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A high dairy protein intake in infancy, maternal pre-pregnancy BMI, and delivery mode are documented early programming factors that modulate the later risk of obesity and other health outcomes, but the mechanisms of action are not understood. The Childhood Obesity Project is a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants. Participating infants were either breastfed (BF) or randomized to receive higher (HP) or lower protein (LP) content formula in the first year of life. At the ages 5.5 years (n = 276) and 8 years (n = 232), we determined plasma metabolites by liquid chromatography tandem-mass-spectrometry of which 226 and 185 passed quality control at 5.5 years and 8 years, respectively. We assessed the effects of infant feeding, maternal pre-pregnancy BMI, smoking in pregnancy, delivery mode, parity, birth weight and length, and weight gain (0–24 months) on the metabolome at 5.5 and 8 years. At 5.5 years, plasma alpha-ketoglutarate and the acylcarnitine/BCAA ratios tended to be higher in the HP than in the LP group, but no metabolite reached statistical significance (Pbonferroni>0.09). There were no group differences at 8 years. Quantification of the impact of early programming factors revealed that the intervention group explained 0.6% of metabolome variance at both time points. Except for country of residence that explained 16% and 12% at 5.5 years and 8 years, respectively, none of the other factors explained considerably more variance than expected by chance. Plasma metabolome was largely unaffected by feeding choice and other early programming factors and we could not prove the existence of a long term programming effect of the plasma metabolome.

Rheumatoid arthritis (RA) is an autoimmune disorder in which gut and oral microbiota play a crucial role. Diet is a modifiable factor that can influence both microbiota composition and arthritis outcome, previous studies have suggested associations between dietary habits and RA, with contrasting results. We investigate the protective effect of the Mediterranean diet (MD) on disease activity and the gut microbiota profile in RA patients. Sixty consecutive RA patients were enrolled upon filling a validated 14-item questionnaire for the assessment of adherence to the Mediterranean diet (Prevention with Mediterranean Diet-PREDIMED). Then, 16S analysis was employed to explore the gut microbiota within the two cohorts of patients. Patients with high adherence to MD (20) had a significantly lower C-reactive protein (p &lt, 0.037) and disease activity (p &lt, 0.034) than the 40 patients with low/moderate adherence to MD. An inverse association between MD and disease activity was confirmed by multivariate analysis after adjustments for all the different demographic, clinical and serologic variables. A healthier gut microbiota composition was observed in the high adherence group, with a significant decrease in Lactobacillaceae and an almost complete absence of Prevotella copri with respect to the low/moderate adherence group. In conclusion, our findings support the protective role of MD on disease activity and microbiota composition in RA patients, and suggest the feasibility of shifting the habitual diet to modulate the gut microbiota and promote the benefits associated with MD.

The aim of this paper is to discuss the current evidence regarding short and long-term health respiratory effects of nutrients and dietary patterns during the first 1000 days from conception. Population of interest included children from birth to two years and their mothers (during pregnancy and lactation). Studies were searched on MEDLINE® and Cochrane database, inserting individually and using the Boolean ANDs and ORs, 'nutrients', 'micronutrients', 'LC-PUFA', 'Mediterranean Diet', 'human milk', 'complementary food', 'pregnancy', 'respiratory disease', 'pulmonary disease', 'asthma', 'epigenetics', 'first 1000 days', 'maternal diet' and 'respiratory health'. All sources were retrieved between 01-09-2015 and 07-12-2016. While unhealthy maternal dietary patterns (high fat intake) during pregnancy can result in alteration of foetal lung development, with increased risk of respiratory disorders, Mediterranean diet has been associated with a lower risk of allergic sensitisation and allergic rhinitis. Breastfeeding has beneficial effects on respiratory infections while evidences about its protective effect on allergic disorders are unclear. During complementary feeding there is no evidence to avoid or encourage exposition to 'highly allergenic' foods to have modification of tolerance development. In children from birth to two years of age, Mediterranean diet has been associated with a lower risk of atopy, wheezing and asthma. Micronutrients, antioxidant and LCPUFA supplementation is not recommended and a whole food approach should be preferred, except for Vitamin D.

