A comprehensive review and meta-analysis of 20 randomized controlled trials (RCTs) has revealed that while preventive azithromycin in pregnancy and labor offers certain benefits, it may not significantly reduce maternal or neonatal mortality. This study, conducted by researchers from the All India Institute of Medical Sciences, was recently published in eClinicalMedicine.
Background
The use of azithromycin, a broad-spectrum macrolide antibiotic, has been extensively studied in the context of maternal and neonatal health outcomes. A notable 2016 U.S. trial found that administering azithromycin to women undergoing cesarean delivery resulted in a 49% reduction in postoperative infections. This led to routine recommendations for azithromycin prophylaxis for cesarean births by both the American College of Obstetrics and Gynecology and the World Health Organization.
Another RCT conducted across seven countries demonstrated that an oral dose of azithromycin before vaginal birth reduced the risk of maternal sepsis or mortality by 33% compared to a placebo. Despite these findings, subsequent studies have shown that prophylactic azithromycin does not impact neonatal mortality. Additionally, there are concerns about the increased carriage of azithromycin-resistant bacteria in newborns.
Study Methodology
To provide an updated and comprehensive assessment, the researchers reviewed 20 RCTs encompassing 56,381 participants. Most of these studies (18 out of 20) were conducted in low- and middle-income countries. The studies evaluated both single-dose intrapartum azithromycin (11 RCTs) and antenatal administration (9 RCTs).
The primary outcomes of interest were maternal and neonatal mortality. The researchers used multivariate logistic regression to estimate the effects, adjusting for confounders such as maternal age, body mass index, and socioeconomic factors.
Key Findings
Maternal and Neonatal Mortality
The meta-analysis found that intrapartum azithromycin had little to no effect on maternal mortality (5 RCTs; 44,436 participants; risk ratio [RR], 1.02; 95% confidence interval [CI], 0.86 to 1.20; very low-certainty evidence) or neonatal mortality (3 RCTs; 44,131 participants; RR, 1.26; 95% CI, 0.65 to 2.42; low-certainty evidence). Similarly, antenatal azithromycin’s effect on neonatal mortality was uncertain (3 RCTs; 5,304 participants; RR, 0.74; 95% CI, 0.35 to 1.56; very low-certainty evidence) and on maternal mortality (3 RCTs; 8,167 participants; RR, 1.62; 95% CI, 0.67 to 3.91; low-certainty evidence).
Benefits and Risks
Despite the lack of significant impact on mortality, single-dose intrapartum azithromycin did provide some benefits. It was associated with a reduction in certain maternal infections (systemic sepsis, endometritis, and surgical-site infections) and neonatal infections (superficial skin infections and omphalitis). Additionally, it led to reduced antibiotic use in both mothers and newborns.
Antenatal azithromycin had little to no effect on preterm birth but was linked to a reduced risk of low birth weight. Importantly, the researchers found no evidence of increased risk for adverse outcomes such as miscarriage, stillbirth, congenital abnormalities, cerebral palsy, or childhood asthma, although these events might not have been adequately captured in the RCTs.
Recommendations and Future Directions
The review supports the continued recommendation of prophylactic azithromycin for women undergoing elective cesarean delivery and potentially extends it to those planning elective vaginal delivery. However, the authors urge caution, emphasizing the need for further trials to explore the optimal timing of administration, dosing schedules, and co-interventions.
“Future trials should also focus on safety aspects, including adequate follow-up of infants for antimicrobial resistance and long-term outcomes,” the authors wrote.
Conclusion
While azithromycin during pregnancy shows promise in reducing certain maternal and neonatal infections, its impact on overall mortality remains uncertain. Continued research is essential to fully understand the benefits and risks, ensuring that both mothers and infants receive the most effective and safe care possible.
