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DOI: 10.1055/s-0043-1776416
Intratracheal Instillation of Budesonide–Surfactant for Prevention of Bronchopulmonary Dysplasia in Extremely Premature Infants
Funding None.![](https://www.thieme-connect.de/media/ajp/2024S01/lookinside/thumbnails/10-1055-s-0043-1776416_23jun0391-1.jpg)
Abstract
Objective This study aimed to determine the effect of intratracheal instillation of a budesonide–surfactant combination on the incidence of bronchopulmonary dysplasia (BPD) or death compared with surfactant alone in extremely preterm infants.
Study Design In this retrospective, single-center study, we included extremely preterm infants (<28 weeks' gestation) who received surfactant for respiratory distress in the first 3 days of life. We compared infants who received budesonide–surfactant combination (intervention group: infants born between February 2016 and October 2021) with surfactant alone (control group: infants born from January 2010 through January 2016). The primary outcome was a composite of BPD grade 2 or 3 (as defined by Jensen et al, 2019) or death before 36 weeks' postmenstrual age (PMA).
Results We included 966 extremely preterm infants (528 in the control group and 438 in the intervention group). While the incidence of death/BPD grade 2 or 3 at 36 weeks of PMA was not different between the two groups (66% in the intervention group vs. 63% in the control group; adjusted relative risk [aRR], 0.99; 95% confidence interval [CI], 0.90–1.07; p-value = 0.69), budesonide was associated with a reduction in the primary outcome only in a subgroup of infants with birth weight ≥ 750 grams (36.8 vs. 43.5%, respectively; aRR 0.75; 95% CI, 0.57–0.98). Primary and secondary outcomes did not differ between the two groups within the subgroup of infants weighing <750 grams.
Conclusion In extremely preterm infants, the budesonide–surfactant combination therapy reduced the rates of BPD or death in infants weighing ≥750 grams; however, this beneficial effect was not seen in infants weighing <750 grams. Further investigation of this treatment may be indicated before it is considered a standard approach to management.
Key Points
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Intratracheal budesonide–surfactant therapy reduces BPD in preterm infants weighing ≥750 grams.
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Intratracheal budesonide–surfactant therapy does not affect BPD in preterm infants weighing <750 grams.
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Intratracheal budesonide–surfactant therapy does not affect the mortality rate in preterm infants.
Keywords
surfactant - intratracheal budesonide - corticosteroid - bronchopulmonary dysplasia - extremely preterm infantsAuthors' Contributions
K.D. was responsible for writing the protocol, designing the study, extracting and analyzing the data, interpreting results, drafting the initial manuscript, and reviewing and revising the manuscript. A.G. was responsible for extracting the data and editing the manuscript. M.Z. contributed to writing the protocol, designing the study, extracting and analyzing the data, interpreting results, and providing feedback on the manuscript. FE contributed to analyzing the data, interpreting results, and providing feedback on the manuscript.
Availability of Data and Materials
The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.
Ethical Approval
This study protocol was reviewed and approved by the University of South Alabama Institutional Review Board (IRB number: 22-125). This study was approved for waiver of Health Insurance Portability and Accountability Act (HIPAA) authorization, and the University of South Alabama Institutional Review Board waived the need for consent. This study was conducted according to the Declaration of Helsinki.
Publication History
Received: 16 June 2023
Accepted: 10 October 2023
Article published online:
01 November 2023
© 2023. Thieme. All rights reserved.
