Focus on neonatal and infantile onset of nephrogenic syndrome of inappropriate antidiuresis: 12 years later.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD), first described in 2005, is a rare genetic X-linked disease, presenting with hyponatremia, hyposmolarity, euvolemia, inappropriately concentrated urine, increased natriuresis, and undetectable or very low arginine-vasopressine (AVP) circulating levels. It can occur in neonates, infants, or later in life. NSIAD must be early recognized and treated to prevent severe hyponatremia, which can show a dangerous impact on neonatal outcome. In fact, it potentially leads to death or, in case of survival, neurologic sequelae. This review is an update of NSIAD 12 years after the first description, focusing on reported cases of neonatal and infantile onset. The different molecular patterns affecting the AVP receptor 2 (V2R) and determining its gain of function are reported in detail; moreover, we also provide a comparison between the different triggers involved in the development of hyponatremia, the evolution of the symptoms, and modality and efficacy of the different treatments available.

COVID-19 Vaccination in Children: An Open Question.

BACKGROUND: A safe and effective vaccine represents the best way to control the COVID-19 pandemic, which has caused more than 4 million deaths to date. Several vaccines have now been approved worldwide, depending on the country. Being administered to healthy people, anti-SARS-CoV-2 vaccines must meet high safety standards, and this is even more important among the pediatric population in which the risk of developing severe disease is significantly lower than adults. However, vaccination of the pediatric population could help in reducing viral spread in the whole population. OBJECTIVE: Our narrative review analyzes and discusses the currently available literature on the advantages and disadvantages of COVID-19 vaccination in the pediatric population. METHODS: A bibliographic research was conducted through Pubmed, Read, and Scopus using COVID-19, SARS-CoV-2, immunization, antibody, COVID-19 vaccine efficacy, COVID-19 vaccine safety, children, adolescents, MIS-C, adverse effects as keywords. RESULTS: Although children are less susceptible to COVID-19 infection, they can develop serious consequences, including multi-inflammatory syndrome. However, any vaccine-related side effects should be evaluated before administering vaccination to children while ensuring complete safety. To date, adverse effects are reported in adolescents and young adults following vaccination; however, these are mostly isolated reports. CONCLUSION: Further investigation is needed to establish whether there is indeed a cause-and-effect relationship in the development of vaccine-related adverse effects. However, to date, COVID-19 vaccination is recommended for children and adolescents older than 12 years of age. However, this question is still under debate and involves ethical, political, and social issues.

COVID-19 and School: To Open or Not to Open, That Is the Question. The First Review on Current Knowledge.

The COVID-19 pandemic has led to an unprecedented closure of schools in terms of duration. The option of school closure, SARS-CoV-2 initially being poorly known, was influenced by the epidemiological aspects of the influenza virus. However, school closure is still under debate and seems unsupported by sure evidence of efficacy in the COVID-19 era. The aim of our narrative review is to discuss the available literature on SARS-CoV-2 spread among children and adolescents, in the school setting, trying to explain why children appear less susceptible to severe disease and less involved in viral spreading. We also tried to define the efficacy of school closure, through an overview of the effects of the choices made by the various countries, trying to identify which preventive measures could be effective for a safe reopening. Finally, we focused on the psychological aspects of such a prolonged closure for children and adolescents. SARS-CoV-2, children, COVID-19, influenza, and school were used as key words in our literature research, updated to 29 March 2021. To our knowledge, this is the first review summarizing the whole current knowledge on SARS-CoV-2 spreading among children and adolescents in the school setting, providing a worldwide overview in such a pandemic context.

COVID-19 and developmental origins of health and disease.

From the moment of the identification of SARS-CoV-2 as an etiological agent of the severe clinical pictures of pneumonia that were being slowly observed all over the world, numerous studies have been conducted to increase the knowledge about what was an unknown virus until then. The efforts were mainly aimed to acquire epidemiological, microbiological, pathogenetic, clinical, diagnostic, therapeutic and preventive information in order to increase the available weapons to fight an infection which was rapidly taking on the characteristics of the pandemic. Given the topicality of the problem, not everything has yet been fully understood and clarified, especially in the maternal-fetal­neonatal field, where we are beginning to question what could be the outcomes of newborn babies born to mothers who contracted SARS-CoV-2 infection during pregnancy. Thus, the aim of this review is to analyze the long-term outcomes of this infection that could affect the offspring, regardless of a possible maternal-fetal transmission, focusing on, above all, the role of maternal immune activation and the expression of the Angiotensin-converting enzyme 2 (ACE2) in particular at the placental level.

