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BACKGROUND In the developing brain, the death of immature oligodendrocytes (OLs) has been proposed to explain a developmental window for vulnerability to white matter injury (WMI). However, in neonatal mice, chronic sublethal intermittent hypoxia (IH) recapitulates the phenotype of diffuse WMI without affecting cellular viability. This work determines whether, in neonatal mice, a developmental window of WMI vulnerability exists in the absence of OLs lineage cellular death. METHODS Neonatal mice were exposed to cell-nonlethal early or late IH stress. The presence or absence of WMI phenotype in their adulthood was defined by the extent of sensorimotor deficit and diffuse cerebral hypomyelination. A separate cohort of mice was examined for markers of cellular degeneration and OLs maturation. RESULTS Compared to normoxic littermates, only mice exposed to early IH stress demonstrated arrested OLs maturation, diffuse cerebral hypomyelination, and sensorimotor deficit. No cellular death associated with IH was detected. CONCLUSIONS Neonatal sublethal IH recapitulates the phenotype of diffuse WMI only when IH stress coincides with the developmental stage of primary white matter myelination. This signifies a contribution of cell-nonlethal mechanisms in defining the developmental window of vulnerability to diffuse WMI. IMPACT The key message of our work is that the developmental window of vulnerability to the WMI driven by intermittent hypoxemia exists even in the absence of excessive OLs and other cells death. This is an important finding because the existence of the developmental window of vulnerability to WMI has been explained by a lethal-selective sensitivity of immature OLs to hypoxic and ischemic stress, which coincided with their differentiation. Thus, our study expands mechanistic explanation of a developmental window of sensitivity to WMI by showing the existence of cell-nonlethal pathways responsible for this biological phenomenon.

This review identifies key distinctive features of the anatomy and physiology of the neonatal airway that contribute to pathology. Additionally, it highlights the importance of a multidisciplinary approach to the evaluation of the airway in certain neonates with respiratory distress in the neonatal intensive care unit. Advancements in airway imaging aid in the evaluation of the neonatal airway. However, a comprehensive airway evaluation is often indicated. This requires a team of subspecialists including neonatologists, radiologists, pediatric otolaryngologists, pulmonologists, and anesthesiologists. Disorders of the airway are a common challenge in the neonatal intensive care unit. For reasons that relate to size, anatomy, and physiology, key differences exist between the neonatal airway and that of the older child or adult. A comprehensive multidisciplinary approach to the neonate with suspected airway pathology can improve timely diagnosis, facilitate early intervention, and potentially help avoid unnecessary additional procedures in the neonatal intensive care unit.

A 2.0 kg early-term infant with congenital heart disease required central venous catheter placement for persistent hypoglycaemia. A 1-French peripherally inserted central catheter (PICC) was placed in the basilic vein of the left forearm and advanced to 13 cm, commensurate with expected appropriate depth given preprocedural measurements. Point-of-care ultrasound (POCUS) was used to confirm catheter location,1 with X-ray for verification. Initial POCUS and X-ray revealed that the catheter was directed superiorly into the left internal jugular vein (figure 1A,B). Figure 1 Ultrasound and chest …

Very low birth weight (VLBW) premature infants experience numerous, often self-limited non-bradycardic episodes of intermittent hypoxemia (IH). We hypothesized that these episodes of IH affect postnatal white matter (WM) development causing hypomyelination and neurological handicap in the absence of cellular degeneration. Based on clinical data from ten VLBW neonates; a severity, daily duration and frequency of non-bradycardic IH episodes were reproduced in neonatal mice. Changes in heart rate and cerebral blood flow during IH were recorded. A short-term and long-term neurofunctional performance, cerebral content of myelin basic protein (MBP), 2'3' cyclic-nucleotide 3-phosphodiesterase (CNPase), electron microscopy of axonal myelination and the extent of cellular degeneration were examined. Neonatal mice exposed to IH exhibited no signs of cellular degeneration, yet demonstrated significantly poorer olfactory discrimination, wire holding, beam and bridge crossing, and walking-initiation tests performance compared to controls. In adulthood, IH-mice demonstrated no alteration in navigational memory. However, sensorimotor performance on rota-rod, wire-holding and beam tests was significantly worse compared to naive littermates. Both short- and long-term neurofunctional deficits were coupled with decreased MBP, CNPase content and poorer axonal myelination compared to controls. In neonatal mice mild, non-ischemic IH stress, mimicking that in VLBW preterm infants, replicates a key phenotype of non-cystic WM injury: permanent hypomyelination and sensorimotor deficits. Because this phenotype has developed in the absence of cellular degeneration, our data suggest that cellular mechanisms of WM injury induced by mild IH differ from that of cystic periventricular leukomalacia where the loss of myelin-producing cells and axons is the major mechanism of injury.