Unobtrusive cot side sleep stage classification in preterm infants using ultra-wideband radar

Background: Sleep is an important driver of development in infants born preterm. However, continuous unobtrusive sleep monitoring of infants in the neonatal intensive care unit (NICU) is challenging.Objective: To assess the feasibility of ultra-wideband (UWB) radar for sleep stage classification in preterm infants admitted to the NICU.Methods: Active and quiet sleep were visually assessed using video recordings in 10 preterm infants (recorded between 29 and 34 weeks of postmenstrual age) admitted to the NICU. UWB radar recorded all infant's motions during the video recordings. From the baseband data measured with the UWB radar, a total of 48 features were calculated. All features were related to body and breathing movements. Six machine learning classifiers were compared regarding their ability to reliably classify active and quiet sleep using these raw signals.Results: The adaptive boosting (AdaBoost) classifier achieved the highest balanced accuracy (81%) over a 10-fold cross-validation, with an area under the curve of receiver operating characteristics (AUC-ROC) of 0.82.Conclusions: The UWB radar data, using the AdaBoost classifier, is a promising method for non-obtrusive sleep stage assessment in very preterm infants admitted to the NICU

Risk Factors for Perioperative Brain Lesions in Infants With Congenital Heart Disease:A European Collaboration

Infants with congenital heart disease are at risk of brain injury and impaired neurodevelopment. The aim was to investigate risk factors for perioperative brain lesions in infants with congenital heart disease. METHODS: Infants with transposition of the great arteries, single ventricle physiology, and left ventricular outflow tract and/or aortic arch obstruction undergoing cardiac surgery <6 weeks after birth from 3 European cohorts (Utrecht, Zurich, and London) were combined. Brain lesions were scored on preoperative (transposition of the great arteries N=104; single ventricle physiology N=35; and left ventricular outflow tract and/or aortic arch obstruction N=41) and postoperative (transposition of the great arteries N=88; single ventricle physiology N=28; and left ventricular outflow tract and/or aortic arch obstruction N=30) magnetic resonance imaging for risk factor analysis of arterial ischemic stroke, cerebral sinus venous thrombosis, and white matter injury. RESULTS: Preoperatively, induced vaginal delivery (odds ratio [OR], 2.23 [95% CI, 1.06–4.70]) was associated with white matter injury and balloon atrial septostomy increased the risk of white matter injury (OR, 2.51 [95% CI, 1.23–5.20]) and arterial ischemic stroke (OR, 4.49 [95% CI, 1.20–21.49]). Postoperatively, younger postnatal age at surgery (OR, 1.18 [95% CI, 1.05–1.33]) and selective cerebral perfusion, particularly at ≤20 °C (OR, 13.46 [95% CI, 3.58–67.10]), were associated with new arterial ischemic stroke. Single ventricle physiology was associated with new white matter injury (OR, 2.88 [95% CI, 1.20–6.95]) and transposition of the great arteries with new cerebral sinus venous thrombosis (OR, 13.47 [95% CI, 2.28–95.66]). Delayed sternal closure (OR, 3.47 [95% CI, 1.08–13.06]) and lower intraoperative temperatures (OR, 1.22 [95% CI, 1.07–1.36]) also increased the risk of new cerebral sinus venous thrombosis. CONCLUSIONS: Delivery planning and surgery timing may be modifiable risk factors that allow personalized treatment to minimize the risk of perioperative brain injury in severe congenital heart disease. Further research is needed to optimize cerebral perfusion techniques for neonatal surgery and to confirm the relationship between cerebral sinus venous thrombosis and perioperative risk factors

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

The emergence of functional architecture during early brain development

Early human brain development constitutes a sequence of intricate processes resulting in the ontogeny of functionally operative neural circuits. Developmental trajectories of early brain network formation are genetically programmed and can be modified by epigenetic and environmental influences. Such alterations may exert profound effects on neurodevelopment, potentially persisting throughout the lifespan. This review focuses on the critical period of fetal and early postnatal brain development. Here we collate findings from neuroimaging studies, with a particular focus on functional MRI research that interrogated early brain network development in both health and high-risk or disease states. First, we will provide an overview of the developmental processes that take place from the embryonic period through early infancy in order to contextualize brain network formation. Second, functional brain network development in the typically developing brain will be discussed. Third, we will touch on prenatal and perinatal risk factors that may interfere with the trajectories of functional brain wiring, including prenatal substance exposure, maternal mental illness and preterm birth. Collectively, studies have revealed the blueprint of adult human brain organization to be present in the neonatal brain. Distinct attributes of human brain architecture have even been detected in the developing fetal brain from as early as 24 postconceptional weeks. During postnatal brain development, the brain's wiring pattern is further sculpted and modulated to become the full facsimile of the adult human brain, with functional brain network refinement being more rigorous than structural brain network maturation. Advances in neuroimaging techniques have paved the way towards a comprehensive understanding of the maturational pathways of brain network development and of how early developmental adversity may affect these trajectories. Such insights are fundamental for our understanding of human brain functioning, for early identification of infants at risk, as well as for future neuroprotective strategies

Premature Birth and Developmental Programming: Mechanisms of Resilience and Vulnerability

The third trimester of pregnancy represents a sensitive phase for infant brain plasticity when a series of fast-developing cellular events (synaptogenesis, neuronal migration, and myelination) regulates the development of neural circuits. Throughout this dynamic period of growth and development, the human brain is susceptible to stress. Preterm infants are born with an immature brain and are, while admitted to the neonatal intensive care unit, precociously exposed to stressful procedures. Postnatal stress may contribute to altered programming of the brain, including key systems such as the hypothalamic–pituitary–adrenal axis and the autonomic nervous system. These neurobiological systems are promising markers for the etiology of several affective and social psychopathologies. As preterm birth interferes with early development of stress-regulatory systems, early interventions might strengthen resilience factors and might help reduce the detrimental effects of chronic stress exposure. Here we will review the impact of stress following premature birth on the programming of neurobiological systems and discuss possible stress-related neural circuits and pathways involved in resilience and vulnerability. Finally, we discuss opportunities for early intervention and future studies

Nonprotein-bound iron in postasphyxial reperfusion injury of the newborn

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