Inhaled nitric oxide therapy in neonates and children: reaching a European consensus

Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has subsequently been used extensively in the management of neonates and children with cardiorespiratory failure. This paper assesses evidence for the use of iNO in this population as presented to a consensus meeting jointly organised by the European Society of Paediatric and Neonatal Intensive Care, the European Society of Paediatric Research and the European Society of Neonatology. Consensus Guidelines on the Use of iNO in Neonates and Children were produced following discussion of the evidence at the consensus meeting

European Training Requirements in Neonatology 2021: the ESPR, EAP, and UEMS accredited European syllabus for neonatal training

Introduction: The European Union stipulates transnational recognition of professional qualifications for several sectoral professions, including medical doctors. The Union of European Medical Specialists (UEMS), in its “Charter on Training of Medical Specialists,” defines the principles for high-level medical training. These principles are manifested in the framework for European Training Requirements (ETR), ensuring medical training reflects modern medical practice and current scientific findings. In 1998, the European Society for Paediatric Research developed the first ETR for Neonatology. We present the ETR Neonatology in its third iteration (ETR III), ratified by the European Academy of Paediatrics (EAP), and approved by UEMS in 2021. Methods: In generating the ETR III, existing European policy documents on training requirements, including national syllabi and the European Standards of Care for Newborn Health were considered. To ensure the ETR III meets a pan-European standard of expertise in Neonatology, input from representatives from 27 European national paediatric/neonatal societies, and a European parent organisation, was sought. Results: The ETR III summarises the requirements of contemporary training programs in Neonatology and offers a system for accrediting trainers and training centres. We describe the content of the ETR III training syllabus and means of gaining and assessing competency as a medical care provider in Neonatology. Conclusion: Graduates of courses following the ETR III Neonatology will obtain a certificate of satisfactory training completion which should be accepted by all European member states as a baseline qualification to practice as a specialist in neonatal medicine, enabling mutual recognition of status throughout Europe

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO):Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017.</p

Prenatal exposure to methadone or buprenorphine impairs cognitive performance in young adult rats

Background Concerns have been raised about the use of opioid maintenance treatment (OMT) during pregnancy and negative effects for the offspring. While neonatal outcomes and short-term effects are relatively well described, studies examining long-term effects in adolescents and adults are absent. The aim of the present study was to examine effects on learning and memory in young adult rats prenatally exposed to methadone or buprenorphine. Methods Female rats were implanted with a 28-day osmotic minipump delivering methadone (10 mg/kg/day), buprenorphine (1 mg/kg/day) or vehicle 5 days prior to mating. To examine possible effects on cognitive functioning, young adult offspring were included in three different behavioral tests that examine recognition memory, nonspatial, and spatial learning and memory. In addition, offspring growth and maternal behavior after birh were investigated. Results Prenatal exposure to methadone or buprenorphine caused impaired recognition memory and nonspatial reference learning and memory in young adult rats compared with the vehicle-treated group. Methadone-exposed offspring, but not the buprenorphine-exposed, also showed reduced long-term spatial memory. We did not observe any changes in maternal behavior or offspring growth after prenatal exposure to methadone or buprenorphine, suggesting that the impaired cognitive functioning is due to the opioid exposure rather than reduced maternal caregiving. Conclusion The present findings of long-term cognitive impairments in methadone- and buprenorphine-exposed offspring points to a negative impact of OMT on neurobiological development

Effects of the Cyclooxygenase Inhibitor Ibuprofen on Retinal and Choroidal Blood Flow during Hyperoxia in Newborn Piglets

Purpose: The effect of the cyclooxygenase inhibitor ibuprofen (IB) on choroidal (ChBF) and retinal (RBF) blood flow during hyperoxia was examined in 21 spontaneously breathing newborn piglets. Methods: ChBF and RBF were measured using radiolabelled microspheres before and 30 min after either saline or IB (30 mg/kg, IV) infusion in room air and subsequently, after 90 min of hyperoxia (O2). Results: The basal RBF and ChBF did not change after IB infusion. However, during hyperoxia a significant decrease in RBF was observed in the IB group (54 ± 5 to 37 ± 3 ml/min/100gp < 0.02) and in the control group (54 ± 3 to 37 ± 5 ml/min/100g, p < 0.02). Also, ChBF decreased in the IB group (2,635 ± 446 to 1,670 ± 199 ml/min/100 g, p < 0.02) and in the control group, (2,997 ± 346 to 2,014 ± 246 ml/min/100 g, p < 0.02) during hyperoxia. Conclusions: Despite cyclooxygenase inhibition with IB, RBF and ChBF decreased to the same extent as in the control group following exposure to O2 These data suggest that hyperoxia decrease RBF and ChBF through mechanisms and/or mediators other than the cyclooxygenase by-products of arachidonic acid metabolism