TY - JOUR
T1 - Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation
T2 - A Randomized Clinical Trial
AU - Onland, Wes
AU - Cools, Filip
AU - Kroon, Andre
AU - Rademaker, Karin
AU - Merkus, Maruschka P.
AU - Dijk, Peter H.
AU - van Straaten, Henrica L.
AU - Pas, Arjan B. Te
AU - Mohns, Thilo
AU - Bruneel, Els
AU - van Heijst, Arno F.
AU - Kramer, Boris W.
AU - Debeer, Anne
AU - Zonnenberg, Inge
AU - Marechal, Yoann
AU - Blom, Henry
AU - Plaskie, Katleen
AU - Offringa, Martin
AU - van Kaam, Anton H.
AU - Nuytemans, Debbie H.
AU - de Loo, Moniek van
AU - Kemper, E. Marleen
AU - Vereeck, Inez
AU - van der Heide-Jalving, Marja
AU - de Kort, Ellen
AU - Cavartorta, Eric
AU - Rassart, Anne
AU - Eerdekens, An
AU - Stuijvenberg, Margriet
AU - Matthijsse, Rene
AU - de Boode, Willem
AU - Niemarkt, Hendrik
AU - van Hattum, Ilse
AU - Jebbink, Liesbeth Groot
AU - Mulder-de Tollenaer, Susanne M.
AU - Tan, Ratna
AU - Theyskens, Claire
AU - van Weissenbruch, Mirjam
AU - Dierckx, Elke
AU - Rigo, Vincent
AU - Vrijlandt, Elianne
AU - van der Tweel, Ingeborg
AU - van Baal, Caroline
AU - de Wildt, Saskia
AU - SToP-BPD Study Group
AU - Data Safety Monitoring Comm
N1 - Funding Information:
Funding/Support: This trial was funded by a
Publisher Copyright:
© 2019 American Medical Association. All Rights Reserved.
PY - 2019/1/29
Y1 - 2019/1/29
N2 - 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.
AB - 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.
KW - POSTNATAL CORTICOSTEROIDS
KW - RISK-FACTORS
KW - MORBIDITY
KW - CHILDREN
KW - PREVENT
KW - TREAT
U2 - 10.1001/jama.2018.21443
DO - 10.1001/jama.2018.21443
M3 - Article
C2 - 30694322
SN - 0098-7484
VL - 321
SP - 354
EP - 363
JO - JAMA-Journal of the American Medical Association
JF - JAMA-Journal of the American Medical Association
IS - 4
ER -