Tri-ponderal mass index and left ventricular hypertrophy in a cohort of caucasian children and adolescents with obesity.

BACKGROUND: Pediatric obesity is a global emerging burden for society; among its health-related consequences there are hypertension (HTN) and left ventricular hypertrophy (LVH). Several anthropometric indices have been investigated for the early identification of cardiovascular risk in children. The aim of the present study was to assess whether tri-ponderal mass index (TMI) was associated with LVH in a cohort of Caucasian children and adolescents with obesity. METHODS: In this observational study, 63 children and adolescents with obesity aged 7-to-16 years were enrolled. During outpatient visits, adiposity, and cardio-metabolic indices (BMI z-score, WHR, TMI, ABSI) were collected. All subjects underwent a 24-hour ambulatory blood pressure monitoring (ABPM) and transthoracic echocardiography. RESULTS: Children and adolescents with obesity with LVH had significantly higher BMI z-score (p = 0.009), WHR (p = 0.006) and TMI (p = 0.026) compared to children without LVH. WC and WHR were the only indices significantly associated with left ventricular mass index (LVMI). CONCLUSION: Left ventricular remodeling is associated with the cardio-metabolic risk markers WC and WHR, but not with the adiposity index TMI among children with obesity.

Glycomacropeptide-Based Protein Substitutes for Children with Phenylketonuria in Italy: A Nutritional Comparison.

Advancements in food science technology have allowed the development of new products for the therapeutic management of inherited metabolic diseases such as phenylketonuria (PKU). Glycomacropeptide (GMP), a peptide derived from casein, is naturally low in phenylalanine (Phe) and, thus, adequate for protein substitutes (PSs) for the management of PKU in children. This review aims primarily to analyse the differences in the nutritional composition of GMP-based protein substitutes in different formulations (ready to drink, powdered, and bars), and secondarily to assess the quality of these products, comparing their nutritional composition with that of standard amino acid (L-AA) mixtures. Thirty-five GMP-based PSs produced by six different companies were included in this review: twenty-one powdered PSs, eight ready to drink, and six bars. The analysis revealed great heterogeneity not only among the different formulations (powdered, ready to drink, and bars) but also within the same group, in terms of energy content and nutritional composition. GMP-based PSs were shown to have higher contents of sugars and saturated fatty acids compared to L-AA PSs, especially in ready-to-drink formulations and bars. The latter also provided the highest amounts of energy among the GMP-based products. This finding may be related to a higher risk of developing overweight and obesity. The greater palatability of these GMP-based PSs, combined with improved nutritional quality, could not only improve adherence to diet therapy but also reduce the incidence of obesity-related comorbidities in PKU.

Space research to explore novel biochemical insights on Earth.

Travel to space has overcome unprecedent technological challenges and this has resulted in transfer of these technological results on Earth to better our lives. Health technology, medical devices, and research advancements in human biology are the first beneficiaries of this transfer. The real breakthrough came with the International Space Station, which endorsed multidisciplinary international scientific collaborations and boosted the research on pathophysiological adaptation of astronauts to life on space. These studies evidenced that life in space appeared to have exposed the astronauts to an accelerated aging-related pathophysiological dysregulation across multiple systems. In this review we emphasize the interaction between several biomarkers and their alteration in concentrations/expression/function by space stress factors. These altered interactions, suggest that different biochemical and hormonal factors, and cell signals, contribute to a complex network of pathophysiological mechanisms, orchestrating the homeostatic dysregulation of various organs/metabolic pathways. The main effects of space travel on altering cell organelles biology, ultrastructure, and cross-talk, have been observed in cell aging as well as in the disruption of metabolic pathways, which are also the causal factor of rare inherited metabolic disorders, one of the major pediatric health issue. The pathophysiologic breakthrough from space research could allow the development of precision health both on Earth and Space by promoting the validation of improved biomarker-based risk scores and the exploration of new pathophysiologic hypotheses and therapeutic targets. Nonstandard abbreviations: International Space Station (ISS), Artificial Intelligence (AI), European Space Agency (ESA), National Aeronautics and Space Agency (NASA), Low Earth Orbit (LEO), high sensitive troponin (hs-cTn), high sensitive troponin I (hs-cTn I), high sensitive troponin T, Brain Natriuretic Peptide (BNP), N terminal Brain Natriuretic Peptide (NT-BNP), cardiovascular disease (CVD), parathyroid hormone (PTH), urinary hydroxyproline (uHP), urinary C- and N-terminal telopeptides (uCTX and uNTX), pyridinoline (PYD), deoxypyridinoline (DPD), half-time (HF), serum Bone Alkaline Phosphatase (sBSAP), serum Alkaline Phosphatase (sAP), Carboxy-terminal Propeptide of Type 1 Procollagen (P1CP), serum Osteocalcin (sOC)), advanced glycation end products (AGEs), glycated hemoglobin A1c (HbA1c), Insulin-like growth factor 1 (IGF1), Growth Hormone (GH), amino acid (AA), ß-hydroxy-ß methyl butyrate (HMB), maple syrup urine disease (MSUD), non-communicable diseases (NCDs).

