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Prophylactic early low-dose hydrocortisone and survival without bronchopulmonary dysplasia among extremely preterm infants born at 22–27 weeks’ gestation

Journal of Perinatology (2024)Cite this article

Subjects

Abstract

Objective

To compare survival without BPD among extremely preterm infants (EPI) who received prophylactic early low-dose hydrocortisone (PEH) with those who did not (non-PEH).

Study design

This single-center retrospective study compared risk-adjusted rates of survival without BPD, BPD, bowel perforation, and late-onset sepsis among infants (22–27 weeks’ gestation at birth) who received PEH (n = 82) and who did not (n = 205).

Results

Infants in the PEH group were of lower gestational age, lower birthweight, and higher day-1 risk of death/BPD. After adjusting for risk of death/BPD, PEH-treated infants demonstrated increased survival without BPD (aOR 2.04, 95%CI 1.1–3.7), and lower BPD rates (aOR 0.46, 95%CI 0.25–0.87). Importantly, bowel perforation or sepsis rate were similar among both groups.

Conclusion

After risk adjustment, PEH-treated infants demonstrated improved survival without BPD and did not increase rates of bowel perforation or sepsis. In our cohort of infants, PEH was safe and effective among the sickest preterm neonates.

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Data availability

All data presented in Fig. 1 and Tables 1–3 are available upon request.

References

  1. Bell EF, Hintz SR, Hansen NI, Bann CM, Wyckoff MH, DeMauro SB, et al. Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018. JAMA. 2022;327:248–63.

    Article  PubMed  Google Scholar 

  2. Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007;357:1946–55.

    Article  CAS  PubMed  Google Scholar 

  3. Day CL, Ryan RM. Bronchopulmonary dysplasia: new becomes old again! Pediatr Res. 2017;81:210–13.

    Article  PubMed  Google Scholar 

  4. DeMauro SB. The Impact of Bronchopulmonary Dysplasia on Childhood Outcomes. Clin Perinatol. 2018;45:439–52.

    Article  PubMed  Google Scholar 

  5. Harris C, Morris S, Lunt A, Peacock J, Greenough A. Influence of bronchopulmonary dysplasia on lung function in adolescents who were born extremely prematurely. Pediatr Pulmonol. 2022;57:3151–7.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Van Marter LJ, Kuban KC, Allred E, Bose C, Dammann O, O’Shea M, et al. Does bronchopulmonary dysplasia contribute to the occurrence of cerebral palsy among infants born before 28 weeks of gestation? Arch Dis Child Fetal Neonatal Ed. 2011;96:F20–9.

    Article  PubMed  Google Scholar 

  7. Yallapragada SG, Savani RC, Goss KN. Cardiovascular impact and sequelae of bronchopulmonary dysplasia. Pediatr Pulmonol. 2021;56:3453–63.

    Article  PubMed  Google Scholar 

  8. Álvarez-Fuente M, Arruza L, Muro M, Zozaya C, Avila A, López-Ortego P, et al. The economic impact of prematurity and bronchopulmonary dysplasia. Eur J Pediatr. 2017;176:1587–93.

    Article  PubMed  Google Scholar 

  9. Gilfillan M, Bhandari A, Bhandari V. Diagnosis and management of bronchopulmonary dysplasia. BMJ. 2021;375:n1974.

    Article  PubMed  Google Scholar 

  10. Laughon MM, Langer JC, Bose CL, Smith PB, Ambalavanan N, Kennedy KA, et al. Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants. Am J Respir Crit Care Med. 2011;183:1715–22.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jensen EA, Foglia EE, Schmidt B. Evidence-Based Pharmacologic Therapies for Prevention of Bronchopulmonary Dysplasia: Application of the Grading of Recommendations Assessment, Development, and Evaluation Methodology. Clin Perinatol. 2015;42:755–79.

    Article  PubMed  Google Scholar 

  12. Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. 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;387:1827–36.

    Article  CAS  PubMed  Google Scholar 

  13. Shaffer ML, Baud O, Lacaze-Masmonteil T, Peltoniemi OM, Bonsante F, Watterberg KL. Effect of Prophylaxis for Early Adrenal Insufficiency Using Low-Dose Hydrocortisone in Very Preterm Infants: An Individual Patient Data Meta-Analysis. J Pediatr. 2019;207:136–42.e5.

    Article  CAS  PubMed  Google Scholar 

  14. Owen LS, Manley BJ, Davis PG, Doyle LW. The evolution of modern respiratory care for preterm infants. Lancet. 2017;389:1649–59.

    Article  PubMed  Google Scholar 

  15. 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:S146–53.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wright CJ, Kirpalani H. Targeting inflammation to prevent bronchopulmonary dysplasia: can new insights be translated into therapies? Pediatrics. 2011;128:111–26.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cummings JJ, Pramanik AK, FAAP; COMMITTEE ON FETUS AND NEWBORN. Postnatal Corticosteroids to Prevent or Treat Chronic Lung Disease Following Preterm Birth. Pediatrics; 2022;149:e2022057530.

  18. Watterberg KL, Scott SM. Evidence of early adrenal insufficiency in babies who develop bronchopulmonary dysplasia. Pediatrics. 1995;95:120–5.

