Malnutrition management in children with chronic kidney disease.

Chronic kidney disease (CKD) encompasses diverse conditions such as congenital anomalies, glomerulonephritis, and hereditary nephropathies, necessitating individualized nutritional interventions. Early detection is pivotal due to the heightened risk of adverse outcomes, including compromised growth and increased healthcare costs. The nutritional assessment in pediatric CKD employs a comprehensive, multidisciplinary approach, considering disease-specific factors, growth metrics, and dietary habits. The prevalence of malnutrition, as identified through diverse tools and guidelines, underscores the necessity for regular and vigilant monitoring. Nutritional management strategies seek equilibrium in calorie intake, protein requirements, and electrolyte considerations. Maintaining a well-balanced nutritional intake is crucial for preventing systemic complications and preserving the remaining kidney function. The nuanced landscape of enteral nutrition, inclusive of gastrostomy placement, warrants consideration in scenarios requiring prolonged support, with an emphasis on minimizing risks for optimized outcomes. In conclusion, the ongoing challenge of managing nutrition in pediatric CKD necessitates continuous assessment and adaptation. This review underscores the significance of tailored dietary approaches, not only to foster growth and prevent complications but also to enhance the overall quality of life for children grappling with CKD.

The non-clinical burden of febrile seizures: a systematic review.

Febrile seizures (FS) can be frightening for parents, even though they are usually harmless. Various questionnaires have been used to assess parental reactions and awareness about FS, revealing insufficient knowledge. Studies have shown that educational interventions significantly reduce parental concerns, improve knowledge, and promote better first-aid measures. Providing clear information and emotional support to parents is important to reduce their concerns and improve FS management. Healthcare providers should give comprehensive information about FS, including the risk of recurrence, and provide clear instructions on their management. The economic impact of FS includes direct and indirect costs. Studies have shown a decrease of hospitalizations and associated costs due to improved clinical adherence to guidelines, which also reduces the inappropriate use of healthcare resources. This systematic review provides a comprehensive overview of the existing literature on parental anxiety and education about FS, as well as their economic impact, aiming at identifying areas for improvement in the management of FS and providing valuable insights for healthcare providers and policymakers to better address the non-clinical burden of this condition.

A systematic review and meta-analysis of nutritional and dietary interventions in randomized controlled trials for skin symptoms in children with atopic dermatitis and without food allergy: An EAACI task force report.

This systematic review and meta-analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo-controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta-analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta-analysis of SCORAD outcomes was conducted using random-effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta-analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well-designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies.

Febrile Seizures: A Systematic Review of Different Guidelines.

BACKGROUND: Febrile seizures (FS) are the most common neurological disorder in pediatric age. FS affect 2% to 12% of children and result from a complex interplay of genetic and environmental factors. Effective management and unambiguous recommendations are crucial for allocating health care resources efficiently and ensuring cost-effectiveness in treating FS. METHODS: This systematic review compares existing guidelines to provide insights into FS management. Seven guidelines published between 1991 and 2021, from Japan, United Kingdom, United States, Mexico, India, and Italy, were included. Data extraction covered definitions, diagnostic criteria, hospital admission criteria, diagnostic tests, management, and prophylaxis recommendations. RESULTS: Hospital admission criteria varied but typically included age <18 months and complex FS. Neuroimaging and lumbar puncture recommendations varied, with most guidelines suggesting limited use. Pharmacologic prophylaxis was generally discouraged for simple FS but considered only for high-risk cases, due to the benign nature of FS and the potential side effects of antiseizure medications. CONCLUSIONS: Guidelines on FS exhibit similarities and differences, highlighting the need for standardized management and improved parental education to enhance clinical outcomes and reduce economic and social costs associated with FS. Future research should focus on creating updated international guidelines and ensuring their practical implementation.

Allelic heterogeneity and abnormal vesicle recycling in PLAA-related neurodevelopmental disorders.

The human PLAA gene encodes Phospholipase-A2-Activating-Protein (PLAA) involved in trafficking of membrane proteins. Through its PUL domain (PLAP, Ufd3p, and Lub1p), PLAA interacts with p97/VCP modulating synaptic vesicles recycling. Although few families carrying biallelic PLAA variants were reported with progressive neurodegeneration, consequences of monoallelic PLAA variants have not been elucidated. Using exome or genome sequencing we identified PLAA de-novo missense variants, affecting conserved residues within the PUL domain, in children affected with neurodevelopmental disorders (NDDs), including psychomotor regression, intellectual disability (ID) and autism spectrum disorders (ASDs). Computational and in-vitro studies of the identified variants revealed abnormal chain arrangements at C-terminal and reduced PLAA-p97/VCP interaction, respectively. These findings expand both allelic and phenotypic heterogeneity associated to PLAA-related neurological disorders, highlighting perturbed vesicle recycling as a potential disease mechanism in NDDs due to genetic defects of PLAA.

