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The SARS-CoV-2 virus and its rapid spread have made it a global health concern. The aim of this was to investigate the microbial and metabolic faecal profiles of paediatric patients hospitalised for COVID-19 to try to identify biomarkers of predisposition to severity. The study included 16 patients (aged 4–14 years old) from six different Spanish hospitals and 20 age-matched healthy controls. The gut microbiota was characterised by sequencing of 16S rDNA amplicons and internal transcribed space amplicons, while the metabolic profile was analysed by liquid chromatography high resolution mass spectrometry. A different microbial profile was observed between patients and controls, with a significantly higher abundance of sequences belonging to the phyla Bacteroidota and Pseudomonadota in patients. A different metabolic profile was observed between the two groups. Non-infected children had higher faecal levels of vitamins such as niacin, thiamine, and vitamin D3 derivatives, which were negatively correlated with the abundance of pathogenic bacteria, such as members of Enterobacteriaceae . Hospitalisation due to SARS-CoV-2 infection in children was associated with changes in the gut microbiota and an altered metabolomic profile. For the first time, several relevant biological compounds were found to be reduced in the faeces of children hospitalised with COVID-19 compared to healthy controls.

Childhood is a window of opportunity for the prevention of the obesity pandemic. Since “the first 1000 days of life” is a period in which healthy eating habits must be acquired, it should be the target for preventive strategies. Baby-led weaning (BLW) is an emergent way of weaning that could influence children’s health. The nutrition committees of the main pediatric societies affirm there is not enough evidence to support which is the best method of weaning. The aim was to determinate the influence of BLW on the infant’s weight gain compared to the traditional spoon-feeding, and to assess if it could decrease the risk of obesity in children. A systematic review was conducted, following the PRISMA method. Pubmed, Web of Science, Embase, and Cochrane Library were searched. Out of 747 articles, eight studies (2875 total infants) were included (two randomized control trials, 6 observational studies). Results were indecisive, while some studies seem to demonstrate lower weight gain in infants that apply BLW, others show inconclusive results. The risk of bias in all included studies was moderate or high. In conclusion, more clinical trials and prospective studies should be done prior to providing a general recommendation about the best method of weaning to reduce the risk of obesity.

Introduction: Acute lymphoblastic leukaemia (ALL) is the most prevalent cancer in childhood and is one of the leading causes of death annually. Antineoplastic treatments are associated with a high risk of malnutrition, which is important for continuous growth and development. Objective: This systematic review aimed to evaluate the effect of these treatments on the nutritional status of paediatric patients with ALL. Data were collected from the PubMed, Scopus, and Web of Science databases following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) method. All the studies in which nutritional status was assessed in human beings diagnosed with ALL up to 18 years and published in English or Spanish between January 1900 and December 2023 were included. Results: A total of 18 articles and 1692 participants were analysed in this review. Article quality was evaluated using the ROBINS-I tool. This systematic review has been registered on PROSPERO (CRD42024505111). ALL treatment has a negative impact on the nutritional status of these patients and played an important role in their growth and global development. ALL treatments can modify hunger perception and the palatability of food. Conclusions: Nutritional status is important for patient prognosis and survival. Nutritional evaluation, a specific nutritional assessment, and follow-up should be recommended for these patients to decrease the nutritional impact on global health. More homogeneous studies must be conducted to reach robust conclusions regarding the best type of nutritional intervention for these patients.

Background/ObjectivesLiver-expressed antimicrobial peptide 2 (LEAP-2) was recently identified as an endogenous non-competitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a). LEAP-2 blunts ghrelin-induced feeding and its plasma levels are modulated in response to nutritional status in humans. Despite the relevant role of ghrelin in childhood, puberty, and childhood obesity, the potential implication of LEAP-2 in these aspects remains totally unknown. We aimed to investigate the regulation of circulating plasma LEAP-2 in childhood and adolescent either lean or obese.Methods and resultsPlasma levels of LEAP-2 were analyzed in a cross-sectional study with lean and obese children and adolescents (n = 150). Circulating LEAP-2 levels were significantly higher in girls than in boys independently of whether they were obese or lean. In addition, LEAP-2 was significantly increased (p < 0.001) in pubertal than in prepubertal girls, while no changes were found in boys between both developmental stages. Moreover, in girls LEAP-2 was positively correlated with insulin, IGF-1, HOMA-IR and triglycerides and negatively with ghrelin. In boys, LEAP-2 was positively correlated with leptin and negatively with vitamin D levels.ConclusionThis study reveals a sexual dimorphism in LEAP-2 levels in children and adolescents. These changes and the higher levels during puberty imply that LEAP-2 may contribute to some of the biological adaptations occurring during pubertal development in terms of food intake, energy balance, growth rate, and puberty onset. Future studies assessing LEAP-2 levels in longitudinal studies and its implications in growth rate, puberty onset, and reproductive hormones will help to understand the relevance of this hormone in this stage of life.

