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

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) 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.