Peer-reviewed article
Timing of Prophylactic Intrapartum Azithromycin Administration and Efficacy in Prevention of Maternal and Infant Infections: A Secondary Analysis of a Randomized Controlled Trial.
Boelig RC, Kavi A, Moore JL, Babineau DC, Metgud MC et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study analyzed data from a large international trial testing whether the timing of azithromycin administration during labour affected its ability to prevent infections in mothers and newborns. The drug reduced maternal infection risk regardless of how long before delivery it was given, but did not prevent infant infections. The findings suggest that pregnant women planning vaginal delivery benefit from a single dose of azithromycin at any point during labour.
Key points
- Azithromycin reduced maternal infection risk by approximately 29% whether given ≤12 hours or >12 hours before delivery
- The drug provided no benefit in preventing neonatal infections at any time interval
- Analysis included 29,236 pregnant women (≥28 weeks gestation) from multiple international sites
- In Sub-Saharan Africa, greater benefit was observed when azithromycin was given >12 hours before delivery
- Timing of intrapartum azithromycin administration does not need to be restricted for maternal infection prevention
Limitations
This is a secondary analysis of an existing trial, so the study cannot determine why azithromycin did not prevent neonatal infections or explain the regional variation observed in Sub-Saharan Africa. The analysis does not provide information about longer-term neonatal outcomes or potential adverse effects.
Abstract
Objective A multi-centre international trial (A-PLUS), demonstrated that a single dose of 2 g oral azithromycin in labour reduced the risk of maternal sepsis or death, but not neonatal mortality. We aimed to determine whether the efficacy of azithromycin in prevention of any maternal infection or neonatal infection varied by time interval from azithromycin administration to delivery. Design This is a secondary analysis of a randomized controlled trial. Setting Multi-centre international randomized controlled trial. Population Pregnant patients ≥ 28 weeks gestation (singleton or multiple gestation) presenting in labour for planned vaginal delivery. Outcomes The primary outcome for this secondary analysis was maternal infection and the secondary outcome was any neonatal infection. Methods The estimated relative risks (and 95% confidence interval) of any maternal or neonatal infection comparing azithromycin to placebo were obtained by fitting a Poisson model adjusting for site, treatment arm, hours between drug administration and delivery (as continuous measure, and ≤ 12 or > 12 h for maternal and ≤ 9 or > 9 h for neonatal), and the two-way interaction between treatment arm and hours between drug administration and delivery. Results Included in the analysis were n = 14 569 randomized to azithromycin and n = 14 667 to placebo. There was no evidence that the benefit of azithromycin on reducing the risk of any maternal infection varied by time from dose to delivery (RR 0.71 (0.64-0.79) and RR 0.71 (0.54-0.94) for ≤ 12 and > 12 h respectively, interaction p = 0.987), although there was an observed interaction in Sub-Saharan Africa subgroup with reduced risk observed with administration > 12 vs. ≤ 12 (RR 0.21 (0.08-0.54) vs. RR 0.52 (0.41-0.66), interaction p = 0.03). There was no benefit observed in prevention of infant infection regardless of time from dose to delivery (≤ 9 or > 9 h) (RR 1.00 (0.95-1.06) and RR 1.01 (0.88-1.15) interaction p = 0.997). Conclusion The benefit observed with a single intrapartum dose of azithromycin for prevention of any maternal infection in the setting of planned vaginal delivery was not observed to vary by time interval from azithromycin administration to delivery, although in some populations there may be greater benefit with delivery > 12 h from administration. Pregnant patients presenting for planned vaginal birth benefit from a single dose of 2 g azithromycin regardless of how soon delivery is anticipated.
Findings the Hub has extracted
Each claim below is labelled by its type of design and links back to this report.
- Intervention
- Single 2g oral dose of azithromycin administered intrapartum to pregnant women in labour
- Population
- Pregnant patients ≥28 weeks gestation (singleton or multiple gestation) presenting in labour for planned vaginal delivery in multiple international sites
Key finding
Maternal infection reduced by 29% with azithromycin given ≤12 hours before delivery (RR 0.71, 95% CI 0.64-0.79)
RC et al. · Europe PMC · 2 Jan 2026