Intrapartum administration of a single dose of oral azithromycin significantly reduced the incidence of maternal sepsis and death after childbirth, according to results of the A-PLUS trial involving participants from low- and middle-income countries and published in the New England Journal of Medicine. These findings were also presented at the 43rd Annual Pregnancy Meeting of the Society for Maternal-Fetal Medicine on Feb. 9, 2023.

The international, placebo-controlled randomized trial included women who were planning a vaginal birth or those who were in labor at ≥28 gestation from seven countries namely Bangladesh, Pakistan, Kenya, the Democratic Republic of the Congo, Zambia, Guatemala and India. Out of the total 29,278 participants included in the study, 14590 were randomized to intrapartum administration of single oral dose of azithromycin 2 g and 14688 to placebo.

Only 1.5% of the women who were given azithromycin during labor developed sepsis, a primary outcome of the study, compared to 2.3% in the placebo group with relative risk of 0.67, while the incidence of maternal death in both groups was 0.1% with RR of 1.23. However, there was no difference in the composite of stillbirth or neonatal death or sepsis, another primary outcome of the study, between the two groups; 10.5% vs. 10.3%, respectively with relative risk of 1.02.

About 9.8% infants in the azithromycin developed neonatal sepsis in vs 9.6% in the placebo group with RR of 1.03. The incidence of stillbirth in the two groups was 0.4% (RR 1.06) and that of neonatal deaths was 1.5% (RR 1.03).

The incidence of endometritis and other infections, the secondary outcomes, was less among women in the azithromycin group vs placebo group. They were also less likely to require hospital re-hospitalizations and make unscheduled visits to the hospital.

In this study, a single dose of azithromycin administered during labor significantly reduced maternal sepsis and death among women planning to deliver vaginally but not neonatal sepsis or death. These findings therefore suggest a potential strategy to reduce maternal mortality particularly in resource-poor settings.

References

1. Tita AT, et al; A-PLUS Trial Group. Azithromycin to prevent sepsis or death in women planning a vaginal birth. N Engl J Med. 2023 Feb 9. doi: 10.1056/NEJMoa2212111.
2. Tita AT, et al. Intrapartum oral azithromycin to prevent maternal and newborn sepsis or death: a multinational RCT. Am J Obstet Gynecol. 2023 Jan.;228 (1 Suppl):S764. DOI:https://doi.org/10.1016/j.ajog.2022.11.1304.