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Background: Higher early-life animal protein intake is associated with a higher childhood obesity risk compared to plant protein intake. Differential DNA methylation may represent an underlying mechanism., Methods: We analysed associations of infant animal and plant protein intakes with DNA methylation in early (2-6 years, N  = 579) and late (7̄-12 years, N  = 604) childhood in two studies. Study-specific robust linear regression models adjusted for relevant confounders were run, and then meta-analysed using a fixed-effects model. We also performed sex-stratified meta-analyses. Follow-up analyses included pathway analysis and eQTM look-up., Results: Infant animal protein intake was not associated with DNA methylation in early childhood, but was associated with late-childhood DNA methylation at cg21300373 ( P  = 4.27 × 10¯ 8 , MARCHF1 ) and cg10633363 ( P  = 1.09 × 10¯ 7 , HOXB9 ) after FDR correction. Infant plant protein intake was associated with early-childhood DNA methylation at cg25973293 ( P  = 2.26 × 10 -7 , C1orf159 ) and cg15407373 ( P  = 2.13 × 10 -7 , MBP ) after FDR correction. There was no overlap between the findings from the animal and plant protein analyses. We did not find enriched functional pathways at either time point using CpGs associated with animal and plant protein. These CpGs were not previously associated with childhood gene expression. Sex-stratified meta-analyses showed sex-specific DNA methylation associations for both animal and plant protein intake., Conclusion: Infant animal protein intake was associated with DNA methylation at two CpGs in late childhood. Infant plant protein intake was associated with DNA methylation in early childhood at two CpGs. A potential mediating role of DNA methylation at these CpGs between infant protein intake and health outcomes requires further investigation.

We aimed to investigate the eating frequency (EF) in children over age, and examined the influence of country, sex, feeding mode and weight status on EF. We used the dietary data of the Childhood Obesity Project, which comprised European children from five countries. Dietary data of 3-days weighed and estimated records were available monthly from 1 to 9 and at 12-, 24-, 36-, 48-, 60-, 72- and 96-months old. Generalized additive mixed effects models were used to estimate EF trajectories with EF as outcome and applying age splines. Additionally, the models were further adjusted for country, feeding mode, sex or weight status. Data from 1244 children were analysed. EF was highest at 1 month with on average 7.3 ± 1.9 feeds per day, and fell to 5.1 ± 1.1 eating occasions at the age 96 months. Night feeding was similarly often than day feeding at 1 month but declined thereafter. Significant differences in EF were observed between countries ( p < 0.05), with the highest EF in Poland, and between infant feeding modes, with a higher EF in breastfed than non-breastfed infants ( p < 0.05). Sex and body weight were not associated with EF. Despite the importance of EF towards total energy intake, no association with weight status was found.

Purpose: We aimed to characterize the distribution of energy and macronutrient intakes across eating occasions (EO) in European children from preschool to school age., Methods: Data from 3-day weighed food records were collected from children at ages 3, 4, 5, 6 and 8 years from Belgium, Germany, Italy, Poland and Spain. Food intakes were assigned to EO based on country-specific daytimes for breakfast, lunch, supper and snacks (morning, afternoon). The average energy and nutrient intakes were expressed as percentage of total energy intake (%E). Nutrients were additionally expressed as percentage per EO (%E EO ). Foods were assigned to food groups; variation in intake was calculated via coefficient of variation (CV). We analyzed age trends in diurnal intake using mixed-effects beta regression., Results: The 740 healthy children included in the analysis consumed the largest proportion of daily energy at lunch (31%E ± 8, M ± SD) and supper (26%E ± 8), followed by breakfast (19%E ± 7) and snacks [afternoon (16%E ± 8); morning (8%E ± 7)], with the most variable intake at morning snack (CV = 0.9). The nutrient composition at lunch and supper was highest for fat (36 ± 9%E Lunch ; 39 ± 11%E Supper ) and protein (18 ± 5%E Lunch ; 18 ± 6%E Supper ) and at breakfast and snacks for carbohydrates (54 ± 12%E Breakfast ; 62 ± 12%E Snacks ). High-sugar content foods were consumed in relatively large proportions at breakfast and snacks. Food intakes varied significantly with age, with lower snack intakes at later ages (p < 0.001)., Conclusion: Possibly unhealthy EOs with high-fat intakes and high-sugar-content foods were observed. Changes in nutrient composition of EOs may be beneficial for health., Trial Registry: ClinicalTrials.gov: NCT00338689; 19/June/2006., (© 2022. The Author(s).)

