Am J Perinatol 2024; 41(S 01): e1858-e1865
DOI: 10.1055/s-0043-1769795
Review Article

Long-term Effects of Intratracheal Budesonide and Surfactant for the Prevention of Bronchopulmonary Dysplasia: A Narrative Review

1   Department of Mother, Child and Public Health, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
,
Chiara Di Sipio Morgia
1   Department of Mother, Child and Public Health, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
,
Michael Hall
2   Department of Neonatal Medicine, School of Health Sciences, University of Southampton, Southampton, United Kingdom
› Author Affiliations
Funding None.

Abstract

Objective This study aimed to compare the safety and efficacy of intratracheal administration of budesonide and surfactant with surfactant alone for bronchopulmonary dysplasia (BPD) prevention in premature infants with respiratory distress syndrome.

Study Design A literature search was performed in MEDLINE, Embase, Cochrane, ClinicalTrials.gov, and gray literature. Assessment of quality was conducted using CASP tool, ROBIS tool, and GRADE framework.

Results A systematic review and meta-analysis and three observational studies were identified. Budesonide was associated with reduced incidence and severity of BPD, reduced mortality, patent ductus arteriosus, need for additional surfactant doses, hypotension, duration of invasive ventilation, hospital stays, salbutamol prescriptions, and hospitalizations in the first 2 years of life. The safety of budesonide on neurodevelopmental outcomes at 2 to 3 years of corrected age was reported.

Conclusion Budesonide might be associated with a reduction in BPD incidence and severity, without evidence of impaired neurodevelopment at 2 to 3 years of age. According to the GRADE framework, the level of evidence is low due to significant heterogeneity of studies and other bias.

Key Points

  • BPD prevention is urgently needed.

  • Intratracheal budesonide and surfactant for neonatal RDS could reduce BPD.

  • The grade of evidence for this intervention is low due to study heterogeneity and other bias.

Note

Part of the research conducted for this paper was included in a dissertation successfully submitted to the School of Health Sciences, University of Southampton, in partial fulfilment of the award of the MSc Neonatology.




