New antioxidant drugs for neonatal brain injury

The brain injury concept covers a lot of heterogeneity in terms of aetiology involving multiple factors, genetic, hemodynamic, metabolic, nutritional, endocrinological, toxic, and infectious mechanisms, acting in antenatal or postnatal period. Increased vulnerability of the immature brain to oxidative stress is documented because of the limited capacity of antioxidant enzymes and the high free radicals (FRs) generation in rapidly growing tissue. FRs impair transmembrane enzyme Na(+)/K(+)-ATPase activity resulting in persistent membrane depolarization and excessive release of FR and excitatory aminoacid glutamate. Besides being neurotoxic, glutamate is also toxic to oligodendroglia, via FR effects. Neuronal cells die of oxidative stress. Excess of free iron and deficient iron/binding metabolising capacity are additional features favouring oxidative stress in newborn. Each step in the oxidative injury cascade has become a potential target for neuroprotective intervention. The administration of antioxidants for suspected or proven brain injury is still not accepted for clinical use due to uncertain beneficial effects when treatments are started after resuscitation of an asphyxiated newborn. The challenge for the future is the early identification of high-risk babies to target a safe and not toxic antioxidant therapy in combination with standard therapies to prevent brain injury and long-term neurodevelopmental impairment

Performances of low level hospital health caregivers after a neonatal resuscitation course

Background: High fidelity simulation has been executed to allow the evaluation of technical and non-technical skills of health caregivers. Our objective was to assess technical and non-technical performances of low level hospitals health caregivers who attended a Neonatal Resuscitation course using high fidelity simulation in a standard-setting scenario. Methods: Twenty-three volunteers were asked to manage a simple scenario (infant with secondary apnea) after the course. Technical and non-technical skills were assessed by using previously published scores. Performances were assessed during the scenario and after 2 months by filmed video recordings. Results: Sixteen (69.5%) participants failed to pass the minimum required technical score. Staff experience and participation in previous courses were associated to higher score in technical and non-technical skills, while working in level I or II hospitals did not affect the scores. Previous experience in neonatal resuscitation requiring positive pressure ventilation was associated to better non-technical performance. Technical and non-technical scores were significantly correlated (r = 0.67, p = 0.0005). Delayed and direct evaluation of technical skills provided the same scores. Conclusions: A neonatal resuscitation course, performed by using a high fidelity simulation manikin, had a limited impact on technical and non-technical skills of participants working in low level hospitals. Training programs should be tailored to the participants\u2019 professional background and to the more relevant sessions

Automated cot-side tracking of functional brain age in preterm infants

Objective A major challenge in the care of preterm infants is the early identification of compromised neurological development. While several measures are routinely used to track anatomical growth, there is a striking lack of reliable and objective tools for tracking maturation of early brain function; a cornerstone of lifelong neurological health. We present a cot-side method for measuring the functional maturity of the newborn brain based on routinely available neurological monitoring with electroencephalography (EEG). Methods We used a dataset of 177 EEG recordings from 65 preterm infants to train a multivariable prediction of functional brain age (FBA) from EEG. The FBA was validated on an independent set of 99 EEG recordings from 42 preterm infants. The difference between FBA and postmenstrual age (PMA) was evaluated as a predictor for neurodevelopmental outcome. Results The FBA correlated strongly with the PMA of an infant, with a median prediction error of less than 1 week. Moreover, individual babies follow well-defined individual trajectories. The accuracy of the FBA applied to the validation set was statistically equivalent to the training set accuracy. In a subgroup of infants with repeated EEG recordings, a persistently negative predicted age difference was associated with poor neurodevelopmental outcome. Interpretation The FBA enables the tracking of functional neurodevelopment in preterm infants. This establishes proof of principle for growth charts for brain function, a new tool to assist clinical management and identify infants who will benefit most from early intervention.Peer reviewe

