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Dietary diversity (DD) plays a crucial role in fostering high-quality diets, but its association with health outcomes, particularly body adiposity and non-communicable diseases (NCDs), is inconsistent. This may be due to a lack of a standardized method for estimating DD. Our study investigates the association between two DD indices, namely the dietary diversity score (DDS) and food variety score (FVS), and anthropometric measures, biochemical parameters, and diet quality in a large population sample from the I.Family study across research centers in eight European countries. In our cross-sectional analysis of 3035 participants, DDSs varied among countries, with a higher prevalence in the third DDS tertile among those with higher education. DDS showed a positive association with diet quality across all age groups. Higher DDS tertile individuals showed increased fiber, fruit, and vegetable intake, greater meal frequency, and lower ultra-processed food consumption. No relevant biochemical differences were observed across DDS tertiles, and a higher DDS was associated with lower overweight/obesity prevalence only in adults. No significant associations were found with FVS. Our findings emphasize the need to consider food groups for a more accurate estimation of diet quality. This aligns with studies suggesting DDS alone is not an independent risk factor for obesity in children and adolescents. Public health programs should prioritize food diversity to promote improved nutrition and overall well-being in communities.

Abstract Background Physical activity (PA) during childhood is important for preventing future metabolic syndrome (MetS). To examine the relationship between PA and MetS in more detail, accurate measures of PA are needed. Previous studies have only utilized a small part of the information available from accelerometer measured PA. This study investigated the association between measured PA and MetS in children with a new method for data processing and analyses that enable more detailed interpretation of PA intensity level. Methods The association between PA pattern and risk factors related to MetS was investigated in a cross- sectional sample of children (n = 2592, mean age 10.9 years, 49.4% male) participating in the European multicenter I. Family study. The risk factors examined include body mass index, blood pressure, high-density lipoprotein cholesterol, insulin resistance and a combined risk factor score (MetS score). PA was measured by triaxial accelerometers and raw data was processed using the 10 Hz frequency extended method (FEM). The PA output was divided into an intensity spectrum and the association with MetS risk factors was analyzed by partial least squares regression. Results PA patterns differed between the European countries investigated, with Swedish children being most active and Italian children least active. Moderate intensity physical activity was associated with lower insulin resistance (R 2 = 2.8%), while vigorous intensity physical activity was associated with lower body mass index (R 2 = 3.6%), MetS score (R 2 = 3.1%) and higher high-density lipoprotein cholesterol (R 2 = 2.3%). PA of all intensities was associated with lower systolic- and diastolic blood pressure, although the associations were weaker than for the other risk factors (R 2 = 1.5% and R 2 = 1.4%). However, the multivariate analysis implies that the entire PA pattern must be considered. The main difference in PA was observed between normal weight and overweight children. Conclusions The present study suggests a greater importance of more PA corresponding to an intensity of at least brisk walking with inclusion of high-intense exercise, rather than a limited time spent sedentary, in the association to metabolic health in children. The methods of data processing and statistical analysis enabled accurate analysis and interpretation of the health benefits of high intensity PA that have not been shown previously.

Abstract Background In children the relationship between a healthy diet and psychosocial well-being has not been fully explored and the existing evidence is inconsistent. This study investigates the chronology of the association between children’s adherence to healthy dietary guidelines and their well-being, with special attention to the influence of weight status on the association. Methods Seven thousand six hundred seventy five children 2 to 9 years old from the eight-country cohort study IDEFICS were investigated. They were first examined between September 2007 and June 2008 and re-examined again 2 years later. Psychosocial well-being was measured using self-esteem and parent relations questions from the KINDL® and emotional and peer problems from the Strengths and Difficulties Questionnaire. A Healthy Dietary Adherence Score (HDAS) was calculated from a 43-item food frequency questionnaire as a measure of the degree to which children’s dietary intake follows nutrition guidelines. The analysis employed multilevel logistic regression (country as random effect) with bidirectional modeling of dichotomous dietary and well-being variables as both exposures and outcomes while controlling for respective baseline values. Results A higher HDAS at baseline was associated with better self-esteem (OR 1.2, 95% CI 1.0;1.4) and fewer emotional and peer problems (OR 1.2, 95% CI 1.1;1.3 and OR 1.3, 95% CI 1.2;1.4) 2 years later. For the reversed direction, better self-esteem was associated with higher HDAS 2 years later (OR 1.1 95% CI 1.0;1.29). The analysis stratified by weight status revealed that the associations between higher HDAS at baseline and better well-being at follow-up were similar in both normal weight and overweight children. Conclusion Present findings suggest a bidirectional relation between diet quality and self-esteem. Additionally, higher adherence to healthy dietary guidelines at baseline was associated with fewer emotional and peer problems at follow-up, independent of children’s weight status.

We trace the development of azimuthal anisotropy (vn, n=2,3) via parton–parton collision history in two transport models. The parton vn is studied as a function of the number of collisions of each parton in Au + Au and d+Au collisions at sNN=200 GeV. It is found that the majority of vn comes from the anisotropic escape probability of partons, with no fundamental difference at low and high transverse momenta. The contribution to vn from hydrodynamic-type collective flow is found to be small. Only when the parton–parton cross-section is set unrealistically large does this contribution start to take over. Our findings challenge the current paradigm emerged from hydrodynamic comparisons to anisotropy data.

