Introduction: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in extremely preterm infants and is associated with poor clinical outcomes. Uncertainty exists on whether early pharmacotherapeutic treatment of a clinically symptomatic and echocardiography-confirmed haemodynamically significant PDA in extremely preterm infants improves outcomes. Given the wide variation in the approach to PDA treatment in this gestational age (GA) group, a randomised trial design is essential to address the question. Before embarking on a large RCT in this vulnerable population, it is important to establish the feasibility of such a trial. Methods and analysis: Design: a multi-centre, open-labelled, parallel-designed pilot randomised controlled trial. Participants: preterm infants born <26 weeks of gestation with a PDA diagnosed within 72 hours after birth. Intervention (selective early medical treatment (SMART) strategy): selective early pharmacological treatment of a moderate-severe PDA shunt (identified based on pre-defined clinical signs and routine screening echocardiography) within the first 72 postnatal hours with provision for repeat treatment if moderate-severe shunt persists. Comparison (early conservative management strategy): no treatment of PDA in the first postnatal week. Primary outcomes: (1) proportion of eligible infants recruited during the study period; (2) proportion of randomised infants treated outside of protocol-mandated therapy. Sites and sample size: the study is being conducted in seven neonatal intensive care units across Canada and the USA with a target of 100 randomised infants. Analysis: the primary feasibility outcomes will be expressed as proportions. A pre-planned Bayesian analysis will be conducted for secondary clinical outcomes such as mortality, severe intraventricular haemorrhage, procedural PDA closure and chronic lung disease to aid stakeholders including parent representatives decide on the appropriateness of enrolling this vulnerable population in a larger trial if the feasibility of recruitment in the pilot trial is established. Ethics and dissemination: The study has been approved by the IWK Research Ethics Board (#1027298) and six additional participating sites. On the completion of the study, results will be presented at national and international meetings, published in peer-reviewed journals and incorporated into existing systematic reviews. Trial registration number: NCT05011149 (WHO Trial Registration Data Set in Appendix A). Protocol version: Ver 7.2 (dated July 19, 2023).

Objective An alternative therapy for preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) is needed when cyclooxygenase inhibitors fail or where treatment is contraindicated due to coexisting renal failure, necrotizing enterocolitis, and/or intestinal perforation. No studies have evaluated the efficacy of per rectum (PR) acetaminophen. The study aimed to evaluate the efficacy of PR acetaminophen in modulating the risk of PDA ligation. Study Design A retrospective matched case–control study was conducted to compare neonates born <29 weeks' gestation with evidence of hsDA, in an era when rescue rectal acetaminophen was used (January 2014–March 2018) as a treatment strategy, versus historical controls (July 2006–August 2012). All patients underwent comprehensive echocardiography assessment of ductal shunt volume according to a standardized protocol. Acetaminophen treated neonates were matched according to demographics, gestation, preintervention echocardiography features, and comorbidities. Control patients were selected when an echocardiography was performed at an equivalent postnatal age. Infants with a genetic syndrome, severe congenital malformation, or major forms of congenital heart disease excluding small atrial septal defect or ventricular septal defect, PDA, or patent formale ovale were excluded. The primary outcome was surgical ligation of the PDA. Secondary outcomes included echocardiography indices of hemodynamic significance, the composite of death, or severe BPD (defined by ventilator dependence at 36 weeks postmenstrual age). Descriptive statistics and univariate (t-tests, Fisher's exact test, and Mann–Whitney U test) analyses were used to evaluate clinical and echocardiography characteristics of the groups and compare outcomes. Results Forty infants (20 cases and 20 controls), with similar demographic and echocardiography features, were compared. Cases received 6.8 ± 0.7 days (60 mg/kg/day) of PR acetaminophen. Responders (n = 12, 60%) had echocardiography evidence of reduced ductal diameter (2.2 mm [1.9–2.6] to 1.1 mm [0–1.7], p = 0.002), left ventricular output (363 ± 108–249 ± 61 mL/min/kg; p = 0.002) and left atrium to aortic root ratio (1.7 ± 0.3–1.3 ± 0.2; p = 0.002) following treatment. The rate of PDA ligation was 50% lower (p = 0.02) and composite outcome of death or severe bronchopulmonary dysplasia was reduced (p = 0.04) in the acetaminophen group. Conclusion Rectal acetaminophen was associated with improvement in echocardiography indices of PDA shunt volume, a 50% reduction in PDA ligation rates and a reduction in the composite outcome of death or severe BPD. Pharmacologic and further prospective clinical studies are needed. Key Points

Background/Objectives: Bronchopulmonary dysplasia (BPD) remains a major morbidity among extremely premature infants, with variability in the application of evidence-based interventions between and within neonatal intensive care units (NICUs). We evaluated a multi-component, risk-guided personalized implementation strategy for BPD prevention in a real-world setting. Methods: We conducted a prospective observational study of infants <29 weeks’ gestation at birth admitted to a quaternary NICU. The intervention combined risk stratification and structured longitudinal care planning rounds (LCPRs) that included standardized documentation, multidisciplinary facilitation, and associated continuous quality improvement strategies. Implementation outcomes were assessed using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. Secondary outcomes included care processes, provider-reported measures, and exploratory clinical outcomes. Results: Over six months, 41 infants were included. Risk stratification was consistently applied and all fifteen high-risk infants received LCPR, demonstrating targeted reach. Multidisciplinary participation was broad, with implementation fidelity reflected by consistent screening, structured documentation, and timely care plan execution. Practice standardization was observed, including consistent corticosteroid use (100%), earlier initiation of systemic postnatal steroids (median 16 days), and selective adjunctive therapy use. Providers reported improved teamwork, care coordination, and confidence. Rates of BPD or mortality were comparable between higher-risk infants receiving LCPR and lower-risk infants, despite greater illness severity in the LCPR group. Respiratory severity scores showed a downward trend after implementation, though this did not reach statistical significance (p = 0.07). Strategy use continued beyond the study period indicating early sustainability. Conclusions: A multi-component, risk-guided implementation strategy can be effectively integrated into routine NICU practice, improving care processes while maintaining clinical outcomes in high-risk infants compared with lower-risk infants.

It has come to the publisher's attention that the name of Maura H.F. Resende was inadvertently omitted from the manuscript published in Volume 40, Number 11 (DOI: 10.1055/s-0041-1735214). The author's name has now been added to the article. Article published online: 22 April 2024 © 2024. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA