Effectiveness and safety of early combined utilization of budesonide and surfactant by airway for bronchopulmonary dysplasia prevention in premature infants with RDS: A meta-analysis.

ABSTRACT

OBJECTIVE: To address the effectiveness and safety of early airway combined utilization of budesonide and surfactant for bronchopulmonary dysplasia (BPD) prevention in premature infants with respiratory distress syndrome (RDS). METHODS: Literature retrieval was carried out in the PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, CQ VIP, and China National Knowledge Infrastructure databases, searching from the inception to September 2021. Stata 16.0 software was used for statistical analysis. RESULTS: This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway have a superiority on BPD incidence (risk ratio [RR] = 0.62; 95% confidence interval [CI] 0.54-0.71, p < 0.001], mortality (RR = 0.64; 95%CI 0.45-0.92, p = 0.016), the composite outcome of BPD or mortality (RR = 0.58; 95%CI 0.50-0.68, p < 0.001), the additional doses of surfactant (RR = 0.53; 95%CI 0.44-0.63, p < 0.001), the duration of assisted ventilation (standard mean difference [SMD] = -1.14; 95%CI -1.58 to -0.70, p < 0.001), duration of invasive ventilation(SMD = -1.77; 95% CI -2.61 to -0.93, p < 0.001), and hospital stays (SMD = -1.11; 95% CI -1.73 to -0.49, p = 0.001) in preterm infants with RDS. And these benefits were not associated with increased adverse outcomes. Furthermore, a decreased incidence of patent ducts arterious (PDA) (RR = 0.79; 95% CI 0.65 to 0.97, p = 0.028) was found in premature infants treated with budesonide and surfactant. Subgroup analysis based on budesonide delivery methods (inhalation or intratracheal instillation) indicated that the decrease of mortality (RR = 0.63; 95% CI 0.43-0.93, p = 0.019), duration of assisted ventilation (SMD = -0.95; 95% CI -1.30 to -0.61, p < 0.001), hospital stays (SMD = -1.23; 95% CI -2.05 to -0.41, p = 0.003) and PDA incidence (RR = 0.80; 95% CI 0.65 to 0.99, p = 0.044) were mainly in budesonide intratracheal instillation subgroup, rather than in budesonide inhalation subgroup. CONCLUSIONS: This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway might be an effective and safe clinical practice for BPD prevention in premature infants with RDS, especially when budesonide was delivered by intratracheal instillation. However, many of the included studies were small and were from Asian origin. More well-designed randomized controlled trials with larger sample sizes and longer follow-up from all over the world ought to be conducted in the future.