Background/Objectives The aim of this study was to examine the effect of physical activity (PA) and sedentary behaviour (SB) on body mass index (BMI) and fat mass index (FMI) in children over the course of five years and identify potential bi-directional associations. Subjects/Methods Data were drawn from the EU Childhood Obesity Project (CHOP). PA and SB were measured with the SenseWear Armband 2 at the ages of 6 (T1), 8 (T2) and 11 (T3) years. Height and weight were measured and BMI was calculated at each time point, resulting in 1254 complete observations from 600 children. Bio impedance analysis was used to measure body fat mass and eventually calculate FMI. To examine the longitudinal association between PA/SB and BMI/FMI as well as to account for repeated measure on these children, mixed model analysis was employed. Results Higher levels of total PA and moderate-to-vigorous PA (MVPA) were associated with lower BMI and FMI and higher SB with higher BMI and FMI over the five year period. When looking at the age dependent effects, negative associations of MVPA (βMVPA x age: − 0.05, 95% confidence interval (CI): − 0.09 – -0.01, p = 0.007) and positive associations of SB (βSB x age: 0.04, 95% CI: 0.02–0.06, p

Childhood obesity prevalence is rising in countries worldwide. A variety of etiologic factors contribute to childhood obesity but little is known about underlying biochemical mechanisms. We performed an individual participant meta-analysis including 1,020 pre-pubertal children from three European studies and investigated the associations of 285 metabolites measured by LC/MS-MS with BMI z-score, height, weight, HOMA, and lipoprotein concentrations. Seventeen metabolites were significantly associated with BMI z-score. Sphingomyelin (SM) 32:2 showed the strongest association with BMI z-score (P = 4.68 × 10 −23 ) and was also closely related to weight, and less strongly to height and LDL, but not to HOMA. Mass spectrometric analyses identified SM 32:2 as myristic acid containing SM d18:2/14:0. Thirty-five metabolites were significantly associated to HOMA index. Alanine showed the strongest positive association with HOMA (P = 9.77 × 10 −16 ), while acylcarnitines and non-esterified fatty acids were negatively associated with HOMA. SM d18:2/14:0 is a powerful marker for molecular changes in childhood obesity. Tracing back the origin of SM 32:2 to dietary source in combination with genetic predisposition will path the way for early intervention programs. Metabolic profiling might facilitate risk prediction and personalized interventions in overweight children., SCOPUS: ar.j, info:eu-repo/semantics/published

OBJECTIVES: Physical activity (PA) is presumed to decline during childhood and adolescence, but only few long-term studies about PA development during this period of life exist. We assessed PA and sedentary behavior (SB) over a 5-year period to gain a better understanding of the extent of change in activity and potential influencing factors. METHODS: PA and SB of 600 children from the Childhood Obesity Project were objectively measured with the SenseWear Armband 2 at the ages of 6, 8, and 11 years, resulting in 1254 observations. Longitudinal changes of total PA, moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and SB were modeled with mixed-effects models. RESULTS: Total PA revealed a significant quadratic decline with age (P < .001), resulting in a change of total PA by −75.3 minutes per day from 6 to 11 years. LPA linearly declined (P < .001) by 44.6 minutes per day, MVPA quadratically declined (P < .001) by an overall 30.7 minutes, whereas SB increased significantly (+107 minutes; P = .001). Boys showed a steeper decline in LPA (P = .003) and MVPA (P < .001) than did girls. Higher fat mass index and BMI z scores were associated with lower levels of total PA and MVPA and higher levels of SB (all P < .001). CONCLUSIONS: We showed that PA decreased, and SB increased in earlier years than previously thought. MVPA remained relatively stable until 8 years, but revealed a drop-off at 11 years, identifying this period as a crucial time for intervention.

