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European Journal of Pediatrics

, Volume 164, Issue 8, pp 472–481 | Cite as

Early neonatal dexamethasone treatment for prevention of bronchopulmonary dysplasia. Randomised trial and meta-analysis evaluating the duration of dexamethasone therapy

  • Eija Anttila
  • Outi Peltoniemi
  • Dominique Haumont
  • Egbert Herting
  • Henk ter Horst
  • Kirsti Heinonen
  • Pentti Kero
  • Päivi Nykänen
  • Sidarto Bambang Oetomo
  • Mikko HallmanEmail author
  • Study Group
Original Paper

Abstract

The aim of the aborted trial was to determine whether the short early dexamethasone (DX) given after the birth improves the early outcome. We also reviewed the evidence (meta-analysis) to determine whether the duration of early DX treatment influences the early outcome, particularly in terms of bronchopulmonary dysplasia (BPD). The participants of the randomised multicentre, double-blinded placebo-controlled trial had a birth weight 500–999 g, gestation ≤31.0 weeks, and respiratory failure by the age of 4 h. The infants received either four doses of DX (0.25 mg/kg at 12 h intervals) or placebo. The meta-analysis was performed to determine the beneficial and adverse effects of early short (<96 h duration) versus early prolonged (>96 h) DX treatment. The trial was discontinued after 109 infants had been enrolled. There was a non-significant improvement in the outcome (survival without BPD, severe intracranial haemorrhage or periventricular leukomalacia; RR 1.27; 95% CI 0.87–1.85). The risks for gastrointestinal perforation and hyperglycaemia tended to increase. A total of 15 trials were included in the meta-analysis: 10 involved prolonged (i.e. >96 h; 1594 infants) and five short interventions (1069 infants). Early prolonged DX decreased the RR for BPD to 0.72 (95% CI 0.61–0.87), whereas early short DX course did not significantly decrease the risk (RR 0.82; 95% CI 0.64–1.05). Gastrointestinal haemorrhages and perforations were significantly increased only in the early prolonged DX group. Conclusion:The dosage and duration of early corticosteroid given to small premature infants influences the risk of the side-effects and the early outcome.

Keywords

Bronchopulmonary dysplasia Dexamethasone Meta-analysis Prematurity Randomised controlled trial 

Abbreviations

BPD

bronchopulmonary dysplasia

CI

confidence interval

DX

dexamethasone

ELBW

extremely low birth weight (<1000 g)

ICH

intracranial haemorrhage

NEC

necrotising enterocolitis

PDA

patent ductus arteriosus

PVL

periventricular leukomalacia

RDS

respiratory distress syndrome

ROP

retinopathy of prematurity

RR

relative risk

Notes

Acknowledgements

The study was supported by grants from the Foundation for Pediatric Research, the Foundation of Alma and K. A. Snellman and the Sigrid Juselius Foundation (Finland). We thank the Department of Pharmacy, Oulu University Hospital, for performing the randomisation, coding and blinding of the study drugs. The attending physicians and participating centres were: D. Haumont (Coordinator; Steering Committee), I. Van Herreweghe, Department of Paediatrics University Hospital of St Pierre, Brussels, Belgium; E. Herting (Coordinator; Steering Committee), K. Harms, U. Gottschalk, Department of Paediatrics, University of Göttingen, Germany; S. B. Oetomo (Coordinator; Steering Committee), H. ter Horst, Department of Paediatrics, University Hospital of Groningen, The Netherlands; K. Heinonen (Coordinator; Steering Committee), P. Nykänen, Department of Paediatrics, Kuopio University Central Hospital, Finland; E. Anttila (Study Coordinator), M. Hallman (Chairman, Planning and Steering Committee), O. Peltoniemi (meta-analysis), M-L. Pokela, T. Saarela, Department of Paediatrics, University of Oulu University Central Hospital, Finland; P. Kero (Coordinator; Steering Committee), Department of Paediatrics, Turku University Central Hospital, Finland; J. Kokkonen (Chairman of the Safety Monitoring Committee), Department of Paediatrics, Oulu University Central Hospital, Finland.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Eija Anttila
    • 1
  • Outi Peltoniemi
    • 1
  • Dominique Haumont
    • 2
  • Egbert Herting
    • 3
  • Henk ter Horst
    • 4
  • Kirsti Heinonen
    • 5
  • Pentti Kero
    • 6
  • Päivi Nykänen
    • 5
  • Sidarto Bambang Oetomo
    • 4
  • Mikko Hallman
    • 1
    Email author
  • Study Group
    • 1
  1. 1.Department of PaediatricsUniversity of OuluOulu Finland
  2. 2.Department of PaediatricsUniversity Hospital of St PierreBrussels Belgium
  3. 3.Department of PaediatricsUniversity of GöttingenGöttingen Germany
  4. 4.Department of PaediatricsUniversity Hospital of GroningenGroningen The Netherlands
  5. 5.Department of PaediatricsUniversity of KuopioKuopio Finland
  6. 6.Department of PaediatricsUniversity of TurkuTurku Finland

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