Effect of Prophylaxis for Early Adrenal Insufficiency Using Low-Dose Hydrocortisone in Very Preterm Infants: An Individual Patient Data Meta-Analysis - 25/01/19

Doi : 10.1016/j.jpeds.2018.10.004

Michele L. Shaffer, PhD ¹, Olivier Baud, MD, PhD ^2,^3,^4,^* , Thierry Lacaze-Masmonteil, MD, PhD ^5,⁶, Outi M. Peltoniemi, MD, PhD ^7,⁸, Francesco Bonsante, MD ⁹, Kristi L. Watterberg, MD ¹⁰
¹ Department of Statistics, University of Washington, Seattle, WA
² Division of Neonatology and Pediatric Intensive Care, Department of Pediatrics, University Hospitals Geneva, Geneva, Switzerland
³ University of Geneva, Switzerland
⁴ University Paris Diderot, Paris, France
⁵ Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
⁶ Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada
⁷ PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Finland
⁸ Department of Pediatrics and Adolescence, Oulu University Hospital, Finland
⁹ Réanimation Néonatale et Pédiatrique, Néonatologie, Centre d'Etudes Périnatales de l'Océan Indien (CEPOI, EA 7388), Centre Hospitalier Universitaire de la Réunion, Site Sud – Saint Pierre, France
¹⁰ Division of Neonatology, Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, NM

^*Reprint requests: Olivier Baud, MD, PhD, Division of Neonatology, Department of Pediatrics, University Hospitals, Rue Willy-Donzé 6, 1205 Genève, Geneva, Switzerland.Division of NeonatologyDepartment of PediatricsUniversity HospitalsRue Willy-Donzé 6, 1205 GenèveGenevaSwitzerland

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 25 January 2019

Abstract

Objective

To assess the effect of prophylaxis for early adrenal insufficiency using low-dose hydrocortisone on survival without bronchopulmonary dysplasia (BPD) in very preterm infants using an individual patient data meta-analysis.

Study design

All existing randomized controlled trials testing the efficacy of the prophylaxis of early adrenal insufficiency using low-dose hydrocortisone on survival without BPD were considered for inclusion when data were available. The primary outcome was the binary variable survival without BPD at 36 weeks of postmenstrual age.

Results

Among 5 eligible studies, 4 randomized controlled trials had individual patient data available (96% of participants identified; n = 982). Early low-dose hydrocortisone treatment for 10-15 days was associated with a significant increase in survival without BPD (OR, 1.45; 95% CI, 1.11-1.90; P = .007; I² = 0%), as well as with decreases in medical treatment for patent ductus arteriosus (OR, 0.72; 95% CI, 0.56-0.93; P = .01; I² = 0%) and death before discharge (OR, 0.70; 95% CI, 0.51-0.97; P = .03; I² = 0%). The therapy was associated with an increased risk of spontaneous gastrointestinal perforation (OR, 2.50; 95% CI, 1.33-4.69; P = .004; I² = 31.9%) when hydrocortisone was given in association with indomethacin exposure. The incidence of late-onset sepsis was increased in infants exposed to hydrocortisone (OR, 1.34; 95% CI, 1.02-1.75; P = .04; I² = 0%), but no adverse effects were reported for either death or 2-year neurodevelopmental outcomes as assessed in an aggregate meta-analysis.

Conclusions

This individual patient data meta-analysis showed that early low-dose hydrocortisone therapy is beneficial for survival without BPD in very preterm infants.

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Abbreviations : BPD, NDI, PDA, PMA, RCT

Plan

Methods

Individual Patient Data Acquisition, Data Processing, and Quality Assessment

Outcomes and Subgroups of Interest

Planned Subgroup Analyses

Long-Term Outcomes

Discussion

Supported by a research grant from the French Ministry of Health and funded by the Département de la Recherche Clinique et du Développement, Assistance Publique-Hôpitaux de Paris (AOM 06 025 and AOM 11 129). The sponsor had no role in the data analysis and reporting. The authors declare no conflicts of interest.