Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 144 No. 1314 (2014)

Non-neurological, steroid-related adverse events in very low birth weight infants: a prospective audit

  • Sebastian Benedikt Röhr
  • Harald Sauer
  • Sven Gottschling
  • Hashim Abdul-Khaliq
  • Ludwig Gortner
  • Holger Nunold
  • Stefan Gräber
  • Sascha Meyer
Cite this as:
Swiss Med Wkly. 2014;144:w13954


BACKGROUND AND STUDY PURPOSE: To assess the incidence of cardiac and metabolic adverse events in very low birth weight (VLBW) infants receiving systematic steroids.

PATIENTS AND METHODS: Prospective single centre audit in VLBW infants (<1,500 g) at the neonatal intensive care unit at the University Children’s Hospital of Saarland, Germany.

RESULTS: A total of 72 VLBW infants (38 female) were included in this report (mean birth weight: 967 ± 338 g; range: 320–1490 g). Birth weight, gestational age and Apgar scores were significantly lower in the steroid group (p <0.01). Mortality rate was 8/72 (7/34 in the steroid treated vs nontreated 1/38; odds ratio [OR]: 9.6; 95% confidence interval [CI]: 1.1–82.6 p = 0.02). In 34/72 infants, steroids were given (22 hydrocortisone alone; 12 combination of hydrocortisone and dexamethasone). The most common indication for use of steroids was respiratory distress syndrome (RDS) and respiratory insufficiency (30/34). Adverse events that occurred more often in the steroid group included hypertrophic cardiomyopathy (14/34 vs 0/38; p <0.001); thrombus formation (8/34 vs 1/38; OR: 11.4; 95% CI: 1.3-96.6; p <0.05), hyperglycaemia (27/34 vs 3/38; OR: 45.0; 95% CI: 10.6–190.4; p <0.01), hypernatraemia (15/34 vs 7/38; OR: 3.5; 95% CI: 1.2–10.1; p <0.05), and sepsis/infections (8/34 vs 1/38; OR: 11.4; 95% CI: 1.3–96.6; p <0.05). No significant differences were seen between hydrocortisone alone and the combination of hydrocortisone with dexamethasone. Birth weight and severity of RDS were predictors of steroid use (p <0.01).

CONCLUSIONS: The use of steroids was significantly associated with severe short-term adverse events – most importantly hypertrophic cardiomyopathy and thrombus formation. These complications must be taken into consideration when administering steroids to VLBW infants.


