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

被引：110

作者：

Onland, Wes ^{[1
]}

Cools, Filip ^{[2
]}

Kroon, Andre ^{[3
]}

Rademaker, Karin ^{[4
]}

Merkus, Maruschka P. ^{[5
]}

Dijk, Peter H. ^{[6
]}

van Straaten, Henrica L. ^{[7
]}

Pas, Arjan B. Te ^{[8
]}

Mohns, Thilo ^{[9
]}

Bruneel, Els ^{[10
]}

van Heijst, Arno F. ^{[11
]}

Kramer, Boris W. ^{[12
]}

Debeer, Anne ^{[13
]}

Zonnenberg, Inge ^{[14
]}

Marechal, Yoann ^{[15
]}

Blom, Henry ^{[16
]}

Plaskie, Katleen ^{[17
]}

Offringa, Martin ^{[1
,18
]}

van Kaam, Anton H. ^{[1
,14
]}

Nuytemans, Debbie H. ^{[1
]}

de Loo, Moniek van ^{[1
]}

Kemper, E. Marleen ^{[19
]}

Vereeck, Inez ^{[2
]}

van der Heide-Jalving, Marja ^{[4
]}

de Kort, Ellen ^{[9
]}

Cavartorta, Eric ^{[20
]}

Rassart, Anne ^{[20
]}

Eerdekens, An ^{[13
]}

Stuijvenberg, Margriet ^{[6
]}

Matthijsse, Rene ^{[11
]}

de Boode, Willem ^{[11
]}

Niemarkt, Hendrik ^{[12
]}

van Hattum, Ilse ^{[12
]}

Jebbink, Liesbeth Groot ^{[7
]}

Mulder-de Tollenaer, Susanne M. ^{[7
]}

Tan, Ratna ^{[8
]}

Theyskens, Claire ^{[10
]}

van Weissenbruch, Mirjam ^{[14
]}

Dierckx, Elke ^{[21
]}

Rigo, Vincent ^{[22
]}

Vrijlandt, Elianne ^{[23
]}

van der Tweel, Ingeborg ^{[24
]}

van Baal, Caroline ^{[24
]}

de Wildt, Saskia ^{[25
]}

机构：

[1] Univ Amsterdam, Dept Neonatol, Emma Childrens Hosp, Amsterdam UMC, Amsterdam, Netherlands

[2] Univ Ziekenhuis Brussel, Dept Neonatol, Brussels, Belgium

[3] Erasmus MC, Dept Neonatol, Rotterdam, Netherlands

[4] Univ Med Ctr Utrecht, Dept Neonatol, Utrecht, Netherlands

[5] Univ Amsterdam, Clin Res Unit, Amsterdam UMC, Amsterdam, Netherlands

[6] Univ Groningen, Dept Neonatol, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Groningen, Netherlands

[7] Isala Med Ctr, Dept Neonatol, Zwolle, Netherlands

[8] Leiden Univ, Dept Neonatol, Med Ctr, Leiden, Netherlands

[9] Maxima Med Ctr, Dept Neonatol, Veldhoven, Netherlands

[10] Ziekenhuis Oost Limburg, Dept Neonatol, Genk, Belgium

[11] Radboud Univ Nijmegen, Dept Neonatol, Med Ctr, Amalia Childrens Hosp, Nijmegen, Netherlands

[12] Med Univ Ctr Maastricht, Dept Neonatol, Maastricht, Netherlands

[13] Univ Ziekenhuis Leuven, Dept Neonatol, Leuven, Belgium

[14] Vrije Univ Amsterdam, Dept Neonatol, Emma Childrens Hosp, Amsterdam UMC, Amsterdam, Netherlands

[15] Ctr Hosp Univ Charleroi, Dept Neonatol, Charleroi, Belgium

[16] Univ Ziekenhuis Antwerpen, Dept Neonatol, Antwerp, Belgium

[17] St Augustinus Ziekenhuis, Dept Neonatol, Antwerp, Belgium

[18] Univ Toronto, Div Neonatol & Child Hlth Evaluat Sci, Hosp Sick Children, Res Inst, Toronto, ON, Canada

[19] Univ Amsterdam, Amsterdam UMC, Dept Pharm, Amsterdam, Netherlands

[20] Ctr Hosp Univ Marie Curie, Dept Neonatol, Charleroi, Belgium

[21] St Augustinus Ziekenhuis, Antwerp, Belgium

[22] CHU Liege, CHR Citadelle, Liege, Belgium

[23] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Groningen, Netherlands

[24] Univ Med Ctr Utrecht, Julius Ctr, Dept Biostat & Res Support, Utrecht, Netherlands

[25] Radboud Univ Nijmegen, Med Ctr, Amalia Childrens Hosp, Nijmegen, Netherlands

来源：

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2019年 / 321卷 / 04期

关键词：

POSTNATAL CORTICOSTEROIDS; RISK-FACTORS; MORBIDITY; CHILDREN; PREVENT; TREAT;

D O I：

10.1001/jama.2018.21443

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：354 / 363

页数：10

共 35 条

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