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EBNEO Commentary: Umbrella Review Evaluating Interventions to Decrease Risk of Bronchopulmonary Dysplasia in Preterm Neonates


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Read Sara Stucker and Ellen Diego's EbNeo review of the paper "Abiramalatha T, Ramaswamy VV, Bandyopadhyay T, Somanath SH, Shaik NB, Pullattayil AK, Weiner GM. Interventions to Prevent Bronchopulmonary Dysplasia in Preterm Neonates: An Umbrella Review of Systematic Reviews and Meta-analyses. JAMA Pediatrics 2022; 176:502-516. PMID 35226067." 

Read full review here!


Acta Paediatrica - 2024 - Stucker - EBNEO commentary Umbrella review evaluating interventions to decrease risk of.pdf

"Bronchopulmonary Dysplasia (BPD) continues to affect preterm infants despite medical advances. Identifying effective prevention strategies is difficult due to the multifactorial nature of the disease. This umbrella review evaluated 154 systematic reviews with meta-analyses of randomized control trials (RCTs) to identify interventions effective at preventing BPD or mortality at 36 weeks’ postmenstrual age (PMA) in preterm infants. One hundred and ten of those systematic reviews are rated as high quality with 12 comparisons showing significant benefits from the intervention in reducing the risk of BPD or mortality at 36 weeks’ PMA with high certainty of evidence (COE).

Essential components of assessing umbrella reviews include evaluating for a focused question, appropriate study inclusion, and quality assessment of included studies (1). The authors of this paper selected a focused question and conducted a comprehensive literature review from multiple databases, likely capturing the majority of relevant studies. Established quality scoring tools (GRADE and AMSTAR2) assessed meta-analyses and systematic reviews with independent evaluation by 2 authors and detailed descriptions of grading criteria provided in the supplemental materials (2, 3).

Umbrella reviews only evaluate interventions previously studied in systematic reviews with meta-analyses of RCTs, limiting available studies for inclusion and the ability to perform in-depth adverse outcome analysis. Correctly interpreting consolidated statistical data is essential for accurate analysis and evaluation. For example, iNO, oxygen saturations of 85-89%, and vitamin A were associated with decreased risk of BPD, but not the combined outcome of BPD or mortality. The authors concluded this may suggest an increased risk of mortality, however, an editorial reply from Dr. Romero Lopez provided an alternative analysis using the example of Vitamin A (4). The editorial reply importantly emphasizes that observing the effect of an intervention on some but not all elements of a composite outcome does not imply the intervention has the opposite effect on the remaining elements. In this case, the study reported mortality data and did not see an increased risk (5). Facilitating an open dialogue discussing statistical analysis and conclusions is essential for deepening provider understanding of literature analysis and appropriate application to clinical practice to improve care.

This study provides the clinician with valuable scaffolding to guide further literature evaluation focusing on adverse outcome analysis and applying as appropriate to clinical decision-making. Adherence to high COE strategies for BPD reduction can be assessed at the facility-level by performing a best practice gap analysis for clinical protocol development and targeted quality improvement. Quality improvement studies have successfully decreased BPD rates by combining multiple interventions supported in this umbrella review into respiratory care bundles, including the use of delivery room CPAP and avoiding endotracheal intubation. At least one center has successfully maintained BPD rates of 5-7% for decades, supporting the feasibility and sustainability of utilizing a bubble CPAP care bundle to optimize care (6). Other studies have successfully decreased rates of intubation and BPD via respiratory care bundle implementation that includes initiation of CPAP in the delivery room, strict intubation and extubation criteria, and standardization of respiratory care provided (7,8,9)..


Critical Appraisal Skills Programme. CASP Systematic Review Checklist. Available at: casp-uk.net/casp-tools-checklists/ 2022. Accessed: August 3rd, 2023. 

Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: A critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ 2017; 358: j4008. 

Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. Journal of Clinical Epidemiology 2011; 64: 401–406. 

Mar Romero Lopez M. Comment on “Interventions to Prevent Bronchopulmonary Dysplasia in Preterm Neonates.” JAMA Network, 2022. Available at: jamanetwork.com/journals/jamapediatrics/article-abstract/2789460

Darlow BA, Graham PJ, Rojas-Reyes MX. Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants. Cochrane Database Syst Rev. 2016; 8:CD000501. 

Aly H, Mohamed MA. An experience with a bubble CPAP bundle: is chronic lung disease preventable? Pediatric Research 2020; 88: 444–450.

Levesque BM, Kalish LA, LaPierre J, Welch M, Porter V. Impact of implementing 5 potentially better respiratory practices on neonatal outcomes and costs. Pediatrics 2011; 128. 

Kakkilaya VB, Weydig HM, Smithhart WE, Renfro SD, Garcia KM, Brown CM, et al. Decreasing continuous positive airway pressure failure in preterm infants. Pediatrics 2021; 148.

Kubicka Z, Zahr E, Rousseau T, Feldman HA, Fiascone J. Quality improvement to reduce chronic lung disease rates in very-low birth weight infants: High compliance with a respiratory care bundle in a small NICU. Journal of Perinatology 2018; 38: 285–292."

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