Dataset Information

Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.

ABSTRACT:

Background

Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown.

Methods

We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age.

Results

We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups.

Conclusions

In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

SUBMITTER: Watterberg KL

PROVIDER: S-EPMC9107291 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.

Watterberg Kristi L KL Walsh Michele C MC Li Lei L Chawla Sanjay S D'Angio Carl T CT Goldberg Ronald N RN Hintz Susan R SR Laughon Matthew M MM Yoder Bradley A BA Kennedy Kathleen A KA McDavid Georgia E GE Backstrom-Lacy Conra C Das Abhik A Crawford Margaret M MM Keszler Martin M Sokol Gregory M GM Poindexter Brenda B BB Ambalavanan Namasivayam N Hibbs Anna Maria AM Truog William E WE Schmidt Barbara B Wyckoff Myra H MH Khan Amir M AM Garg Meena M Chess Patricia R PR Reynolds Anne M AM Moallem Mohannad M Bell Edward F EF Meyer Lauritz R LR Patel Ravi M RM Van Meurs Krisa P KP Cotten C Michael CM McGowan Elisabeth C EC Hines Abbey C AC Merhar Stephanie S Peralta-Carcelen Myriam M Wilson-Costello Deanne E DE Kilbride Howard W HW DeMauro Sara B SB Heyne Roy J RJ Mosquera Ricardo A RA Natarajan Girija G Purdy Isabell B IB Lowe Jean R JR Maitre Nathalie L NL Harmon Heidi M HM Hogden Laurie A LA Adams-Chapman Ira I Winter Sarah S Malcolm William F WF Higgins Rosemary D RD

The New England journal of medicine 20220301 12

<h4>Background</h4>Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown.<h4>Methods</h4>We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at lea ...[more]

PMID: 35320643

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Project description:ImportanceBronchopulmonary dysplasia (BPD) occurs in approximately 40% of infants born at younger than 30 weeks' gestation and is associated with adverse pulmonary and neurodevelopmental outcomes.ObjectiveTo test whether administration of inhaled nitric oxide to preterm infants requiring positive pressure respiratory support on postnatal days 5 to 14 improves the rate of survival without BPD.Design, setting, and participantsThis intent-to-treat study was a randomized clinical trial performed at 33 US and Canadian neonatal intensive care units. Participants included 451 neonates younger than 30 weeks' gestation with birth weight less than 1250 g receiving mechanical ventilation or positive pressure respiratory support on postnatal days 5 to 14. Enrollment spanned from December 23, 2009, to April 23, 2012, and neurodevelopmental outcome studies were completed by April 4, 2014.InterventionsPlacebo (nitrogen) or inhaled nitric oxide initiated at 20 ppm was decreased to 10 ppm between 72 and 96 hours after starting treatment and then to 5 ppm on day 10 or 11. Infants remained on the 5-ppm dose until completion of therapy (24 days).Main outcomes and measuresThe primary outcome was the rate of survival without BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes included BPD severity, postnatal corticosteroid use, respiratory support, survival, and neurodevelopmental outcomes at 18 to 24 months' PMA.ResultsIn total, 222 infants (52.3% male [n = 116]) received placebo, and 229 infants (50.2% male [n = 115]) received inhaled nitric oxide. Their mean (SD) gestation was 25.6 (1.5) vs 25.6 (1.4) weeks, and their mean (SD) birth weight was 750 (164) vs 724 (160) g. Survival without BPD at 36 weeks' PMA was similar between the placebo and inhaled nitric oxide groups (31.5% [n = 70] vs 34.9% [n = 80]) (odds ratio, 1.17; 95% CI, 0.79-1.73). Rates for severe BPD (26.6% [55 of 207] vs 20.5% [43 of 210]) and postnatal corticosteroid use for BPD (41.0% [91 of 222] vs 41.5% [95 of 229]) and the mean (SD) days of positive pressure respiratory support (55 [40] vs 54 [42]), oxygen therapy (88 [41] vs 91 [59]), and hospitalization (105 [37] vs 108 [54]) were equivalent between the 2 groups. No differences in the incidence of common morbidities were observed. Respiratory outcomes on discharge to home, at 1 year, and at age 18 to 24 months' PMA and neurodevelopmental assessments at 18 to 24 months' PMA did not differ between groups.Conclusions and relevanceInhaled nitric oxide, initiated at 20 ppm on postnatal days 5 to 14 to high-risk preterm infants and continued for 24 days, appears to be safe but did not improve survival without BPD at 36 weeks' PMA or respiratory and neurodevelopmental outcomes at 18 to 24 months' PMA.Trial registrationclinicaltrials.gov Identifier: NCT00931632.