  1. Barrington KJ. The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs. BMC Pediatrics. 2001;1:1.
  2. O’Shea TM, Kothadia JM, Klinepeter KL, Goldstein DJ, Jackson BG, et al. Randomized placebo-controlled trial of a 42-day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants: outcome of study participants at 1-year adjusted age. Pediatrics. 1999;104:15–21.
  3. Shinwell ES, Karplus M, Reich D, Weintraub Z, Blazer S, Bader D, et al. Early postnatal dexamethasone treatment and increased incidence of cerebral palsy. Arch Dis Child Fetal Neonatal Ed. 2000; 83:F177–81.
  4. Committee on Fetus and Newborn. Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants. Pediatrics. 2002;109:330–8.
  5. Watterberg KL; American Academy of Pediatrics. Committee on Fetus and NewbornPolicy statement – postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia. Pediatrics. 2010;126(4):800–8. doi: 10.1542/peds.2010-1534. Epub 2010 Sep 6.
  6. Watterberg KL, Shaffer ML, Mishefske MJ, Leach CL, Mammel MC, Couser RJ, et al. Growth and neurodevelopmental outcomes after early low-dose hydrocortisone treatment in extremely low birth weight infants. Pediatrics. 2007;120(1):40–8.
  7. Payne NR, Finkelstein MJ, Liu M, Kaempf JW, Sharek PJ, Olsen S. NICU Practices and Outcomes Associated With 9 Years of Quality Improvement Collaboratives. Pediatrics. 2010;125:437–46.
  8. Yoder BA, Harrison M, Clark RH. Time-related changes in steroid use and bronchopulmonary dysplasia in preterm infants. Pediatrics. 2009;124:673–9.
  9. Higgins S, Friedlich P, Seri I. Hydrocortisone for hypotension and vasopressor dependence in preterm neonates: a meta-analysis. J Perinatol. 2010;30:373–8.
  10. Ibrahim H, Sinha IP, Subhedar NV. Corticosteroids for treating hypotension in preterm infants. Cochrane Database Syst Rev 2011 Dec 7; 12:CD003662.
  11. Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB, and the DART Study Investigators. Outcome at 2 years of age of infants from the DART Study: A Multicenter, international, randomized, controlled trial of low-dose dexamethasone. Pediatrics. 2007;119:716–21.
  12. Wilson-Costello D, Walsh MC, Langer JC, Guillet R, Laptook AR, Stoll BJ, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Impact of Postnatal Corticosteroid Use on Neurodevelopment at 18 to 22 Months’ Adjusted Age: Effects of dose, timing, and risk of bronchopulmonary dysplasia in extremely low birth weight infants. Pediatrics. 2009;123:e430–7.
  13. Finer NN, Powers RJ, Ou C-hS, Durand D, Wirtschafter D, Gould JB; California Perinatal Quality Care Collaborative Executive Committee. Prospective evaluation of postnatal steroid sdministration: A 1-Year experience from the California Perinatal Quality Care Collaborative. Pediatrics. 2006;117:704–13.
  14. Dani C, Bertini G, Simone P, Rubaltelli Firmino F. Hypertrophic cardiomyopathy in preterm infants treated with methylprednisolone for bronchopulmonary dysplasia. Pediatrics. 2006;117:1866–7.
  15. Khalid YA, Fadi BF, Paula H, Salman MM, Mohamad M. Transient hypertrophic cardiomyopathy in the newborn following multiple doses of antenatal corticosteroids. Am J Perinatol. 1999;16:17–21.
  16. Vimala J, Prabhu A, Pavithran S, Kumar RN. Hydrocortisone induced hypertrophic cardiomyopathy. Int J Cardiol. 2011;150:e94-5
  17. Skelton R, Gill AB, Parsonsb JM. Reference ranges for cardiac dimensions and blood flow velocity in preterm infants. Heart. 1998; 80:281–5.
  18. Ogilvy-Stuart AL, Beardsall K. Management of hyperglycaemia in the preterm infant. Arch Dis Child Fetal Neonatal Ed. 2010;95(2):F126–31.
  19. National Healthcare Safety Network DoHQP, Centers for Disease Control and Prevention: CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Available at: (Accessed June 10th, 2013)
  20. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T. Neonatal necrotizing enterocolitis: therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.
  21. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163(7):1723–9.
  22. 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(4):529–34.
  23. International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 2005;123(7):991–9.
  24. Voigt M, Rochow N, Hesse V, Olbertz D, Schneider KT, Jorch G. Short communication about percentile values of body measures of newborn babies. Z Geburtshilfe Neonatol. 2010;214:242–29.
  25. Wynn JL, Wong HR. Pathophysiology and treatment of septic shock in neonates. Clin Perinatol. 2010;37(2):439–79. doi: 10.1016/j.clp.2010.04.002.
  26. Derendorf H, Mollmann H, Barth J, Mollmann C, Tunn S, Krieg M. Pharmacokinetics and oral bioavailability of hydrocortisone. J Clin Pharmacol. 1991;31:473–6.
  27. Parikh NA, Kennedy KA, Lasky RE, McDavid GE, Tyson JE. Pilot randomized trial of hydrocortisone in ventilator-dependent extremely preterm infants: effects on regional brain volumes. J Pediatr. 2013;162(4):685–90.
  28. Fortin-Pellerin E, Petersen C, Lefebvre F, Barrington KJ, Janvier A. Evolving neonatal steroid prescription habits and patient outcomes. Acta Paediatr. 2013;102:799–804.
  29. Natarajan G, Pappas A, Shankaran S, Kendrick DE, Das A, Higgins RD, et al. Outcomes of extremely low birth weight infants with bronchopulmonary dysplasia: impact of the physiologic definition. Early Hum Dev. 2012;88(7):509–15.
  30. Doyle LW, Ehrenkranz RA, Halliday HL. Dexamethasone treatment after the first week of life for bronchopulmonary dysplasia in preterm infants: a systematic review. Neonatology. 2010;98(4):289–96.
  31. Barrington KJ. The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs. BMC Pediatr. 2001;1:132.
  32. Doyle LW, Halliday HL, Ehrenkranz RA, Davis PG, Sinclair JC. Impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk for chronic lung disease. Pediatrics. 2005;115:655–661 33.
  33. Helbock HJ, Insoft RM, Conte FA. Glucocorticoid-responsive hypotension in extremely low birth weight neonates. Pediatrics. 1993;92:715–7.
  34. Parikh NA, Lasky RE, Kennedy KA, Moya FR, Hochhauser L, et al. Postnatal dexamethasone therapy and cerebral tissue volumes in extremely low birth weight infants. Pediatrics. 2007;119:265–72.
  35. Stichtenoth G, Demmert M, Bohnhorst B, Stein A, Ehlers S, Heitmann F, et al. Major contributors to hospital mortality in very-low-birth-weight infants: data of the birth year 2010 cohort of the German Neonatal Network. Klin Padiatr. 2012;224:276–81.
  36. Phillips JP, Montague EQ, Aragon M, Lowe JR, Schrader RM, et al. Prematurity affects cortical maturation in early childhood. Pediatr Neurol. 2011;45:213–9.
  37. Parikh NA, Kennedy KA, Lasky RE, McDavid GE, Tyson JE. Pilot randomized trial of hydrocortisone in ventilator-dependent extremely preterm infants: effects on regional brain volumes. J Pediatr. 2013;162:685–90.
  38. Kersbergen KJ, de Vries LS, van Kooij BJ, Išgum I, Rademaker KJ, van Bel F, et al. Hydrocortisone treatment for bronchopulmonary dysplasia and brain volumes in preterm infants. J Pediatr. 2013 May 2.
  39. Halliday HL, Ehrenkranz RA, Doyle LW. Early (<8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2010;(1):CD001146. Review.
  40. Zecca E, Papacci P, Maggio L, Gallini F, Elia S, et al. Cardiac adverse effects of early dexamethasone treatment in preterm infants: a randomized clinical trial. J Clin Pharmacol. 2001;41(10):1075–81.
  41. Gill AW, Warner G, Bull L Iatrogenic neonatal hypertrophic cardiomyopathy. Pediatr Cardiol. 1996;17:335–9.
  42. Aoyama T, Matsui T, Novikov M, Park J, Hemmings B, Rosenzweig A. Serum and glucocorticoid-responsive kinase-1 regulates cardiomyocyte survival and hypertrophic response. Circulation. 2005;111:1652–9.
  43. Muangmingsuk S, Ingram P, Gupta MP, Arcilla RA, Gupta M. Dexamethasone induced cardiac hypertrophy in newborn rats is accompanied by changes in myosin heavy chain phenotype and gene transcription. Mol Cell Biochem. 2000;209:165–74.
  44. * Röhr SB, Sauer H, Gortner L, Gräber S, Meyer S. Cardiovascular and metabolic side effects associated with hydrocortisone and dexamethasone use in VLBW infants: a single-centre experience. Acta Paediatr 2013;10:e436.

Most read articles by the same author(s)