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Systemic steroids and bronchopulmonary dysplasia: a systematic review and meta-analysis

Journal of Perinatology (2024)Cite this article

Subjects

Abstract

Importance

It is unclear if systemic steroids decrease the risk of Bronchopulmonary Dysplasia (BPD) while increasing the risk of neurodevelopmental impairment (NDI).

Objective

Conduct a systematic review of randomized controlled trials of systemic steroids to evaluate the risk of BPD, mortality, and NDI in premature infants ≤30 weeks.

Data sources

MEDLINE, EBSCOhost, Web of Science, Cochrane Library, Embase, and CINAHL.

Study selection

Randomized clinical trials of Dexamethasone (DEX) or Hydrocortisone (HC) to prevent BPD in premature infants ≤ 30 weeks.

Data extraction and synthesis

Data were extracted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Random-effects meta-analyses and multivariable meta-regression were conducted.

Main outcomes and measures

Primary outcomes were BPD, mortality, and NDI. Secondary outcomes were hypertension, hyperglycemia, sepsis, intestinal perforation, necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP). The a priori hypothesis was that steroids would reduce the risk of BPD without increasing NDI.

Results

There were 6377 preterm infants in the 44 (32 DEX, 13 HC) selected studies. DEX significantly reduced the risk of BPD, RR = 0.66, (95% CI, 0.56–0.78). The most effective DEX regimen was medium cumulative dose (2 to 3 mg/kg), RR = 0.43 (95% CI, 0.29–0.65); day of initiation <8 days: RR = 0.68, (95% CI, 0.59–0.79); and treatment for ≥14 days: RR = 0.67 (95% CI, 0.55–0.80). HC did not significantly decrease the risk of BPD, RR = 0.98, (95% CI, 0.87–1.10). Neither DEX, (RR = 0.92, 95% CI, 0.78–1.09) nor HC (RR = 0.83, 95% CI, 0.68–1.01) decrease the risk of mortality. The risk of CP was not increased by either DEX (RR = 1.09, 95% CI, 0.55–2.17) or HC (RR = 1.18, 95% CI, 0.75–1.87). There were no significant differences between steroids and placebo for MDI/PDI scores. Multivariable meta-regression models showed that DEX significantly reduced the risk of BPD without increased risk of CP. DEX increased the risk of hypertension and hyperglycemia. Studies showed high heterogeneity, differing treatment regimen, missing data and different rates of follow-up.

Conclusion and relevance

DEX, but not HC, significantly decreased the risk of BPD. Neither steroid showed an increased risk of NDI or mortality.

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Fig. 1: Study flow diagram.
Fig. 2: Meta-analyses of DEX regimen and the risk of BPD.
Fig. 3: Bubble Plots of Steroid Regimen associated with Cerebral Palsy.

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Acknowledgements

The authors thank the contributions of Hayrettin Okut, PhD, who advised us on statistical aspects of model development, including programming in R.

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Authors and Affiliations

  1. Department of Pediatrics, University of Kansas School of Medicine—Wichita, Wichita, KS, USA

    Talkad S. Raghuveer, Richa Lakhotia & Stephanie A. Binder

  2. Office of Research, University of Kansas School of Medicine—Wichita, Wichita, KS, USA

    Rosey E. Zackula

  3. Pediatrix Medical Group of Kansas, Wichita, KS, USA

    Richa Lakhotia & Stephanie A. Binder

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Contributions

TSR: conceptualized, formulated the research methodology, wrote the original draft, reviewed and edited the manuscript, supervised/administered the whole project and guarantor for the project. REZ: conceptualized, formulated the research methodology, performed formal analysis, curated data and wrote the original draft, reviewed and edited the manuscript. RL: conceptualized, formulated the research methodology, wrote the original draft, reviewed and edited the manuscript. SAB: conceptualized, formulated the research methodology, wrote the original draft, reviewed and edited the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Talkad S. Raghuveer.

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TSR, REZ, RL, and SAB have no relevant conflicts to disclose. This study was not supported by funding from any source.

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Raghuveer, T.S., Zackula, R.E., Lakhotia, R. et al. Systemic steroids and bronchopulmonary dysplasia: a systematic review and meta-analysis. J Perinatol (2024). https://doi.org/10.1038/s41372-024-02097-w

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