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Estimating the effect of diuretics and inhaled corticosteroids for evolving bronchopulmonary dysplasia in preterm

Jonathan L Slaughter1,2,3, Mark A Klebanoff1,2,3,4, Erinn M Hade5

  • 1Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.

Paediatric and Perinatal Epidemiology
|January 9, 2024
PubMed

Insights

Diuretics administered to infants with evolving bronchopulmonary dysplasia (BPD) were associated with reduced mortality and BPD severity. Inhaled corticosteroids (ICS) did not show a significant association with improved outcomes in these preterm infants.

Area of Science:

  • Neonatal Medicine
  • Pediatric Pulmonology
  • Clinical Pharmacology

Background:

  • Off-label use of diuretics and inhaled corticosteroids (ICS) is common for extremely preterm infants with evolving bronchopulmonary dysplasia (BPD).
  • The effectiveness of these treatments in reducing mortality or BPD severity, and the optimal timing for intervention, remain unclear.
  • Evolving BPD presents significant challenges in neonatal intensive care, necessitating evidence-based treatment strategies.

Purpose of the Study:

  • To investigate the independent association of diuretic treatment and ICS administration with mortality and moderate-to-severe BPD at 36-weeks postmenstrual age (PMA).
  • To analyze treatment effects in two distinct cohorts: early evolving BPD (10-27 days postnatal) and progressively evolving BPD (28 days to 36 weeks PMA).
  • To provide evidence to guide clinical decision-making regarding the management of evolving BPD in extremely preterm infants.

Main Methods:

  • Retrospective analysis of extremely preterm neonates (born <28 weeks gestation) admitted to NICU between 2006-2016, using Paediatric Health Information System (PHIS) data.
  • Defined cohorts based on respiratory support at 10 days (early evolving BPD) and 28 days (progressively evolving BPD) postnatal.
  • Utilized marginal structural models to evaluate the effect of new diuretic and ICS exposure on mortality or BPD severity at 36 weeks PMA, adjusting for time-dependent confounding.

Main Results:

  • Diuretic use during early evolving BPD was associated with a reduced risk of mortality or moderate/severe BPD (aRR 0.77; 95% CI 0.65, 0.93).
  • Diuretics during progressively evolving BPD showed a weaker association with reduced mortality or BPD risk (aRR 0.86; 95% CI 0.75, 0.99).
  • Inhaled corticosteroids (ICS) were not significantly associated with reduced mortality or BPD severity in either the early or progressively evolving BPD cohorts.

Conclusions:

  • Diuretic treatment for evolving bronchopulmonary dysplasia in extremely preterm infants is associated with improved outcomes, including reduced mortality and BPD severity.
  • Inhaled corticosteroids (ICS) did not demonstrate a significant benefit in reducing mortality or BPD severity for infants with evolving BPD.
  • Findings suggest that diuretics may be a valuable therapeutic option for managing evolving BPD, while the role of ICS requires further investigation.
Abstract

Keywords:
bronchopulmonary dysplasiadiureticsinhaled corticosteroidneonatepharmacoepidemiologypreterm birth

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