GLUT-1DS resistant to ketogenic diet: from clinical feature to in silico analysis. An exemplificative case report with a literature review.

Glucose transporter type 1 deficiency syndrome (GLUT-1DS) is characterized by alterations in glucose translocation through the blood-brain barrier (BBB) due to mutation involving the GLUT-1 transporter. The fundamental therapy is ketogenic diet (KD) that provide an alternative energetic substrate - ketone bodies that across the BBB via MCT-1 - for the brain. Symptoms are various and include intractable seizure, acquired microcephalia, abnormal ocular movement, movement disorder, and neurodevelopment delay secondary to an energetic crisis for persistent neuroglycopenia. KD is extremely effective in controlling epileptic seizures and has a positive impact on movement disorders and cognitive impairment. Cases of KD resistance are rare, and only a few of them are reported in the literature, all regarding seizure. Our study describes a peculiar case of GLUT-1DS due to a new deletion involving the first codon of SLC2A1 gene determining a loss of function with a resistance to KD admitted to hospital due to intractable episodes of dystonia. This patient presented a worsening of symptomatology at higher ketonemia values but without hyperketosis and showed a complete resolution of symptomatology while maintaining low ketonemia values. Our study proposes an in-silico genomic and proteomic analysis aimed at explaining the atypical response to KD exhibited by our patient. In this way, we propose a new clinical and research approach based on precision medicine and molecular modelling to be applied to patients with GLUT-1DS resistant to first-line treatment with ketogenic diet by in silico study of genetic and altered protein product.

Evidences of emerging pain consciousness during prenatal development: a narrative review.

BACKGROUND: The study of consciousness has always been considered a challenge for neonatologists, even more when considering the uterine period. Our review aimed to individuate at what gestational age the fetus, which later became a premature infant, can feel the perception of external stimuli. Therefore, the aim of our review was to study the onset of consciousness during the fetal life. MATERIALS AND METHODS: A literature search was performed in Medline-PubMed database. We included all papers found with the following MeSH words: "consciousness or cognition or awareness or comprehension or cognitive or consciousness of pain" in combination with "embryo or fetus or fetal life or newborn." Studies were selected if titles and/or abstracts suggested an association between formation of consciousness (the basics of neurodevelopment) and preterm infant or fetus. Titles and abstracts were first screened by three independent reviewers according to Cochrane Collaboration's recommendations. RESULTS: From the literature review, we found only 8 papers describing the onset of consciousness in the transition period from fetus to premature newborn. Therefore, according to these papers, we temporally analyzed the formation of the thalamocortical connections that are the basis of consciousness. CONCLUSIONS: We can conclude that from a neuroanatomical point of view, it is rather unlikely that the infant can be seen as a conscious human before 24 weeks of gestational age, thus before all the thalamocortical connections are established. Further literature data have to confirm this hypothesis.

Neonates Born to COVID-19 Mother and Risk in Management within 4 Weeks of Life: A Single-Center Experience, Systematic Review, and Meta-Analysis.

OBJECTIVE: The new coronavirus infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized as a global public health emergency, and neonates may be more vulnerable due to their immature immune system. The first aim of this study was to report our experience on the management of neonates from mothers with SARS-CoV-2 infection focusing on a 28-day follow-up since birth. The second aim is to assess how many data on neonatal outcomes of the first month of life are reported in literature, performing a systematic review and meta-analysis. STUDY DESIGN: We report our experience based on routine management of neonates born to mothers with SARS-CoV-2 infection and follow-up until 28 days of life. RESULTS: In our experience at discharge, 1/48 (2.08%) of entrusted (mother refusing personal protective equipment) and none of separated presented positive nasopharyngeal swab (p = NS). All babies show good outcome at 28 days of life. The literature data show that the percentage of positive separated infants is significantly higher than the percentage of infants entrusted to positive mothers with appropriate control measures (13.63 vs. 2.4%; p = 0.0017). Meta-analysis of studies focused on follow-up showed a 2.94% higher risk of incidence of SARS-CoV-2 infection in entrusted newborns than in separated newborns (95% confidence interval: 0.39-22.25), but this was not significant (p = 0.30). CONCLUSION: A vertical transmission in utero cannot be totally excluded. Since in newborns, the disease is often ambiguous with mild or absent symptoms, it is important to define the most efficient joint management for infants born to COVID-19 positive mothers, being aware that the risk of horizontal transmission from a positive mother, when protective measures are applied, does not seem to increase the risk of infection or to affect the development of newborns from birth to first four weeks of life, and encourages the benefits of breastfeeding and skin-to-skin practice. KEY POINTS: · Entrusting the newborn to the positive mother does not increase the risk of infection.. · Our follow-up shows that newborns have good growth and outcome at one month of life.. · Applying protective measures we suggest breastfeeding and skin-to-skin practice..