Fetal and early life represent a period of developmental plasticity during which metabolic pathways are modified by environmental and nutritional cues. Little is known on the pathways underlying this multifactorial complex. We explored whether 6 months old breast-fed infants could be clustered into metabolically similar groups and that those metabotypes could be used to predict later obesity risk.Plasma samples were obtained from 183 breast-fed infants aged 6 months participating in the European multicenter Childhood Obesity Project study. We measured amino acids along with polar lipid concentrations (acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins). We determined the metabotypes using a Bayesian agglomerative clustering method and investigated the properties of these clusters with respect to clinical, programming, and metabolic factors up to 6 years of age.We identified 20 metabolite clusters comprising 1 to 39 children. Phosphatidylcholines predominantly influenced the clustering process. In the largest clusters (n ≥ 14), large differences existed for birth length (unadjusted P 0.0001) and length and weight at 6 months (unadjusted P 0.0001 and P = 0.012, respectively). Infants tended to cluster together by country (unadjusted P 0.001). The body mass index (BMI) z score at 6 years of age tended to differ (unadjusted P = 0.07).Our exploratory study provided evidence that breast-fed infants are not metabolically homogeneous and that variation in metabolic profiles among infants may provide insight into later development and health. This work highlights the potential of metabotypes for identifying inter-individual differences that may form the basis for developing personalized early preventive strategies.

Salicylic acid (SA), a phenolic compound produced by plants, may play a beneficial role on health. This pilot study evaluated whether there might be an association between serum SA and fruit and vegetable (FV) consumption in obese and normal-weight children. Thirty-four obese children (17 boys and 17 girls) and 34 normal-weight children were recruited. Dietary intake was evaluated by the 7-day dietary record. Serum SA was measured using gas chromatography-mass spectrometry method. FV intake in obese and normal-weight children was not different between groups (175.00 (97.66) g versus 192.29 (90.54) g, p = .455). Obese children had lower serum SA than normal-weight children [mean difference, −0.025; 95% CI (−0.044; −0.006) μmol/L]. Serum SA was not associated with daily intake of FV in obese (p = .111) and normal-weight (p = .092) children. Further studies are needed to evaluate the role of FV on serum SA, taking into account also the quantity and the type.

Summary Objective A recent study evidenced by metyrapone test a central adrenal insufficiency (CAI) in 60% of Prader–Willi syndrome (PWS) children. These results were not confirmed in investigations with low [Low-Dose Tetracosactrin Stimulation Test (LDTST), 1 μg] or standard-dose tetracosactrin stimulation tests. We extended the research by LDTST in paediatric patients with PWS. Design Cross-sectional evaluation of adrenal stress response to LDTST in a PWS cohort of a tertiary care referral centre. Patients Eighty-four children with PWS. Measurements Assessment of adrenal response by morning cortisol and ACTH dosage, and 1-μg tetracosactrin test. Response was considered appropriate when cortisol reached 500 nm; below this threshold, patients were submitted to a second test. Responses were correlated with the patients’ clinical and molecular characteristics to assess genotype–phenotype correlation. Results Pathological cortisol peak responses to the LDTST were registered in 12 patients (14·3%) who had reduced basal (169·4 ± 83·3 nm) and stimulated (428·1 ± 69·6 nm) cortisol levels compared to patients with normal responses (367·1 ± 170·6 and 775·9 ± 191·3 nm, P

