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Background: Bronchopulmonary dysplasia (BPD) is the most common respiratory morbidity after preterm birth but requires diagnosis at 36 weeks postmenstrual age (PMA). Dexamethasone is often used to treat infants at high-risk of BPD. The ability for earlier prediction of BPD, based on steroid response, could be useful as a surrogate marker for new therapies.
Objective: To construct a model that predicts severe BPD or death at 36 weeks PMA based on clinical response to dexamethasone.
Design/Methods: Retrospective chart review of preterm infants treated with dexamethasone between 2010-2020 at a Level IV NICU with data collected on demographics, age of steroid initiation, mode and level of ventilatory support during treatment, and pCO2 on day 1, 3, and 7 of steroid use. Highest mode of ventilation was assessed as either high frequency oscillatory ventilation, conventional invasive ventilation, or any form of non-invasive ventilatory support; while support level was represented by respiratory severity score (RSS = MAP*FiO2). BPD outcomes were defined according to the 2017 BPD Collaborative definition. The composite of mild, moderate, or severe (type 1) BPD was used as referent group to assess odds against the composite of severe (type 2) BPD or death.
A regularized logistic model was fitted using the following variables: gestational age, sex, age of steroid initiation, baseline (Day 1) and percent change from baseline (Day 7 vs Day 1) in RSS and pCO2, and ventilator mode change from baseline. The resulting predicted probabilities were divided into quartiles to obtain a discrete risk level (level 1 to 4).
Results: 94 infants were treated with dexamethasone prior to 36-week BPD assessment. A 10,000-iteration bootstrap was performed, and a risk score was predicted for infants not included in the resampled data at each iteration. The proportion of those with severe (type 2) BPD or death at each risk level were evaluated (Figure). For comparison, predictions were also made with a baseline model using only demographic data. Increasing risk category was well aligned with rising outcome incidence, increasing from ~20% of infants at level 1 to just over 55% of infants at level 4.
Conclusion(s): The addition of changes in ventilatory parameters with dexamethasone improved BPD prediction compared to baseline demographics alone. Incorporating drug response phenotype into a BPD model may enable more rapid development of future therapeutics.
Presented at the 2021 PAS Virtual Conference
Pediatrics | Pharmacy and Pharmaceutical Sciences
Nitkin, Christopher R.; Feldman, Keith; Cuna, Alain; Oschman, Alexandra; Truog, William E.; Norberg, Michael; Taylor, Jane; and Lewis, Tamorah, "Response to dexamethasone predicts diagnosis of severe (type 2) bronchopulmonary dysplasia or death" (2021). Posters. 199.