Intrapartum oral azithromycin for maternal infection prophylaxis and the risk of postpartum hemorrhage: A secondary analysis of the A-PLUS trial

Objective: A single oral dose of azithromycin (AZM) given during labor to women planning a vaginal delivery reduced maternal infections including sepsis, with a stronger effect in sub-Saharan Africa than South Asia. Since maternal infection contributes to labor dysfunction and postpartum hemorrhage (PPH), we evaluated the effect of AZM on the risk of PPH and blood transfusion. Methods: This was an unplanned secondary analysis of the Azithromycin Prevention in Labor Use Study (A-PLUS) randomized controlled trial at eight sites in seven low- and middle-income countries in sub-Saharan Africa, South Asia, and Latin America. The population consisted of pregnant women in labor at ≥28 weeks' gestation in health facilities randomized to either 2 g AZM or placebo. Based on an intent-to-treat analysis, the risk of PPH and blood transfusion was compared between AZM and placebo arms using Poisson regression adjusting for arm and site as fixed effects. The main outcome measures were (1) PPH (500 mL or greater) after delivery; and (2) postpartum blood transfusion after delivery. Results: A total of 29 278 participants were randomized to APLUS; 14 590 to AZM and 14 688 to placebo. The risk of PPH did not significantly differ between AZM and placebo arms (1.4% in AZM; 1.6% in placebo; relative risk [RR] = 0.88; 95% confidence interval [CI]: 0.73, 1.07). The risk of blood transfusion also did not significantly differ between AZM and placebo arms (0.5% in AZM; 0.5% in placebo; RR = 0.90; 95% CI: 0.65, 1.25). There was also evidence indicating that the effect of AZM on the risk of blood transfusion, but not PPH, was beneficial in sub-Saharan Africa but not in South Asia (P value for two-way interaction = 0.002). Conclusion: A single intrapartum oral dose of AZM did not significantly reduce the overall risk of PPH or blood transfusion. ClinicalTrials.gov Identifier: NCT03871491.