Azithromycin for preventing bronchopulmonary dysplasia in preterm infants: A systematic review and meta‐analysis

Abstract Context Azithromycin has anti‐ Ureaplasma and anti‐inflammatory properties that might help reduce lung injury in preterm infants. Objective To test the efficacy and safety of prophylactic or therapeutic azithromycin in preventing bronchopulmonary dysplasia (BPD) in preterm infants with unknown or proven Ureaplasma status. Methods We searched PubMed, Web of Science, and Cochrane Library until 13 September 2020. Two authors independently assessed the eligibility, risk of bias, and extracted the data. We performed a random‐effects model meta‐analysis to yield pooled relative risk (RR) or mean difference (MD) with 95% confidence interval (CI). We used the Cochrane GRADE methodology for summarizing the results. Results We included five randomized clinical trials. The meta‐analysis revealed no significant differences in BPD (RR, 0.92; 95% CI, 0.71, 1.19; low‐quality evidence), death (RR, 0.75; 95% CI, 0.52, 1.10; low‐quality evidence), and BPD or death (RR, 0.90; 95% CI, 0.74, 1.10; low‐quality evidence). However, a significantly lower BPD or death (RR, 0.83; 95% CI, 0.70, 0.99) and a trend toward lower BPD (RR, 0.83; 95% CI, 0.66, 1.03) with azithromycin therapy was noted in Ureoplasma positive neonates. No differences in secondary outcomes were noted, except for significantly lower supplemental oxygen days with azithromycin (MD, −6.06; 95% CI, −7.40, −4.72; moderate‐quality evidence). The test for subgroup differences between short (<7 days) and long (>7 days) course of azithromycin were nonsignificant for all the outcomes. Conclusion Low‐quality evidence suggests azithromycin therapy reduces BPD or death in preterm infants with positive Ureoplasma , but not in all preterm infants.