The incidence of skipping breakfast in pediatric subjects is rising, and a relationship with overweight (OW) and obesity (OB) has been shown. Associations with cardiovascular outcomes and skipping breakfast in adults have been reported. The purpose of this systematic review was to summarize the association of skipping breakfast with body weight and metabolic outcomes in the pediatric population. We searched relevant databases (2008–2018) and identified 56 articles, of which 39 were suitable to be included, basing on inclusion criteria (observational; defined breakfast skipping; weight and/or metabolic outcomes). Overall, 286,804 children and adolescents living in 33 countries were included. The definitions of OW/OB, skipping breakfast, and the nutrient assessment were highly heterogeneous. Confounding factors were reported infrequently. The prevalence of skipping breakfast ranged 10–30%, with an increasing trend in adolescents, mainly in girls. Skipping breakfast was associated with OW/OB in the 94.7% of the subjects. The lack of association was shown mainly in infants. Moreover, 16,130 subjects were investigated for cardiometabolic outcomes. Skipping breakfast was associated with a worse lipid profile, blood pressure levels, insulin-resistance, and metabolic syndrome. Five studies reported a lower quality dietary intake in breakfast skippers. This review supports skipping breakfast as an easy marker of the risk of OW/OB and metabolic diseases, whether or not it is directly involved in causality. We encourage intervention studies using standardized and generalizable indicators. Data on confounders, time of fasting, chronotypes, and nutrition quality are needed to establish the best practice for using it as a tool for assessing obesity risk.

The purposes of this study were to evaluate the differences in Mediterranean diet and its components among primary and secondary school children and adolescents living in northern Italy, and the associations with the weight status. Adherence was assessed by the KIDMED (Mediterranean Diet Quality Index) questionnaire on 669 subjects (6–16 years) attending five schools of Novara. The adherence was poor in 16.7%, average in 63.7%, and high in 19.6% of the students. Poor adherence was more frequent in primary than in secondary schools (20.7% vs. 13.7%, p < 0.04). Some unhealthy behaviors were more prevalent in younger children. Children of other ethnic origins had a mixed behavior, choosing both traditional healthy and unhealthy foods. Besides male gender and primary school, in Italian children, the risk of overweight was directly associated with eating at fast-food restaurants (OR: 1.890, CI 95% 1.002–3.563), and inversely with consumption of vegetables more than once a day (OR: 0.588, CI 95% 0.349–0.991), and olive oil at home (OR: 0.382, CI 95% 0.176–0.826). In children of other ethnic origins, this risk was associated with skipping breakfast (OR: 16.046, CI 95% 1.933–133.266), or consuming commercial baked good or pastries for breakfast (OR: 10.255, CI 95% 1.052–99.927). The overall KIDMED score correlated with height (β: 0.108; p < 0.005). Poor food quality is replacing the Mediterranean dietary pattern in children and adolescents, in particular among younger children. Because the risk of overweight was associated with different components of the Mediterranean diet depending on ethnic origins, tailored nutritional programs remain a need.

Background & aims: Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality. Methods: Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466). 101 youths (6e18 years, Tanner stage !2) with obesity and insulin-resistance on diet were randomized to 2 Â 10 9 CFU/AFU/day of Bifidobacterium breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) (51) or placebo (50) for 8 weeks with a 4-weeks wash-out period. Results: All subjects (M/F 54/47) completed the first 8 weeks, and 82 (M/F 43/39) the last part without adverse events. Mixed-effects models revealed a carry-over effect on many variables in the entire study, narrowing the analysis to the first 8 weeks before the wash-out periods. All subjects improved metabolic parameters, and decreased weight and Escherichia coli counts. Probiotics improved insulin sensitivity at fasting (QUICKI, 0.013 CI95%0.0e0.03) and during OGTT (ISI, 0.654 CI95%-0.11e1.41). Cytokines, GLP1, and target microbial counts did not vary. Of 25 SCFAs, acetic acid and acetic acid pentyl-ester relative abundance remained stable in the probiotics, while increased in the placebo (p < 0.02). A signature of five butanoic esters identified three clusters, one of them had better glucose responses during probiotics. Conclusion: An 8 weeks treatment with B. breve BR03 and B632 had beneficial effects on insulin sensitivity in youths with obesity. Microbiota functionality could influence metabolic answers to probiotics. Long-term studies to confirm and enrich our findings are justified. Tailored probiotic treatments could be an additional strategy for obesity. Trial registration: NCT03261466.