Corrigendum: Newborn screening for X-linked adrenoleukodystrophy in Italy: diagnostic algorithm and disease monitoring.

[This corrects the article DOI: 10.3389/fneur.2022.1072256.].

An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy.

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life.

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.

Dietary Inflammatory Potential in Pediatric Diseases: A Narrative Review.

Inflammatory status is one of the main drivers in the development of non-communicable diseases (NCDs). Specific unhealthy dietary patterns and the growing consumption of ultra-processed foods (UPFs) may influence the inflammation process, which negatively modulates the gut microbiota and increases the risk of NCDs. Moreover, several chronic health conditions require special long-term dietary treatment, characterized by altered ratios of the intake of nutrients or by the consumption of disease-specific foods. In this narrative review, we aimed to collect the latest evidence on the pro-inflammatory potential of dietary patterns, foods, and nutrients in children affected by multifactorial diseases but also on the dietetic approaches used as treatment for specific diseases. Considering multifactorial diet-related diseases, the triggering effect of pro-inflammatory diets has been addressed for metabolic syndrome and inflammatory bowel diseases, and the latter for adults only. Future research is required on multiple sclerosis, type 1 diabetes, and pediatric cancer, in which the role of inflammation is emerging. For diseases requiring special diets, the role of single or multiple foods, possibly associated with inflammation, was assessed, but more studies are needed. The evidence collected highlighted the need for health professionals to consider the entire dietary pattern, providing balanced and healthy diets not only to permit the metabolic control of the disease itself, but also to prevent the development of NCDs in adolescence and adulthood. Personalized nutritional approaches, in close collaboration between the hospital, country, and families, must always be promoted together with the development of new methods for the assessment of pro-inflammatory dietary habits in pediatric age and the implementation of telemedicine.

Chrononutrition and metabolic health in children and adolescents: a systematic review and meta-analysis.

CONTEXT: Obesity has emerged as a global health issue for the pediatric population, increasing the need to investigate physiopathological aspects to prevent the appearance of its cardiometabolic complications. Chrononutrition is a field of research in nutritional sciences that investigates the health impact of 3 different dimensions of feeding behavior: regularity of meals, frequency, and timing of food intake. OBJECTIVE: We carried out a systematic review and meta-analysis to investigate the association between chrononutrition in children and adolescents and the risk of overweight/obesity or a cluster of metabolic abnormalities related to glucose and lipid metabolism, blood pressure, and cardiovascular disease risk. DATA EXTRACTION: A literature search was performed using PubMed, EMBASE, and The Cochrane Library for relevant articles published before August 2022. DATA ANALYSIS: A total of 64 articles were included in the narrative synthesis (47 cross-sectional and 17 cohort studies), while 16 studies were included in the meta-analysis. Meta-analysis showed that non-daily breakfast consumers (≤6 d/wk) had a higher risk of overweight/obesity (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.08-1.82] compared with daily breakfast eaters (7 d/wk). Similarly, irregular breakfast consumption (only 0-to-3 times/wk) increased the risk of abdominal obesity (waist-to-height ratio ≥ 0.5) compared with regular consumption (5-to-7 times/wk) (OR, 1.38; 95% CI, 1.26-1.49). There was evidence to suggest that a regular frequency of meal consumption (≥4 times/d) is preventive against overweight/obesity development compared with fewer meals (≤3 times/d) (OR, 0.83; 95% CI, 0.70-0.97). In the narrative synthesis, snacking habits showed controversial results, while food timing was the most understudied dimension. CONCLUSION: Overall, our data indicate a potential implication of chrononutrition in affecting pediatric metabolic health; however, the evidence of this association is limited and heterogeneous. Further prospective and intervention studies with a consistent approach to categorize the exposure are needed to elucidate the importance of chrononutrition for pediatric metabolic health.

