Pulmonary surfactant combined with budesonide in the treatment of neonatal respiratory distress syndrome

Newborn respiratory distress syndrome (RDS) is a disease that is unique to newborn infants and caused by a shortage of pulmonary surfactant (PS). Since hyaline membranes were observed in the alveoli of animal models of RDS, research has been conducted to supplement PS deficiency (1). It has been 30 years since PS replacement therapy was first offered for neonatal RDS (NRDS) in China. A recent article entitled “A systematic review and meta-analysis of pulmonary surfactant combined with budesonide in the treatment of neonatal respiratory distress syndrome” published in Translational Pediatrics caught our attention (2).

The authors have provided us with a meta-analysis evaluating PS in combination with budesonide in treating NRDS. The meta-analysis revealed that for infants with NRDS, the use of budesonide in combination with animal-derived PS can successfully shorten hospital stays, decrease the need for invasive mechanical ventilation, and lower the incidence of bronchopulmonary dysplasia, but it does not raise the incidence of fatal complications or other connected outcomes. Although the authors have discussed some shortcomings of this study, several limitations should be noticed.

To begin with, while the authors stated that they presented the article in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting checklist (3), it was discovered that this review was not International Prospective Register of Systematic Reviews (PROSPERO) registered nor had a Centre for Reviews and Dissemination (CRD) number after careful examination. In addition, there is a small error in the article. The authors stated there are 10 articles in this study involving 527 children, but it can be seen from the data in Tab. 1 that the total number of patients in 10 articles have reached 1,177, which is clearly a contradiction.

Secondly, we found some subtle differences in the definition of outcome indicators in the articles included by the authors. In Fig. 3, the authors analyzed the effect of PS combined with budesonide on invasive mechanical ventilation time in infants with NRDS. However, Pan et al. defined the duration of ventilator use as the study outcome, and Wang et al. defined the duration of assisted ventilation as the study outcome (4,5). Both definitions include not only invasive mechanical ventilation, but also non-invasive mechanical ventilation, which may affect the results of the meta-analysis. Similarly, in Fig. 6, the outcome indicator discussed by the authors was the mortality rate of infants with NRDS, while in the study of Pan et al., the outcome was limited to the case fatality rate at 36 weeks of corrected gestational age, which may lead to the accuracy of the results (4,5). More than that, the authors did not specify the severity of bronchopulmonary dysplasia. Most studies defined neonates requiring oxygen dependence for more than 28 days, while bronchopulmonary dysplasia is defined as requiring more than 21% oxygen in Wang et al. and Yeh et al.’s studies (5,6). These differences may also affect the conclusion of this meta-analysis.

Thirdly, interventions are often different in different studies, and the authors considered that different administration methods might affect the results of the meta-analysis, so a subgroup analysis was conducted to exclude the influence of the mode of administration on the results. Therefore, it is suggested that the authors should also conduct a subgroup analysis for different drug dosages, which would make the results more accurate and reliable.

In the end, most of the articles included by the authors are in Chinese, which may have a certain publication bias. The authors did not use funnel plots for qualitative assessment of publication bias nor statistical tests (e.g., Begg’s or Egger’s tests) for quantitative assessment. In addition, sensitivity analysis is necessary for meta-analysis, yet the authors did not conduct sensitivity analysis to make the results more convincing. These are some of the details we think the authors should add.

In summary, Yi et al. carried out a good-quality meta-analysis to analyze the effect of PS combined with budesonide in the treatment of NRDS. We appreciate the contribution of the authors and believe that this is a valuable study. There is a generational change taking place in the era of PS, rather than just improving infant survival, this will likely lead to better outcomes and a lower complication rate.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was a standard submission to Translational Pediatrics. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-30/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

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