Pyridoxine Add-On Treatment for the Control of Behavioral Adverse Effects Induced by Levetiracetam in Children: A Case-Control Prospective Study.

BACKGROUND: Few studies on adult and pediatric patients have shown pyridoxine efficacy as additional therapy for those receiving levetiracetam (LEV) to prevent and mitigate behavioral adverse effects (BAEs). OBJECTIVE: The aim of our study was to analyze the safety and efficacy of pyridoxine supplementation in the prevention of LEV adverse effects, including suicidal ideation. METHODS: This randomized, case-control trial included patients receiving LEV as monotherapy treatment. Patients were subdivided into 2 groups, according to whether they were treated with LEV only (group 1) or LEV with supplemental pyridoxine (group 2). RESULTS: In both cohorts, the most frequent BAEs were irritability/aggression followed by depression and confusion. Those patients (92%) who initiated pyridoxine after 1 month of LEV treatment did not need to change or suspend LEV ( P < 0.001), and BAE improved after 9.06 ± 3.05 days of pyridoxine supplementation. None of the patients complained of symptoms of pyridoxine toxicity, and no new adverse effects of LEV off-label were reported. CONCLUSIONS: In our study, we found pyridoxine to be safe and effective in controlling LEV-induced BAEs in children.

Pyridoxine-dependent epilepsies: an observational study on clinical, diagnostic, therapeutic and prognostic features in a pediatric cohort.

The aim of our study was to describe the clinical, electroencephalogram, molecular findings and the diagnostic and therapeutic flow-chart of children with pyridoxine-dependent epilepsies (PDEs). We performed a retrospective observational study on children with PDEs, diagnosed and followed-up in Italian Pediatric Departments. In each centre, the authors collected data from a cohort of children admitted for intractable seizures, responsive to pyridoxine administration and resistant to other anticonvulsant therapies. Data were retrospectively analysed from January 2016 to January 2017. Sixteen patients (13 males, and 3 females) were included. We found that 93.75% of patients underwent conventional anticonvulsant therapy before starting pyridoxine administration and 62.5% had ex-juvantibus diagnosis, as specific serum diagnostic tests had been performed in only 37.5% of patients by alpha-AASA and pipecolic acid blood and urine dosage. The most common type of seizure was generalized tonic-clonic in 7 patients and the most common EEG pattern was characterized by a "burst suppression" pattern. Before pyridoxine administration, other anticonvulsant drugs were used in 93.75% of patients, with consequent onset of drug-resistance. Phenobarbital was the most frequently used drug as first-line treatment. The importance of our study relies on the need of a deeper knowledge of PDEs in terms of early diagnosis, avoiding incorrect treatment and related adverse events, clinical and EEG pathognomonic features, and genetic aspects of the disease.

Change in Coefficient of Fatigability Following Rapid, Repetitive Movement Training in Post-Stroke Spastic Paresis: A Prospective Open-Label Observational Study.

