Patent ductus arteriosus treatment in very preterm infants: a European population-based cohort study (EPICE) on variation and outcomes

Background: Spontaneous closure of patent ductus arteriosus (PDA) occurs frequently in very preterm infants and despite the lack of evidence for treatment benefits, treatment for PDA is common in neonatal medicine. Objectives: To study regional variation in PDA treatment in very preterm infants (≤31 weeks gestational weeks), its relation to differences in perinatal characteristics and associations with bronchopulmonary dysplasia (BPD) and survival without major neonatal morbidity. Methods: Population-based cohort study in 19 regions in 11 European countries 2011-2012. 6,896 infants with data on PDA treatment were included. Differences in infant characteristics were studied across regions using a propensity score derived from perinatal risk factors for PDA treatment. Primary outcomes were a composite of BPD or death before 36 weeks postmenstrual age, or survival without major neonatal morbidity. Results: The proportion of PDA treatment varied from 10 to 39% between regions (p<0.001). and this difference could not be explained by differences in perinatal characteristics . Regions were categorized according to low (<15%, n=6), medium (15-25%, n=9) or high (>25%, n=4) proportion of PDA treatment. Infants treated for PDA, compared to not treated, were at higher risk of BPD or death in all regions, with an overall propensity score adjusted risk ratio of 1.33 (95% confidence interval 1.18-1.51). Survival without major neonatal morbidity was not related to PDA treatment. Conclusions: PDA treatment varies largely across Europe without associated variations in perinatal characteristics or neonatal outcomes. This finding calls for more uniform guidance for PDA diagnosis and treatment in very preterm infants.