Meal timing is suggested to influence the obesity risk in children. Our aim was to analyse the effect of energy and nutrient distributions at eating occasions (EO), including breakfast, lunch, supper, and snacks, on the BMI z-score (zBMI) during childhood in 729 healthy children. BMI and three-day dietary protocols were obtained at 3, 4, 5, 6, and 8 years of age, and dietary data were analysed as the percentage of the mean total energy intake (TEI; %E). Intakes at EOs were transformed via an isometric log-ratio transformation and added as exposure variables to linear mixed-effects models. Stratified analyses by country and recategorization of EOs by adding intake from snacks to respective meals for further analyses were performed. The exclusion of subjects with less than three observations and the exclusion of subjects who skipped one EO or consumed 5% energy or less at one EO were examined in sensitivity analyses. Around 23% of the children were overweight at a given time point. Overweight and normal-weight children showed different distributions of dietary intakes over the day; overweight children consumed higher intakes at lunch and lower intakes of snacks. However, no significant effects of timing of EOs on zBMI were found in regression analyses.

Background: Maternal perception of child weight status in children with overweight or obesity has received a lot of attention but data on paternal perception of children from presumably healthy cohorts are lacking., Objective: We aimed to investigate paternal and maternal perception of child weight status at the age of 8 years in a cohort of 591 children from 5 European countries., Material and Methods: Included were 8-year-old children and their parents participating in the European Childhood Obesity Project (EU CHOP). Weight and height of children and parents were measured and Body Mass Index (BMI, kg/m 2 ) was calculated. Both parents were asked to assess their perception of child weight status using Eckstein scales and their concern about child overweight. The agreement between mother and father perceptions was assessed by Cohen kappa coefficient and their relationship was analyzed by linear mixed effects models based on ordinal logistic regression, accounting for country, child gender and BMI, parental BMI, level of education, concern and type of feeding during first year of life., Results: Data from children and both parents were available for 432 girls and boys. Mean BMI was comparable in boys and girls (16.7 ± 2.31 vs. 16.9 ± 2.87 kg/m 2 , P = 0.55). In total, 172 children (29.3%) were overweight or obese. There was a high degree of agreement between mother and father perceptions of their child's weight status (Cohen kappa 0.77). Multivariate modelling showed that perception levels significantly increased with child BMI but were globally lower than assessed. They differed between countries, gender and types of feeding during first year of life, were influenced by education level of the father but were not related to parental BMI and concern about childhood overweight., Conclusions: The study showed no overall differences between mothers and fathers in rating their child's weight status but both parents had a propensity to underestimate their child's actual weight, particularly in boys. The EU CHOP trial registered at clinicaltrials.gov as NCT00338689., (© 2021. The Author(s).)

There is growing evidence that insufficient sleep has negative effects on the mental health of children. The aim of this study is to examine the associations between device-measured sleep duration and internalizing and externalizing problems in 8-year-old children. The study is a secondary analysis of data from the Childhood Obesity Project conducted in five European countries. Nocturnal sleep duration was measured with the SenseWear™ Armband 2. Parents rated their child's internalizing and externalizing problems on the Child Behaviour Checklist. Behaviour scores were dichotomized at the 90th percentile based on sex- and country-specific z-scores. Logistic regression models were applied to test the associations between sleep duration and behaviour. Data were available for 406 8-year-old children. The average sleep duration was 9.25 h per night (SD: 0.67) with 1464 nights measured in total. The sleep duration recommendation of the American Academy of Sleep Medicine for school-aged children (9-12 h) was met by 66.7% of children. One hour of additional sleep per night significantly reduced the risk of having internalizing problems (adjusted OR = 0.51; 95% CI 0.29-0.91). Children who adhered to the sleep duration recommendation had a lower risk for internalizing problems (adjusted OR = 0.45; 95% CI 0.21-0.99). Sleep duration and externalizing problems showed no significant association. Longer sleep duration was associated with a reduced risk of having internalizing problems but not externalizing problems. Results highlight that it is important to ensure adequate sleep duration throughout primary-school years for the optimal emotional health of children. Trial registration number: NCT00338689. Registered: June 19, 2006., (© 2021. The Author(s).)

