & Tools initiative of the Bill and Melinda Gates Foundation.