    Article  CAS  PubMed  Google Scholar 

  19. Bagnoli F, Mori A, Fommei C, Coriolani G, Badii S, Tomasini B. ACTH and cortisol cord plasma concentrations in preterm and term infants. J Perinatol. 2013;33:520–4.

    Article  CAS  PubMed  Google Scholar 

  20. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, et al. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Respir Crit Care Med. 2019;200:751–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Walsh MC, Yao Q, Gettner P, Hale E, Collins M, Hensman A, et al. Impact of a physiologic definition on bronchopulmonary dysplasia rates. Pediatrics. 2004;114:1305–11.

    Article  PubMed  Google Scholar 

  23. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–34.

    Article  CAS  PubMed  Google Scholar 

  24. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Watterberg KL, Gerdes JS, Cole CH, Aucott SW, Thilo EH, Mammel MC, et al. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics. 2004;114:1649–57.

    Article  PubMed  Google Scholar 

  26. Watterberg KL, Walsh MC, Li L, Chawla S, D’Angio CT, Goldberg RN, et al. Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia. N. Engl J Med. 2022;386:1121–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Onland W, Cools F, Kroon A, Rademaker K, Merkus MP, Dijk PH, et al. Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2019;321:354–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Demauro SB, Dysart K, Kirpalani H. Stopping the swinging pendulum of postnatal corticosteroid use. J Pediatr. 2014;164:9–11.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cuna A, Lagatta JM, Savani RC, Vyas-Read S, Engle WA, Rose RS, et al. Association of time of first corticosteroid treatment with bronchopulmonary dysplasia in preterm infants. Pediatr Pulmonol. 2021;56:3283–92.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Harmon HM, Jensen EA, Tan S, Chaudhary AS, Slaughter JL, Bell EF, et al. Timing of postnatal steroids for bronchopulmonary dysplasia: association with pulmonary and neurodevelopmental outcomes. J Perinatol. 2020;40:616–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Huysman MW, Hokken-Koelega AC, De Ridder MA, Sauer PJ. Adrenal function in sick very preterm infants. Pediatr Res. 2000;48:629–33.

    Article  CAS  PubMed  Google Scholar 

  32. Wu G, Jaeger LA, Bazer FW, Rhoads JM. Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications. J Nutr Biochem. 2004;15:442–51.

    Article  CAS  PubMed  Google Scholar 

  33. Watterberg KL, Scott SM, Backstrom C, Gifford KL, Cook KL. Links between early adrenal function and respiratory outcome in preterm infants: airway inflammation and patent ductus arteriosus. Pediatrics. 2000;105:320–24.

    Article  CAS  PubMed  Google Scholar 

  34. Clyman RI, Mauray F, Roman C, Rudolph AM, Heymann MA. Glucocorticoids alter the sensitivity of the lamb ductus arteriosus to prostaglandin E2. J Pediatr. 1981;98:126–28.

    Article  CAS  PubMed  Google Scholar 

  35. Greenberg RG, McDonald SA, Laughon MM, Tanaka D, Jensen E, Van Meurs K, et al. Online clinical tool to estimate risk of bronchopulmonary dysplasia in extremely preterm infants. Arch Dis Child Fetal Neonatal Ed. 2022:fetalneonatal-2021-323573. https://doi.org/10.1136/archdischild-2021-323573. Epub ahead of print.

  36. Cuna A, Liu C, Govindarajan S, et al. Usefulness of an online risk estimator for bronchopulmonary dysplasia in predicting corticosteroid treatment in infants born preterm. J Pediatr. 2018;197:23–28.e2.

    Article  PubMed  Google Scholar 

  37. Baud O, Laughon M, Lehert P. Survival without bronchopulmonary dysplasia of extremely preterm infants: a predictive model at birth. Neonatology. 2021;118:385–93.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, University of Florida College of Medicine Jacksonville, Jacksonville, FL, USA

    Sanket D. Shah, P. Sireesha Nandula, Mark L. Hudak & Josef Cortez

  2. Division of Neonatology, Advent Health, Orlando, FL, USA

    Samarth Shukla

  3. Department of Pediatrics, University of Florida College of Medicine Jacksonville, Jacksonville, FL, USA

    Shannon Vice, Marwa Elgendy & Shiva Gautam

  4. Department of Biostatistics and Department of Pediatrics, University of Florida, Gainesville, FL, USA

    Shiva Gautam

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Contributions

SDS participated in methodology, collected data, analyzed data, drafted the initial manuscript, and critically reviewed and revised the manuscript. SS, PSN, SV participated in methodology, collected data, and critically reviewed the manuscript. ME collected and verified data, and critically reviewed the manuscript. SG analyzed data, critically reviewed and revised the manuscript. MLH reviewed and revised the manuscript critically. JC conceptualized and designed the study, coordinated and verified data collection, analyzed data, and critically reviewed and revised the manuscript for important intellectual content.

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Correspondence to Josef Cortez.

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Shah, S.D., Shukla, S., Nandula, P.S. et al. Prophylactic early low-dose hydrocortisone and survival without bronchopulmonary dysplasia among extremely preterm infants born at 22–27 weeks’ gestation. J Perinatol (2024). https://doi.org/10.1038/s41372-024-01923-5

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  • DOI: https://doi.org/10.1038/s41372-024-01923-5

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