The management of Patent Ductus Arteriosus (PDA) in extremely premature infants is a highly controversial topic among neonatologists. A recent, large-scale, randomized clinical trial provides robust evidence that may shift clinical practice. The study, involving infants born between 22 and 28 weeks’ gestation, compared active treatment (medication) against a monitoring approach. Expectant PDA Management led to a substantial increase in survival rates without worsening the combined risk of death or bronchopulmonary dysplasia (BPD).
Key Findings from The PDA Randomized Clinical Trial
Researchers randomized 482 infants to either an expectant management group or an active treatment group. The active treatment regimen included standard PDA medications, specifically acetaminophen, ibuprofen, or indomethacin. The primary endpoint for the trial was the composite outcome of death or BPD at 36 weeks’ postmenstrual age. Significantly, the incidence of the primary outcome was nearly identical between the groups. Consequently, 80.9% of the expectant group and 79.6% of the active treatment group experienced the composite outcome (Adjusted Risk Difference, 1.2%; P=.73).
The Case for Expectant PDA Management
However, a critical finding emerged when researchers analyzed the components of the primary outcome separately. Mortality before 36 weeks’ postmenstrual age was more than twice as high in the active treatment group compared to the expectant management group (9.6% vs 4.1%). Therefore, survival was substantially higher with expectant management alone. The trial was stopped early for futility and safety after the interim analysis because of this significant survival difference favoring the expectant group. Moreover, a previous meta-analysis similarly found that active treatment of hemodynamically significant PDA was associated with increased mortality compared with expectant management, reinforcing the current trial’s findings. In fact, infections resulting in death were four times more common in the medication group.
Implications for Clinical Practice
This landmark trial provides the strongest evidence yet against routine early drug treatment for PDA. Expectant management, which involves close monitoring and treating only if symptoms worsen, should be considered the safer initial approach for most extremely preterm infants. Active pharmacologic closure does not improve the rate of BPD or death/BPD overall. Conversely, it appears to increase the risk of death, potentially due to medication side effects or increased infection risk. Consequently, the findings suggest a need for a revision of standard protocols for PDA management worldwide. This approach is particularly relevant in settings like India, where conservative management and the use of drugs like oral paracetamol are already part of existing guidelines.
Frequently Asked Questions
Q1: What was the primary finding of the PDA Randomized Clinical Trial?
The trial found that the composite outcome of death or bronchopulmonary dysplasia (BPD) did not differ significantly between the expectant management group and the active treatment (medication) group. However, a major finding was that survival was substantially higher in the expectant management group.
Q2: Did expectant management increase the risk of BPD?
No, the incidence of death or BPD at 36 weeks’ postmenstrual age was statistically similar: 80.9% in the expectant management group versus 79.6% in the active treatment group.
Q3: Why was the active treatment group associated with higher mortality?
The trial showed that death before 36 weeks’ postmenstrual age was significantly higher in the active treatment group (9.6%) compared to the expectant management group (4.1%). The higher mortality may be due to medication-related adverse effects. The study noted that infections resulting in death were four times more common in the active treatment group.
References
- Laughon MM et al. Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial. JAMA. 2025 Dec 09. doi: 10.1001/jama.2025.23330. PMID: 41364689.
- Expectant Care Improves Survival for Preterm Infants with PDA. RTI International. 2025 Dec 09.
- Active Treatment vs Expectant Management of Patent Ductus Arteriosus in Preterm Infants: A Meta-Analysis. PMC, NIH. 2025 May 27.