Despite major advances in obstetrics and neonatal intensive care, preterm infants frequently suffer from neurological impairments in later life. Preterm and also full-term neonates are generally susceptible to injury caused by reactive oxygen species due to the immaturity of endogenous radical scavenging systems. It is well known that high oxygen levels experienced during the critical phase of maturation can profoundly influence developmental processes. Supraphysiological oxygen concentrations used for resuscitation or in the care of critically ill infants are known to have deleterious effects on the developing lung and retina, contributing to the pathophysiology of neonatal diseases like bronchopulmonary dysplasia and retinopathy of prematurity. Moreover, experimental work from the last decade suggests that hyperoxia also leads to neuronal and glial cell death, contributing to the injury of white and grey matter observed in preterm infants. During the critical phase of brain maturation, hyperoxia can alter developmental processes, resulting in the disruption of neural plasticity and myelination. However, oxygen therapy can often not be avoided in neonatal intensive care. Therefore, in situations requiring oxygen supplementation, in addition to the development of appropriate monitoring systems, protective and/or regenerative strategies are highly warranted. Here, we summarise the clinical and experimental evidence as well as potential therapeutic strategies, providing an overview of the pathophysiology of oxygen exposure on the developing central nervous system and its impact on neonatal brain injury.

Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

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Pancreatic β-cells are finely tuned to secrete insulin so that plasma glucose levels are maintained within a narrow physiological range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is the inappropriate secretion of insulin in the presence of low plasma glucose levels and leads to severe and persistent hypoglycaemia in neonates and children. Mutations in 12 different key genes (ABCC8,

BACKGROUND Real-time continuous glucose monitoring (rtCGM) systems have shown to be a low-pain, safe and effective method in preventing hypo- and hyperglycemia in people with diabetes of various age groups. Evidence on rtCGM use in infants, and in patients with conditions other than diabetes, remains limited. OBJECTIVE This case study describes the off-label use of rtCGM, and the use of an open-source app for glucose monitoring, in a newborn with prolonged hypoglycemia secondary to transient congenital hyperinsulinism during the perinatal period. METHODS rtCGM was introduced at 39 hours of age. CBG checks were performed regularly. In order to benefit from customizable alert settings and include hypoglycemic sensor glucose levels below 40 mg/dL, the open-source app xDrip+ was introduced at 9 days of age. RESULTS Time-in-Range (45-180 mg/dL) remained consistent above 90%, whereas Time-in-Hypoglycemia (<45 mg/dL) decreased, and mean glucose was maintained above 70 mg/dL at 72 h of life and after. Daily sensor glucose profiles showed cyclic fluctuations that were less pronounced over time. CONCLUSIONS While off-label use of medication is both common practice and a necessity in newborn infants, there are few examples for off-label uses of medical devices, rtCGM being a notable exception. Real-time information allowed us to better understand glycemic patterns and to improve the quality of glycemic control accordingly. Severe hypoglycemia was prevented, measurement of serum levels of insulin and further lab diagnostics were performed much faster, whilst the patient’s individual burden caused by invasive procedures has been reduced. A wider customizability of threshold and alert settings would be beneficial for user groups with glycemic instability other than people with diabetes, and hospitalized infants in particular. Further research in the field of personal and off-label open-source rtCGM use, differences between native and open-source algorithms in translating raw sensor data, as well as customization of commercially available rtCGM systems is needed. CLINICALTRIAL Does not apply.