BACKGROUND: In post-stroke patients, the possibility of performing an active ankle dorsiflexion movement is favorable for the recovery of gait. Moreover, the fatigue due to repetitive active ankle dorsiflexion could reduce the speed gait. We assessed the change in coefficient of fatigability of active ankle dorsiflexion after a home-based self-rehabilitative procedure in post-stroke patients. METHODS: In a prospective open-label observational study conducted in 2 university hospitals, a home-based self-rehabilitation treatment comprising two 12-minute sessions per day (3 times per week for 3 months) was performed by 10 outpatients with post-stroke lower limb impairment. Each session consisted of three 1-minute series of repeated active ankle dorsiflexion efforts at maximal speed on the paretic side, each one followed by 3-minute bouts of triceps surae stretch. Coefficients of fatigability of dorsiflexion and 10-meter barefoot ambulation speed were evaluated at baseline and at the end of the program. RESULTS: At 3 months of follow-up, there was a decrease in the coefficients of fatigability of ankle dorsiflexion, both with knee flexed and extended (respectively from 8% to 2% and from 6% to 2%; P < .01), associated with an increase in comfortable ambulation speed (from .24 to .26 m/s; P < .05). CONCLUSIONS: The reduction of coefficient of fatigability of ankle dorsiflexion, together with walking speed improvement, suggested the effectiveness of self-rehabilitation using alternated periods of self-stretch and rapid alternating efforts in the paretic lower limb after stroke.

The immunomodulatory effect of probiotics beyond atopy: an update.

BACKGROUND: In the past decades, the theory of "allergen avoidance" was considered the standard treatment for preventing the onset of allergic diseases. Recently, the concept of "immune tolerance" has replaced this old theory, and induction of tolerance by exposure is actually considered the appropriate method for preventing atopic diseases and other immunomediated pathologies. On the other hand, it is obvious that for public health reasons, abandoning current medical and hygienic practices is not desirable; therefore, safe alternatives, such as probiotics, have been suggested for providing necessary microbial stimulation. OBJECTIVE: The purpose of our review is to describe the immunomodulatory and anti-inflammatory properties of probiotics, reporting literature data on their effect when used for the treatment of immunomediated diseases. MATERIALS AND METHODS: Articles reporting the evidence on the use of probiotics in immunomediated diseases, such as atopy, cow's milk allergy and rheumatoid arthritis (RA), and in inflammatory diseases, such as inflammatory bowel diseases (IBDs), with or without statistical meta-analysis, were selected in three different search engines: (1) MEDLINE via PubMed interface, (2) Scopus and (3) Google Scholar for all articles published from inception to July 2013. Titles and abstracts of identified papers were screened by two independent reviewers to determine whether they met the eligibility criteria of interest to develop our review. Subsequently, full texts of the remaining articles were independently retrieved for eligibility by the two reviewers. RESULTS AND DISCUSSION: The recent literature is focusing its interest towards the immunologic properties of relatively harmless organisms, including lactobacilli and bifidobacteria, helminths and saprophytic mycobacteria that may skew immune responses towards immunoregulation by inducing Treg cells, rather than eliciting a pro-inflammatory immune response. For this reason, recent researches have been addressed on the use of probiotics to promote immunoregulation in atopic diseases, such as atopic/eczema dermatitis syndrome and food allergy, as well as in inflammatory-based diseases such as IBDs, RA and bronchial asthma.

Polysomnographic evaluation of non-invasive ventilation in children with neuromuscular disease.

BACKGROUND AND OBJECTIVE: In the last 20 years, research efforts have been focused on the use of non-invasive ventilation (NIV) as a mean of avoiding tracheostomy in patients affected by neuromuscular diseases (NMD). Nocturnal NIV has been a particular focus as sleep is a risk factor for respiratory failure in NMD patients. The objective of our study was to evaluate the efficacy of nocturnal NIV in improving the respiratory function of NMD patients evaluated by polysomnography (PSG) and arterial blood gas (ABG) analysis parameters. METHODS: Ten children affected by NMD underwent PSG and ABG analysis evaluation at the onset of their respiratory failure and during nocturnal NIV therapy. RESULTS: We found a statistically significant improvement of the lowest oxygen desaturation (nadir SaO2 ), apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) after NIV treatment in all patients. Mean SaO2 also improved, although this result was not statistical significant, while the percentage of episodes of desaturation with a SaO2 <90% and <80% decreased with a statistical significance (P < 0.0001). After NIV, only one patient showed an episode of desaturation lasting more than 5 min (10.6 min length), and we also found an improvement of daytime blood gas parameters with a normalization of these indexes. CONCLUSIONS: NIV was effective in improving respiratory parameters at night in patients affected by respiratory muscular weakness, as evaluated by PSG and ABG analysis.