Recurrent upper respiratory tract infections in early childhood: a newly defined clinical condition.

BACKGROUND: Recurrent Upper Respiratory Tract Infections (R-URTIs) pose a significant challenge in pediatric healthcare, affecting both children and their families. This study aimed to investigate the prevalence, risk factors, and clinical implications of R-URTI in children aged 0-5 years. METHODS: This observational study involved a sample of 483 children aged 0-5 years, focusing on establishing a practical and dynamic definition of R-URTI. Family pediatricians prospectively collected socio-demographic information, medical history, and recorded the occurrence of URTI episodes. Children were followed from recruitment until March 2021, predating the COVID-19 outbreak. RESULTS: A substantial prevalence of R-URTIs was found, estimating it at 5-10% among this age group. To define R-URTI, a practical and dynamic criterion was proposed: children experiencing a minimum of four URTI episodes, each lasting four days or more, within a six-month period, with intervals of well-being in between. CONCLUSIONS: The study highlighted that specific risk factors for R-URTI were elusive, suggesting that this condition may affect children regardless of their family or clinical history. Moreover, the study's stratification by age group and times of observation facilitated patient-specific clinical decision-making. The proposed definition may represent a valuable tool for clinicians in diagnosing and addressing R-URTI cases.

Corrigendum: Neuroimaging in PRUNE1 syndrome: a mini-review of the literature.

[This corrects the article DOI: 10.3389/fneur.2023.1301147.].

Sharenting: hidden pitfalls of a new increasing trend- suggestions on an appropriate use of social media.

BACKGROUND: The term "sharenting", defining the practice of sharing children's photos on social media, has become widespread globally. This phenomenon introduces new risks for children, often overlooked by parents lacking experience or caution in protecting their children from potential harms. MAIN BODY: Parents share multimedia contents with positive intentions, but the lack of immediate risk perception prevails. An Italian study revealed that a significant percentage of parents (68%) frequently share their children's photos on social platforms, often without considering potential risks. Pediatricians play a crucial role in raising awareness among parents regarding the dangers associated with online sharing and must empower families with defensive strategies to safeguard children's privacy. CONCLUSIONS: The commentary emphasizes the need for increased parental assistance in comprehending the risks of sharenting and using social media prudently. Pediatricians are pivotal in guiding parents, striking a balance between the natural urge to share children's progress and an awareness of associated risks. Immediate action by scientific societies involves training and informing parents through various digital and print resources. A concrete regulation of this phenomenon is needed to protect children's rights, but prioritizing digital awareness and education seems pivotal in mitigating sharenting-related risks.

A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce.

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta-analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta-analysis was performed using random-effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower-middle, 12 in upper-middle, and only two in high-income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta-analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta-analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high-income countries.

Nutraceuticals and biotics in pediatric gastrointestinal disorders.

In recent years there has been growing interest in the use of nutraceuticals and biotics in both pediatric and adult clinical practice. The overlapping and often ambiguous symptoms of both functional and organic gastrointestinal disorders have led to a search for alternative therapeutic approaches that avoid the use of synthetic or chemical treatments. However, while nutraceuticals and natural supplements are widely used, their health benefits are often not supported by adequate scientific evidence, and an unregulated use of nutraceuticals can be potentially harmful. The correct use of nutraceuticals, prebiotics, and probiotics can optimize the results of drug therapy in some cases and reduce the risk of side effects. This review aims to provide clinicians with guidance on the use of complementary therapies for pediatric gastrointestinal symptoms and disorders, highlighting the scarcity of studies on the kinetics and dynamics of nutraceuticals and biotics. While it is generally difficult to associate their intakes with adverse events due to the often-coexisting pharmacological treatments, it is essential to avoid the abandonment of traditional drugs with proven efficacy in the treatment of single diseases. Overall, the use of nutraceuticals, prebiotics, and probiotics in pediatric gastroenterological practice requires caution and medical supervision. Further research is needed to determine the effects of alternative therapies on pediatric gastrointestinal symptoms and disorders, and to ensure their safe and effective use in the clinical practice.

Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species.

The debate continues on the best age to stop breastfeeding.

