Patent Ductus Arteriosus Treatment in Very Preterm Infants: A European Population-Based Cohort Study (EPICE) on Variation and Outcomes

Abstract

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: The aim of this work was to study regional variations in PDA treatment in very preterm infants (≤31 weeks of gestation), its relation to differences in perinatal characteristics, and associations with bronchopulmonary dysplasia (BPD) and survival without major neonatal morbidity. Methods: This was a population-based cohort study in 19 regions in 11 European countries conducted during 2011 and 2012. A total of 6,896 infants with data on PDA treatment were included. The differences in infant characteristics were studied across regions using a propensity score derived from perinatal risk factors for PDA treatment. The 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. The regions were categorized according to a low (<15%, n = 6), medium (15-25%, n = 9), or high (>25%, n = 4) proportion of PDA treatment. Infants treated for PDA, compared to those 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.

Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology

“…However, it is clear that closure of PDA does not necessarily decrease the incidence of BPD raising doubts that the relationship between PDA and BPD is more of an association rather than causation 95,96 . In fact, some studies indicate that PDA closure by medical or surgical therapies is associated with worsening BPD 97,98 . It is possible that PDA therapy-associated complications such as lung fluid retention and lung inflammation may have contributed to worsening of BPD in PDA-treated patients.…”

The type and timing of patent ductus arteriosus treatment was associated with neurodevelopment when extremely preterm infants reached 6.5 years

“…Various confounders were of importance in the analyses of the study data, foremost gestational age and IVH. In previous studies, gestational age has also been strongly associated with IVH, PDA treatment and neurodevelopmental outcomes 1,2,14,15 . Clinically, IVH is a contraindication to NSAID drug treatment and could therefore be related to the risk of undergoing a primary PDA operation 5 .…”

“…Treating patent ductus arteriosus (PDA) is one of the more common neonatal interventions following extremely preterm (EPT) birth 1‐4 . The rationale for pharmacological treatment, with non‐steroidal anti‐inflammatory drugs (NSAID) or paracetamol, or surgical closure of a haemodynamically significant PDA in EPT infants is to limit PDA induced disturbances on the cerebrum, gut, kidney and pulmonary circulation.…”

Defining “Haemodynamic Significance” of the Patent Ductus Arteriosus: Do We Have All the Answers?

“…The major advantage of the early targeted approach is that preterm infants with a small or non-haemodynamically significant PDA are not exposed to the potentially detrimental side effects of COX inhibitors, including acute kidney injury, intestinal perforation and thrombocytopenia [9]. However, similar to the prophylactic strategy, studies examining the early targeted approach did not demonstrate improvements in important neonatal outcomes, such as IVH, NEC or retinopathy of prematurity, when compared to expectant management [10, 11]. Subsequent to these findings, and in combination with the high rates of spontaneous PDA closure noted for babies born less than 29 weeks’ gestation, the early targeted strategy was largely superseded by the conservative approach to PDA management in many neonatal units [12, 13].…”