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

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