Early Paracetamol for PDA Shows No Survival Benefit in Very Preterm Babies: Research Reveals
France: Early preventive treatment of patent ductus arteriosus (PDA) with acetaminophen does not improve survival without serious complications in extremely preterm infants and should not be routinely recommended, a large randomized clinical trial published in JAMA Pediatrics has found.
The study was led by Jean-Christophe Rozé from the Department of Neonatal Medicine at Nantes University Hospital, France, along with an international team of investigators.
Management of PDA in very preterm infants remains controversial. Nonsteroidal anti-inflammatory drugs have traditionally been used to promote ductal closure but are associated with potential adverse effects. Acetaminophen has emerged as a possible alternative, with some early data suggesting it may close the ductus with fewer complications. However, whether preventive use shortly after birth improves meaningful clinical outcomes has remained uncertain.
To address this question, researchers conducted a double-blind, placebo-controlled trial across 43 neonatal intensive care units in 14 European countries. The study enrolled 778 infants born between 23 weeks 0 days and 28 weeks 6 days of gestation between October 2020 and April 2024. Data analysis was completed in 2025.
Infants were randomly assigned to receive either intravenous acetaminophen or a placebo within 12 hours of birth. Dosing was adjusted according to gestational age. Those born at 27 to 28 weeks received a 20 mg/kg loading dose followed by 7.5 mg/kg every six hours for five days. Infants born at 23 to 26 weeks received a higher loading and maintenance dose. The placebo group received isotonic sodium chloride.
The primary endpoint was survival without severe neonatal morbidity at 36 weeks’ postmenstrual age. Secondary outcomes included echocardiographic closure of the ductus arteriosus by day seven.
The following findings were reported:
- Survival without major morbidity at 36 weeks’ postmenstrual age was 66.2% in the acetaminophen group and 63.6% in the placebo group, with no statistically significant difference.
- Prophylactic acetaminophen did not improve the primary outcome of survival without severe morbidity.
- Ductal closure by day seven occurred in 71.2% of infants receiving acetaminophen compared with 52.2% in the placebo group.
- Despite higher rates of ductal closure, no associated long-term clinical benefit was observed.
- Overall, adverse events were similar between groups.
- Cholestasis was more frequent in the acetaminophen group (6.4%) than in the placebo group (2.6%).
- No other significant safety differences were identified.
The investigators concluded that routine prophylactic use of acetaminophen for PDA in extremely preterm infants does not improve survival free of serious morbidity and may increase the risk of liver-related complications. While the drug effectively promotes earlier ductal closure, the absence of clinical benefit underscores the need to prioritize outcomes that meaningfully impact neonatal health.
These findings provide important evidence to guide neonatal practice and suggest that preventive acetaminophen therapy for PDA should not be adopted in very preterm populations.
Reference:
Rozé J, Cambonie G, Flamant C, et al. Prophylactic Treatment of Patent Ductus Arteriosus With Acetaminophen: A Randomized Clinical Trial. JAMA Pediatr. Published online February 16, 2026. doi:10.1001/jamapediatrics.2025.6150
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