Trends and challenges in home enteral feeding methods for children with gastrointestinal disorders: an expert review on bolus feeding delivery methods.

INTRODUCTION: New evidence supports the benefits of bolus feeding for children receiving home enteral feeding (HEN). Current home methods of bolus feeding have certain limitations, particularly in mobile or restless patients. Therefore, innovative delivery methods have been introduced to provide more flexible methods of reducing feeding time and formula handling. AREAS COVERED: This manuscript presents an expert review of the updates in HEN for children and the results of an online user experience questionnaire about an innovative new cap-based bolus feeding system. A literature bibliographic search was conducted on Medline via PubMed up to September 2023 to collect relevant studies. We presented recent evidence demonstrating a dramatic increase in HEN use among children requiring EN and its benefits on patients' nutritional status and quality of life. In addition, the article examined the clinical and social benefits of bolus feeding and current challenges in delivery methods. We described the benefits of the new system and its user experience. EXPERT OPINION: The uses and indications for bolus feeding in HEN are increasing among children. However, there are still some unmet needs regarding traditional delivery methods. Innovative techniques can improve flexibility, reduce feeding time, and improve user experience and quality of life.

Possible role of tryptophan metabolism along the microbiota-gut-brain axis on cognitive & behavioral aspects in Phenylketonuria.

Cognitive and psychiatric disorders are well documented across the lifetime of patients with inborn errors of metabolism (IEMs). Gut microbiota impacts behavior and cognitive functions through the gut-brain axis (GBA). According to recent research, a broad spectrum of GBA disorders may be influenced by a perturbed Tryptophan (Trp) metabolism and are associated with alterations in composition or function of the gut microbiota. Furthermore, early-life diets may influence children's neurodevelopment and cognitive deficits in adulthood. In Phenylketonuria (PKU), since the main therapeutic intervention is based on a life-long restrictive diet, important alterations of gut microbiota have been observed. Studies on PKU highlight the impact of alterations of gut microbiota on the central nervous system (CNS), also investigating the involvement of metabolic pathways, such as Trp and kynurenine (KYN) metabolisms, involved in numerous neurodegenerative disorders. An alteration of Trp metabolism with an imbalance of the KYN pathway towards the production of neurotoxic metabolites implicated in numerous neurodegenerative and inflammatory diseases has been observed in PKU patients supplemented with Phe-free amino acid medical foods (AA-MF). The present review investigates the possible link between gut microbiota and the brain in IEMs, focusing on Trp metabolism in PKU. Considering the evidence collected, cognitive and behavioral well-being should always be monitored in routine IEMs clinical management. Further studies are required to evaluate the possible impact of Trp metabolism, through gut microbiota, on cognitive and behavioral functions in IEMs, to identify innovative dietetic strategies and improve quality of life and mental health of these patients.

Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

Glycomacropeptide (GMP) rescued the oxidative and inflammatory activity of free L-AAs in human Caco-2 cells: New insights that support GMP as a valid and health-promoting product for the dietary management of phenylketonuria (PKU) patients.

Phenylketonuria represents the most prevalent inborn error of amino acid metabolism. In early diagnosed patients adequate and continued dietary treatment results in a good neurologic outcome. However, due to the natural protein and phenylalanine-restricted diet, oxidative stress represents a concern in phenylketonuric patients. Clear evidences suggest that the pathophysiology of PKU is also dependent by mitochondrial impairment and oxidative stress. In this context due to the tight connection between oxidative and inflammatory stress and noncommunicable diseases (NCDs) development, it is reasonable to hypothesize that PKU patients may present a higher risk to develop NCDs during their life. Currently available protein substitutes on the market include free amino acids (L-AAs), prolonged-release protein substitute and formula containing glycomacropeptide (GMP). Our results suggest that free L-AAs significanlty worsens the intestinal hydrogen peroxide (H2O2) and lipopolysaccharides (LPS)-induced oxidative and inflammatory status in Caco-2 cells, which are significantly restored towards physiological condition by GMP alone and when present in a 1:1 mixture with free L-AAs, providing new preclinical piece of information which can shed a shadow on the mechanism of action of these products on PKU patients and their future management.

