Neonates with congenital heart disease (CHD) are at an increased risk of developing necrotizing enterocolitis (NEC), an acute inflammatory intestinal injury most commonly associated with preterm infants. The rarity of this complex disease, termed cardiac NEC, has resulted in a dearth of information on its pathophysiology. However, a higher incidence in term infants, effects on more distal regions of the intestine, and potentially a differential immune response may distinguish cardiac NEC as a distinct condition from the more common preterm, classical NEC. In this review, risk factors, differentiated from those of classical NEC, are discussed according to their potential contribution to the disease process, and a general pathogenesis is postulated for cardiac NEC. Additionally, biomarkers specific to cardiac NEC, clinical outcomes, and strategies for achieving enteral feeds are discussed. Working towards an understanding of the mechanisms underlying cardiac NEC may aid in future diagnosis of the condition and provide potential therapeutic targets.

Introduction: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in extremely preterm infants and is associated with poor clinical outcomes. Uncertainty exists on whether early pharmacotherapeutic treatment of a clinically symptomatic and echocardiography-confirmed haemodynamically significant PDA in extremely preterm infants improves outcomes. Given the wide variation in the approach to PDA treatment in this gestational age (GA) group, a randomised trial design is essential to address the question. Before embarking on a large RCT in this vulnerable population, it is important to establish the feasibility of such a trial. Methods and analysis: Design: a multi-centre, open-labelled, parallel-designed pilot randomised controlled trial. Participants: preterm infants born <26 weeks of gestation with a PDA diagnosed within 72 hours after birth. Intervention (selective early medical treatment (SMART) strategy): selective early pharmacological treatment of a moderate-severe PDA shunt (identified based on pre-defined clinical signs and routine screening echocardiography) within the first 72 postnatal hours with provision for repeat treatment if moderate-severe shunt persists. Comparison (early conservative management strategy): no treatment of PDA in the first postnatal week. Primary outcomes: (1) proportion of eligible infants recruited during the study period; (2) proportion of randomised infants treated outside of protocol-mandated therapy. Sites and sample size: the study is being conducted in seven neonatal intensive care units across Canada and the USA with a target of 100 randomised infants. Analysis: the primary feasibility outcomes will be expressed as proportions. A pre-planned Bayesian analysis will be conducted for secondary clinical outcomes such as mortality, severe intraventricular haemorrhage, procedural PDA closure and chronic lung disease to aid stakeholders including parent representatives decide on the appropriateness of enrolling this vulnerable population in a larger trial if the feasibility of recruitment in the pilot trial is established. Ethics and dissemination: The study has been approved by the IWK Research Ethics Board (#1027298) and six additional participating sites. On the completion of the study, results will be presented at national and international meetings, published in peer-reviewed journals and incorporated into existing systematic reviews. Trial registration number: NCT05011149 (WHO Trial Registration Data Set in Appendix A). Protocol version: Ver 7.2 (dated July 19, 2023).

Hemodynamic Precision Neonatal Intensive Care Unit Using Targeted. JoVE publishes peer-reviewed scientific video protocols to accelerate biological, medical, chemical and physical research. Watch our scientific video articles. JoVE is the world-leading producer and provider of science videos with the mission to improve scientific research, scientific journals, and education. Millions of scientists, educators and students at thousands of universities, colleges, hospitals and biopharmaceutical companies worldwide use JoVE for their research, teaching and learning.

Background: A hemodynamically significant patent ductus arteriosus (hsPDA) is common in preterm infants and may impact systemic and cerebral blood flow. This study explores Doppler flow patterns in systemic arteries including celiac artery/trunk (CeT), superior mesenteric artery (SMA) and middle cerebral artery (MCA) in preterm neonates with varying PDA shunt patterns, utilizing targeted neonatal echocardiography (TNE). Methods: Retrospective multicenter study of preterm infants (born <32 weeks gestation, <40 days of life) who underwent comprehensive TNE. Infants were categorized into 3 groups based on PDA shunt characteristics as follows: (1) No transductal shunt or trivial PDA with PDA score <6, (2) Left-to-right PDA (L-R PDA) and PDA score ≥8 and (3) Bidirectional PDA shunt with at least 10% of time spent right-to-left (R-L) and PDA score <6. Results: In total, 86 patients with a median [IQR] gestational age of 26.1 weeks [23.8–27.7] weeks and birth weight of 767 [596, 1016] grams were included and classified into 3 groups: No PDA ( n = 29), hsPDA ( n = 48) and bidirectional PDA ( n = 27). Abnormal systemic arterial Doppler patterns (absent or reversed diastolic flow in the Celiac artery) were present in 2 (5.7%), 15 (44.1%), and 1 (5.9%) of the patients in the no PDA, hsPDA, and bidirectional PDA groups respectively. Diastolic flow reversal in any of the systemic vessels evaluated was demonstrated only in the hsPDA group. Conclusion: This physiologic study demonstrates altered systemic Doppler patterns, which suggests a decreased ability to preserve lower body blood flow in premature infants with hsPDA. Further prospective studies are warranted to describe the association of these physiologic findings with clinical outcomes such as necrotizing enterocolitis. Clinical Trial Registration (if any): None (not applicable).