Human Milk Oligosaccharides and Their Pivotal Role in Gut-Brain Axis Modulation and Neurologic Development: A Narrative Review to Decipher the Multifaceted Interplay.

BACKGROUND: Human milk oligosaccharides (HMOs), which are unique bioactive components in human milk, are increasingly recognized for their multifaceted roles in infant health. A deeper understanding of the nexus between HMOs and the gut-brain axis can revolutionize neonatal nutrition and neurodevelopmental strategies. METHODS: We performed a narrative review using PubMed, Embase, and Google Scholar to source relevant articles. The focus was on studies detailing the influence of HMOs on the gut and brain systems, especially in neonates. Articles were subsequently synthesized based on their exploration into the effects and mechanisms of HMOs on these interconnected systems. RESULTS: HMOs significantly influence the neonatal gut-brain axis. Specific concentrations of HMO, measured 1 and 6 months after birth, would seem to agree with this hypothesis. HMOs are shown to influence gut microbiota composition and enhance neurotransmitter production, which are crucial for brain development. For instance, 2'-fucosyllactose has been demonstrated to support cognitive development by fostering beneficial gut bacteria that produce essential short-chain fatty acids. CONCLUSIONS: HMOs serve as crucial modulators of the neonatal gut-brain axis, underscoring their importance in infant nutrition and neurodevelopment. Their dual role in shaping the infant gut while influencing brain function presents them as potential game-changers in neonatal health strategies.

PYRIDOXINE-dependent epilepsy (PDE): An observational study of neonatal cases on the role of pyridoxine in patients treated with standard anti-seizure medications.

BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). MATERIALS AND METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

Opening interrupter technique in pre-school children with chronic respiratory diseases: a perspective case-control study in the diagnosis of airway hyperesponsiveness.

BACKGROUND: Optimal treatment for pediatric respiratory diseases is strictly related to follow-up evaluations of lung function. The aim of our study was to show the efficacy of the Opening Interrupter Technique in diagnosing the presence of airway obstruction in pre-school children. MATERIALS AND METHODS: Our study was a prospective case-control study, evaluating 82 patients affected by asthma and/or cystic fibrosis (CF) and 50 healthy pre-school children, as control group. All patients were 3- to 5-years old and they were followed by our Pediatric Department, University of Catania, Italy, from February 2011 to June 2012. Measurements of respiratory resistance (o-Rint) by the opening interrupter technique were made with the MasterScreen PFT device, Jaeger GmbH, Würzburg, Germany, during quiet breathing. The presence of airway obstruction was detected as a value of o-Rint higher than two standard deviations (SD) compared with the theoretical data. RESULTS: We found higher values of o-Rint in asthmatic patients than in the control group, with a high statistical difference (p < 0.0001). The same results were found when we compared patients with CF and the control group (p < 0.0001). Nevertheless, we did not find any significant statistical difference between respiratory resistances measured in asthmatic and patients with CF (p > 0.05). There was a significant inverse correlation between o-Rint and height only in asthmatic and patients with CF, but not in healthy controls (p < 0.05). CONCLUSIONS: In our study, the opening interrupter technique was efficient in detecting the presence of obstruction in chronic patients affected by asthma and CF.

Mood and anxiety spectrum disorders detected by neuropsychiatric interviews in young adults born preterm: A prospective cohort study.