The ongoing debate on the optimal duration of breastfeeding in high-income countries is challenging. The decision to continue breastfeeding beyond the introduction of solids according to WHO indications involves multifaceted considerations, such as nutritional needs, psychological factors and cultural influences, given the growing number of immigrants. The impact on maternal health, sleep routines and family dynamics should be carefully weighed too. CONCLUSION: Next studies should investigate associations of different modalities and periods of breastfeeding with physical and neurodevelopmental outcomes, including psychological aspects. A personalised and gradual approach is suggested, guided by informed decisions and a supportive network.

Severe Unilateral Microtia with Aural Atresia, Hair White Patch, Stereotypes in a Young Boy with De novo 16p13.11 Deletion: Reasons for a New Genotype-Phenotype Correlation.

Background Microtia is an uncommon congenital malformation ranging from mild anatomic structural abnormalities to partial or complete absence of the ear leading to hearing impairment. Congenital microtia may present as a single malformation (isolated microtia) or sometimes associated with other congenital anomalies involving various organs. Microtia has been classified in three degrees according to the complexity of the auricular malformation and to anotia referred to the total absence of the ear. Genetic role in causing auricular malformation has been widely demonstrated, and genotype-phenotype correlation has been reported in cases of syndromic microtia. Case Presentation We report here a young patient with a third degree of scale classification and aural atresia. The patient showed unspecific facial dysmorphism, speech delay, precocious teething, hair white patch, and stereotypic anomalous movements. Genetic analysis displayed a de novo 16p13.11 deletion. Conclusion Microtia with aural atresia is an uncommon and severe birth defect, which affects functional and esthetic aspects, often associated with other malformations. As traumatic this disorder may be for the parents, the microtia and aural atresia are treatable, thanks to the improving and evolving surgical techniques. Based on the genetic analysis and the clinical features observed in the present case, a genotype-phenotype correlation has been proposed.

A PAK1 Mutational Hotspot Within the Regulatory CRIPaK Domain is Associated With Severe Neurodevelopmental Disorders in Children.

BACKGROUND: P-21-activated kinases (PAKs) are protein serine/threonine kinases, part of the RAS/mitogen-activated protein kinase pathway. PAK1 is highly expressed in the central nervous system and crucially involved in neuronal migration and brain developmental processes. Recently, de novo heterozygous missense variants in PAK1 have been identified as an ultrarare cause of pediatric neurodevelopmental disorders. METHODS: We report a series of children affected with postnatal macrocephaly, neurodevelopmental impairment, and drug-resistant epilepsy. Repeated electroencephalographic (EEG) and video-EEG evaluations were performed over a two- to 10-year period during follow-up to delineate electroclinical histories. Genetic sequencing studies and computational evaluation of the identified variants were performed in our patient cohort. RESULTS: We identified by whole-exome sequencing three novel de novo variants in PAK1 (NM_001128620: c.427A>G, p.Met143Val; c.428T>C, p.Met143Thr; c.428T>A, p.Met143Lys) as the underlying cause of the disease in our families. The three variants affected the same highly conserved Met143 residue within the cysteine-rich inhibitor of PAK1 (CRIPaK) domain, which was identified before as a PAK1 inhibitor target. Computational studies suggested a defective autoinhibition presumably due to impaired PAK1 autoregulation as a result of the recurrent substitution. CONCLUSIONS: We delineated the electroclinical phenotypes of PAK1-related neurological disorders and highlight a novel mutational hotspot that may involve defective autoinhibition of the PAK1 protein. The three novel variants affecting the same hotspot residue within the CRIPaK domain highlight potentially impaired PAK1-CRIPaK interaction as a novel disease mechanism. These findings shed light on possible future treatments targeted at the CRIPaK domain, to modulate PAK1 activity and function.

Refeeding Syndrome in Pediatric Age, An Unknown Disease: A Narrative Review.

Refeeding syndrome (RS) is characterized by electrolyte imbalances that can occur in malnourished and abruptly refed patients. Typical features of RS are hypophosphatemia, hypokalemia, hypomagnesemia, and thiamine deficiency. It is a potentially life-threatening condition that can affect both adults and children, although there is scarce evidence in the pediatric literature. The sudden increase in food intake causes a shift in the body's metabolism and electrolyte balance, leading to symptoms such as weakness, seizures, and even heart failure. A proper management with progressive increase in nutrients is essential to prevent the onset of this condition and ensure the best possible outcomes. Moreover, an estimated incidence of up to 7.4% has been observed in pediatric intensive care unit patients receiving nutritional support, alone or as an adjunct. To prevent RS, it is important to carefully monitor feeding resumption, particularly in severely malnourished individuals. A proper strategy should start with small amounts of low-calorie fluids and gradually increasing the calorie content and amount of food over several days. Close monitoring of electrolyte levels is critical and prophylactic use of dietary supplements such as thiamine may be required to correct any imbalances that may occur. In this narrative review, we aim to provide a comprehensive understanding of RS in pediatric clinical practice and provide a possible management algorithm.