Attrition may lead to bias in epidemiological cohorts, since participants who are healthier and have a higher social position are less likely to drop out. We investigated possible selection effects regarding key exposures and outcomes in the IDEFICS/I.Family study, a large European cohort on the etiology of overweight, obesity and related disorders during childhood and adulthood. We applied multilevel logistic regression to investigate associations of attrition with sociodemographic variables, weight status, and study compliance and assessed attrition across time regarding children's weight status and variations of attrition across participating countries. We investigated selection effects with regard to social position, adherence to key messages concerning a healthy lifestyle, and children's weight status. Attrition was associated with a higher weight status of children, lower children's study compliance, older age, lower parental education, and parent's migration background, consistent across time and participating countries. Although overweight (odds ratio 1.17, 99% confidence interval 1.05–1.29) or obese children (odds ratio 1.18, 99% confidence interval 1.03–1.36) were more prone to drop-out, attrition only seemed to slightly distort the distribution of children's BMI at the upper tail. Restricting the sample to subgroups with different attrition characteristics only marginally affected exposure-outcome associations. Our results suggest that IDEFICS/I.Family provides valid estimates of relations between socio-economic position, health-related behaviors, and weight status.

OBJECTIVES:Neuroimaging data suggest that pediatric overweight and obesity are associated with morphological alterations in gray matter (GM) brain structures, but previous studies using mainly voxel-based morphometry (VBM) showed inconsistent results. Here, we aimed to examine the relationship between youth obesity and the volume of predefined reward system structures using magnetic resonance (MR) volumetry. We also aimed to complement volumetry with VBM-style analysis. METHODS:Fifty-one Caucasian young subjects (32 females; mean age: 13.8±1.9, range: 10.2-16.5 years) were included. Subjects were selected from a subsample of the I.Family study examined in the Hungarian center. A T1-weighted 1 mm3 isotropic resolution image was acquired. Age- and sex-standardized body mass index (zBMI) was assessed at the day of MRI and ~1.89 years (mean±SD: 689±188 days) before the examination. Obesity related GM alterations were investigated using MR volumetry in five predefined brain structures presumed to play crucial roles in body weight regulation (hippocampus, amygdala, accumbens, caudate, putamen), as well as whole-brain and regional VBM. RESULTS:The volumes of accumbens and amygdala showed significant positive correlations with zBMI, while their GM densities were inversely related to zBMI. Voxel-based GM mass also showed significant negative correlation with zBMI when investigated in the predefined amygdala region, but this relationship was mediated by GM density. CONCLUSIONS:Overweight/obesity related morphometric brain differences already seem to be present in children/adolescents. Our work highlights the disparity between volume and VBM-derived measures and that GM mass (combination of volume and density) is not informative in the context of obesity related volumetric changes. To better characterize the association between childhood obesity and GM morphometry, a combination of volumetric segmentation and VBM methods, as well as future longitudinal studies are necessary. Our results suggest that childhood obesity is associated with enlarged structural volumes, but decreased GM density in the reward system.

Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings.

Objective: The question of whether breastfeeding has a protective effect against the development of overweight or obesity later in life remains controversial, especially during adolescence. The objective was to assess the relationship between breastfeeding and adolescents' body composition. Methods: The HELENA study is a cross-sectional study involving 3,528 adolescents from 10 European cities. The outcome measures were body weight and height, subscapular skinfolds as well as waist circumferences. Breastfeeding, smoking status, and parental socioeconomic status were assessed by self-administered questionnaires. Dietary intake was recorded using two 24-hour recall surveys. Two adjustment approaches were used: i) covariance analysis adjusted for confounding factors (propensity score adjustment) and ii) multivariate quantile regression. Results: After adjustment, no significant associations were observed between breastfeeding and body composition parameters (BMI Z-score; sum of skinfolds; waist-to-height ratio). An adjusted quantile regression analysis showed a non-significant trend for a protective effect of breastfeeding toward the highest percentiles of adiposity in boys but not in girls. This is of particular interest with respect to the superiority of the waist-to-height ratio over waist circumference and BMI for detecting cardiometabolic risk factors. Conclusion: This first European study, including a large set of factors influencing adolescents' body composition, showed a non-significant trend toward a protective effect of breastfeeding on highest percentiles of adolescent's abdominal adiposity.

BACKGROUND: The early life course is assumed to be a critical phase for childhood obesity; however the significance of single factors and their interplay is not well studied in childhood populations. OBJECTIVES: The investigation of pre-, peri- and postpartum risk factors on the risk of obesity at age 2 to 9. METHODS: A case-control study with 1,024 1:1-matched case-control pairs was nested in the baseline survey (09/2007-05/2008) of the IDEFICS study, a population-based intervention study on childhood obesity carried out in 8 European countries in pre- and primary school settings. Conditional logistic regression was used for identification of risk factors. RESULTS: For many of the investigated risk factors, we found a raw effect in our study. In multivariate models, we could establish an effect for gestational weight gain (adjusted OR = 1.02; 95%CI 1.00-1.04), smoking during pregnancy (adjusted OR = 1.48; 95%CI 1.08-2.01), Caesarian section (adjusted OR = 1.38; 95%CI 1.10-1.74), and breastfeeding 4 to 11 months (adjusted OR = 0.77; 95%CI 0.62-0.96). Birth weight was related to lean mass rather than to fat mass, the effect of smoking was found only in boys, but not in girls. After additional adjustment for parental BMI and parental educational status, only gestational weight gain remained statistically significant. Both, maternal as well as paternal BMI were the strongest risk factors in our study, and they confounded several of the investigated associations. CONCLUSIONS: Key risk factors of childhood obesity in our study are parental BMI and gestational weight gain; consequently prevention approaches should target not only children but also adults. The monitoring of gestational weight seems to be of particular importance for early prevention of childhood obesity.