Vitamin D (vitD) deficiency is associated with a wide range of chronic diseases and conditions, including obesity, and with an increasing severity of metabolic dysregulation, such as insulin resistance, hyperlipidemia, liver disease, and hypertension, both in children and adults. However, the nature of the association between low vitD status and obesity remains unclear. This fact has motivated the scientific community to conduct genetic association analyses between 25-hydroxyvitamin D (25[OH]D)-related genes and obesity traits. In this line, the variation in the vitD receptor (VDR) gene represents the bulk of the findings. Specifically, polymorphisms in the VDR gene have been associated with obesity traits in some but not all, studies. Thus, results regarding this matter remain inconclusive. Other genes aside from VDR have also been investigated in relation to obesity-related traits. However, again, findings have been inconsistent. In general, results point to the fact that the DBP/GC gene could be an important protein-linking obesity and vitD status. On the other hand, several studies have attempted to determine the molecular mechanism of the relationship between 25(OH)-D levels and obesity. Some of these studies suggest that vitD, due to its fat-soluble characteristic, is retained by the adipose tissue and has the capacity to metabolize 25(OH)-D locally, and this can be altered during obesity. Additionally, vitD is capable of regulating the gene expression related to adipogenesis process, inflammation, oxidative stress, and metabolism in mature adipocytes. Therefore, the aim of the present review was to evaluate the association between obesity and vitD deficiency describing the main molecular mechanism of the relationship and the link with genetic factors.

High blood pressure (BP) is a risk factor for cardiovascular disease and sodium consumption is related to high BP. Moreover, sugar-sweetened beverages (SSB) and the Dietary Approach to Stop Hypertension (DASH) influence BP. For this reason, we investigated whether: 1) children with risk of elevated BP had a higher consumption frequency (CF) of energy-dense salty foods (EDSF), high-sugary foods (HSF) and SSB or a low DASH score; and 2) children with a higher CF of EDSF showed a worse anthropometric and metabolic profile. Anthropometry, BP and general biochemical parameters were measured in 687 Spanish children (5–16 years) with normal or excess weight. A food frequency questionnaire was used to calculate EDSF, HSF and SSB consumption, and modified DASH score. Results showed that sex and pubertal stage influenced modified DASH score. Diastolic hypertension was associated to higher CF of EDSF in the whole sample and to higher CF of SSB in pubertal children, both independently of nutritional status. In addition, CF of EDSF was positively associated with CF of HSF and SSB and inversely associated with modified DASH score. Targeted policies and intervention programs, specific for different age ranges, should be established that aim to reduce salt consumption from snacks and processed foods, which could reduce HSF and SSB consumption as well.

Most of the available tools to assess adherence to Mediterranean diet (MedDiet) were constructed for adults, having limited applicability to children and adolescents. The aim of this study is to validate a specific questionnaire to assess adherence to MedDiet in children aged 3 to 6 years (MED4CHILD questionnaire). The validation was performed in a baseline examination of a cohort of children who were recruited in schools in seven cities. Of the total sample of 1509 children, we included 858 children aged 3 to 6 years with complete information on adherence to the MedDiet, food consumption, anthropometry and cardiometabolic characteristics. Adherence to the MedDiet was assessed using an 18-item questionnaire, adapted from validated questionnaire for adults using the Delphi method. Food and beverage consumption was assessed using a validated COME-Kids Food and Beverage Frequency Questionnaire. Anthropometric measurements and cardiometabolic risk factors were assessed using standard methods. Statistical analyses included kappa agreement, ANOVA and linear regression models. Higher MED4CHILD scores were associated with higher intakes of food characteristic of the MedDiet. The MED4CHILD questionnaire showed moderate validity, especially for key items of the Mediterranean diet (kappa ranging from 0.333 to 0.665). Direct significant associations were found between MED4CHILD scores and cardiometabolic profile, including waist circumference ( p ), triglycerides and HOMA-IR ( p  < 0.05). Conclusion : The 18-item MED4CHILD questionnaire showed moderate validity for assessing adherence to the MedDiet in children aged 3 to 6 years, in terms of agreement with food and beverage consumption and favourable cardiometabolic profile. What is known : • The Mediterranean diet has been linked to a number of health benefits and the assessment of children's adherence to this diet is important for public health and research. • The tools available to assess MedDiet compliance are mainly for adults. What is new : • The MED4CHILD questionnaire is a simple, inexpensive and rapid tool for assessing MedDiet compliance in children. • This tool showed moderate relative validity and a high score was associated with a favourable cardiometabolic profile.

