Avoiding Procedural Closure of the Patent Ductus Arteriosus Following Late Acetaminophen Therapy in Preterm Infants

Introduction: Management of a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants beyond 3 weeks of age continues to be a debate. Clinical equipoise exists between pharmacologic agents versus procedural closure techniques (surgical ligation or transcatheter occlusion). The efficacy of acetaminophen for early closure of hsPDA has been demonstrated, but there remains a paucity of data for late closure. Hypothesis: To test the hypothesis that late administration of acetaminophen for a hsPDA is associated with reduced rates of procedural closure in preterm infants. Methods: We performed a post-hoc analysis of preterm infants (<37 weeks) referred to Boston Children’s Hospital for ongoing management of a hsPDA from January 2019 to January 2023. We compared neonates with a hsPDA exposed and not exposed to acetaminophen at > 3 weeks of age. The primary outcome was avoidance of procedural closure. We assessed for predictors of closure following acetaminophen therapy. Results: We identified 110 preterm infants (median gestational age of 25 weeks at birth) referred for closure of a hsPDA beyond 3 weeks of age (Fig). Late acetaminophen was used in 26 patients (median postnatal age of 31 days). Late acetaminophen was associated with higher rates of non-procedural PDA closure 10/26 (38%), compared to 6/84 (7%) of infants who did not receive late acetaminophen (OR 0.12, CI 0.04 - 0.39, p < 0.01). Presence of flow reversal in the descending aorta was associated with lower likelihood of PDA closure with late acetaminophen (OR 0.09, CI 0.01 - 0.85, p=0.017). Conclusions: This study found that preterm infants with a hsPDA treated with late acetaminophen had a decreased need for procedural closure. Infants who responded were less likely to have flow reversal in the descending aorta, suggesting that consideration of a course of late acetaminophen prior to procedural closure of a hsPDA in preterm neonates should be selective and based on patient-specific risk factors.