ObjectivesWe investigated cross-sectionally and longitudinally the relationship between FTO rs9939609 and obesity-related characteristics in the European children of the IDEFICS project and the interaction of this variant with a lifestyle intervention.Population and methodsA cohort of 16224 children (2-9 years) was recruited into a population-based survey (T0) from eight European countries. A second survey (T1) reassessed the children two years later. A random sample of 4405 children was extracted for genetic studies. 3168 children were re-examined two years later. Half of them underwent a lifestyle intervention program. The FTO rs9939609 was genotyped. Weight, height, waist circumference, triceps and subscapular skinfolds were measured at T0 and T1.ResultsAt T0, the risk A allele of rs9939609 was significantly associated with higher values of body mass index (BMI), waist circumference and skinfolds (age, sex, and country-adjusted p-values: all pConclusionsWe confirmed the association between the FTO rs9939609 and body mass and overweight/obesity risk in European children. The main finding of the study is that the A allele carriers present higher increase of body mass and central adiposity over time and higher risk of developing overweight/obesity during growth, independently from intervention measures.

To evaluate the impact of stress on children's well-being, it is important to have valid and reliable stress assessment methods. Nevertheless, selection of an appropriate method for a particular research question may not be straightforward, as there is currently no consensus on a reference method to measure stress in children. This paper examined to what extent childhood stress can be estimated accurately by commonly applied stress measures.Two hundred and seventy-two girls between 5 and 11 years old participated in this study as part of the ChiBS project. Child-reported estimates of stress were collected through the Coddington Life Events Scale (CLES). Serum, saliva and hair samples were collected for cortisol analyses. The intercorrelations of cortisol in the different biological samples were investigated by Spearman rank correlations and Bland-Altman plots. Next, CLES-scores, salivary and hair cortisol concentrations were compared triangularly with the true, but unknown childhood stress using the Triads method, based on pair-wise Spearman's correlation coefficients and the calculation of validity coefficients.Serum cortisol (free and total) was positively correlated with salivary morning and AUC cortisol. Hair cortisol correlated with salivary morning and AUC cortisol, but not with serum cortisol. In relation to recent childhood stress (0–3 months ago), the highest validity coefficients were observed for salivary cortisol measurements, while for periods more distant in the past hair cortisol measurements displayed the highest validity coefficients.This paper investigated the relationship between cortisol measurements in different biological samples, showing a lack of association and disagreement between measures of single-point, short-term cortisol versus long(er)-term cortisol. In addition, this paper examined to what extent childhood stress can be accurately estimated by stressor questionnaires and biological markers in girls. Salivary cortisol was shown to most accurately indicate true childhood stress for short periods in the past (i.e. last three months), whereas hair cortisol may be preferred above salivary measurements for periods more distant and thus for chronic stress assessment.

Abstract Childhood obesity is a complex disorder that appears to be influenced by an interacting system of many factors. Taking this complexity into account, we aim to investigate the causal structure underlying childhood obesity. Our focus is on identifying potential early, direct or indirect, causes of obesity which may be promising targets for prevention strategies. Using a causal discovery algorithm, we estimate a cohort causal graph (CCG) over the life course from childhood to adolescence. We adapt a popular method, the so-called PC-algorithm, to deal with missing values by multiple imputation, with mixed discrete and continuous variables, and that takes background knowledge such as the time-structure of cohort data into account. The algorithm is then applied to learn the causal structure among 51 variables including obesity, early life factors, diet, lifestyle, insulin resistance, puberty stage and cultural background of 5112 children from the European IDEFICS/I.Family cohort across three waves (2007–2014). The robustness of the learned causal structure is addressed in a series of alternative and sensitivity analyses; in particular, we use bootstrap resamples to assess the stability of aspects of the learned CCG. Our results suggest some but only indirect possible causal paths from early modifiable risk factors, such as audio-visual media consumption and physical activity, to obesity (measured by age- and sex-adjusted BMI z-scores) 6 years later.

Abstract Background It is unclear whether a hypothetical intervention targeting either psychosocial well-being or emotion-driven impulsiveness is more effective in reducing unhealthy food choices. Therefore, we aimed to compare the (separate) causal effects of psychosocial well-being and emotion-driven impulsiveness on European adolescents’ sweet and fat propensity. Methods We included 2,065 participants of the IDEFICS/I.Family cohort (mean age: 13.4) providing self-reported data on sweet propensity (score range: 0 to 68.4), fat propensity (range: 0 to 72.6), emotion-driven impulsiveness using the UPPS-P negative urgency subscale, and psychosocial well-being using the KINDLR Questionnaire. We estimated, separately, the average causal effects of psychosocial well-being and emotion-driven impulsiveness on sweet and fat propensity applying a semi-parametric doubly robust method (targeted maximum likelihood estimation). Further, we investigated a potential indirect effect of psychosocial well-being on sweet and fat propensity mediated via emotion-driven impulsiveness using a causal mediation analysis. Results If all adolescents, hypothetically, had high levels of psychosocial well-being, compared to low levels, we estimated a decrease in average sweet propensity by 1.43 [95%-confidence interval: 0.25 to 2.61]. A smaller effect was estimated for fat propensity. Similarly, if all adolescents had high levels of emotion-driven impulsiveness, compared to low levels, average sweet propensity would be decreased by 2.07 [0.87 to 3.26] and average fat propensity by 1.85 [0.81 to 2.88]. The indirect effect of psychosocial well-being via emotion-driven impulsiveness was 0.61 [0.24 to 1.09] for average sweet propensity and 0.55 [0.13 to 0.86] for average fat propensity. Conclusions An intervention targeting emotion-driven impulsiveness, compared to psychosocial well-being, would be marginally more effective in reducing sweet and fat propensity in adolescents.

