Patent ductus arteriosus, bronchopulmonary dysplasia and pulmonary hypertension - a complex conundrum with many phenotypes?

The association between patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD) and chronic pulmonary hypertension (cPH) in extremely low gestational age neonates (ELGANs) is an area gaining considerable interest. This triad of entities are all intertwined in a complex and multifactorial relationship. PDA can contribute to the development of BPD by increasing pulmonary blood flow, leading to lung injury and inflammation. Additionally, both PDA and BPD can contribute to the development of cPH by increasing pulmonary blood flow and vascular resistance leading to right ventricular dysfunction. The paper by Nawaytou et al., bravely attempts to make sense of it all. The authors attempted to divide PH associated with BPD into a predominantly flow based PH (associated with PDA left to right shunting) and PVR based PH (associated with vascular maladaptive changes). They reported a distinct association between the duration of PDA exposure and the former but not the latter. </p

Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT) [version 1; peer review: awaiting peer review]

A patent ductus arteriosus (PDA) in preterm infants is associated with increased ventilator dependence and chronic lung disease, necrotizing enterocolitis, intraventricular haemorrhage, and poor neurodevelopmental outcome. Randomised controlled trials of early PDA treatment have not established a drop in the aforementioned morbidities. Those trials did not physiologically categorise PDA severity. Incorporating the specific physiological features of a haemodynamic significant PDA may evolve our understanding of this phenomenon, allowing accurate triaging using echocardiography and targeted treatment. Our group has recently demonstrated that a PDA severity score (PDAsc) derived at 36-48 hours of age can accurately predict the later occurrence of chronic lung disease or death (CLD/Death). Using echocardiography, we assessed PDA characteristics, as well as left ventricular diastolic function and markers of pulmonary overcirculation, and from this formulated a PDAsc. Gestation was also incorporated into the score. We hypothesise that in preterm infants at high risk of developing CLD/Death based on a PDAsc, early treatment with Ibuprofen compared with placebo will result in a reduction in CLD/Death. This is a single centre double-blind two arm randomised controlled trial conducted in the neonatal intensive care unit in the Rotunda Hospital, Dublin. Echocardiogram is carried out in the first 36-48 hours of life to identify preterm infants with a PDAsc ≥ 5.0 and these infants are randomised to Ibuprofen or placebo. Primary outcomes are assessed at 36 weeks post menstrual age. This pilot study's purpose is to assess the feasibility of performing the trial and to obtain preliminary data to calculate a sample size for a definitive multi-centre trial of early PDA treatment using a PDAsc. We aim to recruit a total of 60 infants with a high risk PDA over three years.  Trial Registration: ISRCTN ISRCTN13281214 (26/07/2016) and the European Union Drug Regulating Authorities Clinical Trials Database 2015-004526-33 (03/12/2015). </p

Multicentre prospective observational study exploring the predictive value of functional echocardiographic indices for early identification of preterm neonates at risk of developing chronic pulmonary hypertension secondary to chronic neonatal lung disease

Introduction: Although chronic pulmonary hypertension (cPH) secondary to chronic neonatal lung disease is associated with increased mortality and respiratory and neurodevelopmental morbidities, late diagnosis (typically ≥36 weeks postmenstrual age, PMA) and the use of qualitative echocardiographic diagnostic criterion (flat interventricular septum in systole) remain significant limitations in clinical care. Our objective in this study is to evaluate the utility of relevant quantitative echocardiographic indices to identify cPH in preterm neonates, early in postnatal course and to develop a diagnostic test based on the best combination of markers. Methods and analysis: In this ongoing international prospective multicentre observational diagnostic accuracy study, we aim to recruit 350 neonates born Ethics and dissemination: Ethics approval has been received by the Mount Sinai Hospital Research Ethics Board (REB) (#16-0111-E), Sunnybrook Health Sciences Centre REB (#228-2016), NHS Health Research Authority (IRAS 266498), University of Iowa Human Subjects Office/Institutional Review Board (201903736), Rotunda Hospital Research and Ethics Committee (REC-2019-008), and UBC Children's and Women's REB (H19-02738), and is under review at Boston Children's Hospital Institutional Review Board. Study results will be disseminated to participating families in lay format, presented to the scientific community at paediatric and critical care conferences and published in relevant peer-reviewed journals. Trail registration number: NCT04402645.</p