Association between Hemodynamically Significant Patent Ductus Arteriosus and Bronchopulmonary Dysplasia Federico Schena, MD, Gaia Francescato, MD, PhD, Alessia Cappelleri, MD, Irene Picciolli, MD, Alessandra Mayer, MD, Fabio Mosca, MD, and Monica Fumagalli, MD Objective To assess whether the duration and magnitude of the shunt with patent ductus arteriosus (PDA) are related to a higher incidence of bronchopulmonary dysplasia (BPD) or death. Study design A total of 242 infants #28 weeks gestational age were evaluated retrospectively between 2007 and 2012; 105 (43.3%) developed BPD or died (group 1) and 137 (56.6%) did not (group 2). A review of all echocardio- graphic evaluations performed from birth up to 36 weeks of postconceptional age or final ductal closure was carried out, to detect the presence of PDA, and estimate the severity of ductal shunt through the “PDA staging system” proposed by McNamara and Sehgal. Results Group 1 presented with a hemodynamically significant ductus arteriosus (DA) (E3 and/or E4-PDA) for a longer period of time vs group 2: 4.8 vs 2.3 days, respectively (P < .001). Persistence of a nonsignificant DA (E2) was not associated with development of BPD (P = .16). Each week of a hemodynamically significant DA represented an added risk for BPD (OR 1.7), and the duration of a small, nonsignificant DA (E2) did not. Surgical ligation of PDA itself was not found to be an independent risk factor for BPD. In the subgroup of patients who received ligation, a later ligation (33 vs 23 days) and a prolonged PDA were the only factors associated to BPD or death. Conclusions A shared scoring system of the severity of ductal shunt is helpful to correctly evaluate the associ- ation between PDA morbidities, to compare scientific studies, and to guide treatment. (J Pediatr 2015;-:---). P atent ductus arteriosus (PDA) occurs in up to 70% of preterm infants born before 28 weeks gestation. Its frequency depends on the population, timing of investigation and diagnostic criteria, and it is inversely related to gestational age. The persistency of a ductus arteriosus (DA) in premature infants can cause pulmonary hyperemia and edema, and a decrease in renal, mesenteric and cerebral perfusion. It has been associated with mortality 1 and severe morbidity, including intraven- tricular hemorrhage, 2 necrotizing enterocolitis, 3 and retinopathy of prematurity. 4 PDA has been related to pulmonary function impairment, prolonged ventilator dependency, 5 and development of broncho- pulmonary dysplasia (BPD), either independently 6 or as an additional risk factor together with sepsis, low birth weight, and respiratory distress syndrome (RDS). 6,7 However, this association with BPD is not proven to be causal. In fact, it is unclear whether such morbidity must be considered to be related to the potential negative effects of the ductal shunt itself, or indirectly to the treatments, the choice of which has become controversial over time. Recent randomized controlled trials 8,9 were designed to assess the relationship between timing and type of treatment and the success of PDA closure and the development of morbidities. Although nonsteroidal anti-inflammatory drugs such as indo- methacin and ibuprofen have been shown to be effective in producing ductal closure, 8,10 and, therefore, have become a sub- stitute for surgical ligation, the long-term benefits of these interventions on BPD, necrotizing enterocolitis, or survival have yet to be established. There is a high likelihood of spontaneous closure during the neonatal period, and evidence that preterm in- fants with mild signs of PDA do not necessarily benefit from early pharmacologic treatment if compared with a more conser- vative management. 9 Later or selective surgical ligation appears to be associated with a lower occurrence of neonatal morbidity and development of BPD, 11 retinopathy of prematurity, and neurodevelopmental impairment. 12 Uncertainty over the efficacy of currently used treatments in reducing mortality and morbidity and their potential adverse effects has led some authors to propose PDA as an “innocent physiological bystander” and to suggest a more conservative approach. 13 From the Neonatology and Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2015.03.012 Ao Aortic BPD Bronchopulmonary dysplasia DA Ductus arteriosus E/A Early passive to late atrial contractile phase of transmitral filling ratio FiO 2 Fraction of inspired oxygen HSDA Hemodynamically significant ductus arteriosus LA Left atrium PDA Patent ductus arteriosus RDS Respiratory distress syndrome 1