111 - Neurosedative Exposures in Hospitalized Infants with Grade 2/3 Bronchopulmonary Dysplasia

Poster Number: 111
Publication Number: 111.2966

Background: Bronchopulmonary dysplasia (BPD) is an independent risk factor for adverse neurodevelopmental outcomes. The mechanisms that underlie this association remain uncertain. Neurosedatives are among the most commonly prescribed medications for infants with grade 2/3 BPD. Exposure to these drugs during infancy may be harmful to the developing brain, however, the cumulative exposure to neurosedatives in infants with grade 2/3 BPD remains poorly characterized.

Objective: To characterize (1) common exposures by drug class and specific medications, (2) temporal trends, and (3) inter-center variation in cumulative daily neurosedative exposures between 36 weeks’ post-menstrual age (PMA) and hospitalization discharge or 1-year corrected age, in a multi-center cohort of hospitalized infants with grade 2/3 BPD.

Design/Methods: A retrospective cohort study was performed of subjects born < 32 weeks’ gestation enrolled in the Pediatric Health Information Systems database with grade 2/3 BPD between January 1, 2012 and December 31, 2022. Temporal trends in exposures were evaluated by drug class using linear regression. Zero-inflated Poisson regression models were used to estimate inter-center variation in the marginal means of cumulative daily neurosedative exposures, adjusting for BPD grade.

Results: Among 10,052 included subjects from 45 centers, a total of 987,858 cumulative daily neurosedative exposures were observed from birth to hospital discharge, with 676,384 (68%) occurring after 36 weeks’ PMA. Total cumulative daily exposures were right-skewed with 91% (621,153/676,384) of exposures observed in 25% of cohort subjects. Opiates and morphine sulfate accounted for the greatest number of cumulative daily exposures for drug class and medication, respectively (Table 1). Total cumulative daily neurosedative exposures for drug class remained stable over the study period, but alpha-agonist exposures (dexmedetomidine and clonidine) increased over time (Figure 2). The estimated marginal means of cumulative daily neurosedative exposures varied significantly by center. (Figure 3)

Conclusion(s): The majority of cumulative daily neurosedative exposures occurred in a sub-population of infants with grade 2/3 BPD. Though opiates and benzodiazepines were the most commonly prescribed drug classes, temporal increases in alpha-agonist exposures convey an urgent need for further studies that evaluate the safety and efficacy of these medications in infants with grade 2/3 BPD.