Background & Aims: Only limited information is available on the usefulness of the waist-to-height ratio (WHtR) as an abdominal obesity marker in children. Our aim was to compare the ability of a WHtR >90th percentile, a WHtR ≥0.50, a WHtR ≥0.55 and a BMI z-score ≥2 SD to predict cardiometabolic risk in children followed-up at different ages., Methods: We evaluated data from 660 children at 5, 8 and 11 years of age who participated in the Childhood Obesity Project trial in 5 European countries. We classified children with or without cardiometabolic (CMet) risk (yes vs. no) according to the presence of ≥2 parameters (blood pressure, HOMA-IR, triglyceride levels and high-density lipoprotein (HDL) cholesterol levels) ≥90th percentile., Results: The odds ratio for CMet risk in children at all followed-up ages was statistically significant for all measures. The OR for the WHtR≥0.55 cut-off was 29.1 (5.6, 151.7) at 5 years of age, 11.8 (4.1, 33.8) at 8 year of age and 3.6 (1.7, 7.7) at 11 years of age, compared to the WHtR<0.55 cut-off. The WHtR≥0.55 cut-off showed a higher OR at younger ages than the BMI z-score ≥2SD, WHtR ≥90th percentile and WHtR≥0.50 cut-offs and a higher positive predictive value (82% at 5 years of age compared to 55%, 36% and 41%, respectively)., Conclusion: A WHtR≥0.55 is a suitable cut-off for screening children at high cardiometabolic risk in the general young European population., Competing Interests: Conflict of interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: We aimed to characterize the association of dietary sugar intake with blood lipids and glucose-related markers in childhood., Methods: Data from the multicentric European Childhood Obesity Project Trial were used. Three-day weighed dietary records were obtained at 8 years of age along with serum concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), glucose, and insulin. Total sugar intake comprised all mono- and disaccharides; different sugar sources were defined. Linear regression models were applied to investigate the cross-sectional association of total sugar intake with blood lipids and glucose-related markers with adjustment for total energy intake using the residual method., Results: Data were available for 325 children. Children consumed on average 332 kcal (SD 110) and 21% (SD 6) of energy from total sugar. In an energy-adjusted model, an increase of 100 kcal from total sugar per day was significantly associated with a z score HDL-C decrease (- 0.14; 95% CI - 0.01, - 0.27; p value = 0.031). Concerning different food groups of total sugar intake, 100 kcal total sugar from sweetened beverages was negatively associated with z score HDL-C (- 1.67; 95% CI - 0.42, - 2.91; p value = 0.009), while total sugar from milk products was positively related to z score HDL-C (1.38, 95% CI 0.03, 2.72; p value = 0.045). None of the other blood lipids or glucose-related markers showed a significant relationship with total sugar intake., Conclusion: Increasing dietary total sugar intake in children, especially from sweetened beverages, was associated with unfavorable effects on HDL-C, which might increase the long-term risk for dyslipidemia and cardiovascular disease., Clinical Trial Registry: ClinicalTrials.gov Identifier: NCT00338689; Registered: June 19, 2006. URL: https://clinicaltrials.gov/ct2/show/NCT00338689?term=NCT00338689&rank=1 .

