Corticosteroid response predicts bronchopulmonary dysplasia status at 36 weeks in preterm infants treated with dexamethasone: A pilot study. Issue 7 (16th May 2022)

• Record Type: Journal Article
• Authors: Feldman, Keith; Nitkin, Christopher R.; Cuna, Alain; Oschman, Alexandra; Truog, William E.; Norberg, Michael; Nyp, Michael; Taylor, Jane B.; Lewis, Tamorah
• Is Part Of: Pediatric pulmonology. Volume 57:Issue 7(2022)
• Page Start: 1760
• Page End: 1769
• Publication Date: 2022-05-16
• Subjects: bronchopulmonary dysplasia (BPD) -- evidence‐based medicine and outcomes -- neonatal pulmonary medicine -- pharmacology; Pediatric respiratory diseases -- Periodicals; Pediatrics -- Periodicals; 618.922
• DOI: 10.1002/ppul.25928
• Languages: English
• ISSNs: 8755-6863

Abstract

Abstract: Importance: A major barrier to therapeutic development in neonates is a lack of standardized drug response measures that can be used as clinical trial endpoints. The ability to quantify treatment response in a way that aligns with relevant downstream outcomes may be useful as a surrogate marker for new therapies, such as those for bronchopulmonary dysplasia (BPD). Objective: To construct a measure of clinical response to dexamethasone that was well aligned with the incidence of severe BPD or death at 36 weeks' postmenstrual age. Design: Retrospective cohort study. Setting: Level IV Neonatal Intensive Care Unit. Participants: Infants treated with dexamethasone for developing BPD between 2010 and 2020. Main Outcome(s) and Measure(s): Two models were built based on demographics, changes in ventilatory support, and partial pressure of carbon dioxide ( p CO2 ) after dexamethasone administration. An ordinal logistic regression and regularized binary logistic model for the composite outcome were used to associate response level to BPD outcomes defined by both the 2017 BPD Collaborative and 2018 Neonatal Research Network definitions. Results: Ninety‐five infants were treated with dexamethasone before 36 weeks. Compared to the baseline support and demographic data at the time of treatment, changes in ventilatory support improved ordinal model sensitivity and specificity. For the binary classification, BPD incidence was well aligned with risk levels, increasing from 16% to 59%. Conclusions and Relevance: Incorporation of response variables as measured by changes in ventilatory parameters and p CO2 following dexamethasone administration were associated with downstream outcomes. Incorporating drug response phenotype into a BPD model may enable more rapid development of future therapeutics.