Project description:Early lung inflammation has been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). We aimed to establish the efficacy and safety of systemic hydrocortisone for the prevention of BPD. A systematic review and meta-analysis were undertaken, with a detailed electronic literature search. Trials involving preterm infants were included if they were randomised to receive systemic hydrocortisone or a placebo. The primary outcome was the composite of survival without BPD at 36-week postmenstrual age (PMA). Results are presented as relative risk (RR) or risk difference (RD) with 95% confidence intervals (CIs), along with numbers needed to treat (NNT) or harm (NNH). After filtering, 12 studies using early (within 1 week of birth) and two using late hydrocortisone were identified. Early systemic hydrocortisone significantly increased the chances of survival without BPD (RR 1.13, 95% CI [1.01, 1.26], NNT 18), and survival without moderate-to-severe neurodevelopmental impairment (1.13 [1.02, 1.26], NNT 14). Infants who received hydrocortisone had a higher risk of intestinal perforation (1.69 [1.07, 2.68], NNH 30), primarily with concurrent treatment for patent ductus arteriosus.Conclusion: Early systemic hydrocortisone is a modestly effective therapy for the prevention of BPD in preterm infants, although some safety concerns remain. No conclusions could be drawn for late hydrocortisone due to the paucity of studies. What is Known: • Preterm infants are at high risk of developing bronchopulmonary dysplasia (BPD) and early lung inflammation plays a significant role in its pathogenesis. • Both early and late systemic dexamethasone seems to reduce the incidence of BPD, but its use is associated with serious neurodevelopmental impairment at follow-up. What is New: • Early systemic hydrocortisone significantly improved survival without BPD at 36 weeks and survival without moderate to severe neurodevelopmental impairment on follow up. • Incidence of gastrointestinal perforation associated with concurrent treatment for PDA was significantly higher, although early systemic hydrocortisone reduced the need for treatment of PDAs.

Project description:Bronchopulmonary dysplasia (BPD) is a major complication in prematurely born infants. Pulmonary hypertension (PH) associated with BPD (BPD-PH) is characterized by alveolar diffusion impairment, abnormal vascular remodeling, and rarefication of pulmonary vessels (vascular growth arrest), which lead to increased pulmonary vascular resistance and right heart failure. About 25% of infants with moderate to severe BPD develop BPD-PH that is associated with high morbidity and mortality. The recent evolution of broader PH-targeted pharmacotherapy in adults has opened up new treatment options for infants with BPD-PH. Sildenafil became the mainstay of contemporary BPD-PH therapy. Additional medications, such as endothelin receptor antagonists and prostacyclin analogs/mimetics, are increasingly being investigated in infants with PH. However, pediatric data from prospective or randomized controlled trials are still sparse. We discuss comprehensive diagnostic and therapeutic strategies for BPD-PH and briefly review the relevant differential diagnoses of parenchymal and interstitial developmental lung diseases. In addition, we provide a practical framework for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH from the 2018 World Symposium on Pulmonary Hypertension, and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies. Finally, current gaps of knowledge and future research directions are discussed. IMPACT: PH in BPD substantially increases mortality. Treatment of BPD-PH should be conducted by an interdisciplinary team and follow our new treatment algorithm while still kept tailored to the individual patient. We discuss recent developments in BPD-PH, make recommendations on diagnosis, monitoring and treatment of PH in BPD, and address current gaps of knowledge and potential research directions. We provide a practical framework, including a new treatment algorithm, for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH (2018 WSPH) and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies for BPD-PH.

Dataset Information

Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.

Background

Methods

Results

Conclusions

Publications

Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.

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