Single dose of azithromycin reduces maternal sepsis or death

Ten percent of maternal deaths are caused by infections that occur shortly before, during or after delivery. Maternal infections and sepsis, which is a serious complication of infections, are among the top five causes of maternal mortality worldwide. Maternal infection also increases the risk of neonatal sepsis, which accounts for 16 percent of newborn deaths.

A new study published today in the New England Journal of Medicine provides evidence that a single oral dose of azithromycin, a common antibiotic, reduced the risk of maternal sepsis or death by 33 percent in women who delivered vaginally. The results from the Azithromycin Prevention in Labor Use Study, or A-PLUS, trial led by investigators at the University of Alabama at Birmingham enhances information from previous UAB-led trials, which showed azithromycin administered before cesarean delivery reduced maternal infections.

The multi-country, randomized trial was conducted at eight sites in seven low- and middle-income countries in Africa, Asia and Latin America. The study was funded by the National Institutes of Health and the Bill & Melinda Gates Foundation and conducted by the NICHD Global Network for Women’s and Children’s Health Research. Published results were presented simultaneously at the Society for Maternal-Fetal Medicine’s annual meeting in San Francisco, California.

“The World Health Organization and others have prioritized reducing maternal sepsis to reduce maternal deaths,” said Alan Tita, M.D., Ph.D., professor in the UAB Department of Obstetrics and Gynecology and director of the UAB Center for Women’s Reproductive Health and Mary Heersink Institute for Global Health, and associate dean for Global and Women’s Health. “Studies confirming the effectiveness of azithromycin for vaginal delivery, which is the most common mode of delivery, were lacking. We wanted to find a low-cost intervention that could be used globally to address this problem.”

From September 2020-August 2022, more than 29,000 women were randomized to either an active or placebo group. Those in the active group were given a single 2-gram dose of azithromycin. Maternal sepsis or death, the study’s primary outcome, occurred in 1.6 percent of women in the active group versus 2.4 percent in the placebo group. Additionally, rates of several secondary outcomes including specific maternal infections such as endometritis, wound infections and urine infections were lower in the azithromycin group.

“In addition to the decrease in maternal infections, there were fewer maternal hospital readmissions and unscheduled visits for care in the first 42 days after delivery, which is consistent with findings from the large United States trial in women who underwent a cesarean birth,” said Waldemar A. Carlo, M.D., co-director of the Division of Neonatology at the UAB Marnix E. Heersink School of Medicine and Children’s of Alabama, co-lead of the A-PLUS trial and principal investigator of the UAB NICHD Global Network site.

While findings showed azithromycin reduced the risk of maternal sepsis or death, the intervention did not reduce the risk of sepsis or death in newborns. However, there were no adverse newborn effects.

Funding for the trial was provided by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development and a grant from the Foundation for the National Institutes of Health through the Maternal, Newborn & Child Health Discovery & Tools initiative of the Bill & Melinda Gates Foundation.

A-PLUS partners include 14 organizations from within the United States and internationally that make up the NICHD Global Network for Women’s and Children’s Health Research. UAB leveraged a partnership with investigators from the University Teaching Hospitals in Zambia, ongoing for more than 20 years.