The Influence of Ketogenic Diet on Gut Microbiota: Potential Benefits, Risks and Indications.

The ketogenic diet (KD) restricts carbohydrate consumption, leading to an increase in ketone bodies, such as acetoacetate, ß-hydroxybutyrate, and acetone, which are utilized as energy substrates. This dietary approach impacts several biochemical processes, resulting in improved clinical management of various disorders, particularly in childhood. However, the exact mechanisms underlying the efficacy of KD remain unclear. Interestingly, KD may also impact the gut microbiota, which plays a pivotal role in metabolism, nutrition, and the development of the immune and nervous systems. KD has gained popularity for its potential benefits in weight loss, blood sugar control, and certain neurological conditions. This narrative review sums up KD-related studies published over 30 years. While short-term studies have provided valuable insights into the effects of KD on the gut microbiota, persistent uncertainties surround its long-term efficacy and potential for inducing dysbiosis. The significant influence of KD on epigenetic mechanisms, intracellular pathways, and gut microbial composition underscores its potential as a therapeutic choice. However, a judicious consideration of the potential risks associated with the strict adherence to a low-carbohydrate, high-fat, and high-protein regimen over prolonged periods is imperative. As KDs gain popularity among the adolescent and young adult demographic for weight management, it becomes imperative to undertake additional research to comprehensively assess their impact on nutritional status and gut microbiota, ensuring a holistic and sustainable approach to medical nutrition.

Leading reasons for antibiotic prescriptions in pediatric respiratory infections: influence of fever in a primary care setting.

BACKGROUND: Antibiotic overuse in children is a significant public health concern, as it can lead to the emergence and spread of antibiotic-resistant bacteria. Although respiratory infections account for most antibiotic prescriptions in children, many of these infections are viral and do not require antibiotics. In this study, we aimed to investigate the use of antibiotics in children with respiratory infections in a primary care setting and to explore the possible role of fever on antibiotic prescription. METHODS: We conducted a prospective observational study that evaluated preschool children aged 0-5 years who were assessed by their primary care pediatricians for respiratory infectious diseases between October 2019 and March 2021. The study involved 69 public primary care pediatricians and a total of 678 pediatric episodes for respiratory infections. RESULTS: Amoxicillin/clavulanate was the most frequently prescribed drug. Bronchitis accounted for most of inappropriate antibiotic prescriptions (73%). Furthermore, the presence of fever was associated with a ~ 300% increase in the likelihood of prescribing antibiotics for respiratory infections that do not typically require antibiotics. CONCLUSION: Our findings emphasize the need for adherence to international guidelines and recommendations in the primary care of children to reduce unnecessary antibiotic use and prevent the development of antibiotic resistance. This study also underscores the potential relevance of new studies to evaluate antibiotic prescription attitudes in other clinical settings and geographical areas.

Early acute cerebellar ataxia after meningococcal B vaccine: a case report of a 7-month-old infant and a review of the literature.

BACKGROUND: Acute cerebellar ataxia (ACA) and acute cerebellitis represent disorders characterized by a para-infectious, post-infectious, or post-vaccination cerebellar inflammation. They are relatively common neurologic disorders among children, and may follow infections, or, more rarely, vaccinations. Few cases are instead described among infants. Although the immunization with meningococcal group B (MenB) vaccine has been associated with some neurological side effects, suspected ACA has been reported only once in the literature. CASE PRESENTATION: we describe a 7-month-old female that presented ACA within 24 h from the MenB second dose vaccination. Extensive laboratory studies and magnetic resonance imaging excluded other causes. We then conducted an extended review of other vaccine related cases reported in the literature, focusing on the clinical characteristics of ACA and finding that ataxia and cerebellitis of para- or post-infectious cause are very rarely described in the first year of life. We collected 20 articles published in the last 30 years, including an amount of 1663 patients (1-24 years) with ACA. CONCLUSIONS: a very small number of suspected post-vaccinal ataxias has been described in recent years, compared to other causes, and vaccination remains an unquestionable medical need. Further research is needed to clarify the complex pathogenesis of this disorder and its eventual link with vaccinations.