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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

Wes Onland, Filip Cools, André A. Kroon, Karin J. Rademaker, Maruschka P. Merkus, Peter Hendrik Dijk, Henrica L.M. van Straaten, Arjan B te Pas, Thilo Mohns, Els Bruneel, Arno F J Van Heijst, Boris W Kramer, Anne Debeer, Inge A Zonnenberg, Yoann Maréchal, Henry Blom, Katleen Plaskie, Martin Offringa, Anton H. van Kaam
Published 2019 · Medicine
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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
This paper references
10.1203/00006450-200301000-00011
Pulmonary Effects of Triiodothyronine (T3) and Hydrocortisone (HC) Supplementation in Preterm Infants less than 30 Weeks Gestation: Results of the THORN Trial—Thyroid Hormone Replacement in Neonates
Sumita Biswas (2003)
10.1016/S0022-3476(00)90009-X
Circulating neutrophil concentration and respiratory distress in premature infants.
Paula Juliana Ferreira (2000)
10.1542/peds.2004-1275
Structural and Functional Brain Development After Hydrocortisone Treatment for Neonatal Chronic Lung Disease
Gregory A. Lodygensky (2005)
10.1002/14651858.CD001145.pub4
Late (> 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.
Lex W. Doyle (2017)
Short- and long-term effects of neonatal glucocorticoid therapy: is hydrocortisone an alternative to dexamethasone? Acta Paediatr
M van der Heide-Jalving (2003)
10.1542/peds.112.5.e359
Cognitive and academic consequences of bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes.
Elizabeth J. Short (2003)
10.1001/jamapediatrics.2018.2029
Association of Race/Ethnicity With Very Preterm Neonatal Morbidities
Teresa M. Janevic (2018)
10.1186/1471-2431-13-59
A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants
Tanis R. Fenton (2013)
Early lowdose hydrocortisone in very preterm infants: a randomized, placebo-controlled trial
F Bonsante (2007)
10.1542/peds.2007-2258
Effects of Higher Versus Lower Dexamethasone Doses on Pulmonary and Neurodevelopmental Sequelae in Preterm Infants at Risk for Chronic Lung Disease: A Meta-analysis
Wes Onland (2008)
10.1007/s12519-016-0024-z
Respiratory management of extremely low birth weight infants: survey of neonatal specialists
Sumesh Parat (2016)
10.1016/j.jpeds.2004.12.040
Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high-risk infants.
Outi M. Peltoniemi (2005)
10.1542/peds.2004-1159
Prophylaxis of Early Adrenal Insufficiency to Prevent Bronchopulmonary Dysplasia: A Multicenter Trial
Kristi L. Watterberg (2004)
10.1136/adc.86.1.40
Home oxygen status and rehospitalisation and primary care requirements of infants with chronic lung disease
Anne Greenough (2002)
10.1001/jama.2017.18954
Guidelines for Statistical Analysis Plans.
David L. Demets (2017)
10.1002/14651858.CD001146
Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants.
Henry L. Halliday (2001)
Guidelines on neonatal steroids
HL Halliday (2001)
10.1136/adc.2007.119545
Postnatal hydrocortisone treatment for chronic lung disease in the preterm newborn and long-term neurodevelopmental follow-up
Karin J. Rademaker (2007)
10.1177/1740774507087552
Randomized Trials in Vulnerable Populations
Deborah J Cook (2008)
10.1001/archopht.123.7.991
The International Classification of Retinopathy of Prematurity revisited.
Isaac Ben-Sira (2005)
10.1046/j.1365-2524.2001.00279.x
Supporting young adults with hemiplegia: services and costs.
Jennifer K Beecham (2001)
10.1007/s00431-005-1623-1
Population-based study of bronchopulmonary dysplasia in very low birth weight infants in Switzerland
Juliane Hentschel (2005)
10.1016/j.jpeds.2016.12.035
Respiratory Support for Very Low Birth Weight Infants Receiving Dexamethasone
Yamini V Virkud (2017)
10.1016/j.prrv.2017.07.002
Pulmonary sequelae and functional limitations in children and adults with bronchopulmonary dysplasia.
Daniel T. Malleske (2018)
10.1203/01.pdr.0000246200.76860.de
Differences in Behavioral Outcome and Motor Development at School Age After Neonatal Treatment for Chronic Lung Disease with Dexamethasone versus Hydrocortisone
Rosa Karemaker (2006)
10.1136/fn.88.5.F432
Neonatologists are using much less dexamethasone
Eric S. Shinwell (2003)
10.1016/j.jpeds.2006.10.051
Neonatal hydrocortisone treatment: neurodevelopmental outcome and MRI at school age in preterm-born children.