Oxidative Stress in the Newborn

Oxidative stress (OS) occurs when there is an unbalance between free radicals (FR) production and antioxidant capacity. OS can be a risk factor for fetal programming, representing a key process linking adverse fetal growth, impaired fetal well-being or preterm birth, and later increased risks of diseases in adolescence and adulthood. Adverse outcome to the offspring can extend beyond the neonatal period and includes neurodevelopmental disorders (motor and cognitive problems, attention deficit hyperactivity, and psychotic disorders), asthma, insulin resistance, diabetes mellitus, hypertension, coronary heart disease, and stroke. Free radicals can alter gene expression or damage lipids, proteins, and DNA at a critical developmental point leading to a higher susceptibility to many disorders

Plasma Biomarkers of Oxidative Stress in Neonatal Brain Injury

Perinatal encephalopathy is a leading cause of lifelong disability. Increasing evidence indicates that the pathogenesis of perinatal brain damage is much more complex than originally thought, with multiple pathways involved. An important role of oxidative stress (OS) in the pathogenesis of brain injury is recognized for preterm and term infants. This article examines potential reliable and specific OS biomarkers that can be used in premature and term infants for the early detection and follow-up of the most common neonatal brain injuries, such as hypoxic-ischemic encephalopathy, intraventricular hemorrhage, and periventricular leukomalacia. The next step will be to explore the correlation between brain-specific OS biomarkers and functional brain outcomes

New pharmacologic and therapeutic approaches for hypoxic-ischemic encephalopathy in the newborn

Abstract Hypoxic-ischemic encephalopathy is still an important cause of neonatal mortality and long-term disabilities. The understanding of the differential responses to hypoxia-ischemia as an initial insult leading to cellular degeneration in brain has opened the way to develop new pharmacologic and therapeutic approaches. Due to the complex pathophysiology, therapies can target early pathways such as oxidative stress, inflammation and apoptosis or delayed pathways such as the privation of growth factors and cell death. Pharmacological interventions should start at different points of time according to their mechanisms of action. The association of moderate hypothermia with neuroprotective drugs may decrease cell injury and optimize endogenous repair. More basic science research focusing on the mechanisms of injury are required. Moreover, clinical trials are needed to detect safely and effectiveness drugs and to establish the optimal time of action for each on

Brain susceptibility to oxidative stress in the perinatal period

Oxidative stress (OS) occurs at birth in all newborns as a consequence of the hyperoxic challenge due to the transition from the hypoxic intrauterine environment to extrauterine life. Free radical (FRs) sources such as inflammation, hyperoxia, hypoxia, ischaemia-reperfusion, neutrophil and macrophage activation, glutamate and free iron release, all increases the OS during the perinatal period. Newborns, and particularly preterm infants, have reduced antioxidant defences and are not able to counteract the harmful effects of FRs. Energy metabolism is central to life because cells cannot exist without an adequate supply of ATP. Due to its growth, the mammalian brain can be considered as a steady-state system in which ATP production matches ATP utilisation. The developing brain is particularly sensitive to any disturbances in energy generation, and even a short-term interruption can lead to long-lasting and irreversible damage. Whenever energy failure develops, brain damage can occur. Accumulating evidence indicates that OS is implicated in the pathogenesis of many neurological diseases, such as intraventricular haemorrhage, hypoxic-ischaemic encephalopathy and epilepsy

Petechial rash associated with Parvovirus B19 in children: case report and literature review

Human Parvovirus B19 (B19V) infection usually causes erythema infectiosum (EI). In recent decades, several uncommon exanthems have been described in association with B19V. Recently, haemorrhagic manifestations such as purpuric-petechial rash have been reported. We describe an unusual paediatric case of B19V associated with generalized petechial eruption, and a review of the recent literature

Therapeutic hypothermia in a late preterm infant

Therapeutic hypothermia is a recognized treatment for term infants with hypoxic-ischemic encephalopathy (HIE) in reducing rate of death or neurodevelopmental disabilities. Little is known about applications of this treatment to preterm newborns. Studies in animal experimental models demonstrated the efficacy of hypothermia in preterm fetuses but clinical application to newborn infants are limited to restricted cases, as severe necrotizing enterocolitis (NEC). We present a case of therapeutic whole body cooling in a baby at 34 weeks and 6 days of gestational age with HIE