Publication History

Received: 02 March 2023

Accepted: 28 April 2023

Article published online:
06 June 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Sweet DG, Carnielli V, Greisen G. et al. European Consensus Guidelines on the management of respiratory distress syndrome - 2019 update. Neonatology 2019; 115 (04) 432-450
  • 2 Dell'Orto V, Nobile S, Correani A. et al. Early nasal continuous positive airway pressure failure prediction in preterm infants less than 32 weeks gestational age suffering from respiratory distress syndrome. Pediatr Pulmonol 2021; 56 (12) 3879-3886
  • 3 Lee SM, Sie L, Liu J, Profit J, Lee HC. Evaluation of trends in bronchopulmonary dysplasia and respiratory support practice for very low birth weight infants: a population-based cohort study. J Pediatr 2022; 243: 47-52.e2
  • 4 Laughon M, Allred EN, Bose C. et al; ELGAN Study Investigators. Patterns of respiratory disease during the first 2 postnatal weeks in extremely premature infants. Pediatrics 2009; 123 (04) 1124-1131
  • 5 Nobile S, Marchionni P, Vento G. et al. New insights on early patterns of respiratory disease among extremely low gestational age newborn. Neonatology 2017; 112 (01) 53-59
  • 6 Siffel C, Kistler KD, Lewis JFM, Sarda SP. Global incidence of bronchopulmonary dysplasia among extremely preterm infants: a systematic literature review. J Matern Fetal Neonatal Med 2021; 34 (11) 1721-1731
  • 7 Jensen EA, Dysart K, Gantz MG. et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants. an evidence-based approach. Am J Respir Crit Care Med 2019; 200 (06) 751-759
  • 8 Jordan BK, McEvoy CT. Trajectories of lung function in infants and children: setting a course for lifelong lung health. Pediatrics 2020; 146 (04) e20200417
  • 9 Katz TA, Vliegenthart RJS, Aarnoudse-Moens CSH. et al. Severity of bronchopulmonary dysplasia and neurodevelopmental outcome at 2 and 5 years corrected age. J Pediatr 2022; 243: 40-46.e2
  • 10 Thébaud B, Goss KN, Laughon M. et al. Bronchopulmonary dysplasia. Nat Rev Dis Primers 2019; 5 (01) 78
  • 11 Barrette AM, Roberts JK, Chapin C. et al. Antiinflammatory effects of budesonide in human fetal lung. Am J Respir Cell Mol Biol 2016; 55 (05) 623-632
  • 12 Cummings JJ, Pramanik AK. AAP Committee on Fetus and Newborn. Postnatal corticosteroids to prevent or treat chronic lung disease following preterm birth. Pediatrics 2022; 149 (06) e2022057530
  • 13 Doyle LW, Cheong JL, Hay S, Manley BJ, Halliday HL, Soll R. Early (< 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2021; 10 (10) CD001146
  • 14 Critical Appraisal Skills Programme. CASP (cohort study) checklist [online] (2018). Accessed February 12, 2021 at: https://casp-uk.net/casp-tools-checklists/
  • 15 ROBIS. Tool to assess risk of bias in systematic reviews (2016). Accessed February 20, 2021 at: https://www.bristol.ac.uk/population-health-sciences/projects/robis/robis-tool/
  • 16 Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ. GRADE Working Group. What is “quality of evidence” and why is it important to clinicians?. BMJ 2008; 336 (7651): 995-998
  • 17 Cochrane Developmental, Psychosocial and Learning Problems. Data collection form for intervention reviews for RCTs and non-RCTs. Accessed February 10, 2021 at: https://dplp.cochrane.org/data-extraction-forms
  • 18 De Lourdes Levy M, Larcher V, Kurz R. Ethics Working Group of the Confederation of European Specialists in Paediatrics (CESP), Statement of the Ethics Working Group of the Confederation of European Specialists in Paediatrics (CESP). Informed consent/assent in children. Eur J Pediatr 2003; 162 (09) 629-633
  • 19 Fernandez C, Albersheim S, Hilliard R, Razack S, Templeton C, Tsai E. Ethical issues in health research in children. Paediatr Child Health 2008; 13 (08) 707-720
  • 20 Bassler D, Shinwell ES, Hallman M. et al; Neonatal European Study of Inhaled Steroids Trial Group. Long-term effects of inhaled budesonide for bronchopulmonary dysplasia. N Engl J Med 2018; 378 (02) 148-157
  • 21 Yeh TF, Chen CM, Wu SY. et al. Intratracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia. Am J Respir Crit Care Med 2016; 193 (01) 86-95
  • 22 Yeh TF, Lin HC, Chang CH. et al. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics 2008; 121 (05) e1310-e1318
  • 23 Sadeghnia A, Beheshti BK, Mohammadizadeh M. The effect of inhaled budesonide on the prevention of chronic lung disease in premature neonates with respiratory distress syndrome. Int J Prev Med 2018; 9: 15
  • 24 Du FL, Dong WB, Zhang C. et al. Budesonide and poractant alfa prevent bronchopulmonary dysplasia via triggering SIRT1 signaling pathway. Eur Rev Med Pharmacol Sci 2019; 23 (24) 11032-11042
  • 25 Heo M, Jeon GW. Intratracheal administration of budesonide with surfactant in very low birth weight infants to prevent bronchopulmonary dysplasia. Turk J Pediatr 2020; 62 (04) 551-559
