Interventions to Prevent Bronchopulmonary Dysplasia in Preterm Neonates: An Umbrella Review of Systematic Reviews and Meta-analyses

Bronchopulmonary dysplasia (BPD) has multifactorial etiology and long-term adverse consequences. An umbrella review enables the evaluation of multiple proposed interventions for the prevention of BPD.To summarize and assess the certainty of evidence of interventions proposed to decrease the risk of BPD from published systematic reviews.MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science were searched from inception until November 9, 2020.Meta-analyses of randomized clinical trials comparing interventions in preterm neonates that included BPD as an outcome.Data extraction was performed in duplicate. Quality of systematic reviews was evaluated using Assessment of Multiple Systematic Reviews version 2, and certainty of evidence was assessed using Grading of Recommendation, Assessment, Development, and Evaluation.(1) BPD or mortality at 36 weeks' postmenstrual age (PMA) and (2) BPD at 36 weeks' PMA.A total of 154 systematic reviews evaluating 251 comparisons were included, of which 110 (71.4%) were high-quality systematic reviews. High certainty of evidence from high-quality systematic reviews indicated that delivery room continuous positive airway pressure compared with intubation with or without routine surfactant (relative risk [RR], 0.80 [95% CI, 0.68-0.94]), early selective surfactant compared with delayed selective surfactant (RR, 0.83 [95% CI, 0.75-0.91]), early inhaled corticosteroids (RR, 0.86 [95% CI, 0.75-0.99]), early systemic hydrocortisone (RR, 0.90 [95% CI, 0.82-0.99]), avoiding endotracheal tube placement with delivery room continuous positive airway pressure and use of less invasive surfactant administration (RR, 0.90 [95% CI, 0.82-0.99]), and volume-targeted compared with pressure-limited ventilation (RR, 0.73 [95% CI, 0.59-0.89]) were associated with decreased risk of BPD or mortality at 36 weeks' PMA. Moderate to high certainty of evidence showed that inhaled nitric oxide, lower saturation targets (85%-89%), and vitamin A supplementation are associated with decreased risk of BPD at 36 weeks' PMA but not the competing outcome of BPD or mortality, indicating they may be associated with increased mortality.A multipronged approach of delivery room continuous positive airway pressure, early selective surfactant administration with less invasive surfactant administration, early hydrocortisone prophylaxis in high-risk neonates, inhaled corticosteroids, and volume-targeted ventilation for preterm neonates requiring invasive ventilation may decrease the combined risk of BPD or mortality at 36 weeks' PMA.