Ketogenic diet in children and adolescents: The effects on growth and nutritional status.

The ketogenic diet is known to be a possible adjuvant treatment in several medical conditions, such as in patients with severe or drug-resistant forms of epilepsy. Its use has recently been increasing among adolescents and young adults due to its supposed weight-loss effect, mediated by lipolysis and lowered insulin levels. However, there are still no precise indications on the possible use of ketogenic diets in pediatric age for weight loss. This approach has also recently been proposed for other types of disorder such as inherited metabolic disorders, Prader-Willi syndrome, and some specific types of cancers. Due to its unbalanced ratio of lipids, carbohydrates and proteins, a clinical evaluation of possible side effects with a strict evaluation of growth and nutritional status is essential in all patients following a long-term restrictive diet such as the ketogenic one. The prophylactic use of micronutrients supplementation should be considered before starting any ketogenic diet. Lastly, while there is sufficient literature on possible short-term side effects of ketogenic diets, their possible long-term impact on growth and nutritional status is not yet fully understood, especially when started in pediatric age.

Bioactive compounds in childhood obesity and associated metabolic complications: Current evidence, controversies and perspectives.

Obesity represents the most frequent chronic disease among children worldwide, with a significant global burden on society. Metabolically unhealthy obesity (MUO) can affect children since their first years of life, and novel therapeutic strategies to tackle metabolic complications are under investigation. This review focuses on bioactive compounds and their possible beneficial effects on obesity, particularly omega-3, docosahexaenoic acid, vitamin D, biotics, polysaccharide macromolecules, polyphenols, inositols, alpha lipoic acid, and bromelaine. Our aim is to summarize current evidence about bioactive compounds in the treatment of obesity, highlighting recent findings on their use in children and adolescents. Most studied molecules are omega-3 and vitamin D, despite the heterogeneity between the studies. Moreover, given the emerging interest in the gut-brain axis in the link between metabolic health and microbiota, various studies on prebiotics, probiotics, synbiotics, postbiotics and polysaccharide macromolecules have been considered. Some preclinical studies seem to highlight a possible role of the polyphenols, even if their clinical evidence is still discussed. Lastly, we describe possible effects of inositols and alpha-lipoic acid. Despite some dietary supplements seem to be promising in overweight subjects, only in a few of them a dose/response efficacy has been found in the pediatric age. Innovative, well-designed and targeted clinical trials are then needed to prove the beneficial effects of these compounds that could support the standard behavioral therapy for obesity.

Longitudinal Anthropometry and Body Composition in Children With SARS-CoV-2-Associated Multisystem Inflammatory Syndrome.

OBJECTIVES: Acute coronavirus disease 2019 infection has been shown to negatively affect body composition among adult and malnourished or obesity children. Our aim is to longitudinally evaluate body composition in children affected by the Multisystem Inflammatory Syndrome (MIS-C). METHODS: In this cohort study, we recruited 40 patients affected by MIS-C, aged 2-18 years old, who were admitted in our clinic between December 2020 and February 2021. Physical examination for each participant included weight, height, body mass index (BMI) z score, circumferences, and skinfolds assessment. The same measurements were repeated during outpatient follow-up at 10 (T2), 30 (T3), 90 (T4), and 180 (T5) days after hospital discharge. Fat mass and fat free mass were calculated according to skinfolds predictive equations for children and adolescents. A control group was randomly selected among patients attending a pediatric nutritional outpatient clinic. RESULTS: BMI z score significantly decrease between preadmission and hospital discharge. Similarly, arm circumference z score, arm muscular area z score, and arm fat area z score significantly decreased, during hospital stay. Fat mass index (FMI) significantly increased over time, peaking at T3. Fat free mass index decreased during hospitalization. CONCLUSIONS: To the best of our knowledge, this is the first study to assess body composition in a numerically large pediatric MIS-C population from acute infection to 6 months after triggering event. FMI and anthropometric parameters linked to fat deposits were significantly higher 6 months after acute event. Thus, limiting physical activity and having sedentary lifestyle may lead to an accumulation of adipose tissue even in healthy children who experienced MIS-C and long hospitalization.

Integrated Approaches to Combatting Childhood Obesity.