  • 26 Gharehbaghi MM, Ganji S, Mahallei M. A randomized clinical trial of intratracheal administration of surfactant and budesonide combination in comparison to surfactant for prevention of bronchopulmonary dysplasia. Oman Med J 2021; 36 (04) e289
  • 27 Kuo HT, Lin HC, Tsai CH, Chouc IC, Yeh TF. A follow-up study of preterm infants given budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants. J Pediatr 2010; 156 (04) 537-541
  • 28 Kothe TB, Sadiq FH, Burleyson N, Williams HL, Anderson C, Hillman NH. Surfactant and budesonide for respiratory distress syndrome: an observational study. Pediatr Res 2020; 87 (05) 940-945
  • 29 Anderson CD, Kothe TB, Josephsen JB. et al. Budesonide mixed with surfactant did not affect neurodevelopmental outcomes at 6 or 18 months corrected age in observational cohorts. J Perinatol 2021; 41 (07) 1681-1689
  • 30 Moschino L, Nardo D, Bonadies L. et al. Intra-tracheal surfactant/budesonide versus surfactant alone: comparison of two consecutive cohorts of extremely preterm infants. Pediatr Pulmonol 2021; 56 (07) 2114-2124
  • 31 McEvoy CT, Ballard PL, Ward RM. et al. Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE). Pediatr Res 2020; 88 (04) 629-636
  • 32 Venkataraman R, Kamaluddeen M, Hasan SU, Robertson HL, Lodha A. Intratracheal administration of budesonide-surfactant in prevention of bronchopulmonary dysplasia in very low birth weight infants: a systematic review and meta-analysis. Pediatr Pulmonol 2017; 52 (07) 968-975
  • 33 Zhong YY, Li JC, Liu YL. et al. Early intratracheal administration of corticosteroid and pulmonary surfactant for preventing bronchopulmonary dysplasia in preterm infants with neonatal respiratory distress syndrome: a meta-analysis. Curr Med Sci 2019; 39 (03) 493-499
  • 34 Hirano AML, Mocelin DCR, Neves SBGP, de Araùjo MYR, de Albuquerque DEM, Brunow CW. Use of budesonide associated with a pulmonary surfactant to prevent bronchopulmonary dysplasia in premature newborns- a systematic review. J Ped (Rio) 2022; 99 (02) 105-111
  • 35 Yi Z, Tan Y, Liu Y. et al. A systematic review and meta-analysis of pulmonary surfactant combined with budesonide in the treatment of neonatal respiratory distress syndrome. Transl Pediatr 2022; 11 (04) 526-536
  • 36 Tang W, Chen S, Shi D. et al. 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. Pediatr Pulmonol 2022; 57 (02) 455-469
  • 37 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163 (07) 1723-1729
  • 38 Abman SH, Collaco JM, Shepherd EG. et al; Bronchopulmonary Dysplasia Collaborative. Interdisciplinary care of children with severe bronchopulmonary dysplasia. J Pediatr 2017; 181: 12-28.e1
  • 39 Higgins RD, Jobe AH, Koso-Thomas M. et al. Bronchopulmonary dysplasia: executive summary of a workshop. J Pediatr 2018; 197: 300-308
  • 40 Baud O, Maury L, Lebail F. et al; PREMILOC trial study group. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet 2016; 387 (10030): 1827-1836
  • 41 Anderson PJ, De Luca CR, Hutchinson E, Roberts G, Doyle LW. Victorian Infant Collaborative Group. Underestimation of developmental delay by the new Bayley-III Scale. Arch Pediatr Adolesc Med 2010; 164 (04) 352-356
  • 42 Johnson S, Moore T, Marlow N. Using the Bayley-III to assess neurodevelopmental delay: which cut-off should be used?. Pediatr Res 2014; 75 (05) 670-674
  • 43 Bellos I, Fitrou G, Panza R, Pandita A. Comparative efficacy of methods for surfactant administration: a network meta-analysis. Arch Dis Child Fetal Neonatal Ed 2021; 106 (05) 474-487
  • 44 Trembath A, Hornik CP, Clark R, Smith PB, Daniels J, Laughon M. Best Pharmaceuticals for Children Act—Pediatric Trials Network. Comparative effectiveness of surfactant preparations in premature infants. J Pediatr 2013; 163 (04) 955-60.e1
  • 45 Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics 1988; 82 (04) 527-532
  • 46 Koch A, Kreutzer K, von Oldershausen G, Poets CF, Bassler D. NEuroSIS Trial Group. Inhaled glucocorticoids and pneumonia in preterm infants: post hoc results from the NEuroSIS trial. Neonatology 2017; 112 (02) 110-113
  • 47 Mendes ES, Rebolledo P, Campos M, Wanner A. Immediate antiinflammatory effects of inhaled budesonide in patients with asthma. Ann Am Thorac Soc 2014; 11 (05) 706-711
  • 48 Wiedmann TS, Bhatia R, Wattenberg LW. Drug solubilization in lung surfactant. J Control Release 2000; 65 (1-2): 43-47
  • 49 Miller-Larsson A, Mattsson H, Hjertberg E, Dahlbäck M, Tunek A, Brattsand R. Reversible fatty acid conjugation of budesonide. Novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab Dispos 1998; 26 (07) 623-630
  • 50 Vento G, Ventura ML, Pastorino R. et al. Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial. Lancet Respir Med 2021; 9 (02) 159-166