Karin J. Rademaker (2007)
Guidelines for statistical analysis plans. JAMA
DL DeMets (2017)
10.1111/j.1469-8749.2007.00397.x
Intractable spastic cerebral palsy in children: a Dutch cost of illness study.
Marjanke A. Hoving (2007)
10.1186/1471-2431-11-102
Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial
Wes Onland (2011)
and the Practice Committee of the ChildNeurology Society
J Neu (2002)
10.1001/jamapediatrics.2017.5323
Cognitive Outcomes of Children Born Extremely or Very Preterm Since the 1990s and Associated Risk Factors: A Meta-analysis and Meta-regression
E Sabrina Twilhaar (2018)
10.1038/jp.2016.118
Population-based risks of mortality and preterm morbidity by gestational age and birth weight
Rebecca J. Baer (2016)
10.1038/jp.2009.24
Relative adrenal insufficiency in the preterm and term infant
Elaine Frances Fernandez (2009)
10.1002/14651858.CD001145
Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants.
Henry L. Halliday (2000)
10.1001/jama.2015.10244
Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012.
Barbara J. Stoll (2015)
10.1016/j.jpeds.2012.09.054
Pilot randomized trial of hydrocortisone in ventilator-dependent extremely preterm infants: effects on regional brain volumes.
Nehal A. Parikh (2013)
10.2223/jped.1314
[Bronchopulmonary dysplasia].
L Monte (2005)
10.1542/peds.2006-2386
Cost of Hospitalization for Preterm and Low Birth Weight Infants in the United States
Rebecca B. Russell (2007)
10.1056/NEJMe048031
Postnatal corticosteroids for preterm infants--do what we say, not what we do.
Alan H. Jobe (2004)
10.1542/peds.2010-0597
Open-Label Glucocorticoids Modulate Dexamethasone Trial Results in Preterm Infants
Wes Onland (2010)
10.1136/adc.2006.106583
Are postnatal steroids ever justified to treat severe bronchopulmonary dysplasia?
Eric C. Eichenwald (2007)
10.1542/peds.2004-0204
Impact of a Physiologic Definition on Bronchopulmonary Dysplasia Rates
Michele C. Walsh (2004)
10.1542/peds.2006-0359
Changes in the Use of Postnatal Steroids for Bronchopulmonary Dysplasia in 3 Large Neonatal Networks
Michele C. Walsh (2006)
10.1016/j.jpeds.2011.12.038
Risk factors for post-neonatal intensive care unit discharge mortality among extremely low birth weight infants.
Lilia C De Jesus (2012)
超出生体重児に対する早期デキサメサゾン投与の有用性 : National Institute of Child Health and Human Development Neonatal research Network報告 (海外誌掲載論文の和文概要とそれに対するコメント)
Stark Ar (2001)
10.1542/peds.2010-1534
Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia
Kristi L. Watterberg (2010)
Very low birth weight outcomes of the National Institute of Child health and human development neonatal research
JA Lemons (1995)
10.1016/S0021-9924(02)00085-0
Speech and language outcomes of children with bronchopulmonary dysplasia.
Barbara A. Lewis (2002)
10.1542/peds.105.3.542
Early Dexamethasone—Attempting To Prevent Chronic Lung Disease
Robert A. Sinkin (2000)
10.1016/j.healthpol.2008.01.001
A preliminary study into the economic burden of cerebral palsy in China.
Bin Wang (2008)
10.1542/peds.2008-0016
Finding the Optimal Postnatal Dexamethasone Regimen for Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Systematic Review of Placebo-Controlled Trials
Wes Onland (2009)
10.1542/peds.2011-3028
Mortality and Neonatal Morbidity Among Infants 501 to 1500 Grams From 2000 to 2009
Jeffrey D. Horbar (2012)
10.1542/peds.2005-2522
Bronchopulmonary Dysplasia in Very Low Birth Weight Subjects and Lung Function in Late Adolescence
Lex William Doyle (2006)
10.1159/000078175
Lung and Brain Damage in Preterm Newborns
Olaf Dammann (2004)
10.1097/anc.0b013e31829a872c
Necrotizing enterocolitis.
Leslie A. Parker (1995)
10.1542/peds.104.6.1258
Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants.
Kristi L. Watterberg (1999)
10.1542/peds.2006-3158
Growth and Neurodevelopmental Outcomes After Early Low-Dose Hydrocortisone Treatment in Extremely Low Birth Weight Infants
Kristi L. Watterberg (2007)
10.1152/jappl.1997.83.4.1307
Role of neutrophils in lung vascular injury and edema after premature birth in lambs.
David P. Carlton (1997)
10.1093/pch/17.10.573
Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants.
