Cost-effectiveness of intrapartum azithromycin to prevent maternal infection, sepsis, or death in low-income and middle-income countries: a modelling analysis of data from a randomised, multicentre, placebo-controlled trial

Abstract

Background Sepsis is one of the leading causes of maternal mortality globally. In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin for women planning a vaginal birth reduced the risk of maternal sepsis or death and infection. We aimed to evaluate the cost-effectiveness of intrapartum azithromycin for pregnant people planning a vaginal birth in low-income and middle-income countries (LMICs) using A-PLUS trial data. Methods We compared the benefits and costs of intrapartum azithromycin versus standard care across 100 000 model simulations using data from the A-PLUS trial and a probabilistic decision tree model that included 24 mutually exclusive scenarios. A-PLUS was a randomised, double-blind, placebo-controlled trial that enrolled 29 278 women in labour at 28 weeks’ gestation or more at eight sites in the Democratic Republic of the Congo, Kenya, Zambia, Bangladesh, India, Pakistan, and Guatemala. Women randomly assigned to azithromycin received a single intrapartum 2 g oral dose. In this cost-effectiveness analysis, we considered the cost of azithromycin treatment and its effects on a composite outcome of maternal infection, sepsis, or death and its individual components, and health-care use. Our analysis had a health-care sector perspective. We summarised results as an average and 95% CI of the model simulations. We also conducted sensitivity analyses. A-PLUS was registered at ClinicalTrials.gov, number NCT03871491. Findings In model simulations, intrapartum azithromycin resulted in 1592·0 (95% CI 1139·7 to 2024·1) cases of maternal infection, sepsis, or death averted per 100 000 pregnancies, yielding 248·5 (95·3 to 403·7) facility readmissions averted, 866·8 (537·8 to 1193·2) unplanned clinic visits averted, and 1816·2 (1324·5 to 2299·7) antibiotic regimens averted. Using mean health-care costs across the A-PLUS sites, intrapartum azithromycin resulted in net savings of US$32 661 (–52 218 to 118 210) per 100 000 pregnancies and 13·2 (8·3 to 17·9) disability- adjusted life-years averted. The cost of facility readmission, cost of azithromycin, and probability of infection had the greatest impact on the incremental cost. Interpretation In most cases, intrapartum azithromycin is a cost-saving intervention for the prevention of maternal infection, sepsis, or death in LMICs. This evidence supports global consideration of intrapartum azithromycin as an economically efficient preventive therapy to reduce infection, sepsis, or death among women planning a vaginal birth in LMICs. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Foundation for the National Institutes of Health through the Maternal, Newborn, and Child Health Discovery and Tools Initiative of the Bill & Melinda Gates Foundation