Purpose: We determined the association of total sugar intake with body weight and fat mass in children on an energy-equivalent basis and potential changes in the association from 2 to 8 years of age., Methods: Data were available from the Childhood Obesity Project Trial initiated in 2002. Sugar intake was measured by 3-day weighed food protocols at 2, 3, 4, 5, 6, and 8 years of age. Body mass index (BMI) and fat mass index (FMI) were available at the same time points. To investigate the association of sugar intake with anthropometrics over time, linear mixed models were applied. Odds ratios for having a high BMI or FMI (above one standard deviation) were estimated by logistic random-effects models. To control for total energy intake, the residual method was chosen and models were additionally adjusted for total energy intake., Results: Data were available for 809 children with in total 2846 observations. In an isocaloric model, an increase of 100 kcal from sugar per day was significantly associated with lower zBMI (- 0.033; 95% CI -0.061, - 0.005) and zFMI (- 0.050; 95% CI - 0.089, - 0.011). In addition, a 100 kcal higher sugar intake was related to lower odds of having a high zBMI (OR 0.743; 95% CI 0.611, 0.903)., Conclusion: This study provides no indication that increased total sugar intake positively affects BMI on an energy-equivalent basis. Whether the negative association of sugar is due to physiological effects or points more to macronutrient preferences or a reporting bias (lower sugar intake) in children with higher BMI can be debated., Clinical Trial Registry: ClinicalTrials.gov Identifier: NCT00338689; Registered: June 19, 2006. URL: http://clinicaltrials.gov/ct2/show/NCT00338689?term=NCT00338689&rank=1 .

Purpose: The objective of this secondary analysis is to describe the types of commercial complementary foods (CCF) consumed by infants and young children enrolled in the European Childhood Obesity Project (CHOP), to describe the contribution of CCF to dietary energy intakes and to determine factors associated with CCF use over the first 2 years of life., Methods: The CHOP trial is a multicenter intervention trial in Germany, Belgium, Italy, Poland and Spain that tested the effect of varying levels of protein in infant formula on the risk for childhood obesity. Infants were recruited from October 2002 to June 2004. Dietary data on CCF use for this secondary analysis were taken from weighted, 3-day dietary records from 1088 infants at 9 time points over the first 2 years of life., Results: Reported energy intakes from CCF during infancy (4-9 months) was significantly higher (p ≤ 0.002) amongst formula-fed children compared to breastfed children. Sweetened CCF intakes were significantly higher (p ≤ 0.009) amongst formula-fed infants. Female infants were fed significantly less CCF and infant age was strongly associated with daily CCF intakes, peaking at 9 months of age. Infants from families with middle- and high-level of education were fed significantly less quantities of CCF compared to infants with parents with lower education. Sweetened CCF were very common in Spain, Italy and Poland, with over 95% of infants and children fed CCF at 9 and 12 months of age consuming at least one sweetened CCF. At 24 months of age, 68% of the CHOP cohort were still fed CCF., Conclusions: CCF comprised a substantial part of the diets of this cohort of European infants and young children. The proportion of infants being fed sweetened CCF is concerning. More studies on the quality of commercial complementary foods in Europe are warranted, including market surveys on the saturation of the Western European market with sweetened CCF products.

Breastfeeding is associated with a reduced later obesity risk, relative to feeding convention infant formula. Breastfeeding induces less weight gain during the first two years of life, which predicts less obesity up to adulthood. We tested the hypothesis that a high infant protein supply promotes weight gain and obesity risk, mediated by increased plasma amino acids and growth factors, insulin and insulin like growth factor 1 (IGF-1). A large multi-centre double blind trial randomized formula-fed infants to conventional bottle milk with a high protein content, or an intervention formula with a reduced protein content more similar to levels provided with human milk. Protein-reduced formula normalized weight, body mass index and body fatness up to 6 years, relative to a breastfed reference group, and reduced the adjusted odds for obesity 2.6-fold. Available data indicate potential underlying mechanisms. We conclude that infant feeding has very marked long-term programming effects on later BMI, obesity and adiposity, with major public health implications. Breastfeeding lowers the risk for later obesity and adiposity. This provides additional motivation for proactively and enthusiastically promoting, protecting and supporting breastfeeding. A high milk protein intake in infancy increases the long-term risk for obesity and adiposity. Infants not or not fully breastfed should receive infant formula delivering protein in amounts more similar to human milk contents, with high protein quality. Other sources of very high infant protein intakes, particular drinking unmodified cows' milk, should be avoided in infancy., (Copyright © 2019. Published by Elsevier Inc.)

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.

