In the field of neonatology there is wide variation in the approach to patent ductus arteriosus (PDA) evaluation and management. Although observational studies have consistently linked a hemodynamically significant PDA (hsPDA) with many complications of prematurity including intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), adverse neurodevelopmental outcome and mortality1, 2, 3, uncertainty regarding treatment remains. Over 60 randomized trials have failed to demonstrate improved outcomes with medical treatment4; however, these trials have major methodological limitations. Most trials have randomized few, if any, preterm infants born at 22- or 23- weeks’ gestational age (GA). In addition, hemodynamic significance has not been adjudicated according to standardized echocardiography criteria with high rates of spontaneous closure in control groups, medical therapy in the treatment arm is not universally successful, and substantial rates of open-label medical therapy is being provided to control patients. Importantly, these trials fail to focus on the highest risk group of neonates, namely those born <27 weeks and especially the 22+0-23+6 week GA cohort. Extremely preterm infants are surviving in greater numbers5 and at even earlier GAs leading to neonatologists caring for higher risk patients who may have greater risk of PDA attributable morbidity. Biophysiologic contributors to increased burden of illness include a less muscularized ductus3, an imbalance of vasodilators and vasoconstrictors to which the neonates’ response is immature1, delayed postnatal cardiopulmonary adaptation6, impaired response to afterload7, more severe respiratory distress syndrome (RDS)1,7 and immature antioxidant defenses.8 These factors combine to heighten the possible impact of acute and chronic ductal shunt on both morbidity and mortality.

Severe BPD9 is a predictor of morbidity and mortality and has been associated with hsPDA tolerant management in a variety of studies.10, 11, 12 As compared to neonates with grade 1-2 BPD, patients with grade 3 BPD have a greater than 2-fold higher risk of adverse outcomes including severe IVH, retinopathy of prematurity, NEC or bowel perforation, supplemental oxygen at discharge and length of stay.13 It is biologically plausible, as suggested by a recent post-hoc analysis of a pilot randomized trial14, that successful early elimination of hsPDA shunt may be associated with a reduced risk of BPD among extremely preterm neonates. In our center, a comprehensive hemodynamic screening program with a standardized approach to PDA evaluation and therapy was introduced in 2018. The primary aim of this study was to evaluate the impact of early hsPDA management based on targeted neonatal echocardiography (TnECHO) evaluation in extremely preterm infants born at 22+0-23+6 weeks GA, as compared to a historical epoch during which exclusively clinically "symptomatic" treatment after postnatal day 7 in the presence of echocardiography confirmed PDA in a prior epoch, on the primary composite outcome of death <36 weeks or severe BPD.