Strengths and Limitations
BPD, death, NDI
Our analysis has several strengths, including being the first analysis, to our knowledge, of heterogeneity of treatment effect in a randomized clinical trial of corticosteroid exposure in extremely preterm infants. Moreover, this analysis assessed heterogeneity of treatment effect for both efficacy (BPD or death) and safety (NDI or death). In clinical practice, baseline risk of BPD or death is commonly used to weigh the benefits and harms of corticosteroid exposure in practice; however, to our knowledge, no individual patient-level data from a clinical trial have been analyzed to study this question. Moreover, as recommended by the PATH statement,A significant limitation of this investigation is that the available patient population had both a high and narrow distribution of baseline risk for grades 2 to 3 BPD or death, constraining our ability to analyze treatment effect heterogeneity compared with a population with a wider distribution of baseline risk. Finally, this post hoc analysis of the NRN Hydrocortisone Trial may not have been adequately powered to identify treatment effect heterogeneity; clinically relevant interactions between infant characteristics and treatment effect not identified in this analysis may exist.