Infantile functional gastrointestinal disorders are common in the first months of life. Their pathogenesis remains unknown although evidences suggest multiple independent causes, including gut microbiota modifications. Feeding type, influencing the composition of intestinal microbiota, could play a significant role in the pathogenesis. Previous studies supported probiotic supplementation success against colics, however mainly Lactobacillus spp. were tested. The aim of this study was to evaluate the effectiveness against functional gastrointestinal disorders of a Bifidobacterium breve based probiotic formulation including in the study both breast-fed and bottle-fed subjects. Two hundred and sixty-eight newborns were enrolled within 15 days from birth. One hundred and fifty-five of them effectively entered the study and were randomized in probiotic and placebo group, receiving the formulation for 90 days. The probiotic formulation consists of a 1:1 mixture of 2 strains of B. breve prepared in an oily suspension and administered in a daily dosage of 5 drops containing 108 CFU of each strain. Absolute quantification of selected microbial groups in the faeces was performed using qPCR. Anthropometric data, daily diary minutes of crying, number of regurgitations, vomits and evacuations, and colour and consistency of stools were evaluated before and after treatment. The study confirmed the positive role of breast milk in influencing the counts of target microbial groups, in particular the bifidobacteria community. No adverse events upon probiotic administration were reported, suggesting the safety of the product in this regimen. B. breve counts increased significantly in all administered newborns (p < 0.02). The study demonstrates that a 3 months treatment with B. breve strains in healthy breast-fed newborns helps to prevent functional gastrointestinal disorders, in particular reducing 56% of daily vomit frequency (p < 0.03), decreasing 46.5% of daily evacuation over time (p < 0.03), and improving the stool consistency (type 6 at the Bristol Stool chart instead of type 5) in those at term (p < 0.0001). Moreover, a significant reduction (8.65 vs. 7.98 LogCFU/g of feces, p < 0.03) of B. fragilis in the bottle-fed group receiving the probiotic formulation was observed.

Background/objective Data on metabolic impairments in Cushing’s syndrome and GH deficiency all suggest that the relationship between cortisol and GH/IGF-I axis in obesity may have a role in the related diseases. However, studies focusing only on one of these hormones are often controversial in paediatrics. We aimed to explore the simultaneous relationship between cortisol and IGF-I with the metabolic alterations in paediatric obesity. Subjects/methods Retrospective cross-sectional study in a tertiary care center. We recruited 876 (441 males and 435 females) overweight and obese children and adolescents. A complete clinical and biochemical evaluation including OGTT was performed. Cortisol and IGF-I SDS were divided in quartiles and then crossed to explore the reciprocal influence of high/high, low/low, and high/low levels of each one on the metabolic alterations of obesity. Results Subjects in the higher quartiles of IGF-I-SDS and cortisol had an increased risk of hypertension, hypercholesterolemia, high levels of triglycerides, and reduced HDL cholesterol. Diversely, lower IGF-I-SDS quartiles were associated with higher blood glucose, insulin, insulin resistance, and reduced insulin sensitivity levels with the rise of cortisol quartiles. Conclusions We observed that apart from glucose metabolism that is associated with low IGF-I and high cortisol levels, the other parameters known to be associated with increased cardiovascular risk were related to high levels of both IGF-I and cortisol, even if within normal range. Cortisol and IGF-I play a complex role in the comorbidities of obesity, and the evaluation of both variables could clarify some of the discordant results.

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Background: Subclinical hypothyroidism (SH) management in neonatal age opens important questions. We aimed to describe the evolution over time of subclinical hypothyroidism diagnosed in the first three months of life in a population of full-term neonates. Methods: A single-center longitudinal retrospective cohort study in a tertiary care center was conducted. We recruited 32 subjects with SH diagnosed within the first three months of life. We collected clinical, biochemical, and ultrasound data for every subject at the first examination and every six months until four years of age. Results: A total of 43.8% of subjects showed stimulating thyroid hormone (TSH) levels over the limit of 10 mUI/L and underwent treatment (Group 1). Eleven subjects started therapy at the first visit, while three subjects started it after a period of observation; 15.6% (Group 2A) showed a trend of TSH decrease and were finally discharged from the follow-up, while 40.6% (Group 2B) showed a TSH level slightly increased, changeless over time. Conclusions: We demonstrated that more than half of newborns with hyperthyrotropinemia did not require substitutive therapy showing a positive trend toward normalization or a remaining slight increase compared to normal levels. Moreover, our study suggests the need for a follow-up over time to check the TSH levels course.