Abstract The digital environment can pose health risks through exposure to unhealthy content. Yet, little is known about its relation to children’s cognitive functioning. This study investigates the association between digital media (DM) exposure and children’s cognitive functioning. This cross-sectional study is based on examinations of children aged 8–18 years (N = 8673) of the I.Family cohort (2013–2014). Exposure to television, computer, smartphone and internet was self-reported (hours/day). Media multitasking (MMT) was defined as simultaneous use of computers with other digital or non-screen-based activities. Standard instruments were used to assess cognitive inflexibility (score: 0–39), decision-making ability (− 100 to + 100) and impulsivity (12–48). Adjusted regression coefficients and 99.9%CIs were calculated by generalized linear mixed-effects models. In total, 3261 participants provided data for impulsivity, 3441 for cognitive inflexibility and 4046 for decision-making. Exposure to smartphones and media multitasking were positively associated with impulsivity (βsmartphone = 0.74; 99.9%CI = 0.42–1.07; βMMT = 0.73; 99.9%CI = 0.35–1.12) and cognitive inflexibility (βsmartphone = 0.32; 99.9%CI = -0.02–0.66; βMMT = 0.39; 99.9%CI = 0.01–0.77) while being inversely associated with decision-making ability. Extensive smartphone/internet exposure combined with low computer/medium TV exposure was associated with higher impulsivity and cognitive inflexibility scores, especially in girls. DM exposure is adversely associated with cognitive functioning in children and adolescents. Children require protection against the likely adverse impact of digital environment.

Growing evidence shows that maternal nutrition from preconception until lactation has an important effect on the development of non-communicable diseases in the offspring. Biological responses to environmental stress during pregnancy, including undernutrition or overnutrition of various nutrients, are transmitted in part by DNA methylation. The aim of the present narrative review is to summarize literature data on altered DNA methylation patterns caused by maternal macronutrient or vitamin intake and its association with offspring’s phenotype (obesity and related metabolic changes). With our literature search, we found evidence for the association between alterations in DNA methylation pattern of different genes caused by maternal under- or overnutrition of several nutrients (protein, fructose, fat, vitamin D, methyl-group donor nutrients) during 3 critical periods of programming (preconception, pregnancy, lactation) and the development of obesity or related metabolic changes (glucose, insulin, lipid, leptin, adiponectin levels, blood pressure, non-alcoholic fatty liver disease) in offspring. The review highlights that maternal consumption of several nutrients could individually affect the development of offspring’s obesity and related metabolic changes via alterations in DNA methylation.

Abstract Insufficient physical activity (PA) in children is considered one of the major contributors to obesity and cardiometabolic complications later in life. Although regular exercise may contribute to disease prevention and health promotion, reliable early biomarkers are required to objectively discern people performing low PA from those who exercise enough. Here, we aimed to identify potential transcript-based biomarkers through the analysis of a whole-genome microarray in peripheral blood cells (PBC) from physically less active (n = 10) comparing with more active (n = 10) children. A set of genes differentially expressed (p

Abstract Background This study aimed to examine associations of early childhood physical fitness and physical activity (PA) with PA during later childhood/early adolescence while accounting for gender differences. Methods We selected data of N = 4329 children from the IDEFICS/I. Family cohort (age 2.4–11.7 years) with data on baseline fitness and accelerometer measurements. At baseline, physical fitness tests were conducted including Flamingo balance, Backsaver sit and reach, Handgrip strength, Standing Long Jump, 40-m sprint and 20-m Shuttle run (to estimate cardio-respiratory fitness levels). PA was measured with Actigraph accelerometers over 3 days at baseline (ActiTrainer or GT1M) and 7 days at follow-up (GT3X). Evenson cutpoints were used to determine moderate-to-vigorous PA (MVPA) time, and children with ≥60mins/day of average MVPA were deemed as having met WHO guidelines at baseline and follow-up. Linear and logistic regressions were performed to examine longitudinal associations between meeting WHO guidelines, MVPA, and physical fitness tests at baseline with meeting WHO guidelines and MVPA at follow-up. Models were conducted on the entire sample, the sex-stratified sample, and stratified by sex and pubertal status at follow-up. Results Results showed that meeting WHO guidelines for MVPA at baseline was positively associated with MVPA (Standardized Beta (B) = 0.13, 95%CI:(5.6;11.1)) and meeting WHO guidelines at follow-up for the entire sample (OR = 2.1, 95%CI:(1.5; 3.14), and stratified by males (OR = 2.5, 95%CI:(1.5; 4.1)) and females (OR = 1.8, 95%CI:(1.0; 3.2)). This was also found for both male pre/early pubertal and pubertal groups but only in the female pre/early pubertal group, and not the female pubertal group (MVPA: B = .00, 95%CI:(− 6.1; 5.6), WHO: OR = 0.61, 95%CI:(0.23;1.6)). Models indicated that Standing Long jump, 40-m sprint, Shuttle run and Flamingo balance at baseline were associated with MVPA and meeting the guidelines at follow-up. Conclusions Meeting WHO guidelines and certain fitness tests at baseline were strongly associated with MVPA and meeting WHO guidelines at follow-up, but this association varied with sex and pubertal status. Consequently, these findings underline the importance of ensuring sufficient physical activity in terms of quality and quantity for children at the earliest stages of life. Trial registration ISRCTN62310987.

