Open-Source Technology for Real-Time Continuous Glucose Monitoring in the Neonatal Intensive Care Unit: Case Study in a Neonate With Transient Congenital Hyperinsulinism.

BACKGROUND: Use of real-time continuous glucose monitoring (rtCGM) systems has been shown to be a low-pain, safe, and effective method of preventing hypoglycemia 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: The Dexcom G6 rtCGM system (Dexcom, Inc) was introduced at 39 hours of age. Capillary blood glucose checks were performed regularly. In order to benefit from customizable alert settings and detect hypoglycemic episodes, the open-source rtCGM app xDrip+ was introduced at 9 days of age. RESULTS: Time in range (45-180 mg/dL) for interstitial glucose remained consistently above 90%, whereas time in hypoglycemia (<45 mg/dL) decreased. Mean glucose was maintained above 70 mg/dL at 72 hours of life and thereafter. 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 of 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, and measurement of serum levels of insulin and further lab diagnostics were performed much faster, while the patient's individual burden caused by invasive procedures was reduced. Greater customizability of threshold and alert settings would be beneficial for user groups with glycemic instability other than people with diabetes, and for hospitalized newborn infants in particular. Further research in the field of personal and off-label rtCGM use, efficacy studies evaluating the accuracy of low glucose readings, and studies on the differences between algorithms in translating raw sensor data, as well as customization of commercially available rtCGM systems, is needed.

Hyperoxia and the Immature Brain.

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.

Dose-dependent effects of levetiracetam after hypoxia and hypothermia in the neonatal mouse brain.

Perinatal asphyxia to the developing brain remains a major cause of morbidity. Hypothermia is currently the only established neuroprotective treatment available for term born infants with hypoxic-ischemic encephalopathy, saving one in seven to eight infants from developing severe neurological deficits. Therefore, additional treatments with clinically applicable drugs are indispensable. This study investigates a potential additive neuroprotective effect of levetiracetam combined with hypothermia after hypoxia-induced brain injury in neonatal mice. 9-day-old C57BL/6-mice (P9) were subjected either to acute hypoxia or room-air. After 90min of systemic hypoxia (6% O2), pups were randomized into six groups: 1) vehicle, 2) low-dose levetiracetam (LEV), 3) high-dose LEV, 4) hypothermia (HT), 5) HT combined with low-dose LEV and 6) HT combined with high-dose LEV. Pro-apoptotic factors, neuronal structures, and myelination were analysed by histology and on protein level at appropriate time points. On P28 to P37 long-term outcome was assessed by neurobehavioral testing. Hypothermia confers acute and long-term neuroprotection by reducing apoptosis and preservation of myelinating oligodendrocytes and neurons in a model of acute hypoxia in the neonatal mouse brain. Low-dose LEV caused no adverse effects after neonatal hypoxic brain damage treated with hypothermia whereas administration of high-dose LEV alone or in combination with hypothermia increased neuronal apoptosis after hypoxic brain injury. LEV in low- dosage had no additive neuroprotective effect following acute hypoxic brain injury.

Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm 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.