Background: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact., Methods and Findings: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations., Conclusions: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KMG has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. HL has participated as an advisory board member, consultant and speaker for Nestlé Nutrition Institute and Nestlé Finland. DAL has received support from several National and International Government and Charity Funders and from Roche Diagnostics and Medtronic for research unrelated to that presented here. All support had been administered via DAL's institution; not directly to her. The other authors have declared that no competing interests exist.

: media-1vid110.1542/5849572910001PEDS-VA&#95;2018-0994 Video Abstract 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., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background & Aims: Misreporting is a major source of reporting bias in nutritional surveys. It can affect the analysis of associations between diet and disease. Although various methods have been proposed to identify misreporting, their application to infants and young children is difficult. We identify misreporting of energy intake in infants and young children and propose a simplified approach., Methods: 1199 children were enrolled in the Childhood Obesity Programme (CHOP) based in 5 European countries (Belgium, Germany, Italy, Poland and Spain) with repeated measurements of 3-day weighed food protocol and anthropometric indices at 10 time points between ages 1-96 months. Individual cut-offs for the ratio of reported energy intake and estimated energy requirement were calculated to identify misreporters. Misreporting was studied according to age, gender, BMI z-scores and country., Results: We identified a higher proportion of over-reporters (18.9%) as compared to under-reporters (10.6%). The proportion of over-reporting was higher among infants while under-reporting was more prevalent in school-aged children. Under-reporting was higher in boys (12.0%) and in obese/over-weight children (36.3%). Mean values for upper and lower cut-offs for the ratio of reported energy intake and estimated energy requirement in children ≤12 months were 0.80 and 1.20, and 0.75 and 1.25 for children >12 months, respectively. Using these fixed (mean) values, 90.4% (kappa statistic: 0.78) of all misreporters could be identified., Conclusions: Despite intensive measures to obtain habitual intake of children, an essential proportion of nutritional reports were found to be implausible. Both over- and under-reporting should be carefully analysed, even in studies on infants. Fixed cut-offs can be applied to identify misreporting if no individual variation in energy intake can be calculated., Clinical Trial Registry: This trial was registered at https://clinicaltrials.gov/show/NCT00338689., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Dietary habits established in infancy may persist into adulthood and determine long-term health., Objectives: The aims of this work were to describe dietary patterns, predictors of adherence to them, and their tracking from ages 1 to 8 y in European children., Methods: Three-day food diaries were prospectively collected at ages 1, 2, 3, 4, 5, 6 and 8 y. Foods were allocated to 1 of 29 food groups, which were included in exploratory factor analyses at each children's age. The tracking of patterns through childhood was assessed by an estimated general equation model., Results: At age 1 y (n = 633), 2 patterns were identified. One was labeled "core foods" (CORE), since it was positively loaded for vegetables, fish, olive oil, and white and red meat, and negatively loaded for ready-to-eat infant products, sugar, and confectioneries. The other was positively loaded for saturated spreads, sugar, fruit juices, and confectioneries, and negatively loaded for olive oil, fish, and cow milk; this was labeled as the "poor-quality fats and added sugars" (F&S) pattern. From ages 2 to 8 y, 3 patterns were repeatedly identified: CORE, F&S, and a "high protein sources" (PROT) pattern that was positively loaded for milk, flavored milks, fish, eggs, white and processed meat, chips, and olive oil, and negatively loaded for fresh fruits at almost all time points. Of those children in the highest quartiles of the CORE, F&S, and PROT patterns at 2 y, 45%, 72%, and 36%, respectively, remained in the highest quartile at 8 y [OR = 2.01 (1.08, 3.8), OR = 3.6 (1.5, 8.4) and OR = 0.80 (0.4,1.6), respectively; P = 0.510]., Conclusions: Dietary patterns are established between 1 and 2 y of age and track into mid-childhood. A dietary pattern characterized by added sugars, unhealthy fats, and poor consumption of fish and olive oil was the most stable throughout childhood. Further analyses will reveal whether those dietary patterns are associated with metabolic disease risk.