BACKGROUND: The global prevalence of childhood obesity has grown sharply in recent decades. Obesity is considered a public health problem which directly affects the health status of children in numerous ways. To combat this trend, integrated approaches are necessary to prevent childhood obesity. Strategies require a comprehensive perspective at individual and parental level alongside the adoption of measures to engage the community and environment. SUMMARY: Prevention is addressed as crucial in limiting the pediatric obesity epidemic in the long term. Breastfeeding and appropriate complementary feeding are recognized as early dietary factors that affect the future risk of obesity development during the first 2 years of life. During childhood and adolescence, dietary patterns, eating habits, portion size, eating frequencies, and family meals are important dietary factors to target for preventive strategies, as well as parenting style which is influenced by parents' education. Physical activity promotion and the reduction of sedentary behavior are also recommended. The adherence of children and families to obesity prevention programs is highly dependent on socioeconomic factors. Moreover, setting food quality standards and public policies to promote healthy lifestyle habits is strongly advocated. The implementation of cost-effective preventive strategies is of high priority and requires an integrated approach by healthcare services. All stakeholders involved should take an active role in supporting and empowering children and families in order to cope with this multifactorial and complex disease.

Health effects of yogurt consumption during paediatric age: a narrative review.

Yogurt is a fermented milk product characterised by a peculiar nutritional composition with live and viable cultures of bacteria. Few studies have analysed the benefits of yogurt consumption on health outcomes during paediatric age. Recent epidemiological studies evaluating the nutritional impact of yogurt have demonstrated its significant contribution to nutrients intakes among children. Thus, consuming yogurt is a strategy to achieve recommended nutrient intake and healthier dietary choices, with potential impact on obesity and cardiometabolic outcome in children. Yogurt's effects on paediatric infectious diseases, gastrointestinal diseases and atopic-related disorders are ascribed to the specific probiotic strain administered. Interestingly, the benefits of yogurt consumption are most likely due to effects mediated through the gut microbiota and the enhancement of innate and adaptive immune responses. Therefore, supplementing standard yogurt cultures with probiotic strains could be useful to promote health at different paediatric ages, although more evidence is needed regarding the strain-related effects and their interplay within the paediatric immune system.

Unsaturated fatty acids, omega-3 index and hospitalization in MISC.

The growing interest in Omega-3 fatty acids as diagnostic markers or new therapeutic approaches also for COVID-19 disease, led us to investigate the presence of potential correlations between Omega-3 fatty acids' levels in whole blood and days of hospitalization or admission to the paediatric intensive care unit (PICU) in 51 children with MIS-C diagnosis following SARS-CoV-2 infection. A statistically significant negative correlation was observed between days of hospitalization and docosapentaenoic acid (22:5n-3,DPA), docosahexaenoic acid (DHA) and total Omega-3 FA levels. Dividing the study group into quartiles according to Omega-3-Index (O3I), no statistically significant difference was observed with respect to the PICU admission rate. In contrast, the number of days of hospitalization in Q4 (O3I ≥ 2.51 %) was different from the number observed in groups Q1-3 (O3I < 2.51 %), with subjects showing higher O3I needing shorter hospitalizations than the subjects with lower O3I. According to previous study investigating O3I in adults affected by Sars-cov-2 we explored the levels of this nutrients in children with MIS-C. Our exploratory study shows that high DPA, DHA and O3I levels could be effective in reducing the length of hospitalization.

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

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

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.

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.

The Paradox of the Mediterranean Diet in Pediatric Age during the COVID-19 Pandemic.

The outbreak of the COVID-19 pandemic, whose causative agent is Severe Acute Respiratory Syndrome Coronavirus 2, has caused a global crisis that has had a major impact on the health of the global population [...].

Gut microbiota in obesity and related comorbidities in children and adolescents: the role of biotics in treatment.

