Making sense of the evidence: designing randomised controlled trials for preterm infants with high-shunt volume patent ductus arteriosus
File(s)
Published online version
Author(s)
Type
Journal Article
Abstract
Management of the patent ductus arteriosus (PDA) in preterm infants remains controversial. Randomised Controlled Trials (RCT) have shown that administering pharmacotherapy, predominantly Ibuprofen, a cyclooxygenase (COX) inhibitor, to infants selected based on the standard echocardiography approach to diagnosis (e.g. duct diameter and shunt direction), does not improve outcomes, and may lead to harm. It remains uncertain, however, whether eliminating or reducing PDA shunt volume using an intervention with higher efficacy and less adverse effects, or in a more selective population, would show different results. It is possible that an imprecise approach to patient selection exposes low-risk infants to the adverse effects of pharmacotherapy without benefit, and high-risk infants to the synergistic adverse effects of pharmacotherapy and persistent high volume pathologic shunt when treatment fails. Whether targeted management of moderate-high volume PDA shunts, informed by comprehensive echocardiography adjudication, in the highest risk infants is beneficial remains untested in an RCT setting. Furthermore, both pharmacological and non-pharmacological interventions warrant further investigation. High quality practice changing research requires a collaborative approach between haemodynamic specialists, epidemiologists, and trial methodologists to i) define the study population based on phenotypic profiles of high-risk infants; ii) enhance the choice and timing of intervention; and iii) identify outcome measures that are relevant and clinically meaningful to families. In this review, we summarise evidence from RCTs and observational studies by discerning discrepancies and explore potential explanations. Such an approach is essential to establish whether active PDA treatment confers any measurable benefit for high-risk preterm infants.
Date Issued
2026-04-27
Date Acceptance
2026-04-07
Citation
Archives of Disease in Childhood: Fetal and Neonatal Edition, 2026, pp.1-12
ISSN
1359-2998
Publisher
BMJ Publishing Group
Start Page
1
End Page
12
Journal / Book Title
Archives of Disease in Childhood: Fetal and Neonatal Edition
Volume
2026
Copyright Statement
© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/
License URL
Identifier
10.1136/archdischild-2025-330266
Publication Status
Published online
Date Publish Online
2026-04-27