Ann L. Jefferies (2012)
10.1371/journal.pone.0170234
Evidence-Based Neonatal Unit Practices and Determinants of Postnatal Corticosteroid-Use in Preterm Births below 30 Weeks GA in Europe. A Population-Based Cohort Study
Alexandra Nuytten (2017)
10.3389/fped.2017.00006
Gender Differences in Respiratory Morbidity and Mortality of Preterm Neonates
Courtney Townsel (2017)
10.1186/1471-2431-1-1
The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs
Keith Barrington (2001)
10.1038/sj.jp.7210963
Safety, Reliability, and Validity of a Physiologic Definition of Bronchopulmonary Dysplasia
Michele C. Walsh (2003)
10.1212/wnl.58.12.1726
Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
Laura R. Ment (2002)
10.1016/j.ogc.2004.10.005
Fetal and neonatal mortality risks of multiple births.
Greg R. Alexander (2005)
10.1002/14651858.CD001144
Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.
Henry L. Halliday (2000)
10.1503/cmaj.071366
Serious adverse events in academic critical care research
Deborah J Cook (2008)
10.1001/archpedi.161.11.1082
Developmental sequelae in preterm infants having a diagnosis of bronchopulmonary dysplasia: analysis using a severity-based classification system.
Elizabeth J. Short (2007)
10.1203/PDR.0b013e318123f744
Effects of Neonatal Corticosteroid Treatment on Hippocampal Synaptic Function
Chiung-Chun Huang (2007)
10.1016/j.jpeds.2018.01.043
Bronchopulmonary Dysplasia: Executive Summary of a Workshop
Rosemary D. Higgins (2018)
10.1002/14651858.CD001146.pub5
Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.
Lex W. Doyle (2017)
10.3109/14767058.2015.1053862
Chorioamnionitis and neonatal outcome in preterm infants: a clinical overview
Lorenza Pugni (2016)
10.1016/S0022-3476(98)70220-3
Long-term pulmonary sequelae of severe bronchopulmonary dysplasia.
S V Jacob (1998)
10.1002/ppul.20412
Respiratory function at age 8-9 years in extremely low birthweight/very preterm children born in Victoria in 1991-1992.
Lex William Doyle (2006)
10.1186/s13063-018-2505-y
Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (the SToP-BPD study): statistical analysis plan
Wes Onland (2018)
10.1016/j.jpeds.2005.01.047
Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes.
Michele C. Walsh (2005)
10.1136/adc.2005.088823
Preschool healthcare utilisation related to home oxygen status
Anne Greenough (2006)
10.1212/WNL.59.10.1663
Practice parameter: Neuroimaging of the neonate Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society
Laura R. Ment (2002)
Risk factors for post - neonatal intensive care unit dischargemortality among extremely low birth weight infants
LC DeJesus (2012)
10.1016/S0140-6736(16)00202-6
Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial
Olivier Baud (2016)
10.1016/j.ajog.2017.11.554
Mortality and pulmonary outcomes of extremely preterm infants exposed to antenatal corticosteroids
Colm P. Travers (2018)



This paper is referenced by
10.1016/j.siny.2019.03.002
Long-term effects of postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia: Balancing the risks and benefits.
Jeanie L. Y. Cheong (2019)
10.3390/nu11112729
The Impact of Postnatal Systemic Steroids on the Growth of Preterm Infants: A Multicenter Cohort Study
Carlos Zozaya (2019)
10.1101/2020.02.13.20020966
Bias Attributable to Composite Outcome
Fredi Alexander Diaz-Quijano (2020)
10.3310/eme06080
Very low-dose dexamethasone to facilitate extubation of preterm babies at risk of bronchopulmonary dysplasia: the MINIDEX feasibility RCT
Helen Yates (2019)
10.3390/ijms20194815
Decorin Secreted by Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Induces Macrophage Polarization via CD44 to Repair Hyperoxic Lung Injury
Ji Hye Kwon (2019)
10.1055/s-0039-1691802
Update on Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia.
Marco Filippone (2019)
10.1007/s00431-019-03398-5
Efficacy and safety of systemic hydrocortisone for the prevention of bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis
Ian Paul Morris (2019)
10.1055/a-0653-6214
Aktuelles in der Neonatologie
Mario Ruediger (2019)
10.3345/kjp.2019.00178
Bronchopulmonary dysplasia: how can we improve its outcomes?
Tae-Jung Sung (2019)
10.1038/s41372-020-0594-4
Timing of postnatal steroids for bronchopulmonary dysplasia: association with pulmonary and neurodevelopmental outcomes
Heidi M. Harmon (2020)
10.1038/s41572-019-0127-7
Bronchopulmonary dysplasia
Bernard Thébaud (2019)
10.1080/21678707.2020.1769598
Treatment and respiratory support modes for neonates with respiratory distress syndrome
Theodore Dassios (2020)
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