The Effect of Hydrocortisone Treatment After Day Fourteen of Life on Preventing Bronchopulmonary Dysplasia in Preterm Infants

Document Type : Original Article

Authors

1 Department of Neonatology, Tehran University of Medical Sciences, Tehran, Iran

2 Maternal–Fetal and Neonatal Research Center, Tehran University of Medical Sciences, Tehran, Iran

10.22038/ijn.2025.78313.2521

Abstract

Background: This study aimed to evaluate whether administering low-dose hydrocortisone after the first fourteen days of life affects the incidence of bronchopulmonary dysplasia (BPD), mortality, and other short-term complications in mechanically ventilated preterm infants.
Methods: A randomized clinical trial was conducted between 2019 and 2022 in the NICUs of Shariati and Valiasr hospitals in Tehran. Infants received either hydrocortisone or placebo for 10 days and were followed until a corrected gestational age of 36 weeks. Baseline characteristics, primary outcomes, and secondary outcomes were recorded for all participants.
Results: The mean gestational age of infants in this study was 28.2 ± 1.79 weeks. The cohort included 45 male infants (64.3%) and 25 female infants (35.7%). Mortality rates and the need for supportive oxygen treatment were significantly different between the two groups (P < 0.05). The rate of hypertrophic myocarditis also differed significantly (P < 0.05).
Conclusion: In summary, systemic corticosteroid use led to reductions in mortality and BPD by corrected age of 36 weeks. Although there are differences between dexamethasone and hydrocortisone, hydrocortisone decreased mortality but did not significantly reduce BPD incidence. Moreover, late systemic hydrocortisone treatment significantly shortened the duration of mechanical ventilation in infants.
 