INTRODUCTION: Obesity is a complex pathology, globally spread, with a multifactorial pathogenesis, strictly linked with lifestyle, hormones, genetic and epigenetic factors. Evidence supports that obesity, and its comorbidities, are related to changes in gut microbiota, partially responsible of the modulation of energy metabolism. EVIDENCE ACQUISITION: Pediatric obesity has been associated with lower bacterial diversity and differences in composition of the gut microbiota, also varying according to the metabolic status of obese subjects. Indeed, differences in distributions and activity of microorganisms in the gut of metabolically healthy and unhealthy obese children have been highlighted. EVIDENCE SYNTHESIS: Based on human studies, this review aims to discuss gut microbiota alterations in obese children and adolescents and its role in obese-related complications. Moreover, the role of biotics (probiotics, prebiotics, synbiotics and -marginally- postbiotics) has been analyzed as modulator of obesity-related dysbiosis. CONCLUSIONS: As a conclusion, a deeper knowledge about biotic mechanisms of action would be of great interest to implement the clinical care of children and adolescents with obesity and related comorbidities.

Special Diets in Infants and Children and Impact on Gut Microbioma.

Gut microbiota is a complex system that starts to take shape early in life. Several factors influence the rise of microbial gut colonization, such as term and mode of delivery, exposure to antibiotics, maternal diet, presence of siblings and family members, pets, genetics, local environment, and geographical location. Breastfeeding, complementary feeding, and later dietary patterns during infancy and toddlerhood are major players in the proper development of microbial communities. Nonetheless, if dysbiosis occurs, gut microbiota may remain impaired throughout life, leading to deleterious consequences, such as greater predisposition to non-communicable diseases, more susceptible immune system and altered gut-brain axis. Children with specific diseases (i.e., food allergies, inborn errors of metabolism, celiac disease) need a special formula and later a special diet, excluding certain foods or nutrients. We searched on PubMed/Medline, Scopus and Embase for relevant pediatric studies published over the last twenty years on gut microbiota dietary patterns and excluded case reports or series and letters. The aim of this review is to highlight the changes in the gut microbiota in infants and children fed with special formula or diets for therapeutic requirements and, its potential health implications, with respect to gut microbiota under standard diets.

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

Introduction: X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder caused by variants in the ABCD1 gene. The main phenotypes observed in men with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral ALD (cALD). Cerebral ALD consists of a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical decline and is fatal if left untreated. Hematopoietic stem cell transplantation is the standard treatment for cALD as it stabilizes WM degeneration when performed early in the disease. For this reason, early diagnosis is crucial, and several countries have already implemented their newborn screening programs (NBS) with the assessment of C26:0-lysophosphatidylcholine (C26:0-LPC) values as screening for X-ALD. Methods: In June 2021, an Italian group in Lombardy launched a pilot study for the implementation of X-ALD in the Italian NBS program. A three-tiered approach was adopted, and it involved quantifying the values of C26:0-LPC and other metabolites in dried blood spots with FIA-MS/MS first, followed by the more specific ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique and, finally, the genetic confirmation via focused NGS. Discussion: Genetically confirmed patients are set to undergo a follow-up protocol and are periodically evaluated to promptly start a specific treatment if and when the first signs of brain damage appear, as suggested by international guidelines. A specific disease monitoring protocol has been created based on literature data and personal direct experience. Conclusion: The primary aim of this study was to develop a model able to improve the early diagnosis and subsequent follow-up and timely treatment of X-ALD. Ethics: The study was approved by the local ethics committee. The research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Effect of individual- versus collective-based nutritional-lifestyle intervention on the atherogenic index of plasma in children with obesity: a randomized trial.