Background and Aims Renal cystic disease (RCD) includes a spectrum of disorders with heterogenous clinical presentation. Among RCD are autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), ciliopathies, HNF1B-nephropathy, and congenital anomalies of the kidneys and of the urinary tract (CAKUT). Diagnosis is based on clinical criteria, yet, given the extreme genetic heterogeneity and phenotypic overlap among different conditions, confirmation by genetic testing is paramount for correct clinical management and recurrence risk assessment. Although genotype-phenotype correlations are scanty, recently, coexisting variants in the same gene or in multiple cystogenes have been associated with earlier and more severe renal phenotype. The aim of this study is to describe the clinical and molecular characteristics of pediatric patients with early onset of RCD and provide genotype-phenotype correlations. Method A retrospective study was conducted collecting patients with a prenatal or early-childhood ultrasound finding of renal hyper-echogenicity or cysts. All patients were followed at the Pediatric Nephrology Unit of the Città della Salute e della Scienza University Hospital of Torino, Italy. Genetic analyses were mostly performed at the Immunogenetic and Transplant Biology Unit and included clinical exome sequencing (CES), array-CGH, MLPA and single gene testing. Results 65 patients we recruited, 42 males (64.6%) and 23 females (35.4%), mean age 8 ± 5.9 years (range 0-18). The most frequent clinical suspicion was ADPKD (n = 40, 61.5%), followed by CAKUT (n = 9, 13.8%), ARPKD (n = 8, 12.3%), ciliopathy and tuberous sclerosis complex (TSC) (n = 3, 4.6% for each condition), and medullary cystic disease (n = 2, 3.1%). Overall, causative variants (C4/C5) were identified in 39 patients (60.0%), 18 (27.7%) were carriers of variants of uncertain significance (C3) and 8 (12.3%) were inconclusive. Among the 40 patients with a clinical suspicion of ADPKD, 23 received a conclusive genetic diagnosis with 20 (87%) variants in PKD1, 2 (8.7%) in PKD2, one in HNF1B and 14 carried C3 variants. All patients with a clinical suspicion of ARPKD received molecular confirmation and, notably, in one case we observed biallelic variants in PKD1. Among the 21 patients with PKD1 variants, 6 (28.6%) had multiple PKD1 variants and 2 (9.5%) carried an additional PKHD1 variant. TSC diagnosis was confirmed in all 3 cases and two of them (66.7%) carried a contiguous gene TSC2-PKD1 deletion. Two out of 3 (66.7%) patients with a clinical suspicion of ciliopathy carried biallelic variants in BBS10, in one case associated with an additional variant in PKD2. Four (44.4%) CAKUT cases were solved with 3 causative variants in HNF1B (75%) and one in PAX2 (25%), 2 cases (22.2%) carried C3 variants and 3 (33.3%) were inconclusive. Causative variants were de novo in 10 cases (25.6%). Conclusion Our data confirms that genetic evaluation is a powerful tool for the diagnosis of RCD, as witnessed by a detection rate of 60%. Although the clinical suspicion was confirmed in the majority of cases, one suspected ARPKD case carried two PKD1 variants and one suspected ADPKD case carried a whole HNF1B gene deletion, highlighting the need for extensive genetic analysis. Moreover, nine patients had multiple variants potentially contributing with additive effect to a more severe renal phenotype: 6 patients had two variants in PKD1, 2 patients with a PKD1 variant had an additional variant in PKHD1 and one patient had biallelic BBS10 variants plus a nonsense PKD2 variant. In this context, genetic analysis by CES permits simultaneous evaluation of all RCD associated genes, uncovering both multiple variants and clinical phenocopies. In conclusion, the CES driven genetic characterization of pediatric patients with renal cysts allows to avoid misdiagnosis, minimize diagnostic invasive investigations, set up correct follow-up, and define recurrence risk, with a time- and cost- efficient approach.