525 - Dexamethasone Utilization and Respiratory Trajectories in Preterm Infants: A 10-Year Multicenter Cohort Study

Publication Number: 3506.525

Katherine B. Daniel, Boston Children's Hospital, Boston, MA, United States; Rachel G. Greenberg, Duke Clinical Research Institute, Durham, NC, United States; Wesley Jackson, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States; Matthew M. Laughon, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Samia Aleem, Duke University School of Medicine, Durham, NC, United States; Veeral Tolia, Pediatrix, Dallas, TX, United States; Bradley A.. Yoder, University of Utah, Salt Lake City, UT, United States; Samuel Gentle, Yale School of Medicine, New Haven, CT, United States

Background: Bronchopulmonary dysplasia (BPD) remains the most common morbidity of extreme prematurity for which few therapies are safe and effective. While dexamethasone facilitates extubation and reduces BPD incidence, it remains uncertain whether variations in dosing strategy influence respiratory outcomes.

Objective: To describe preterm infants' evolving respiratory support in relation to dexamethasone dosing strategies.

Design/Methods: Cohort study of infants born at <=32 weeks' gestation admitted to >300 neonatal intensive care units and discharged between 2013 and 2023 using the Pediatrix Medical Group Clinical Data Warehouse. Dexamethasone weight-based dosing was extracted for courses of at least 5 days' duration given by oral or intravenous route. Respiratory support modality at the beginning and end of each course was summarized, visualized, and compared using McNemar's and Kruskal-Wallis testing with stratification by dexamethasone starting daily dose tertile. Fraction of inspired oxygen (FiO2) requirement at the beginning and end of each course was visualized and compared using Wilcoxon signed-rank testing. Ventilatory support was summarized, visualized across exposure timeline with stratification by dose tertile, and compared using Wilcoxon signed-rank testing.

Results: Data were available for 1508 courses administered to 1216 infants. The median [IQR] gestational age and birth weight were 25w1d [24w1d-26w3d] and 681 [580-810] g, respectively. Median [IQR] starting daily dose in mg/kg/day was 0.15 [0.1-0.22]. Of 1508 courses, 673 (45%) demonstrated de-escalation in respiratory support modality between the first and last days of dexamethasone administration, while 653 (43%) had no change (Figure 1). At all starting daily dose tertiles, there was a significant decrease in respiratory support (McNemar's p < 0.0001) without a significant difference between tertiles (Kruskal-Wallis p = 0.32). Infants were significantly more likely to require >40% FiO2 (49% vs. 27%, p < 0.0001, Figure 2) and mechanical ventilation (69% vs. 34%, p < 0.0001) on the first day of a dexamethasone course as compared to the last day. The percentage of those receiving mechanical ventilation decreased with increasing dexamethasone exposure across all tertiles of starting daily dose (Figure 3).

Conclusion(s): Dexamethasone use is associated with respiratory support improvements at a variety of dosing regimens. This analysis provides foundational information to inform future clinical trials of dexamethasone utilization in preterm infants at risk for BPD.

Figure 1. Comparing respiratory support at the beginning and end of each dexamethasone course.
Sankey diagram describing change in respiratory support modality at the beginning (left) and end (right) of each dexamethasone course for courses during which infants required respiratory support on day of dexamethasone initiation, stratified by tertile of starting daily dexamethasone dose, when available, and initial respiratory support modality. Counts within each dosing tertile of a given respiratory support modality are provided for all subcategories containing at least 10 courses. Of note, 8 courses did not have respiratory support modality data available on day of dexamethasone termination and are not presented in the figure for clarity.

Figure 2. Comparing oxygen support at the beginning and end of each dexamethasone course.
Sankey diagram describing change in fraction of inspired oxygen (FiO2) support at the beginning (left) and end (right) of each dexamethasone course for courses during which infants required FiO2 >21% on day of dexamethasone initiation. Of note, 13 observations did not have FiO2 data available on day of dexamethasone termination and are not presented in the figure for clarity.

Figure 3. Examining the relationship between dexamethasone exposure and ventilatory support status.
Trends in ventilatory support by day of first course dexamethasone exposure and tertile of starting daily dexamethasone dose. The labels above the x-axis represent the total number of infants 1) who were able to be stratified by tertile of starting dexamethasone daily dose, 2) who had respiratory data available for that day of dexamethasone administration, and 3) whose dexamethasone course continued to this day (for days after day 5).