BACKGROUND: The Atherogenic Index of Plasma is a predictive biomarker of atherosclerosis in adults but there is a lack of studies in paediatric population aimed at evaluating the longitudinal changes of the AIP and of the cardiometabolic blood profile related to nutritional interventions. The aim of this study was to compare the effect of individual- versus collective-based nutritional-lifestyle intervention on the Atherogenic Index of Plasma in schoolchildren with obesity. METHODS: One-hundred sixty-four children aged 6-12 years with Body Mass Index z-score > 2 referred to the Paediatric Obesity Clinic, San Paolo Hospital, Milan, Italy, were consecutively enrolled and randomized to undergo to either an individual- (n = 82) or a collective- (n = 82) based intervention promoting a balanced normo-caloric diet and physical activity. In addition, the individual intervention included a tailored personalized nutritional advice and education based on the revised Coventry, Aberdeen, and London-Refined taxonomy. Both at baseline and after 12 months of intervention, dietary habits and anthropometric measures were assessed, a fasting blood sample were taken for biochemistry analysis. RESULTS: The participation rate at 12 months was 93.3% (n = 153 patients), 76 children in the individual-intervention and 77 children in the collective intervention. At univariate analysis, mean longitudinal change in Atherogenic Index of Plasma was greater in the individual than collective intervention (- 0.12 vs. - 0.05), as well as change in triglyceride-glucose index (- 0.22 vs. - 0.08) and Body Mass Index z-score (- 0.59 vs. - 0.37). At multiple analysis, only change in Body Mass Index z-score remained independently associated with intervention (odds ratio 3.37). CONCLUSION: In children with obesity, an individual-based nutritional and lifestyle intervention, including techniques from the CALO-RE taxonomy, could have an additional beneficial effect over a collective-based intervention, although the actual size of the effect remains to be clarified. Trial Registration Clinical Trials NCT03728621.

Immunomodulatory diet in pediatric age.

In the last few decades, the importance of a functioning immune system and health status has become more evident. Multiple factors are able to influence the development of chronic diseases and diet is one of the most important environmental factors. Evidence demonstrates that dietary patterns high in fat and low in fiber are associated with the development of non-communicable diseases. Moreover, optimal nutritional status can modulate immune maturation and response to inflammation. During inflammatory conditions, nutritional deficiencies may occur, establishing a vicious circle, consequently a balanced nutritional status is essential to prevent and counteract infections. Dietary diversity can prevent allergic diseases and nutrients such as DHA, arginine, vitamins and trace elements have an impact on physical barriers (such as gut mucosal barrier and skin), on the immune system response and on microbiome modulation. Protein deficiencies can compromise innate and adaptive immune functions; arginine availability can affect the immune response in injured states and other disease processes; EPA and DHA can modulate both innate and adaptive immunity; prebiotics have a beneficial effect on the functioning of the immune system. Zinc, copper, selenium and iron are involved in the correct development and function of the immune system. Vitamins D, E, A, B and C have a role on immune system through different mechanisms of action. Since a complex interplay exists between diet, microbiome and epigenetic factors which determine nutrient-induced changes on the immune function, the effect of each single nutrient may be difficult to study. Well-designed intervention studies, investigating the effects of whole dietary pattern, should be performed to clarify impact of foods on the immune function and disease risk.

Brown Adipose Tissue: New Challenges for Prevention of Childhood Obesity. A Narrative Review.

Pediatric obesity remains a challenge in modern society. Recently, research has focused on the role of the brown adipose tissue (BAT) as a potential target of intervention. In this review, we revised preclinical and clinical works on factors that may promote BAT or browning of white adipose tissue (WAT) from fetal age to adolescence. Maternal lifestyle, type of breastfeeding and healthy microbiota can affect the thermogenic activity of BAT. Environmental factors such as exposure to cold or physical activity also play a role in promoting and activating BAT. Most of the evidence is preclinical, although in clinic there is some evidence on the role of omega-3 PUFAs (EPA and DHA) supplementation on BAT activation. Clinical studies are needed to dissect the early factors and their modulation to allow proper BAT development and functions and to prevent onset of childhood obesity.

Semi-Elemental and Elemental Formulas for Enteral Nutrition in Infants and Children with Medical Complexity-Thinking about Cow's Milk Allergy and Beyond.

Children with medical complexities, such as multi-system disorders and/or neurological impairments, often experience feeding difficulties and need enteral nutrition. They frequently have impaired motility and digestive-absorbing functions related to their underlying condition. If a cow's milk allergy (CMA) occurs as a comorbidity, it is often misdiagnosed, due to the symptoms' overlap. Many of the commercialized mixtures intended for enteral nutrition are composed of partially hydrolyzed cow's milk proteins, which are not suitable for the treatment of CMA; thus, the exclusion of a concomitant CMA is mandatory in these patients for obtaining symptoms relief. In this review, we focus on the use of elemental and semi-elemental formulas in children with neurological diseases and in preterm infants as clinical "models" of medical complexity. In children with neurodisabilities, when gastrointestinal symptoms persist despite the use of specific enteral formula, or in cases of respiratory and/or dermatological symptoms, CMA should always be considered. If diagnosis is confirmed, only an extensively hydrolyzed or amino-acid based formula, or, as an alternative, extensively hydrolyzed nutritionally adequate formulas derived from rice or soy, should be used. Currently, enteral formulas tailored to the specific needs of preterm infants and children with neurological impairment presenting concomitant CMA have not been marketed yet. For the proper monitoring of the health status of patients with medical complexity, multidisciplinary evaluation and involvement of the nutritional team should be promoted.

