Single-dose azithromycin during labour prevents maternal death, sepsis

Treatment with a single oral dose of azithromycin, given to women in labour who were planning a vaginal birth, significantly reduced the risk of maternal death or sepsis, according to the A-PLUS* trial presented at SMFM 2023.

Within the first 6 weeks after delivery, women who received azithromycin had a significantly lower risk of the composite outcome of maternal death or sepsis than those who received placebo (1.6 percent vs 2.4 percent; relative risk [RR], 0.67; p<0.01). [SMFM 2023, abstract LB01]

This finding was primarily driven by a 35-percent reduction in the risk of maternal sepsis observed in the azithromycin group over the placebo group (1.5 percent vs 2.3 percent), as maternal deaths were found to be infrequent in both groups.

In addition, the incidence of selected maternal infections was lower among those who received azithromycin compared with placebo. These included endometritis (1.3 percent vs 2.0 percent; RR, 0.66), wound infection (1.6 percent vs 2.2 percent; RR, 0.71), and other infections (1.0 percent vs 1.5 percent; RR, 0.69).

Azithromycin recipients also reported fewer hospital readmission at ≤42 days after delivery (0.9 percent vs 1.3 percent; RR, 0.65) and unscheduled visits for care (9.6 percent vs 12.2 percent; RR, 0.79) than placebo recipients.

“The World Health Organization and others have prioritized the reduction of maternal sepsis to decrease the risk of maternal death,” said lead author Dr Alan Tita from the University of Alabama at Birmingham Marnix E. Heersink School of Medicine in Birmingham, Alabama, US. [N Engl J Med 2023;doi:10.1056/NEJMoa2212111]

In a previous study, women treated with adjunctive azithromycin for caesarean delivery had a 50-percent reduction in the risk of maternal infections and maternal use of healthcare resources. [N Engl J Med 2016;375:1231-1241]

“However, 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,” Tita said in an interview. [https://www.uab.edu/news/health/item/13400-single-dose-of-azithromycin-reduces-maternal-sepsis-or-death]

The current multicountry, open-label trial analysed 29,278 pregnant women in labour at ≥28 weeks’ gestation with a planned vaginal delivery at a healthcare facility. Participants were randomly assigned to receive either a single oral dose of azithromycin 2 grams (n=14,590) or placebo (n=14,688). The two primary outcomes of the study were composite of maternal death or sepsis and composite of stillbirth or neonatal death or sepsis.

With regard to neonatal outcomes, there was no difference in the risk of the composite of stillbirth or neonatal death or sepsis within the first 4 weeks of life between the azithromycin and placebo groups (10.5 percent vs 10.3 percent; RR, 1.02).

Among the individual components of the neonatal composite outcome, both the azithromycin and placebo groups showed similar risks of neonatal death or sepsis (1.52 percent vs 1.49 percent and 9.8 percent vs 9.6 percent, respectively; RR, 1.03 for both) and stillbirth (0.4 percent for both groups).

The incidence of hospital readmissions, admission to special care units, and unscheduled visits for care also did not differ between the two groups.

Overall, the findings showed that treatment with azithromycin prevents maternal death or sepsis, mainly by reducing maternal sepsis and specific maternal infections that lead to sepsis, as well as the use of healthcare resources. However, the intervention had no effect on neonatal outcomes, said Tita.

“Importantly, we wanted to alleviate the burden of maternal infections in populations that give birth predominantly vaginally. Our research shows that just one dose of azithromycin may be a useful, low-cost intervention to reduce sepsis and attendant maternal deaths,” Tita said in a press release.

*A-PLUS: Azithromycin Prevention in Labor Use Study