BACKGROUND: Psychopathology has not yet been studied beyond pediatric age for all degrees of prematurity, including late-preterm, particularly in those who grew up with no apparent neurodevelopmental sequelae. This study aimed to examine psychopathological outcome following preterm birth and admission to neonatal intensive care in young adults without major neurodevelopmental and psychopathological problems that emerged during childhood. METHODS: An Italian single-center prospective cohort study. Eighty-nine young adults (40 admitted to neonatal intensive care unit with less than 37 weeks of gestation and no medical history of other neurological or psychiatric conditions in childhood and 49 healthy peers born at term, matched by age, sex, and education) underwent neuropsychiatric interviews at the age of 20 ± 1 years; MINI International Neuropsychiatric Interview, Beck Depression Inventory and Barratt Impulsive Scale, results were correlated to individual neonatal data and cognitive measures. RESULTS: We found a significantly higher prevalence of psychopathology at MINI score (22.5% vs. 4.2%; χ2 = 6.7; p = 0,010) and prevalence of previous stressful life events in the preterm compared to at-term group. B.D.I. (testing depression) and BIS-11(testing impulsivity) did not highlight a statistically significant difference between the groups. All patients had average I.Q., a statistically significant difference (p < 0.001) was observed between groups with a better performance in controls than cases. CONCLUSIONS: Preterm infants attaining young adult age with otherwise typical development during childhood are at risk of psychopathology and lower resilience to stressful life events. The MINI interview could be a useful tool to highlight the psychopathology of preterm infants attaining adult age.

Need for palliative care from birth to infancy in pediatric patients with neurological diseases.

BACKGROUND: Palliative care is a comprehensive treatment approach that guarantees comfort for pediatric patients and their families from diagnosis to death. The techniques used for neurological patients in the field of palliative care can enhance the quality of care provided to patients with neurological disorders and support their families. PURPOSE: This study aimed to analyze the palliative care protocols in use in our department, describe the palliative course in the clinical setting, and propose the implementation of hospital palliative care for long-term prognosis of patients with neurological diseases. METHODS: This retrospective observational study examined the application of palliative care from birth to early infancy in neurological patients. We studied 34 newborns with diseases affecting the nervous system impairing prognosis. The study was conducted from 2016 to 2020 at the Neonatology Intensive Care Unit and the Pediatric Unit of the San Marco University Hospital in Catania, Sicily, Italy. RESULTS: Despite current legislation in Italy, no palliative care network has been activated to meet the needs of the population. In our center, given the vast number of patients with neurological conditions requiring palliative care, we should activate a straightforward departmental unit for neurologic pediatric palliative care. CONCLUSION: The establishment of specialized reference centers that manage significant neurological illnesses is due to neuroscience research progress in recent decades. Integration with specialized palliative care is sparse but now seems essential.

Simple febrile seizures: new cut off for the duration of the crises.

BACKGROUND: Our study aimed to identify a new cut-off for febrile seizure (FS) with a good prognosis, thereby replacing the 15 min described in the standard definition of simple febrile seizure (SFS). METHODS: Our study was a retrospective observational study (from January 2018 to December 2018) on children admitted to the Pediatric emergency room of the Santobono-Pausilipon Hospital, Naples, Italy, Pediatric Unit of Latina, Rome, Italy, and Policlinico-Vittorio-Emanuele University Hospital, Catania, Italy, for fever, which developed SFS during the hospitalization. All included patients had their seizures classified as SFS according to the international criteria for epilepsy. We assumed a duration cut-off, and we analyzed the EEG results, neurological follow-up at 12 months, and the recurrence of the febrile seizures the following year. Then, with another calculation, we identify an optimal cut-off of 6 min. Finally, we divided the population into two groups: children with seizures having a duration greater than or less than 6 min. RESULTS: We found that the population with FS with a duration greater than 6 min presented EEG alteration at follow-up visits, neurological disorders, and a recurrence of FS during the following year. CONCLUSIONS: We suggest to introduce a new cut-off for the duration of FS that better represents the benign nature of a simple febrile event.

Thrombotic events in children and adolescent patients with SARS-CoV-2 infection: a systematic review with meta-analysis on incidence and management.

OBJECTIVES: The present paper aimed to study the available literature on the hypercoagulability state of pediatric patients affected by COVID-19, and the current management of thrombosis in these patients, considering that no guidelines have been published since now in this age group. METHODS: N 244 titles were screened using the selected MESH words, 180 abstracts and 120 full texts were read, 12 articles were included, and four were analyzed by meta-analysis. RESULTS: Over 1128 COVID-19 positive patients, nearly half of them developed inflammatory sequelae, and 7.35% (40 patients over 544 who developed MIS-C) had thrombotic events. Less than 50% of patients with inflammatory disease were under anticoagulant prophylactic treatment, and doses of anticoagulant protocols vary from different centers. Thrombotic events prevented after the start of unfractionated heparin (UFH) therapy, even if 1.06% (4 patients) died. Only two patients presented complications after anticoagulant treatment, with non-fatal bleeding after UFH treatment. No other complications were reported. No difference in the incidence of thrombotic events between patients under prophylactic low molecular weight heparin (LMWH) and those without was found in meta-analysis (p = 0.32). CONCLUSIONS: Little is known on the incidence and management of hyper coagulopathy in pediatric COVID-19 infection. Further studies have to clarify this topic.

