Highlights
The Baby-OSCAR trial investigated whether early selective treatment of a large patent ductus arteriosus (PDA) with ibuprofen improves clinical outcomes in extremely preterm infants.
Primary findings indicated no statistically significant difference in the composite outcome of death or moderate-to-severe bronchopulmonary dysplasia (BPD) at 36 weeks’ post-menstrual age between the ibuprofen and placebo groups.
Long-term follow-up at 24 months of corrected age revealed no significant improvements in survival without neurodevelopmental impairment or respiratory morbidity.
The study highlights the complexity of PDA management, suggesting that early pharmacological closure of a large PDA may not translate into superior clinical benefits for this vulnerable population.
Background: The Persistent Dilemma of the Patent Ductus Arteriosus
In the transition from intrauterine to extrauterine life, the ductus arteriosus—a vital fetal vascular shunt—typically closes within the first few days of birth. However, in extremely preterm infants born before 28 weeks of gestation, this closure often fails, resulting in a patent ductus arteriosus (PDA). When the PDA is large (defined as a diameter of 1.5 mm or greater), it creates a significant left-to-right shunt, leading to pulmonary over-circulation and systemic steal. This hemodynamic state is epidemiologically associated with increased risks of mortality and morbidities, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, and necrotizing enterocolitis.
For decades, neonatologists have debated the optimal management of PDA. While cyclooxygenase inhibitors like ibuprofen are effective at inducing ductal closure, the clinical community has been divided between prophylactic treatment, early selective treatment based on echocardiographic markers, and conservative management. The core question remains: does pharmacological closure of the PDA actually improve long-term health and developmental outcomes, or is the PDA merely a marker of overall prematurity? The Baby-OSCAR (Outcome after Selective early treatment for Closure of patent ductus ARteriosus) trial was designed to provide high-quality evidence to address this clinical uncertainty.
Study Design and Methodology
Baby-OSCAR was a multicenter, randomized, double-blind, placebo-controlled parallel-group trial conducted across several neonatal units. The trial focused on extremely preterm infants born between 23 weeks 0 days and 28 weeks 6 days of gestation.
Inclusion and Intervention
Infants were eligible if they were less than 72 hours old and had a large PDA (at least 1.5 mm in diameter) confirmed by echocardiography. Participants were randomized to receive either a standard course of intravenous ibuprofen (10 mg/kg initial dose, followed by two doses of 5 mg/kg at 24-hour intervals) or a matching placebo. Randomization was stratified by gestational age and center.
Endpoints
The primary outcome was a composite of death or moderate or severe BPD at 36 weeks of post-menstrual age (PMA). Secondary short-term outcomes included various complications of prematurity, rate of PDA closure, and side effects of treatment. The study also placed significant emphasis on long-term outcomes, specifically survival without moderate or severe neurodevelopmental impairment (NDI) at 24 months of corrected age, and survival without respiratory morbidity. A comprehensive health economic evaluation was also integrated into the trial design.
Key Findings: Primary and Secondary Outcomes
A total of 653 infants were randomized: 326 to the ibuprofen group and 327 to the placebo group. The results provided a sobering look at the efficacy of early selective intervention.
Primary Outcome Results
The composite primary outcome of death or moderate-to-severe BPD at 36 weeks PMA occurred in 69.2% (220/318) of the ibuprofen group compared to 63.5% (202/318) of the placebo group. The adjusted risk ratio (aRR) was 1.09 (95% CI 0.98 to 1.20; p = 0.10). This indicates that early treatment with ibuprofen did not provide a statistically significant benefit in reducing these major neonatal morbidities.
Mortality and Safety
By 36 weeks of gestation, 13.6% of the ibuprofen group had died, compared to 10.3% in the placebo group (aRR 1.32, 95% CI 0.92 to 1.90). While the point estimate favored the placebo group regarding survival, the difference did not reach statistical significance. Two serious adverse events were recorded that were deemed possibly related to ibuprofen treatment, underscoring the potential risks associated with pharmacological ductal closure.
Long-Term Neurodevelopmental and Respiratory Outcomes
One of the most critical aspects of the Baby-OSCAR trial was the follow-up at 24 months of corrected age. Data were available for 263 children in the ibuprofen group and 274 in the placebo group.
Neurodevelopment
The trial found no evidence that ibuprofen treatment improved neurodevelopmental prospects. Survival without moderate-to-severe NI was 53.0% in the ibuprofen group and 51.9% in the placebo group (aRR 1.01, 95% CI 0.86 to 1.18; p = 0.901). This suggests that early ductal closure does not confer a protective effect on the developing brain in this population.
Respiratory Morbidity
Similarly, survival without respiratory morbidity was comparable between the two groups: 31.4% for ibuprofen versus 33.6% for placebo (aRR 0.92, 95% CI 0.70 to 1.20; p = 0.536). The median duration of oxygen supplementation was nearly identical, with 76.0 days in the ibuprofen group and 78.0 days in the placebo group.
Expert Commentary and Limitations
The results of Baby-OSCAR contribute to a growing body of evidence suggesting that the presence of a PDA, even a large one, may not be as harmful as previously thought, or that our current pharmacological tools for closure do not change the underlying disease trajectory. However, several nuances must be considered when interpreting these findings.
The Challenge of Open-Label Rescue
A significant limitation of the trial was the use of open-label therapy. Approximately 29.8% of the infants in the placebo group eventually received open-label treatment for PDA. This crossover may have diluted the potential differences between the two study arms, as many infants in the control group ultimately had their PDA pharmacologically treated later in the clinical course.
Timing of Intervention
The median time to the first dose of treatment was 61 hours. While this falls within the “early” window (less than 72 hours), it is notably later than the timing used in some other prophylactic or early treatment trials. Some experts argue that the window for truly effective intervention might be even narrower, though the Baby-OSCAR data suggests that at 61 hours, the benefit is not apparent.
Clinical Heterogeneity
The trial results emphasize that a large PDA on echocardiography does not always translate to clinical instability that requires intervention. The lack of benefit in the ibuprofen group suggests that many of these PDAs might have closed spontaneously or remained hemodynamically insignificant without treatment.
Conclusion and Future Directions
The Baby-OSCAR trial provides robust evidence that early selective treatment of a large PDA with ibuprofen in extremely preterm infants does not improve survival or reduce the incidence of BPD and neurodevelopmental impairment. These findings support a more conservative approach to PDA management in the first 72 hours of life, even when echocardiographic criteria suggest a large shunt.
Future research should focus on identifying a subset of infants who might still benefit from intervention—perhaps those who remain clinically symptomatic and fail to close their PDA beyond the first week of life. Additionally, an individual patient data meta-analysis of existing trials could help refine treatment thresholds. For now, the Baby-OSCAR trial marks a significant step toward reducing unnecessary pharmacological interventions in the neonatal intensive care unit.
Funding and Clinical Trial Registration
This research was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (Award Number 11/92/15). The trial is registered under the Baby-OSCAR Collaborative Group.
References
Gupta S, Subhedar NV, Bell JL, et al. Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial (Baby-OSCAR trial). Health Technol Assess. 2026 Feb;30(11):1-17. doi: 10.3310/GJSG2422. PMID: 41661090.