Keywords

References

  1. Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012;379(9832):2162-2172.
  2. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75-84.
  3. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;(3):CD004454.
  4. Ramanathan R. Surfactant therapy in preterm infants with respiratory distress syndrome and in near-term or term newborns with acute RDS. J Perinatol. 2006 May;26 Suppl 1(Suppl 1):S51-6; discussion S63-4.
  5. Stevens TP, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2004;(3):CD003063.
  6. Davidson LM, Berkelhamer SK. Bronchopulmonary dysplasia: Chronic lung disease of infancy and long-term pulmonary outcomes. J Clin Med. 2017;6(1):4.
  7. Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al; Eunice kennedy shriver national institute of child health and human development neonatal research network. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA. 2015;314(10):1039-1051.
  8. Tracy MK, Berkelhamer SK. Bronchopulmonary dysplasia and pulmonary outcomes of prematurity. Pediatr Ann. 2019;48(4):e148-e153.
  9. Michael Z, Spyropoulos F, Ghanta S, Christou H. Bronchopulmonary dysplasia: An update of current pharmacologic therapies and new approaches. Clin Med Insights Pediatr. 2018;12:1179556518817322.
  10. Principi N, Di Pietro GM, Esposito S. Bronchopulmonary dysplasia: Clinical aspects and preventive and therapeutic strategies. J Transl Med. 2018 Feb 20;16(1):36.
  11. Voynow JA. "New" bronchopulmonary dysplasia and chronic lung disease. Paediatr Respir Rev. 2017;24:17-18.
  12. Bancalari E, del Moral T. Bronchopulmonary dysplasia and surfactant. Biol Neonate. 2001;80 Suppl 1:7-13.
  13. Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB; COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med. 2008;358(7):700-708.
  14. Melville JM, Moss TJ. The immune consequences of preterm birth. Front Neurosci. 2013;7:79.
  15. Parikh NA, Kennedy KA, Lasky RE, Tyson JE. Neurodevelopmental outcomes of extremely preterm infants randomized to stress dose hydrocortisone. PLoS One. 2015;10(9):e0137051.
  16. Ambalavanan N, Walsh M, Bobashev G, Das A, Levine B, Carlo WA, et al; NICHD Neonatal Research Network. Intercenter differences in bronchopulmonary dysplasia or death among very low birth weight infants. Pediatrics. 2011;127(1):e106-1016.
  17. Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH, Cotton RB, et al. Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. Pediatrics. 1987;79(1):26-30.
  18. Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007;357(19):1946-1955.
  19. Gagliardi L, Bellù R, Lista G, Zanini R; Network Neonatale Lombardo Study Group. Do differences in delivery room intubation explain different rates of bronchopulmonary dysplasia between hospitals? Arch Dis Child Fetal Neonatal Ed. 2011;96(1):F30-35.
  20. Lapcharoensap W, Gage SC, Kan P, Profit J, Shaw GM, Gould JB, et al. Hospital variation and risk factors for bronchopulmonary dysplasia in a population-based cohort. JAMA Pediatr. 2015;169(2):e143676.
  21. McEvoy CT, Jain L, Schmidt B, Abman S, Bancalari E, Aschner JL. Bronchopulmonary dysplasia: NHLBI workshop on the primary prevention of chronic lung diseases. Ann Am Thorac Soc. 2014;11 Suppl 3(Suppl 3):S146-153.
  22. Trembath A, Laughon MM. Predictors of bronchopulmonary dysplasia. Clin Perinatol. 2012;39(3):585-601.
  23. Van Marter LJ, Allred EN, Pagano M, Sanocka U, Parad R, Moore M, et al. Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? The Neonatology Committee for the Developmental Network. Pediatrics. 2000;105(6): 1194-1201.
  24. Vohr BR, Wright LL, Dusick AM, Perritt R, Poole WK, Tyson JE, et al; Neonatal Research Network. Center differences and outcomes of extremely low birth weight infants. Pediatrics. 2004;113(4):781-789.
  25. 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.
  26. Zhou J, Yu Z, Chen C. Hydrocortisone for preventing mortality and bronchopulmonary dysplasia in preterm infants with or without chorioamnionitis exposure: A meta-analysis of randomized trials. Am J Perinatol. 2021;38(7):662-668.
  27. Watterberg KL, Walsh MC, Li L, Chawla S, D'Angio CT, Goldberg RN, et al; Eunice Kennedy Shriver NICHD Neonatal Research Network. Hydrocortisone to improve survival without bronchopulmonary dysplasia. N Engl J Med. 2022;386(12):1121-1131.
  28. Tolia VN, Bahr TM, Bennett MM, Martin G, Greenberg RG, Laughon MM, et al. The association of hydrocortisone dosage on mortality in infants born extremely premature. J Pediatr. 2019;207:143-147.e3.
  29. Doyle LW, Ehrenkranz RA, Halliday HL. Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014;(5):CD001146.
  30. Doyle LW, Ehrenkranz RA, Halliday HL. Postnatal hydrocortisone for preventing or treating bronchopulmonary dysplasia in preterm infants: A systematic review. Neonatology. 2010;98(2):111-117.
  31. Ramaswamy VV, Bandyopadhyay T, Nanda D, Bandiya P, Ahmed J, Garg A, et al. Assessment of postnatal corticosteroids for the prevention of bronchopulmonary dysplasia in preterm neonates: A systematic review and network meta-analysis. JAMA Pediatr. 2021;175(6):e206826.
  32. Tao K. Postnatal administration of systemic steroids increases severity of retinopathy in premature infants. Pediatr Neonatol. 2022;63(3):220-226.
  33. Kidman AM, Manley BJ, Boland RA, Davis PG, Bhatia R. Predictors and outcomes of extubation failure in extremely preterm infants. J Paediatr Child Health. 2021;57(6):913-919.
  34. Halliday HL, Patterson CC, Halahakoon CW; European Multicenter Steroid Study Group. A multicenter, randomized open study of early corticosteroid treatment (OSECT) in preterm infants with respiratory illness: comparison of early and late treatment and of dexamethasone and inhaled budesonide. Pediatrics. 2001;107(2):232-240.
  35. Halliday HL, Ehrenkranz RA. Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2001;(1):CD001144.
  36. Tsukahara H, Watanabe Y, Yasutomi M, Kobata R, Tamura S, Kimura K, et al. Early (4-7 days of age) dexamethasone therapy for prevention of chronic lung disease in preterm infants. Biol Neonate. 1999;76(5):283-290.
  37. Haroon Parupia MF, Dhanireddy R. Association of postnatal dexamethasone use and fungal sepsis in the development of severe retinopathy of prematurity and progression to laser therapy in extremely low-birth-weight infants. J Perinatol. 2001;21(4):242-247.
  38. Morales P, Rastogi A, Bez ML, Akintorin SM, Pyati S, Andes SM, et al. Effect of dexamethasone therapy on the neonatal ductus arteriosus. Pediatr Cardiol. 1998;19(3):225-229.
  39. Termote J, Schalij-Delfos NE, Donders AR, Cats BP. Do postnatal glucocorticoids and retinopathy of prematurity relate? Am J Perinatol. 2000;17(6):291-298.

 

 

 

 

Iranian Journal of Neonatology
Volume 16, Issue 4
October 2025
Pages 21-29

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