NRXN1 Deletion in Two Twins' Genotype and Phenotype: A Clinical Case and Literature Review.

In the literature, deletions in the 2p16.3 region of the neurexin gene (NRXN1) are associated with cognitive impairment, and other neuropsychiatric disorders, such as schizophrenia, autism, and Pitt-Hopkins-like syndrome 2. In this paper, we present twins with deletion 2p16.3 of the NRXN1 gene using a comparative genomic hybridization array. The two children had a dual diagnosis consisting of mild cognitive impairment and neurodevelopmental delay. Furthermore, they showed a dysmorphic phenotype characterized by facio-cranial disproportion, turricephalus, macrocrania, macrosomia, strabismus, and abnormal conformation of both auricles with low implantation. The genetic analysis of the family members showed the presence, in the father's genetic test, of a microdeletion of the short arm of chromosome 2, in the 2p16.3 region. Our case report can expand the knowledge on the genotype-phenotype association in carriers of 2p16.3 deletion and for genetic counseling that could help in the prevention and eventual treatment of this genetic condition. Newborn carriers should undergo neurobehavioral follow-ups for timely detection of warning signs.

Isolated ictal apnea in neonatal age: Clinical features and treatment options. A systematic review.

BACKGROUND: Among autonomic seizures apnea still represent a challenge for physicians, and it might constitute the only isolated sign of neurological disorder. The aim of this review is to describe ictal apnea (IA) and its treatment options. METHODS: MeSH and keywords were combined: "neonatal seizures", "ictal neonatal apnea", "apneic seizures". All identified papers were screened for neonatal seizures titles and abstracts; case reports describing patients with IA as an isolated manifestation of neonatal seizures were included. RESULTS: Eight studies including a total of 13 patients were identified. Among 13 patients, 9 were full-term and 4 were preterm neonates. All patients developed IA within twenty-one days from birth. Etiologies of seizures included: temporal lobe hemorrhage (3 pt), occipital stroke (1 pt), hypoxic-ischemic encephalopathy (HIE) (1 pt), parasagittal injury (1 pt), 18 trisomy (2 pt). Five patients showed no structural CNS alterations. Ten patients had the ictal focus localized in the temporal lobe; the occipital lobe was the second most involved site. Phenobarbital was administered in 76 % of cases with IA (10 pt), and showed efficacy in 74 % of them; 2 required a second anti-epileptic drug (AED) to reach seizure control. Levetiracetam was given to 11 % (2 pt) successfully. Only one was treated with midazolam and one did not require any anticonvulsant. CONCLUSIONS: Not homogeneous data and paucity of isolated IA currently reported in literature limits agreement about definition, management and treatment of entity, however an ever-growing attention is needed, and EEG/aEEG, despite their possible controversies in the diagnosis, should be performed to investigate unexplained forms of apnea.

Neonatal neurologic emergencies requiring access to paediatric emergency units: a retrospective observational study.

