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JAMA. 2019 Jan 29;321(4):354-363. doi: 10.1001/jama.2018.21443.

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.

Author information

1
Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
2
Department of Neonatology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
3
Department of Neonatology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
4
Department of Neonatology, University Medical Center Utrecht, Utrecht, the Netherlands.
5
Clinical Research Unit, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
6
Department of Neonatology, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
7
Department of Neonatology, Isala Medical Center, Zwolle, the Netherlands.
8
Department of Neonatology, Leiden University Medical Center, Leiden, the Netherlands.
9
Department of Neonatology, Maxima Medical Center, Veldhoven, the Netherlands.
10
Department of Neonatology, Ziekenhuis Oost-Limburg, Genk, Belgium.
11
Department of Neonatology, Radboud University Medical Center-Amalia Children's Hospital, Nijmegen, the Netherlands.
12
Department of Neonatology, Medical University Center Maastricht, Maastricht, the Netherlands.
13
Department of Neonatology, Universitair Ziekenhuis Leuven, Leuven, Belgium.
14
Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, Vrije Universteit Amsterdam, Amsterdam, the Netherlands.
15
Department of Neonatology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium.
16
Department of Neonatology, Universitair Ziekenhuis Antwerpen, Antwerp, Belgium.
17
Department of Neonatology, St Augustinus Ziekenhuis, Antwerp, Belgium.
18
Division of Neonatology and Child Health Evaluative Sciences, the Hospital for Sick Children Research Institute, University of Toronto, Canada.

Abstract

Importance:

Dexamethasone initiated after the first week of life reduces the rate of death or bronchopulmonary dysplasia (BPD) but may cause long-term adverse effects in very preterm infants. Hydrocortisone is increasingly used as an alternative, but evidence supporting its efficacy and safety is lacking.

Objective:

To assess the effect of hydrocortisone initiated between 7 and 14 days after birth on death or BPD in very preterm infants.

Design, Setting, and Participants:

Double-blind, placebo-controlled randomized trial conducted in 19 neonatal intensive care units in the Netherlands and Belgium from November 15, 2011, to December 23, 2016, among preterm infants with a gestational age of less than 30 weeks and/or birth weight of less than 1250 g who were ventilator dependent between 7 and 14 days of life, with follow-up to hospital discharge ending December 12, 2017.

Interventions:

Infants were randomly assigned to receive a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) (n = 182) or placebo (n = 190).

Main Outcomes and Measures:

The primary outcome was a composite of death or BPD assessed at 36 weeks' postmenstrual age. Twenty-nine secondary outcomes were analyzed up to hospital discharge, including death and BPD at 36 weeks' postmenstrual age.

Results:

Among 372 patients randomized (mean gestational age, 26 weeks; 55% male), 371 completed the trial; parents withdrew consent for 1 child treated with hydrocortisone. Death or BPD occurred in 128 of 181 infants (70.7%) randomized to hydrocortisone and in 140 of 190 infants (73.7%) randomized to placebo (adjusted risk difference, -3.6% [95% CI, -12.7% to 5.4%]; adjusted odds ratio, 0.87 [95% CI, 0.54-1.38]; P = .54). Of 29 secondary outcomes, 8 showed significant differences, including death at 36 weeks' postmenstrual age (15.5% with hydrocortisone vs 23.7% with placebo; risk difference, -8.2% [95% CI, -16.2% to -0.1%]; odds ratio, 0.59 [95% CI, 0.35-0.995]; P = .048). Twenty-one outcomes showed nonsignificant differences, including BPD (55.2% with hydrocortisone vs 50.0% with placebo; risk difference, 5.2% [95% CI, -4.9% to 15.2%]; odds ratio, 1.24 [95% CI, 0.82-1.86]; P = .31). Hyperglycemia requiring insulin therapy was the only adverse effect reported more often in the hydrocortisone group (18.2%) than in the placebo group (7.9%).

Conclusions and Relevance:

Among mechanically ventilated very preterm infants, administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings do not support the use of hydrocortisone for this indication.

Trial Registration:

Netherlands National Trial Register Identifier: NTR2768.

PMID:
30694322
DOI:
10.1001/jama.2018.21443
[Indexed for MEDLINE]

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