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

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; I 2 = 0%), as well as with decreases in medical treatment for patent ductus arteriosus (OR, 0.72; 95% CI, 0.56-0.93; P = .01; I 2 = 0%) and death before discharge (OR, 0.70; 95% CI, 0.51-0.97; P = .03; I 2 = 0%). The therapy was associated with an increased risk of spontaneous gastrointestinal perforation (OR, 2.50; 95% CI, 1.33-4.69; P = .004; I 2 = 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; I 2 = 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.

Phenotypes of Bronchopulmonary Dysplasia

“…In addition, infants presenting with symptoms and signs of hypotension are sometimes treated with a stress dose of steroids. Thus, an individual patient data meta-analysis, including five eligible studies in extremely preterm infants, evaluating the efficacy of using early low-dose hydrocortisone as prophylaxis of adrenal insufficiency demonstrated that the therapy is beneficial for survival without BPD [100]. The most updated results for the use of hydrocortisone came from the PREMILOC trial [101].…”

Postnatal Corticosteroids Policy for Very Preterm Infants and Bronchopulmonary Dysplasia

“…Dexamethasone is not recommended as routine treatment and should be considered only for infants who are mechanically ventilated after 2 weeks of life [6][7][8]. Recommendations about PNC may change in the future as prophylactic low-dose hydrocortisone has recently been shown to improve survival without BPD [9] with no statistically significant difference in neurodevelopment at 2 years of age [10,11].…”

Are neonatal clinical practice guidelines truly evidence‐based? A case for incorporating family values and preferences

“…Adding to this complexity is the differential impact of these interventions on neonatal outcomes. For example, a recent individual patient data meta‐analysis has shown that use of prophylactic indomethacin to prevent IVH will preclude the use of prophylactic hydrocortisone to improve survival without CLD as their concomitant use increases the risk of spontaneous intestinal perforation (OR 2.50; 95% CI, 1.33 to 4.69) . This study highlights how the use of some interventions could improve some clinical outcomes while potentially worsening others.…”