IntroductionFrom genome wide association study (GWAS) a large number of single nucleotide polymorphisms (SNPs) have previously been associated with blood pressure (BP) levels. A combination of SNPs, forming a genetic risk score (GRS) could be considered as a useful genetic tool to identify individuals at risk of developing hypertension from early stages in life. Therefore, the aim of our study was to build a GRS being able to predict the genetic predisposition to hypertension (HTN) in European adolescents.MethodsData were extracted from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study. A total of 869 adolescents (53% female), aged 12.5–17.5, with complete genetic and BP information were included. The sample was divided into altered (≥130 mmHg for systolic and/or ≥80 mmHg for diastolic) or normal BP. Based on the literature, a total of 1.534 SNPs from 57 candidate genes related with BP were selected from the HELENA GWAS database.ResultsFrom 1,534 SNPs available, An initial screening of SNPs univariately associated with HTN (p

Background: After birth, breast milk (BM) is a known essential source of antioxidants for infants. We analyzed the non-enzymatic total antioxidant capacity (TAC), oxygen radical absorbance capacity (ORAC), and glutathione, calcium, transferrin, and total protein levels of human breast milk before and after Holder pasteurization (HoP). Methods: The collected donor BM samples were pasteurized with HoP. Results: HoP decreased TAC (−12.6%), ORAC (−12.1%), transferrin (−98.3%), and total protein (−21.4%) levels; HoP did not influence the glutathione concentration, and it increased the total calcium (+25.5%) concentration. Mothers who gave birth via Cesarean section had significantly lower TAC in their BM. TAC and glutathione levels were elevated in the BM of mothers over the age of 30. BM produced in the summer had higher glutathione and calcium levels compared to BM produced in the winter. The glutathione concentration in term milk samples was significantly higher in the first two months of lactation compared to the period between the third and sixth months. The transferrin level of BM for female infants was significantly higher than the BM for boys, and mothers with a BMI above 30 had increased transferrin in their samples. Conclusions: Antioxidant levels in human milk are influenced by numerous factors. Environmental and maternal factors, the postpartum age at breast milk collection, and Holder pasteurization of the milk influence the antioxidant intake of the infant.

Abstract Background Many genes and molecular pathways are associated with obesity, but the mechanisms from genes to obesity are less well known. Eating behaviors represent a plausible pathway, but because the relationships of eating behaviors and obesity may be bi-directional, it remains challenging to resolve the underlying pathways. A longitudinal approach is needed to assess the contribution of genetic risk during the development of obesity in childhood. In this study we aim to examine the relationships between the polygenic risk score for body mass index (PRS-BMI), parental concern of overeating and obesity indices during childhood. Methods The IDEFICS/I.Family study is a school-based multicenter pan-European cohort of children observed for 6 years (mean ± SD follow-up 5.8 ± 0.4). Children examined in 2007/2008 (wave 1) (mean ± SD age: 4.4 ± 1.1, range: 2–9 years), in 2009/2010 (wave 2) and in 2013/2014 (wave 3) were included. A total of 5112 children (49% girls) participated at waves 1, 2 and 3. For 2656 children with genome-wide data we constructed a PRS based on 2.1 million single nucleotide polymorphisms. Z-score BMI and z-score waist circumference (WC) were assessed and eating behaviors and relevant confounders were reported by parents via questionnaires. Parental concern of overeating was derived from principal component analyses from an eating behavior questionnaire. Results In cross-lagged models, the prospective associations between z-score obesity indices and parental concern of overeating were bi-directional. In mediation models, the association between the PRS-BMI and parental concern of overeating at wave 3 was mediated by baseline z-BMI (β = 0.16, 95% CI: 0.10, 0.21) and baseline z-WC (β = 0.17, 95% CI: 0.11, 0.23). To a lesser extent, baseline parental concern of overeating also mediated the association between the PRS-BMI and z-BMI at wave 3 (β = 0.10, 95% CI: 0.07, 0.13) and z-WC at wave 3 (β = 0.09, 95% CI: 0.07, 0.12). Conclusions The findings suggest that the prospective associations between obesity indices and parental concern of overeating are likely bi-directional, but obesity indices have a stronger association with future parental concern of overeating than vice versa. The findings suggest parental concern of overeating as a possible mediator in the genetic susceptibility to obesity and further highlight that other pathways are also involved. A better understanding of the genetic pathways that lead to childhood obesity can help to prevent weight gain. Trial registration Registry number: ISRCTN62310987 Retrospectively registered 17 September 2018.

