Timing of Prophylactic Intrapartum Azithromycin Administration and Efficacy in Prevention of Maternal and Infant Infections: A Secondary Analysis of a Randomized Controlled Trial
In-labor oral azithromycin reduced maternal infections even when birth occurred soon after dosing.
*Secondary analysis of randomized trial; Level 2b.
*Secondary analysis of randomized trial; Level 2b.
Citation
Boelig RC, Kavi A, Moore JL, et al. Timing of prophylactic intrapartum azithromycin administration and efficacy in prevention of maternal and infant infections: secondary analysis of a randomized controlled trial. BJOG. 2026;133:976–984. doi:10.1111/1471-0528.70121
Background
A prior large international trial showed a single 2 g oral azithromycin dose during labor lowered maternal sepsis or death. This analysis asked whether benefit depends on the time from dosing to delivery.
Patients
Pregnant patients at least 28 weeks’ gestation (singleton or multiple) admitted in labor for planned vaginal delivery in sites across Africa, South Asia, and Latin America. Exclusions included advanced pushing, fever needing antibiotics, recent macrolide use, heart rhythm disease/cardiomyopathy, and azithromycin allergy. Participants without dose-timing data or delivering more than 120 hours after dosing were excluded from this analysis.
Intervention
Single 2 g oral azithromycin during labor.
Control
Placebo.
Outcome
Maternal: any maternal infection through 6 weeks postpartum (primary). Infant: any infant infection through 6 weeks of life (secondary).
Follow-up Period
Up to 6 weeks after delivery (mother and infant).
Results
| Primary outcome: any maternal infection | Relative risk (azithromycin vs placebo) |
|---|---|
| Delivered ≤12 hours after dose | 0.71 (0.64–0.79) |
| Delivered >12 hours after dose | 0.71 (0.54–0.94) |
Infant infection: no reduction regardless of whether delivery occurred ≤9 hours or >9 hours after dosing.
Limitations
Secondary (post hoc) analysis with multiple subgroup comparisons and no adjustment for multiple testing. Most participants delivered within 12 hours, limiting conclusions for very long labors. Findings mainly reflect low- and middle-income settings.
Funding
National child health institute and Gates Foundation (via Foundation for NIH).
Clinical Application
For planned vaginal births in similar settings, give single-dose oral azithromycin on admission in labor; do not delay based on expected time to delivery.
Discussion
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In this secondary analysis of an RCT, intrapartum 2 g azithromycin reduced any maternal infection similarly whether delivery occurred ≤12 h or >12 h after dosing (RR 0.71 in both; interaction p=0.987). Given timing was not randomized, how valid and applicable is changing practice regardless of anticipated delivery time? In this secondary analysis, the relative risk for any maternal infection with azithromycin versus placebo was 0.71 for delivery ≤12 hours after dosing and 0.71 for delivery >12 hours, with an interaction p-value of 0.987. What is the best interpretation of the interaction p-value?