The prospect of preventing patent ductus arteriosus complications in extremely preterm infants without the gastrointestinal and renal risks associated with traditional NSAIDs has driven intensive research into acetaminophen as a safer alternative. This multinational trial tested whether early acetaminophen administration could meaningfully improve survival outcomes for the most vulnerable newborns.
The randomized controlled trial enrolled 1,407 infants born between 23-28 weeks gestation across 43 European NICUs, administering weight-adjusted acetaminophen doses within 12 hours of birth for five days. The primary endpoint measured survival without severe neonatal morbidities at 36 weeks postmenstrual age, while secondary outcomes tracked ductus arteriosus closure rates.
While acetaminophen demonstrated superior efficacy in closing the patent ductus arteriosus compared to placebo, this mechanical success failed to translate into improved clinical outcomes. The intervention showed no significant benefit for the composite primary endpoint of survival without major morbidities, suggesting that simply achieving ductus closure may not address the complex pathophysiology underlying preterm infant complications.
This finding challenges the assumption that pharmacological ductus closure necessarily improves long-term outcomes in extremely preterm populations. The disconnect between anatomical correction and clinical benefit reflects broader questions about optimal timing and patient selection for ductus arteriosus interventions. The results support a more nuanced approach to preterm cardiac management, where the decision to treat should consider individual risk profiles rather than universal prophylaxis protocols, even with potentially safer medications.