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References
- 1 Stoll BJ, Hansen NI, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (03) 443-456
- 2 Gough A, Spence D, Linden M, Halliday HL, McGarvey LPA. General and respiratory health outcomes in adult survivors of bronchopulmonary dysplasia: a systematic review. Chest 2012; 141 (06) 1554-1567
- 3 Katz-Salamon M, Gerner EM, Jonsson B, Lagercrantz H. Early motor and mental development in very preterm infants with chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2000; 83 (01) F1-F6
- 4 McAleese KA, Knapp MA, Rhodes TT. Financial and emotional cost of bronchopulmonary dysplasia. Clin Pediatr (Phila) 1993; 32 (07) 393-400
- 5 Ogden BE, Murphy SA, Saunders GC, Pathak D, Johnson JD. Neonatal lung neutrophils and elastase/proteinase inhibitor imbalance. Am Rev Respir Dis 1984; 130 (05) 817-821
- 6 Yoon BH, Romero R, Jun JK. et al. Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1997; 177 (04) 825-830
- 7 Groneck P, Goetze-Speer B, Speer CP. Inflammatory bronchopulmonary response of preterm infants with microbial colonisation of the airways at birth. Arch Dis Child Fetal Neonatal Ed 1996; 74 (01) F51-F55
- 8 Doyle LW, Cheong JL, Hay S, Manley BJ, Halliday HL. Early (< 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2021; 10 (10) CD001146
- 9 Doyle LW, Cheong JL, Hay S, Manley BJ, Halliday HL. Late (≥ 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2021; 11 (11) CD001145
- 10 Watterberg KL. American Academy of Pediatrics. Committee on Fetus and Newborn. Policy statement–postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia. Pediatrics 2010; 126 (04) 800-808
- 11 Kelly EA, Busse WW, Jarjour NN. Inhaled budesonide decreases airway inflammatory response to allergen. Am J Respir Crit Care Med 2000; 162 (3 Pt 1): 883-890
- 12 Murphy KR, Hong JG, Wandalsen G. et al. Nebulized inhaled corticosteroids in asthma treatment in children 5 years or younger: a systematic review and global expert analysis. J Allergy Clin Immunol Pract 2020; 8 (06) 1815-1827
- 13 Leflein JG, Szefler SJ, Murphy KR. et al. Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial. Pediatrics 2002; 109 (05) 866-872
- 14 Razi CH, Akelma AZ, Harmanci K, Kocak M, Kuras Can Y. The addition of inhaled budesonide to standard therapy shortens the length of stay in hospital for asthmatic preschool children: a randomized, double-blind, placebo-controlled trial. Int Arch Allergy Immunol 2015; 166 (04) 297-303
- 15 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
- 16 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
- 17 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
- 18 Moraes LHA, Coelho RMD, Neves Dos Santos Beozzo GP, Yoshida RAM, de Albuquerque Diniz EM, de Carvalho WB. Use of budesonide associated with a pulmonary surfactant to prevent bronchopulmonary dysplasia in premature newborns - a systematic review. J Pediatr (Rio J) 2023; 99 (02) 105-111
- 19 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
- 20 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
- 21 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163 (07) 1723-1729
- 22 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
- 23 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
- 24 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
- 25 Yeh TF, Chen CM, Lee KY. et al. Intra-tracheal administration of budesonide using curosurf as vehicle to prevent bronchopulmonary dysplasia in preterm very low birthweight infant- a multicenter randomized double-blind trial. Pediatr. Acad Soc 2023; 750 (02) 151B
- 26 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
- 27 Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL. et al. Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analyses of the NIRTURE study. J Pediatr 2010; 157 (05) 715-9.e1 , 3
- 28 Tottman AC, Alsweiler JM, Bloomfield FH, Pan M, Harding JE. Relationship between measures of neonatal glycemia, neonatal illness, and 2-year outcomes in very preterm infants. J Pediatr 2017; 188: 115-121
- 29 Carlo WA, Finer NN, Walsh MC. et al; SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med 2010; 362 (21) 1959-1969
- 30 Zayek MM, Eyal FG, Smith RC. Comparison of the pharmacoeconomics of calfactant and poractant alfa in surfactant replacement erapy. J Pediatr Pharmacol Ther 2018; 23 (02) 146-151
- 31 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
- 32 Hundscheid T, Onland W, Kooi EMW. et al; BeNeDuctus Trial Investigators. Expectant management or early ibuprofen for patent ductus arteriosus. N Engl J Med 2023; 388 (11) 980-990
- 33 Ohlsson A, Shah SS. Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2011; (07) CD004213
- 34 Clyman RI, Liebowitz M, Kaempf J. et al; PDA-TOLERATE (PDA: TO LEave it alone or Respond And Treat Early) Trial Investigators. PDA-TOLERATE Trial: an exploratory randomized controlled trial of treatment of moderate-to-large patent ductus arteriosus at 1 week of age. J Pediatr 2019; 205: 41-48.e6