Adiposity and obesity result from the interaction of genetic variation and environmental factors from very early in life, possibly mediated by epigenetic processes. Few Epigenome-Wide-Association-Studies have identified DNA-methylation (DNAm) signatures associated with BMI and body composition in children. Body composition by Bio-Impedance-Analysis and genome-wide DNAm in whole blood were assessed in 374 pre-school children from four European countries. Associations were tested by linear regression adjusted for sex, age, centre, education, 6 WBC-proportions according to Houseman and 30 principal components derived from control probes. Specific DNAm variants were identified to be associated with BMI (212), fat-mass (230), fat-free-mass (120), fat-mass-index (24) and fat-free-mass-index (15). Probes in genes SNED1(IRE-BP1), KLHL6, WDR51A(POC1A), CYTH4-ELFN2, CFLAR, PRDM14, SOS1, ZNF643(ZFP69B), ST6GAL1, C3orf70, CILP2, MLLT4 and ncRNA LOC101929268 remained significantly associated after Bonferroni-correction of P-values. We provide novel evidence linking DNAm with (i) altered lipid and glucose metabolism, (ii) diabetes and (iii) body size and composition in children. Both common and specific epigenetic signatures among measures were also revealed. The causal direction with phenotypic measures and stability of DNAm variants throughout the life course remains unclear and longitudinal analysis in other populations is required. These findings give support for potential epigenetic programming of body composition and obesity.

Background: Physical activity (PA) and its health benefits are a continuous point of discussion. Recommendations for children's daily PA vary between guidelines. To better define the amount of PA necessary to prevent overweight and obesity in children, further research is needed. The present study investigates children's compliance to physical activity guidelines (PAGs) and the association between objectively measured PA and body mass index (BMI)., Methods: Participating children were 11 years old (n = 419) and part of the European CHOP trial, which was conducted in Germany, Belgium, Poland, Spain, Italy. At least 2 days of PA measurements were collected from each child using a SenseWear™ armband. BMI was calculated from children's height and weight. Thresholds of min·day -1 in PA needed to differentiate between normal and excess weight (overweight/obesity) were determined with Receiver Operator Characteristics (ROC) analysis. Additionally, adjusted linear and logistic regressions models were calculated for group differences and effects of a 5, 15 and 60 min·day -1 increases in PA on BMI., Results: Median time spent in total PA was 462 min·day -1 (25th percentile; 75th percentile: 389; 534) and 75 min·day -1 (41; 115) in moderate to vigorous PA (MVPA). Girls spent 36 min·day -1 less in MVPA than boys and overweight/obese children 24 min·day -1 less than normal weight children (linear regression, p < 0.001). 63.2% of the children met PAGs of 60 min·day -1 in MVPA. The optimal threshold for min·day -1 in MVPA determined with ROC analysis was 46 min·day -1 . Comparing 5, 15 and 60 min·day -1 increases in PA revealed that an additional 15 min·day -1 of vigorous PA had the same effect as 60 min·day -1 of MVPA. Sedentary time and light PA showed contrary associations to one another, with light PA being negatively and sedentary time being positively associated with excessive weight., Conclusions: Current PAGs are met by 2/3 of children and seem appropriate to prevent excess weight in children. An official recommendation of daily 15-20 min of vigorous PA and further reduction of sedentary time could help to fight youth overweight and thus be of potential public health importance., Trial Registration: ClinicalTrials.gov Identifier: NCT00338689 . Registered: June 19, 2006 (retrospectively registered).

Background: Early adiponectin and leptin in children correlate with those measured at a later age. Prenatal and early life factors may influence the pattern of leptin and adiponectin longitudinal changes. We aimed to identify subgroups of children with distinct trajectories of leptin and adiponectin over the first eight years of life, and to explore determinants predisposing an individual to be included in a specific trajectory class., Methods: The analysis was based on data obtained from the EU Childhood Obesity Project (CHOP) cohort. The current study involved 459 children with adiponectin and leptin measured at 6 months, 5½ and 8 years of age., Results: Three groups of leptin trajectories were identified: low-decreasing, medium-stable, and high-increasing, and two trajectory groups for adiponectin: lower and higher. The risk to be classified in the high-increasing group was higher than in the low-decreasing group for female gender (OR 10.67; 95% CI 4.94-23.05; p < 0.001); formula feeding (OR 3.34; 95% CI 1.11-10.09; p < 0.05); maternal overweight (OR 4.43; 95% CI 2.20-8.94; p < 0.001); and smoking in pregnancy (OR 4.14; 95% CI 2.07-8.29; p < 0.001). No predictors for being in the higher vs. lower adiponectin group were discovered., Conclusions: Mothers' smoking during pregnancy, maternal overweight, and formula feeding distinguished different courses of leptin trajectories; but the effect may be associated with changes in adiposity.

