Summary Background The use of azithromycin reduces maternal infection in women during planned cesarean delivery, but its effect in those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and infant sepsis or death. Methods In this multinational, randomized, placebo-controlled trial, we assigned women who were in labor at or after 28 weeks’ gestation and who were planning a vaginal delivery to receive a single oral dose of 2 g of azithromycin or placebo . The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for the benefit of the mother. Results A total of 29,278 women underwent randomization. The incidence of sepsis or maternal death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI]. %, 0.56 to 0.79; P<0.001), but the incidence of fetal or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (CI 95%, 0.95 to 1.09, P = 0.56). The difference in the maternal primary outcome appeared to be due primarily to the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI). , 0.55 to 0.77); the incidence of death from any cause was 0.1% in both groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in both groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks of birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence of adverse events. Conclusions Among women planning a vaginal birth, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo, but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.) |
Comments
A single dose of the antibiotic azithromycin can help protect mothers from dangerous sepsis infections and death during vaginal delivery, a large new international study by a UVA Health scientist and colleagues has found.
Azithromycin has been shown to benefit women who give birth by cesarean section. But new findings reveal that the common antibiotic reduces mortality for women who give birth vaginally and reduces the risk of developing sepsis, a potentially fatal whole-body infection.
Infections, particularly sepsis, are responsible for 10% of maternal deaths shortly before, during and after childbirth, placing them among the top five causes of maternal mortality worldwide.
“A single dose of the antibiotic azithromycin reduced sepsis and death by half in women in labor,” said researcher William A. Petri Jr., MD, PhD, of the School’s Division of Infectious Diseases and International Health. of Medicine at the University of Virginia. “The simplicity of this intervention should allow your institution around the world to protect mothers during childbirth.”
Safer birth
Petri is part of the Azithromycin Occupational Use Prophylaxis Study (A-PLUS) Trial Group, an international coalition of researchers who set out to determine whether giving the antibiotic during labor would benefit mothers or their children. More than 29,000 women from low- and middle-income countries volunteered to participate in the randomized trial; Half received azithromycin and the other half received a harmless placebo.
Among the 14,637 women who received the placebo, 2.4% developed sepsis or died within six weeks. That compares with just 1.6% of the 14,526 women who received azithromycin.
The difference was clear enough for the researchers to stop the trial early.
The antibiotic did not provide similar benefits to babies, the researchers found. However, they say the benefits for mothers, combined with the lack of harmful side effects, make azithromycin an important new tool to keep mothers safe before, during and after childbirth. (The antibiotic is already recommended for cesarean deliveries 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 US researchers, with the goal of evaluating low-cost, sustainable interventions to improve maternal and child health while building capacity and local research infrastructure.
UVA’s network team 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 from the icddr research centre, by Ruth Lennox from LAMB Hospital.
Petri noted that the findings are the result of an important collaboration of scientists around the world working together to improve the care of pregnant women and help them deliver their babies more safely.
“All of us involved in the network’s work here in Charlottesville are enjoying the opportunity to collaborate across disciplines, each of us enriched by the perspectives of obstetricians, pediatricians and infectious disease specialists,” Petri said. “The network is open to all to propose new international multi-site studies in maternal and child health, and I look forward to innovative ideas and ultimately clinical trials originating here at UVA.”
Final message In this multicenter trial, the use of intrapartum oral azithromycin among women planning a vaginal birth resulted in a lower risk of maternal sepsis or death than placebo, a result that was driven by a reduction in sepsis. However, the intervention did not reduce the risk of sepsis or death in newborns. |
Publication and financing
The researchers have published their findings in The New England Journal of Medicine . A complete list of authors and their affiliations is included in the document.
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 & Melinda Gates Foundation .
