Neonatal intensive care units (NICUs) greatly expand the use of technology. There is a need to accurately diagnose discomfort, pain, and complications, such as sepsis, mainly before they occur. While specific treatments are possible, they are often time-consuming, invasive, or painful, with detrimental effects for the development of the infant. In the last 40 years, heart rate variability (HRV) has emerged as a non-invasive measurement to monitor newborns and infants, but it still is underused. Hence, the present paper aims to review the utility of HRV in neonatology and the instruments available to assess it, showing how HRV could be an innovative tool in the years to come. When continuously monitored, HRV could help assess the baby's overall wellbeing and neurological development to detect stress-/pain-related behaviors or pathological conditions, such as respiratory distress syndrome and hyperbilirubinemia, to address when to perform procedures to reduce the baby's stress/pain and interventions, such as therapeutic hypothermia, and to avoid severe complications, such as sepsis and necrotizing enterocolitis, thus reducing mortality. Based on literature and previous experiences, the first step to efficiently introduce HRV in the NICUs could consist in a monitoring system that uses photoplethysmography, which is low-cost and non-invasive, and displays one or a few metrics with good clinical utility. However, to fully harness HRV clinical potential and to greatly improve neonatal care, the monitoring systems will have to rely on modern bioinformatics (machine learning and artificial intelligence algorithms), which could easily integrate infant's HRV metrics, vital signs, and especially past history, thus elaborating models capable to efficiently monitor and predict the infant's clinical conditions. For this reason, hospitals and institutions will have to establish tight collaborations between the obstetric, neonatal, and pediatric departments: this way, healthcare would truly improve in every stage of the perinatal period (from conception to the first years of life), since information about patients' health would flow freely among different professionals, and high-quality research could be performed integrating the data recorded in those departments.

/pdf/heart-rate-variability-in-the-perinatal-period-a-critical-4460qhuk10.pdf

Heart Rate Variability in the Perinatal Period: A Critical and Conceptual Review

Catecholamines (CA) are released from and resynthesized in the adrenal medulla in response to stress. In the mature animal, stimulus-secretion-synthesis coupling occurs through transsynaptic (neuronal) activity. In contrast, in the immature animal, before functional adrenal innervation, certain stressors (hypoglycemia and glycopenia) do not result in CA release. Additionally, it is not known whether release and biosynthesis remain coupled in the neonate as they are in the adult. Therefore, to evaluate whether neonatal stressors can induce CA biosynthesis at the genomic level "directly" before function adrenal innervation, we studied the expression of the tyrosine hydroxylase (TH) gene, the rate-limiting enzyme in CA biosynthesis. Newborn rat pups were made either hypoxic, hypoglycemic, or cellularly glycopenic (2-deoxyglucose). Neither hypoxic stress nor insulin-induced hypoglycemic stress altered steady state levels of TH mRNA in the neonate. However, cellular glycopenia resulted in a significant 2-fold rise in TH mRNA levels (p < 0.05). As expected, each of these stressors increased TH mRNA levels in the mature adult rat. Thus, neonatal hypoxia and hypoglycemia appear to require intact neurogenic impulse activity, whereas cellular glycopenia may "directly" induce TH RNA, perhaps through hormonal mechanisms. This developmental model allows for the analysis of mechanisms governing adrenal CA release separate from those governing biosynthesis at the level of TH RNA. Acute neonatal hypoxic stress results in adrenal CA release without increasing TH RNA. Intrauterine growth retardation from chronic prenatal hypoxemia results in neonatal CA depletion and decreased CA responsiveness. We speculate that chronic hypoxia alters CA pathways, increasing the susceptibility of these infants to later stressors.

/pdf/neonatal-stress-effects-of-hypoglycemia-and-hypoxia-on-3vip5la9pz.pdf

Neonatal stress: effects of hypoglycemia and hypoxia on adrenal tyrosine hydroxylase gene expression.

Disorders of the Autonomic Nervous System

Clinical Anatomy, Histology, Embryology, and Neuroanatomy

In utero exposure to tetrahydrocannabinol, the psychoactive component of marijuana, is associated with an increased risk for neurodevelopmental defects in the offspring by interfering with the functioning of the endocannabinoid (eCB) system. At the present time, it is not clearly known whether the eCB system is present before neurogenesis. Using an array of biochemical techniques, we analyzed the levels of CB1 receptors, eCBs (AEA and 2-AG), and the enzymes (NAPE-PLD, DAGLα, DAGLβ, MAGL, and FAAH) involved in the metabolism of the eCBs in chick and mouse models during development. The findings demonstrate the presence of eCB system in early embryo before neurogenesis. The eCB system might play a critical role in early embryogenesis and there might be adverse developmental consequences of in utero exposure to marijuana and other drugs of abuse during this period.

/pdf/cannabinoid-receptor-1-signaling-in-embryo-neurodevelopment-2cdzhz906a.pdf

Cannabinoid Receptor 1 Signaling in Embryo Neurodevelopment

The neurons and glia of the sympathetic, parasympathetic, and enteric nervous systems stem from the neural crest, which arises in the embryonic central nervous system. These cells migrate in a manner regulated in space and time along paths dictated by permissive and repulsive molecules from their surroundings, and by interactions between the crest cells. The cells then localize and aggregate to form ganglia, differentiate, and extend neurites to targets. These activities involve an enormous range of growth factor, neurotrophic factor, and cell contact signals in each step, controlling genes for transcription factors, cell adhesion and motility molecules, receptors, neurotransmitters, and neuromodulators.

Autonomic Nervous System Development

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Autonomic Nervous System Development