Intrapartum azithromycin reduces sepsis, mortality for mothers but not neonates

Azithromycin administered to women in labor during planned vaginal delivery reduced their risks for sepsis and death, but not their newborns’ risks for sepsis and death, according to findings presented at The Pregnancy Meeting.

Findings were simultaneously published in The New England Journal of Medicine.

“Sepsis is a top-three cause of maternal and newborn death globally,” Alan T. N. Tita, MD, PhD, professor at the University of Alabama in Birmingham, said during the presentation. “It accounts for 10% of maternal deaths and is on the rise. It also accounts for 16% of newborn deaths. It is a priority for global health organizations, such as WHO.”

Tita and colleagues enrolled 29,278 women who were in labor at 28 or more weeks’ gestation and had a planned vaginal delivery at one of eight sites in seven low- and middle-income countries, which included Guatemala, the Democratic Republic of Congo, Zambia, Kenya, Pakistan, India and Bangladesh. During labor, 14,590 women were randomly assigned to one dose of oral azithromycin 2 mg, and 14,688 women were randomly assigned to placebo.

The researchers outlined two primary outcomes: a composite of maternal sepsis or death within 42 days and a composite of stillbirth or neonatal sepsis or death within 28 days of delivery. Other outcomes were maternal infection, hospital readmission and unscheduled health care visits.

In total, 99.6% of the cohort was followed through 42 days postpartum. Participants were primarily from Asia (55%), followed by Africa (40%) and Latin America (5%). Nearly half (43%) were nulliparous, 18% underwent labor induction and 8.6% were high risk.

Compared with women in the placebo group, women who received azithromycin had lower risks for maternal primary outcome (2.4% vs. 1.6%; RR = 0.67; 95% CI, 0.56-0.79) and maternal sepsis (2.3% vs. 1.5%; RR = 0.65; 95% CI, 0.55-0.77), as well as lower risks for endometritis (2% vs. 1.3%; RR = 0.66; 95% CI, 0.55-0.79), wound infections (2.2% vs. 1.6%; RR = 0.71; 95% CI, 0.6-0.84) and other infections (1.5% vs. 1%; RR = 0.69; 95% CI, 0.56-0.85). These women also had lower risks for hospital readmission (0.9% vs. 1.3%; RR = 0.65; 95% CI, 0.52-0.82) and unscheduled health care visits (9.6% vs. 12.2%; RR = 0.79; 95% CI, 0.73-0.84) compared with women given placebo.

The neonatal primary outcome occurred at similar rates in the azithromycin and placebo groups (10.5% vs. 10.3%), and there were no differences in newborn health resource use.

Results of subgroup analyses were generally in line with the overall findings, although mothers seemed to benefit more from azithromycin if they lived in Africa (RR = 0.47; 95% CI, 0.36-0.61) vs. Asia (RR = 0.88; 95% CI, 0.7-1.1), according to the study.

There were no differences in the frequency of adverse events between groups, Tita said.

“These findings overall are consistent with prior studies when we take differences in outcome definitions into consideration,” Tita said. “These findings also suggest the potential to cost-effectively improve maternal outcomes.”

References:

• Tita ATN, et al. Intrapartum oral azithromycin to prevent maternal and newborn sepsis or death: A multinational RCT. Presented at: The Pregnancy Meeting; Feb. 6-11, 2023; San Francisco.
• Tita ATN, et al. N Eng J Med. 2023;doi:10.1056/NEJMoa2212111.