Abstract Background Media use may influence metabolic syndrome (MetS) in children. Yet, longitudinal studies are scarce. This study aims to evaluate the longitudinal association of childhood digital media (DM) use trajectories with MetS and its components. Methods Children from Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden participating in the IDEFICS/I.Family cohort were examined at baseline (W1: 2007/2008) and then followed-up at two examination waves (W2: 2009/2010 and W3: 2013/2014). DM use (hours/day) was calculated as sum of television viewing, computer/game console and internet use. MetS z-score was calculated as sum of age- and sex-specific z-scores of four components: waist circumference, blood pressure, dyslipidemia (mean of triglycerides and HDL-cholesterol−1) and homeostasis model assessment for insulin resistance (HOMA-IR). Unfavorable monitoring levels of MetS and its components were identified (cut-off: ≥ 90th percentile of each score). Children aged 2–16 years with ≥ 2 observations (W1/W2; W1/W3; W2/W3; W1/W2/W3) were eligible for the analysis. A two-step procedure was conducted: first, individual age-dependent DM trajectories were calculated using linear mixed regressions based on random intercept (hours/day) and linear slopes (hours/day/year) and used as exposure measures in association with MetS at a second step. Trajectories were further dichotomized if children increased their DM duration over time above or below the mean. Results 10,359 children and adolescents (20,075 total observations, 50.3% females, mean age = 7.9, SD = 2.7) were included. DM exposure increased as children grew older (from 2.2 h/day at 2 years to 4.2 h/day at 16 years). Estonian children showed the steepest DM increase; Spanish children the lowest. The prevalence of MetS at last follow-up was 5.5%. Increasing media use trajectories were positively associated with z-scores of MetS (slope: β = 0.54, 95%CI = 0.20–0.88; intercept: β = 0.07, 95%CI = 0.02–0.13), and its components after adjustment for puberty, diet and other confounders. Children with increasing DM trajectories above mean had a 30% higher risk of developing MetS (slope: OR = 1.30, 95%CI = 1.04–1.62). Boys developed steeper DM use trajectories and higher risk for MetS compared to girls. Conclusions Digital media use appears to be a risk factor for the development of MetS in children and adolescents. These results are of utmost importance for pediatricians and the development of health policies to prevent cardio-metabolic disorders later in life. Trial registration ISRCTN, ISRCTN62310987 . Registered 23 February 2018- retrospectively registered.

Abstract Background Since only few longitudinal studies with appropriate study designs investigated the relationship between objectively measured physical activity (PA) and overweight, the degree PA can prevent excess weight gain in children, remains unclear. Moreover, evidence is limited on how childhood overweight determines PA during childhood. Therefore, we analyzed longitudinal trajectories of objectively measured PA and their bi-directional association with weight trajectories of children at 2- and 6-year follow-ups. Methods Longitudinal data of three subsequent measurements from the IDEFICS/I.Family cohort study were used to analyze the bi-directional association between moderate-to-vigorous PA (MVPA) and weight status by means of multilevel regression models. Analyses comprised 3393 (2-year follow-up) and 1899 (6-year follow-up) children aged 2–15.9 years from eight European countries with valid accelerometer data and body mass index (BMI) measurements. For categorized analyses, children’s weight status was categorized as normal weight or overweight (cutoff: 90th percentile of BMI) and children’s PA as (in-) sufficiently active (cutoffs: 30, 45 and 60 min of MVPA per day). Results Children engaging in at least 60 min MVPA daily at baseline and follow-ups had a lower odds of becoming overweight (odds ratio [OR] at 2-year follow-up: 0.546, 95% CI: 0.378, 0.789 and 6-year follow-up: 0.393, 95% CI: 0.242, 0.638), compared to less active children. Similar associations were found for 45 min MVPA daily. On the other side, children who became overweight had the lowest odds to achieve 45 or 60 min MVPA daily (ORs: 0.459 to 0.634), compared to normal weight children. Conclusions Bi-directional associations between MVPA and weight status were observed. In summary, at least 60 min MVPA are still recommended for the prevention of childhood overweight. To prevent excess weight gain, 45 min MVPA per day also showed preventive effects.

Abstract Background The associations between physical activity (PA), sedentary behaviour (SB) and bone health may be differentially affected by weight status during growth. This study aims to assess the cross-sectional and longitudinal associations between PA, SB and bone stiffness index (SI) in European children and adolescents, taking the weight status into consideration. Methods Calcaneus SI was first measured by quantitative ultrasound among children aged 2–9 years old in 2007/08. It was measured again after 2 years in the IDEFICS study and after 6 years in the I. Family study. A sample of 2008 participants with time spent at sports clubs, watching TV and playing computer/games self-reported by questionnaire, and a subsample of 1037 participants with SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) objectively measured using Actigraph accelerometers were included in the analyses. Weight status was defined as thin/normal and overweight/obese according to the extended International Obesity Task Force criteria. Linear mixed-effects models were used to estimate the cross-sectional and longitudinal associations between PA, SB and SI percentiles, stratified by weight status. Results The cross-sectional association between weekly duration of watching TV and SI percentiles was negative in thin/normal weight group (β = − 0.35, p = 0.008). However, baseline weekly duration of watching TV (β = − 0.63, p = 0.021) and change after 2 years (β = − 0.63, p = 0.022) as well as the change in weekly duration of playing computer/games after 6 years (β = − 0.75, p = 0.019) were inversely associated with corresponding changes in SI percentiles in overweight/obese group. Change in time spent at sports clubs was positively associated with change in SI percentiles after 2 years (β = 1.28, p = 0.001), with comparable effect sizes across weight status. In the subsample with accelerometer data, we found a positive cross-sectional association between MVPA and SI percentiles in thin/normal weight group. Baseline MVPA predicted changes in SI percentiles after 2 and 6 years in all groups. Conclusions Our results suggested the beneficial effect of PA on SI. However, the increasing durations of screen-based SB might be risk factors for SI development, especially in overweight/obese children and adolescents.