Thiamine as a Possible Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Encephalopathy.

On the basis that similar biochemical and histological sequences of events occur in the brain during thiamine deficiency and hypoxia/ischemia related brain damage, we have planned this review to discuss the possible therapeutic role of thiamine and its derivatives in the management of neonatal hypoxic-ischemic encephalopathy (HIE). Among the many benefits, thiamine per se as antioxidant, given intravenously (IV) at high doses, defined as dosage greater than 100 mg IV daily, should counteract the damaging effects of reactive oxygen and nitrogen species in the brain, including the reaction of peroxynitrite with the tyrosine residues of the major enzymes involved in intracellular glucose metabolism, which plays a key pathophysiological role in HIE in neonates. Accordingly, it is conceivable that, in neonatal HIE, the blockade of intracellular progressive oxidative stress and the rescue of mitochondrial function mediated by thiamine and its derivatives can lead to a definite neuroprotective effect. Because therapeutic hypothermia and thiamine may both act on the latent period of HIE damage, a synergistic effect of these therapeutic strategies is likely. Thiamine treatment may be especially important in mild HIE and in areas of the world where there is limited access to expensive hypothermia equipment.

Neonatal Congenital Central Hypoventilation Syndrome: Why We Should not Sleep on it. Literature Review of Forty-two Neonatal Onset Cases.

Congenital Central Hypoventilation Syndrome (CCHS), also referred with the expression "Ondine's Curse", is a rare genetic life-long disease resulting from the mutation of PHOX2B gene on chromosome 4p12.3. CCHS represents an autonomic nervous system disorder; its more fearsome manifestation is central hypoventilation, due to a deficient response of chemoreceptors to hypercapnia and hypoxia. Several associated symptoms can occur, such as pupillary anomalies, arrhythmias, reduced heart rate variability, esophageal dysmotility, and structural comorbidities (Hirschsprung's Disease or neural crest tumours). CCHS typical onset is during the neonatal period, but cases of delayed diagnosis have been reported; moreover, both sporadic or familial cases can occur. In preterm newborns, asphyxia and typical prematurity-related findings may overlap CCHS clinical manifestations and make it harder to formulate a correct diagnosis. The early recognition of CCHS allows appropriate management, useful to reduce immediate and long- term consequences.

The first case of neonatal priapism during hypothermia for hypoxic-ischemic encephalopathy and a literature review.

Neonatal priapism is a rare condition with only 26 described cases in literature since 1879. It is defined as a persistent penile erection occurring in the first 28 days of life, lasting at least 4 h that usually happens in the first days (from 2 to 12 days). It is a very different condition compared to the adult one because in newborns it is a relatively benign phenomenon. As a result of this paucity of described cases, classification and management are not well known by most of neonatologists and currently there are no established guidelines for its management. Most cases are idiopathic but other aetiologies are possible (polycythemia, blood transfusion and drugs). We describe our only case, which occurred during hypothermia therapy and review the literature to clarify the best choice in management of this rare entity.

Urinary 1H-NMR Metabolomics in the First Week of Life Can Anticipate BPD Diagnosis.

Despite the advancements in medical knowledge and technology, the etiopathogenesis of bronchopulmonary dysplasia (BPD) is not yet fully understood although oxidative stress seems to play a role, leading to a very demanding management of these patients by the neonatologist. In this context, metabolomics can be useful in understanding, diagnosing, and treating this illness since it is one of the newest omics science that analyzes the metabolome of an individual through the investigation of biological fluids such as urine and blood. In this study, 18 patients admitted to the Neonatal Intensive Care Unit of the Cagliari University Hospital were enrolled. Among them, 11 patients represented the control group and 7 patients subsequently developed BPD. A sample of urine was collected from each patient at 7 days of life and analyzed through 1H-NMR coupled with multivariate statistical analysis. The discriminant metabolites between the 2 groups noted were alanine, betaine, trimethylamine-N-oxide, lactate, and glycine. Utilizing metabolomics, it was possible to detect the urinary metabolomics fingerprint of neonates in the first week of life who subsequently developed BPD. Future studies are needed to confirm these promising results suggesting a possible role of microbiota and oxidative stress, and to apply this technology in clinical practice.

Urine metabolomic profiling in neonatal nephrology.