According to recent epidemiological evidence, early protein intakes that exceeds metabolic requirements (>15% of energy) may increase weight gain during infancy and the risk of developing obesity in childhood: the so-called “early protein hypothesis” [1]. A high protein intake, indeed, especially milk’s protein [2,3], may enhance the secretion of insulin and insulin-like growth factor-I (IGF-I), associated with increased weight gain during the first 2 years of life, increase of adipocyte differentiation and adipogenic activity [4]. In a large number of studies increased weight gain in infancy and early adiposity rebound have been associated with the development of later obesity [4]. The presence of a positive strong association between early protein intake and increased weight gain in early childhood has been recently demonstrated in the European Childhood Obesity Project (CHOP): a multicenter, double-blind intervention trial involving both formula fed infants, randomly assigned to receive, during the first year of life, infant and follow-on formulas with different protein content (high or low), and breastfed infants as control group. This trial showed that both weight-for-length and BMI z-scores were significantly higher in the high protein (HP) compared with the low protein (LP) group at 12 and 24 months [5]. Moreover the body composition analysis at 6 months of life showed that weight gain velocity from baseline to 6 months was significantly associated with fat mass, proving that higher early protein intakes may influence adiposity [6]. Concerning metabolic data, HP group compared with LP group showed higher plasma concentrations of branched chain aminoacids, IGF-I and insulin at 6 months. Moreover, IGF-I concentrations have been associated with weight gain in the first 6 months of life [7]. Additionally IGF-I could partly mediate protein-induced kidney growth in healthy children [8]. This phenomenon was observed in the HP group: children at 6 months of life showed a significantly greater kidney volume compared with the LP group [9]. However the long-term consequences of these results should be further evaluated. Lastly it has been recently published that protein content of infant formulas may influence not only the growth pattern in the first two years, but also the risk of developing obesity at school-age, showing a 2.43 increased risk of obesity at 6 years of age in the HP vs LP group [10]. In conclusion these results suggest that early nutritional intervention programs are needed to avoid negative long-term consequences on health, especially to prevent “non-communicable diseases”in adult age.

Background/Aims: Congenital hyperinsulinism of infancy is a rare disease that needs prompt treatment to avoid brain damage. There are currently no data regarding the clinical and molecular features of Italian patients. Methods: Thirty-three patients with HI and their parents were included. Consanguinity was reported in six patients. Half of patients were macrosomic at birth. None had raised 3-hydroxybutyrylcarnitine or hyperammonemia. Molecular analysis of ABCC8 and KCNJ11 genes was performed in all patients, and subjects with no mutation underwent analysis of HNF4A and GCK. GLUD1 and HADH genes were analyzed in a patient with leucine sensitivity. Results: Mutations in the ABCC8 and KCNJ11 genes were found in 45% of the patients (6 novel). No mutations in HNF4A, GLUD1 and GCK genes were found. Recessive mode of inheritance was found in 21% of patients. A single heterozygous mutation was identified in 24% of probands. 72% of the patients were responsive to medical treatment, and 44% of the 17 patients with no identified mutation achieved spontaneous remission. Nine children, unresponsive to medical therapy, underwent pancreatectomy. Conclusion: This is the first report on hyperinsulinism of infancy in Italy, confirming the complexity of the clinical forms and the heterogeneity of the genetic causes of the disease.

Background and aims Triglycerides-glucose index (TyG index) has been associated with homeostatic model assessment (HOMA) index in healthy adults; this might be useful in identifying individuals at high risk of developing diabetes. Moreover, TyG-index has been related to Triglycerides/HDL ratio and carotid atherosclerosis, indicating strong validity to assess cardiovascular risk. (Lee SH et al 2014, Irace C et al 2013). The primary aim of this study was to assess the TyG in obese children and adolescent. Methods Two hundred sixty-eight obese children and adolescents (Cole TJ et al 2000), mean (SD) age 10.05 (1,82) years, were studied. Anthropometry, fasting glucose and insulin, lipid profile were evaluated. HOMA and TyG index were calculated as following, respectively: [fasting Insulin (μU/l) x fasting glucose (mmol/l)] : 22.5; Ln[fasting triglycerides (mg/dl) x fasting glucose (mg/dl)/2] (Simental-Mendia LE et al 2008). Insulin resistance has been defined as HOMA Index > 95°p for sex and pubertal stage (D’Annunzio G et al . 2009). Results 135 subjects showed insulin resistance, with higher TyG index than those with normal insulin sensitivity (P In all the studied population a positive association between TyG index, HOMA index and Triglycerides/HDL ratio was found (P Conclusions TyG index is a good predictor of decreased insulin sensitivity also in paediatric ages and might be considered also a marker of cardiovascular risk considering the association with waist/height ratio and Triglycerides/HDL ratio.