Maternal infections, including sepsis, during the peripartum period are responsible for a significant proportion of maternal deaths worldwide, accounting for up to 10% of maternal mortality. Additionally, neonatal sepsis is the third most common cause of neonatal death, with maternal infection increasing the risk of neonatal sepsis.
Efforts to reduce maternal sepsis and associated morbidity and mortality have focused on prophylactic antibiotics, with studies demonstrating a reduction in maternal infection rates and associated costs. The Azithromycin Prevention in Labor Use Study (A-PLUS) was conducted to investigate the efficacy of a single oral dose of Azithromycin in reducing maternal sepsis or death, as well as stillbirth, neonatal death, or sepsis, in women in labor who were planning a vaginal delivery.
A large, multicountry randomized trial has found that using azithromycin prophylaxis during vaginal delivery significantly reduces the frequency of maternal sepsis or death compared to placebo but has little effect on stillbirth or neonatal sepsis or death. The study published in the New England Journal Of Medicine involved pregnant women in labor who were planning a vaginal delivery. The results showed that the number of women needing to be treated to prevent one case of maternal death or sepsis was 125, and the same number would need to be treated to prevent one maternal sepsis event.
The study’s primary outcome was the incidence of maternal sepsis or death, and the secondary outcomes included stillbirth, neonatal sepsis or death, and various maternal infections that can cause sepsis. The study found that using azithromycin prophylaxis led to a significantly lower maternal sepsis or death frequency than a placebo, but had little effect on stillbirth or neonatal sepsis or death. Maternal deaths were infrequent in both groups, so the difference between the two groups was primarily driven by the effects of Azithromycin on maternal sepsis.
The study was conducted across multiple countries, with staff members receiving frequent training on key protocol features, including temperature monitoring and criteria for infection outcomes. The trial population broadly reflected the general population of women giving birth in these countries, using WHO clinical definitions of maternal and neonatal sepsis and blinded adjudication of critical outcomes.
While there were limitations to the study, including the variation in the frequencies of prophylactic use of antibiotics and cesarean birth according to the site, the findings are consistent with previous studies involving the use of Azithromycin in women who had undergone a cesarean delivery and received the usual antibiotics, as well as two small trials involving women in labor who were planning a vaginal delivery.
The study highlights the potential benefits of using Azithromycin to prevent maternal sepsis or death during vaginal delivery but also raises concerns about potential harms, including increased antimicrobial resistance and drug side effects and costs. Further studies are needed to evaluate these potential harms and inform the findings’ generalizability.