Herein, authors present a retrospective, multi-center study to determine the number of accesses to Pediatric Emergency Unit (PEU) of patients within 28 days of life, admitted to (1) the Acute and Emergency Pediatric Unit, San Marco University Hospital, Catania, Italy; (2) Garibaldi Hospital for Emergency Care, Catania, Italy; (3) Cannizzaro Hospital for Emergency Care, Catania, Italy. We included neonates admitted for neurologic problems, from January 2015 to December 2020, to the 1-Acute and Emergency Access of the San Marco University Hospital, Catania, Italy [observation center 1 (OC1)]; 2-Garibaldi Hospital for Emergency Care, Catania, Italy (Observation Center 2-OC2); 3-Cannizzaro Hospital for Emergency Care, Catania, Italy (Observation Center 3-OC3). For each patient, we evaluated the severity of urgency, by studying the admission triage-coloured codes, the clinical data at admission and the discharge diagnosis. Neonates who had access to PEU were 812 in the OC1, 3720 in the OC2, and 748 in the OC3 respectively; 69 (8.4%), 138 (3.7%), and 55 (7.4%) was the proportion of neonatal accesses for neurological conditions. We observed that in the study period, the three hospitals had an important decrease of pediatric accesses to their PEU, but the proportion of neonates who had access to the OC1 for neurologic diseases, with respect to the total neonatal accesses, remained stable. We found that the most frequent neurologic disease for which newborns had access to PEU was Cyanosis, (46.1% of all neonatal accesses). Apnea was the second most frequent cause, with a number of 76 accesses (29%). In the literature there are numerous studies on the assessment of diseases that most frequently concern the pediatric patient in an emergency room, but there are very few references on neonatal accesses for urgent neurologic diseases. Therefore, appropriate training is required to avoid unnecessary tests without overlooking potentially serious conditions.

Chorioamnionitis, Inflammation and Neonatal Apnea: Effects on Preterm Neonatal Brainstem and on Peripheral Airways: Chorioamnionitis and Neonatal Respiratory Functions.

Background: The present manuscript aims to be a narrative review evaluating the association between inflammation in chorioamnionitis and damage on respiratory centers, peripheral airways, and lungs, explaining the pathways responsible for apnea in preterm babies born by delivery after chorioamnionitis. Methods: A combination of keywords and MESH words was used, including: "inflammation", "chorioamnionitis", "brainstem", "cytokines storm", "preterm birth", "neonatal apnea", and "apnea physiopathology". All identified papers were screened for title and abstracts by the two authors to verify whether they met the proper criteria to write the topic. Results: Chorioamnionitis is usually associated with Fetal Inflammatory Response Syndrome (FIRS), resulting in injury of brain and lungs. Literature data have shown that infections causing chorioamnionitis are mostly associated with inflammation and consequent hypoxia-mediated brain injury. Moreover, inflammation and infection induce apneic episodes in neonates, as well as in animal samples. Chorioamnionitis-induced inflammation favors the systemic secretion of pro-inflammatory cytokines that are involved in abnormal development of the respiratory centers in the brainstem and in alterations of peripheral airways and lungs. Conclusions: Preterm birth shows a suboptimal development of the brainstem and abnormalities and altered development of peripheral airways and lungs. These alterations are responsible for reduced respiratory control and apnea. To date, mostly animal studies have been published. Therefore, more clinical studies on the role of chorioamninitis-induced inflammation on prematurity and neonatal apnea are necessary.

Prognostic Risk Factors for Severe Outcome in the Acute Phase of Neonatal Hypoxic-Ischemic Encephalopathy: A Prospective Cohort Study.

In the first days after birth, a major focus of research is to identify infants with hypoxic-ischemic encephalopathy at higher risk of death or severe neurological impairment, despite therapeutic hypothermia (TH). This is especially crucial to consider redirection of care, according to neonatal outcome severity. We aimed to seek associations between some neonatal routine parameters, usually recorded in Neonatal Intensive Care Units, and the development of severe outcomes. All consecutive patients prospectively recruited for TH for perinatal asphyxia, born between February 2009 and July 2016, were eligible for this study. Severe outcome was defined as death or major neurological sequelae at one year of age. Among all eligible neonates, the final analysis included 83 patients. Severe outcome was significantly associated with pH and base excess measured in the first hour of life, mode of delivery, Apgar score, Sarnat and Sarnat score, electroencephalogram-confirmed neonatal epileptic seizures, and antiepileptic therapy. Studying univariate analysis by raw relative risk (RR) and 95% confidence intervals (CI), severe outcome was significantly associated with pH (p = 0.011), Apgar score (p = 0.003), Sarnat score (p < 0.001), and Caesarian section (p = 0.015). Conclusions. In addition to clinical examination, we suggest a clinical-electroencephalographic protocol useful to identify neonates at high neurological risk, available before rewarming from TH.