2019
Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation
Publication
Publication
A Randomized Clinical Trial
J A M A: The Journal of the American Medical Association , Volume 321 - Issue 4 p. 354- 363
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.
Additional Metadata | |
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doi.org/10.1001/jama.2018.21443, hdl.handle.net/1765/115001 | |
J A M A: The Journal of the American Medical Association | |
Organisation | Erasmus MC: University Medical Center Rotterdam |
Onland, W., Cools, F., Kroon, A., Rademaker, K., Merkus, M. P., Dijk, P., … Wildt, S. (2019). Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation. J A M A: The Journal of the American Medical Association, 321(4), 354–363. doi:10.1001/jama.2018.21443 |