Metabolomics, the latest "omics" technology aims to study the complete set of low molecular weight metabolites that may change according to the physiological or the pathological state of the organism. Clinical studies dealing with metabolomics in neonatal and pediatric nephrology are very few. In this paper we present the experimental studies in newborn animal models, together with the available data on human newborns. Finally the urine metabolomic profiling of 3 newborns who suffered from severe perinatal asphyxia and were treated with hypothermia. They are located in a different part of the multivariate space, the reason of the differences being the basal metabolic profile (resilience) of each neonate: 1 died and 2 survived (one of them developed an acute kidney injury). The main metabolites responsible for the different metabolic profile among the 3 newborns are presented. In the future each neonatologist and nephrologist should become skilled in the metabolomic field.

Urinary metabolomics of bronchopulmonary dysplasia (BPD): preliminary data at birth suggest it is a congenital disease.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) or chronic lung disease is one of the principal causes of mortality and morbidity in preterm infants. Early identification of infants at the greater risk of developing BPD may allow a targeted approach for reducing disease severity and complications. The trigger cause of the disease comprehends the impairment of the alveolar development and the increased angiogenesis. Nevertheless, the molecular pathways characterizing the disease are still unclear. Therefore, the use of the metabolomics technique, due to the capability of identifying instantaneous metabolic perturbation, might help to recognize metabolic patterns associated with the condition. METHODS: The purpose of this study is to compare urinary metabolomics at birth in 36 newborns with a gestational age below 29 weeks and birth weight <1500 g (very low birth weight - VLBW), admitted in Neonatal Intensive Care Unit (NICU) divided into two groups: the first group (18 cases) consisting of newborns who have not yet developed the disease, but who will subsequently develop it and the second group (18 controls) consisting of newborns not affected by BPD. Urine samples were collected within 24-36 h of life and immediately frozen at -80 °C. RESULTS: The (1)H-NMR spectra were analyzed using a partial least squares discriminant analysis (PLS-DA) model coupled with orthogonal Signal Correction. Using this approach it was possible with urine at birth to discriminate newborns that will be later have a diagnosis of BPD with a high statistics power. In particular, we found five important discriminant metabolites in urine in BPD newborns: lactate, taurine, TMAO, myoinositol (which increased) and gluconate (which decreased). CONCLUSION: These preliminary results seem to be promising for the identification of predictor's biomarkers characterizing the BPD condition. These data may suggest that BPD is probably the result of an abnormal development (respiratory bud, vascular tree, hypodysplasia of pneumocytes) and could be considered a congenital disease (genetics plus intrauterine epigenetics). Early identification of infants at the greater risk of developing BPD may allow a targeted approach for reducing disease severity and complications.

Hyponatremia and hypernatremia in the newborn: in medio stat virtus.

Hyponatremia and hypernatremia are complex clinical problems that occur frequently in full term newborns and in preterm infants admitted to the Neonatal Intensive Care Unit (NICU) although their real frequency and etiology are incompletely known. Pathogenetic mechanisms and clinical timing of hypo-hypernatremia are well known in adult people whereas in the newborn is less clear how and when hypo-hypernatremia could alter cerebral osmotic equilibrium and after how long time brain cells adapt themselves to the new hypo-hypertonic environment. Aim of this review is to present a practical approach and management of hypo-hypernatremia in newborns, especially in preterms.

Neonatal hyponatremia: differential diagnosis and treatment.

Hyponatremia is very frequent in neonates, especially in VLBW. Recent data have shown that hyponatremia is not so benign as previously believed,and several clinical studies have indicated that preterms with mild to moderate chronic hyponatremia may experience poor growth and development retardation. The aim of this review is to present how to differentiate hypovolemic, euvolemic and hypervolemic hypernatremias, suggesting algorithms for practical management.

Neonatal onset of nephrogenic syndrome of inappropriate antidiuresis.

This paper describes the manifestation in a child of a new syndrome characterized by unusual, severe, persistent hyponatremia associated with hyposmolarity, euvolemia, inappropriately concentrated urine and elevated natriuresis. This is the fourth case of this syndrome reported to date, and the first to be reported in a neonate. The clinical features resemble those typically observed in patients with inappropriate antidiuretic hormone secretion, although high arginine vasopressin (AVP) levels are lacking. The findings led the authors to hypothesise a nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The previously described R137C gain-of-function mutation was detected by means of mutation analysis of the V2R gene. Our results indicate that NSIAD is already present during the neonatal period and that molecular analysis of the V2R receptor should therefore be carried out, in all newborns with prolonged euvolemic hyponatremia with hypo-osmolarity, high urinary sodium and normal/low or undetectable AVP levels.