Long-Term Outcomes of Expectant Management Versus Early Ibuprofen for Patent Ductus Arteriosus: 24-Month Follow-Up of the BeNeDuctus Trial.

OBJECTIVE: To assess survival and neurodevelopmental outcome at 24 months' corrected age (CA) for participants in the BeNeDuctus trial, comparing expectant management with early ibuprofen treatment in extremely preterm infants. STUDY DESIGN: In this international, multicenter trial, extremely preterm infants (<28 weeks' gestation) with echocardiographically confirmed PDA between 24-72 hours postnatal age were randomly assigned to expectant management or early ibuprofen treatment. Follow-up was scheduled at 24 months' CA. The primary endpoint of this follow-up study was survival without neurodevelopmental impairment (Bayley Scales of Infant and Toddler Development III score of ≥85 on cognitive and motor domain). Additional outcomes included were biometry, abnormal neurologic examination, and vision or hearing impairment. RESULTS: Follow-up data were available for 234 of 273 patients (85.7%); 117 patients in each study arm. Assessment of the primary endpoint was available for 200/234 patients (85.5%). Survival without neurodevelopmental impairment did not differ between groups, with 51/104 (49%) in the expectant management group and 47/96 (49%) in the early ibuprofen treatment group (relative risk (RR) 1.00; 95% confidence interval 0.76-1.33). No significant differences were observed in the additional follow-up outcomes. CONCLUSIONS: No difference was observed in survival without neurodevelopmental impairment at 24 months' CA between the expectant management and early ibuprofen treatment group in the BeNeDuctus study sample. These results suggest no advantage of routine early ibuprofen treatment for survival and neurodevelopmental outcome.