Abstract Background Lifestyle interventions to prevent paediatric obesity often target family and peer settings; their success is likely to depend on the influence that peers and families exert on children’s lifestyle behaviors at different developmental stages. Objective First, to determine whether children’s lifestyle behavior more closely resembles their peers’ or siblings’ behaviors. Secondly, to investigate longitudinally whether children’s behavioral change is predicted by that of their peers or their siblings as they grow older. Methods The European prospective IDEFICS/I.Family cohort (baseline survey: 2007/2008, first follow-up: 2009/2010, and second follow-up: 2013/2014) aims at investigating risk factors for overweight and related behaviors during childhood and adolescence. The present investigation includes 2694 observations of children and their siblings aged 2 to 18 years. Peers were defined as same-sex, same-age children in the same community and identified from the full cohort. The longitudinal analysis (mean follow-up time: 3.7 years) includes 525 sibling pairs. Children’s lifestyle behaviors including fast food consumption (frequency/week), screen time (hours/week) and sports club participation (hours/week) were assessed by questionnaire. Data were analyzed using multilevel linear models. Results Children’s lifestyle behavior was associated with the respective behavior of their peers and sibling for all 3 behaviors. For fast food consumption, the peer resemblance was more than 6-fold higher than the sibling resemblance and the peer resemblance surpassed the sibling resemblance by the age of 9–10 years. The similarities with peers for fast food consumption and screen time steadily increased, while the similarities with siblings steadily decreased with increasing age of the children (P interaction

Abstract Background Levels of physical activity and variation in physical activity and sedentary time by place and person in European children and adolescents are largely unknown. The objective of the study was to assess the variations in objectively measured physical activity and sedentary time in children and adolescents across Europe. Methods Six databases were systematically searched to identify pan-European and national data sets on physical activity and sedentary time assessed by the same accelerometer in children (2 to 9.9 years) and adolescents (≥10 to 18 years). We harmonized individual-level data by reprocessing hip-worn raw accelerometer data files from 30 different studies conducted between 1997 and 2014, representing 47,497 individuals (2–18 years) from 18 different European countries. Results Overall, a maximum of 29% (95% CI: 25, 33) of children and 29% (95% CI: 25, 32) of adolescents were categorized as sufficiently physically active. We observed substantial country- and region-specific differences in physical activity and sedentary time, with lower physical activity levels and prevalence estimates in Southern European countries. Boys were more active and less sedentary in all age-categories. The onset of age-related lowering or leveling-off of physical activity and increase in sedentary time seems to become apparent at around 6 to 7 years of age. Conclusions Two third of European children and adolescents are not sufficiently active. Our findings suggest substantial gender-, country- and region-specific differences in physical activity. These results should encourage policymakers, governments, and local and national stakeholders to take action to facilitate an increase in the physical activity levels of young people across Europe.

Abstract Background There has been an increase in children growing up in non-traditional families, such as single-parent and blended families. Children from such families have a higher prevalence of obesity and poorer health outcomes, but research on the relationship with obesogenic behaviours is limited. Objectives Therefore, the aim of this study was to investigate whether there are associations between family structures and obesogenic behaviours and related family rules in European children and adolescents. Methods The sample included 7664 children (mean age ± SD: 10.9 ± 2.9) from 4923 families who were participants of the multi-centre I.Family study (2013/2014) conducted in 8 European countries. Family structure was assessed by a detailed interview on kinship and household. Obesogenic behaviours (screen time, sleep duration, consumption of sugar-sweetened beverages (SSBs)) and family rules (rules for computer and television, bedtime routine, availability of SSBs during meals) were determined by standardized questionnaires. Multilevel mixed-effects linear and logistic regression models were used to model the associations of family structure with obesogenic behaviours and family rules. Sex, age, parental education level, number of children and adults in the household and BMI z-score were covariates in the models. Two-parent biological families were set as the reference category. Results Children from single-parent families were less likely to have family rules regarding screen time (OR: 0.62, 95% CI: 0.40–0.94, p = 0.026) with higher reported hours of screen time per week (β = 2.70 h/week, 95% CI: 1.39–4.00, p

