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

J Pediatr. 2019 Apr;207:136-142.e5. doi: 10.1016/j.jpeds.2018.10.004. Epub 2018 Nov 8.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Insufficiency / prevention & control*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Glucocorticoids / administration & dosage
  • Humans
  • Hydrocortisone / administration & dosage*
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Infant, Premature, Diseases / prevention & control*
  • Time Factors
  • Treatment Outcome


  • Glucocorticoids
  • Hydrocortisone