*Corresponding Author: Sharon A. McGrathMorrow, MD, MBA, Division of Pulmonary and Sleep Medicine, Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Email: mcgrathmos@chop.edu
Funding/Support : This work was supported by a R03HD109442 (JMC, SAM), the Johns Hopkins Eudowood Foundation (BCA: Fellowship grant).
The funding sources had no involvement in the writing of the manuscript or the decision to submit.
Keywords: bronchopulmonary dysplasia, diuretics, outpatient
Running Head: Outpatient Diuretic use and BPD
Conflicts of Interests : none
Abbreviations: Neonatal Intensive Care Unit (NICU), bronchopulmonary dysplasia (BPD), National Institute of Health (NIH)

Abstract

Introduction: During NICU hospitalization, children born preterm with bronchopulmonary dysplasia (BPD) are frequently prescribed diuretics for treatment of respiratory symptoms. However, less is known about diuretic use and weaning in the outpatient setting. This study sought to characterize clinical features associated with outpatient diuretic use, and timing of diuretic weaning in children with BPD.
Methods : Data was obtained by chart review from registry 1224 participants born < 32 weeks gestation, discharged between 2008-2023 and recruited from outpatient BPD clinics at Johns
Hopkins Children’s Center and the Children’s Hospital of Philadelphia (97.4% diagnosed with BPD). Data was analyzed using Chi-square tests, t-tests, and ANOVA tests.
Results: Children with BPD prescribed diuretics as outpatients (n=737), were more likely to have lower birth weights, earlier gestational age, and severe BPD compared to those not on diuretics (n=487). Of those prescribed diuretics, most children were on a thiazide alone (46.4%) or a thiazide and a potassium sparing agent (44.8%) with a minority on loop diuretics alone (3.3%) or loop diuretic combinations (4.7%). Most children weaned off diuretics by two years of age. Public insurance, earlier gestational age, technology dependence and loop diuretics were associated with slower diuretic weaning.
Conclusion: Outpatient diuretic use is common in BPD with > 75% of children being weaned by two years of age. No difference was found in weaning of home oxygen between children on one versus no diuretic. Thiazides were most commonly prescribed with slower outpatient diuretic weaning associated with public insurance, technology dependence and loop diuretic use.

Introduction

Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung disease during infancy. (1) In infants with evolving or severe BPD, diuretics are often used by healthcare providers to improve gas-exchange abnormalities and mitigate pulmonary symptoms in the inpatient setting. (2-4) The mechanisms of action of acute and chronic diuretic use in preterm infants with BPD are not entirely understood. Diuretic use in preterm infants with lung disease may decrease pulmonary edema by promoting diuresis and reducing intravascular fluid in the lungs. Furosemide has also been reported to have a direct effect on the lungs through pulmonary vasodilation, which may help improve pulmonary congestion.(5, 6)
Diuretics are also associated with side effects, including electrolyte abnormalities, calcium imbalances and nephrocalcinosis.(7, 8) Indeed despite their frequent use in the NICU, others have only reported short-term benefits from diuretics in infants with BPD.(9) Currently, no standardized guidelines for their use in the NICU exist, likely contributing to significant practice variation across institutions.(10) Further, no guidelines exist for outpatient use or weaning of diuretics in children with BPD.
After initial hospital discharge, outpatient diuretic use is commonly continued in children with BPD, without clear guidance for use or weaning. Studies have revealed differences in weaning diuretics practices between subspecialists and lack of established guidelines for weaning diuretics in children with BPD on supplemental oxygen.(11, 12) Several international societies have suggested diuretic weaning strategies in children with BPD, however consensus between the groups was not found. The American Thoracic Society guidelines suggest that infants with BPD discharged on diuretics should have their medication discontinued on an individual basis, since no standard methods currently exist to stop diuretics.(13) The European Respiratory Society with very low certainty evidence gave a conditional recommendation for letting infants on diuretics outgrow their dose.(14) The Thoracic Society of Australia and New Zealand however, offered no recommendations for long term diuretic therapy or weaning in patients with BPD.(15)
In this study we identified associations between patient characteristics in children with BPD and diuretic use and examined the type(s) of diuretics being prescribed after initial hospital discharge. We also examined how the number and type of prescribed diuretic(s) influenced supplemental oxygen weaning in children with BPD in the outpatient setting.
This analysis was performed through retrospective review of data from 1224 preterm children born < 32 weeks gestation. The vast majority of children carried the diagnosis of BPD (97.4%), were born between 2008-2023 and were recruited from outpatient BPD clinics across two tertiary care centers.