There is growing evidence of long-term effects of early dietary intervention in infancy on later obesity risk. Many studies showed reduced risk of obesity with breastfeeding in infancy, which could be related to the reduced protein intake with human milk compared to infant formula. In a randomized controlled trial (Childhood Obesity Project), we were able to show that infant formula with reduced protein content results in lower BMI both at 2 and 6 years. These effects seem to be mediated mainly by branched-chain amino acids which stimulate the insulin-like growth factor (IGF)-1 axis and insulin release. In this trial, we also showed an influence of high-protein diet on larger kidney size, which seems to be partly explained by a significant effect of free IGF-1 on kidney volume. The IGF-1 axis was shown to regulate early growth, adipose tissue differentiation and early adipogenesis in animals and in humans. Leptin and adiponectin can also be regarded as important endocrine regulators of obesity. These markers were tested in observational studies. Leptin seems to be closely correlated with BMI but changes in adiponectin require further exploration. Still, there is a lack of good data or some results are contradictory to indicate the role of either leptin or adiponectin in infancy for determining later obesity risk., (© 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Breastfeeding induces a different metabolic and endocrine response than feeding conventional infant formula, and it has also been associated with slower weight gain and reduced disease risk in later life. The underlying programming mechanisms remain to be explored. Breastfeeding has been reported to induce lower levels of insulin, insulin-like growth factor-1 and some amino acids (AAs) than formula feeding. In the Childhood Obesity Project (CHOP), infants fed a conventional protein-rich formula had a higher BMI at 2 and 6 years than those fed a protein-reduced formula. At 6 months, higher protein intakes induced increased plasma concentrations of branched-chain AAs (BCAAs) and their oxidation products, short-chain acylcarnitines. With increasing BCAA levels, these short-chain acylcarnitines increased proportionally only until a break point was reached, after which BCAAs seemed to escape their degradation. The resulting marked elevation in BCAA levels with high-protein (HP) intakes appears to contribute to increased insulin levels and to affect β-oxidation of fatty acids. The ratios of long-chain acylcarnitines to free carnitine decreased in infants who received a HP formula, which indicates a reduced initiation of β-oxidation. We conclude that HP intakes inducing high BCAA plasma levels may inhibit fat oxidation and thereby enhance body fat deposition and adiposity., (© 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Background: Early nutrition is recognized as a target for the effective prevention of childhood obesity. Protein intake was associated with more rapid weight gain during infancy-a known risk factor for later obesity., Objective: We tested whether the reduction of protein in infant formula reduces body mass index (BMI; in kg/m(2)) and the prevalence of obesity at 6 y of age., Design: The Childhood Obesity Project was conducted as a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants born between October 2002 and July 2004. Formula-fed infants (n = 1090) were randomly assigned to receive higher protein (HP)- or lower protein (LP)-content formula (within recommended amounts) in the first year of life; breastfed infants (n = 588) were enrolled as an observational reference group. We measured the weight and height of 448 (41%) formula-fed children at 6 y of age. BMI was the primary outcome., Results: HP children had a significantly higher BMI (by 0.51; 95% CI: 0.13, 0.90; P = 0.009) at 6 y of age. The risk of becoming obese in the HP group was 2.43 (95% CI: 1.12, 5.27; P = 0.024) times that in the LP group. There was a tendency for a higher weight in HP children (0.67 kg; 95% CI: -0.04, 1.39 kg; P = 0.064) but no difference in height between the intervention groups. Anthropometric measurements were similar in the LP and breastfed groups., Conclusions: Infant formula with a lower protein content reduces BMI and obesity risk at school age. Avoidance of infant foods that provide excessive protein intakes could contribute to a reduction in childhood obesity. This trial was registered at clinicaltrials.gov as NCT00338689.

BackgroundDNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.MethodsWe examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.ResultsDNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P