Hydrolysed Formulas in the Management of Cow's Milk Allergy: New Insights, Pitfalls and Tips.

An allergy to cow's milk requires the avoidance of cow's milk proteins and, in some infants, the use of a hypoallergenic formula. This review aims to summarize the current evidence concerning different types of hydrolysed formulas (HF), and recommendations for the treatment of IgE- and non-IgE-mediated cow's milk allergy and functional gastrointestinal disorders in infancy, for which some dietary intervention and HF may be of benefit to both immune and motor mechanisms. Current guidelines recommend cow's milk protein (i.e., whey or casein) extensively hydrolysed formula (eHF) as the first choice for cow's milk allergy treatment, and amino acid formulas for more severe cases or those with reactions to eHF. Rice hydrolysed formulas (rHF) have also become available in recent years. Both eHF and rHF are well tolerated by the majority of children allergic to cow's milk, with no concerns regarding body growth or adverse effects. Some hydrolysates may have a pro-active effect in modulating the immune system due to the presence of small peptides and additional components, like biotics. Despite encouraging results on tolerance acquisition, evidence is still not conclusive, thus hampering our ability to draw firm conclusions. In clinical practice, the choice of hypoallergenic formula should be based on the infant's age, the severity, frequency and persistence of symptoms, immune phenotype, growth pattern, formula cost, and in vivo proof of tolerance and efficacy.

Which Milk during the Second Year of Life: A Personalized Choice for a Healthy Future?

Nutrition in early life is a crucial element to provide all essential substrates for growth. Although this statement may appear obvious, several studies have shown how the intake of micro and macronutrients in toddlers differs a lot from the recommendations of scientific societies. Protein intake often exceeds the recommended amount, while the intake of iron and zinc is frequently insufficient, as well as Vitamin D. Nutritional errors in the first years of life can negatively impact the health of the child in the long term. To date, no clear evidence on which milk is suggested during the second year of life is yet to be established. In this study, we compare the nutrient profiles of cow's milk and specific formulas as well as nutritional risks in toddlers linked to growth and childhood obesity development. The purpose of this review is to resume the latest clinical studies on toddlers fed with cow's milk or young children formula (YCF), and the potential risks or benefits in the short and long term.

Impaired Glucose-Insulin Metabolism in Multisystem Inflammatory Syndrome Related to SARS-CoV-2 in Children.

An interaction between metabolic glucose impairment and coronavirus disease 2019 is reported. The development of a severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection has been described. We evaluated the impact of MIS-C on glycemic patterns in pediatric patients. A group of 30 children and adolescents affected by MIS-C were considered; all patients were normal weight. Clinical and biochemical assessments, including surrogate markers of insulin resistance (IR) such as homeostasis model analysis-IR (HOMA-IR) and triglyceride-glucose (TyG) indexes, were recorded. Patients were also invited to undergo an intermittently scanned continuous glucose monitoring (isCGM). HOMA-IR index was calculated in 18 patients (60%), of which 17 (94%) revealed a pathological value. TyG index was computed for all patients and pathological values were detected in all cases. In 15 patients, isCGM data were recorded on average for 9 days (±3 days). Overall, average glucose was 105 mg/dL (±16 mg/dL) and average time spent in the 70-180 mg/dL range (TIR) was 93.76%, with nearly 10% of glucose readings in the 141-180 mg/dL range; glycemic fluctuations over the hyperglycemic threshold were detected in four patients. Regular glucose monitoring may be useful to prevent metabolic imbalance and obtain a better outcome.