Background Human milk (HM) is the first form of communication between mothers and newborns and it is implicated in the infant growth and protection. We recently showed a functional characterization of HM, unmasking the molecular mechanisms related to EVs signaling and its functional role in prematurity. In that study, we identified the need to establish and optimize a standard isolation protocol for human milk extracellular vesicles (mEVs). Methods Four mEVs isolation methods were compared: ultracentrifugation (UC), size exclusion chromatography (SEC), immunoprecipitation with tetraspanin CD9 (IP_CD9) and ExoGAG. Three pools of human milk (each composed of samples from ten donor mothers) were used and isolation of mEVs was performed starting from the same volume for each method. The proteomic, transcriptomic and glycomic composition of the extracellular vesicles obtained after isolation was then analyzed for each method. The sensitivity, specificity and quality of the results were also determined. A comparative analysis of results common across all isolation methods was performed to identify potential signaling pathways associated with mEVs. Results ExoGAG and UC proved to be the most efficient of the four techniques compared for mEVs isolation. However, ExoGAG compared to UC provided a higher concentration of total and vesicle-related proteins and peptides and a higher glycoprotein count keeping all the glycan subgroups. Despite ExoGAG and UC show similar vesicle profiles in terms of size, concentration, tetraspanin subpopulations and EVs markers, ExoGAG was the most efficient technique in terms of accuracy, consistency and reproducibility for omics studies. Furthermore, results allowed us to identify that mEVs components are involved in the signaling pathways of infant biological development, immune system maturation and protein metabolism. Conclusions This study establishes UC and ExoGAG as reliable methods for mEVs isolation and describes its protocol, being ExoGAG the most efficient. Also, the omics analysis show that biomolecules conforming those mEVs are linked to the defense system against external agents (specific role in the immune system pathway) and in the correct establishment of the neural structure (developmental pathway), while providing all the nutritional requirements for the correct growth of the newborn (metabolic pathway). Graphical Abstract

Objective: This study assessed the tolerance of a commercial, extensively hydrolyzed casein formula (eHCF), in a cohort of children with cow’s milk protein allergy (CMPA) as a primary outcome, as well as its effect on growth outcomes. Methods: Observational retrospective study of CMPA patients taking eHCF for at least 4 months. Patients were followed for three visits. Results: A total of 61 evaluable pediatric patients with CMPA were included in the study. The patients had a follow-up period of 8.4 months, with a mean age of 3.1 ± 2.5 months at the first hospital visit, and 11.5 ± 5.3 months at the second follow-up visit. At the first hospital visit, the weight, height, and body mass index (BMI) were recorded as 5.6 ± 1.4 kg, 59.3 ± 6.1 cm, and 15.6 ± 1.7, respectively, increasing to 9.2 ± 1.5 kg, 73.9 ± 6.5 cm, and 16.9 ± 1.4 at the second follow-up visit. The mean Z-scores for weight-for-age (WAZ), height-for-age (HAZ), BMI for age (BAZ), and weight-for-height (WHZ) were −0.36 ± 0.95, −0.26 ± 1.00, −0.29 ± 1.05, and −0.22 ± 1.1, respectively, at the first hospital visit, and 0.09 ± 0.79, 0.05 ± 1.03, 0.10 ± 0.87, and 0.13 ± 0.85 at the second follow-up visit. The eHCF was well tolerated by 100% of patients with no immediate allergic or intestinal reactions recorded during the follow-up visits. Conclusions: The participating physicians rated the tolerance of the eHCF as good in 100% of the patients (95% CI: 94.1–100). Over a follow-up period of 8.4 months, pediatric patients with CMPA consuming the eHCF showed anthropometric Z-scores WAZ, HAZ, BAZ, and WHZ between −1 and 1, within a range close to the mean of a standard normal distribution.

Obesity is associated with a state of chronic low-grade inflammation. Myeloperoxidase (MPO) plays an important role in the initiation and progression of acute and chronic inflammatory diseases, such as cardiovascular disease (CVD). The objectives of the current study were to evaluate plasma MPO levels in prepubertal obese children and to determine whether MPO could be an early biomarker of inflammation and CVD risk. In a prospective multicenter case-control study paired by age and sex of 446 Caucasian prepubertal children ages 6-12 years, 223 normal-weight and 223 obese children were recruited. Blood pressure, waist circumference, weight, and height were measured. In addition to MPO, glucose, insulin, metabolic lipid parameters, oxidized low-density lipoproteins, adiponectin, leptin, resistin, C-reactive protein (CRP), interleukin 6, tumor necrosis factor α, matrix metalloproteinase-9 (MMP-9), and plasminogen activator inhibitor 1 were determined. We found that MPO was elevated in prepubertal obese children and that this enzyme was associated with such proinflammatory and cardiovascular risk biomarkers as CRP, MMP-9, and resistin. Insulin resistance calculated by the homeostatic assessment model was the best predictor of MPO. MPO is an early biomarker of inflammation associated with CVD risk in obese children at the prepubertal age.