Resting energy expenditure in children and adolescents with cerebral palsy: accuracy of available prediction formulas and development of population-specific methods.

Introduction: Energy requirements are difficult to estimate in children with cerebral palsy (CP). Resting energy expenditure (REE), necessary to implement personalized nutritional interventions, is most commonly estimated using prediction formulae since indirect calorimetry, the reference method, is not available in all nutrition units. The aims of the present study were: (1) to evaluate the accuracy of the most commonly used REE prediction formulae developed for healthy children, in children with CP; (2) to assess the accuracy of the REE population-specific formula for CP children proposed in our preliminary report; (3) to develop new population-specific methods. Methods: REE was measured by indirect calorimetry in 100 children and adolescents with spastic quadriplegic cerebral palsy (SQCP) and estimated on the basis of predictive formulas selected by the clinicians [World Health Organization (WHO), Harris-Benedict, Schofield weight, Schofield weight & height, Oxford, Mifflin formulae and a population-specific formula for CP children developed in our preliminary report]. Results: 100 children with SQCP (35 girls, 35%) classified as level V according to gross motor function classification system (GMFCS-V); 64% with oral nutrition, 29% total enteral nutrition (nasogastric tube feeding, percutaneous endoscopic gastrostomy, percutaneous endoscopic transgastric jejunostomy) and 7% mixed nutrition. The median (IQR) REE was 41.96 (17.5) kcal/kg/day.Statistical analysis highlighted a proportional bias between the indirect calorimetry and all considered predictive formulae for REE determination. By studying the relationship between the bias and the mean values of REE, specific conversion equations were obtained. With a pre-specified model having as predictors the variable weight and the variable Triceps Skinfold (TSF) and, as response the variable REE measured by indirect calorimetry, a predictive nomogram was developed to estimate the REE in this population of children. Conclusions: We suggest using predictive formulae for healthy children with caution, and where possible carrying out indirect calorimetry to assess REE in children with CP. However, we propose a new tool which could be developed to become an additional help for assessment of REE in the clinical practice.Future objectives will be to obtain a larger sample size, in a multicenter perspective study, to build a specific predictive model for the REE of the studied population.

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.

Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude.

BACKGROUND: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. METHODS: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. RESULTS: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N). CONCLUSIONS: In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes.

An ESPGHAN position paper on the diagnosis, management and prevention of cow's milk allergy.

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 1 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost and quality of life.

Fat-Soluble Vitamins Deficiency in Pediatric Cholestasis: A Scoping Review.

BACKGROUND: This review aims to identify the current indications and gaps in the management of fat-soluble vitamins in pediatric patients with cholestasis. METHODS: A comprehensive review of the literature using PubMed, Scopus, Web of Science and Embase was performed. Two authors independently identified the most relevant studies published over the past 20 years up to February 2022, including original papers, narrative reviews, observational studies, clinical trials, systematic reviews and meta-analyses. The literature was screened, and preclinical studies about pathogenetic mechanisms were also included. Keywords searched for each fat-soluble vitamin (A, D, E and K), alone or in combination, were "cholestasis", "chronic liver disease", "biliary atresia", "malnutrition" and "nutritional needs". Studies published prior to the selected time range were searched manually and, when considered relevant, included within the list of references. RESULTS: Eight hundred twenty-six articles were initially screened. From these, 48 studies were selected. A comparison of the recommended methods of supplementation for fat-soluble vitamins was then carried out. The causes of malabsorption were explained and current methods for defining deficiency and monitoring complications were summarized. CONCLUSIONS: According to the literature, children with cholestasis are at a higher risk of fat-soluble vitamin deficiency. Although there are general recommendations, the treatment for vitamin deficiency is not uniformly validated.