Systemic corticosteroids for the prevention of bronchopulmonary dysplasia, a network meta-analysis

• Published in: Cochrane database of systematic reviews 2023-08, Vol.8, p.CD013730
• Main Authors: Hay, Susanne, Ovelman, Colleen, Zupancic, John Af, Doyle, Lex W, Onland, Wes, Konstantinidis, Menelaos, Shah, Prakeshkumar S, Soll, Roger
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Hormones - adverse effects; Bronchopulmonary Dysplasia - prevention & control; Cerebral Palsy; Dexamethasone - adverse effects; Humans; Hydrocortisone - therapeutic use; Infant; Infant, Newborn; Network Meta-Analysis
• ISSN: 1469-493X; 1469-493X
• DOI: 10.1002/14651858.CD013730.pub2

Despite considerable improvement in outcomes for preterm infants, rates of bronchopulmonary dysplasia (BPD) remain high, affecting an estimated 33% of very low birthweight infants, with corresponding long-term respiratory and neurosensory issues. Systemic corticosteroids can address the inflammation underlying BPD, but the optimal regimen for prevention of this disease, balancing of the benefits with the potentially meaningful risks of systemic corticosteroids, continues to be a medical quandary. Numerous studies have shown that systemic corticosteroids, particularly dexamethasone and hydrocortisone, effectively treat or prevent BPD. However, concerning short and long-term side effects have been reported and the optimal approach to corticosteroid treatment remains unclear. To determine whether differences in efficacy and safety exist between high-dose dexamethasone, moderate-dose dexamethasone, low-dose dexamethasone, hydrocortisone, and placebo in the prevention of BPD, death, the composite outcome of death or BPD, and other relevant morbidities, in preterm infants through a network meta-analysis, generating both pairwise comparisons between all treatments and rankings of the treatments. We searched the Cochrane Library for all systematic reviews of systemic corticosteroids for the prevention of BPD and searched for completed and ongoing studies in the following databases in January 2023: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and clinical trial databases. We included randomized controlled trials (RCTs) in preterm infants (< 37 weeks' gestation) at risk for BPD that evaluated systemic corticosteroids (high-dose [≥ 4 mg/kg cumulative dose] dexamethasone, moderate-dose [≥ 2 to < 4 mg/kg] dexamethasone, low-dose [< 2 mg/kg] dexamethasone, or hydrocortisone) versus control or another systemic corticosteroid. Our main information sources were the systematic reviews, with reference to the original manuscript only for data not included in these reviews. Teams of two paired review authors independently performed data extraction, with disagreements resolved by discussion. Data were entered into Review Manager 5 and exported to R software for network meta-analysis (NMA). NMA was performed using a frequentist model with random-effects. Two separate networks were constructed, one for early (< seven days) initiation of treatment and one for late (≥ seven days) treatment initiation, to reflect the different patient populations evaluated. We as