Abstract Background Nearly 10 years ago, the World Health Organization reported the increasing prevalence of overweight and obesity worldwide as a challenge for public health due to the associated adverse consequences. Epidemiological studies established a firm relationship between an elevated body mass index and chronic conditions such as diabetes, dyslipidemia, hypertension, heart disease, non-alcoholic fatty liver disease, and some types of cancer. Omic studies demonstrated that microRNA (miRNA) profile changes in tissues correlate with a number of diseases, including obesity. Recent studies showed a remarkable stability of miRNAs also in blood, emphasizing their potential as theranostic agents for a variety of disorders and conditions. A number of miRNAs enriched in homeostasis of obesity and metabolic disorders have been characterized in previous researches. Aim This work was finalized to investigate the differential circulating miRNAs signature in early childhood obesity. Our cross-sectional study analyzed the signature of circulating miRNAs in plasma samples of normal weight (n = 159) and overweight/obese (n = 149) children and adolescents participating to the I.Family study, an EC-funded study finalized to investigate the etiology of overweight, obesity and related disorders and the determinants of food choice, lifestyle, and related health outcomes in children and adolescents of eight European countries (www.ifamilystudy.eu). Results Differences in miRNA signature with respect to anthropometric and biochemical variables were analyzed. A high degree of variability in levels of circulating miRNAs was identified among children from different countries, in line with recent reports supporting the hypothesis that these molecules are likewise affected by environmental and lifestyle factors. A panel of miRNAs differentially expressed in overweight/low-grade obesity children was characterized (miR-551a and miR-501-5p resulted upregulated; miR-10b-5p, miR-191-3p, miR-215-5p, and miR-874-3p resulted downregulated). ROC curves were also constructed for experimentally confirmed miRNAs. Single miRNAs generally exhibited low AUC values with the highest values for miR-874-3p and miR-501-5p which in combination provided an interesting value (AUC = 0.782). Pearson’s analysis confirmed that miR-10b-5p, miR-215-5p, miR-501-5p, miR-551a, and miR-874-3p significantly correlated with BMI z-score. Molecular interactions of obesity-associated miRNAs were also predicted by bioinformatics tools. Conclusions Our work showed that several circulating miRNAs are differentially represented in overweight/low-grade obesity children and adolescents. Although causal pathways cannot be firmly inferred, it is conceivable that circulating miRNAs may be new biomarkers of early childhood obesity. Trial registration ISRCTN, ISRCTN62310987. Registered 23/02/2018 - Retrospectively registered.

Recently, a new version of laser-induced fusion was proposed where implanted nanoantennas regulated and amplified the light absorption in the fusion target [L.P. Csernai et al., Phys. Wave Phenom. 28, 187–99 (2020)]. In this paper we estimate the nanoantenna lifetime in a dynamical kinetic model and describe how electrons are leaving the nanoantenna’s surface, and for how long the plasmonic effect is maintained. Our model successfully shows a nanorod antenna lifetime that will allow future fusion studies with top-energy short laser ignition pulses.

Maternal exposure to some dietary and environmental factors during embryonic development can affect offspring’s phenotype and, furthermore, the risk of developing diseases later in life. One potential mechanism responsible for this early programming may be the modification of the epigenome, such as DNA methylation. Methyl-group donors are essential for DNA methylation and are shown to have an important role in fetal development and later health. The main goal of the present review is to summarize the available literature data on the epigenetic effect (DNA methylation) of maternal methyl-group donor availability on reproductivity, perinatal outcome, and later health of the offspring. In our literature search, we found evidence for the association between alterations in DNA methylation patterns caused by different maternal methyl-group donor (folate, choline, methionine, betaine) intake and reproductivity, birth weight, neural tube defect, congenital heart defect, cleft lip and palate, brain development, and the development of obesity and associated non-communicable diseases in later life. We can conclude that maternal methyl-group donor availability could affect offspring’s health via alterations in DNA methylation and may be a major link between early environmental exposure and the development of diseases in the offspring. However, still, further studies are necessary to confirm the associations and causal relationships.

Breastfeeding is widely supported in clinical and home practices, and it is known that different forms of infant feeding differ in hormone content. Thyroid hormones have essential physiological roles. In our study, we examined thyroid-stimulating hormone (TSH), thyroxine, and albumin levels in breast milk produced for term (n = 16) or preterm (n = 15) infants throughout the first 6 months of lactation. Moreover, we analyzed these components in donor human milk and in three different infant formulas. Term and preterm breast milk samples were collected monthly. The two groups had similar levels of TSH (18.4 ± 1.4 vs. 24.7 ± 2.9 nU/L), but term milk contained higher amounts of thyroxine (11,245.5 ± 73.8 vs. 671.6 ± 61.2 nmol/L) during the examination period. The albumin level was significantly higher in preterm breast milk than in term breast milk (328.6 ± 17.1 vs. 264.2 ± 6.8 mg/L). In preterm breast milk we detected downward trends in the levels of TSH (−30.2%) and thyroxine (−29.2%) in the 3rd through 6th month compared to the first 2 months of lactation. Microbiological safety of donor milk was ensured by Holder pasteurization (HoP). From the Breast Milk Collection Center of Pécs, Hungary, we enrolled 44 donor mothers into the study. HoP decreased TSH (−73.8%), thyroxine (−22.4%), and albumin (−20.9%) concentrations. Infant formulas used by the Neonatal Intensive Care Unit of the University of Pécs were found to not contain the investigated hormones, but their albumin levels were similar to the breast milk samples. The present study shows the lack of thyroid hormones in infant formulas compared to human milk and raises the question of whether formula-fed infants should be supplemented with thyroid hormones.

Obesity in children and adolescents is a public health problem and diet can play a major role in this condition. We aimed to identify sex-specific dietary patterns (DP) and to evaluate the association with overweight/obesity in European adolescents. We conducted a cross-sectional analysis with 2327 adolescents aged between 12.5 to 17.5 years from a multicenter study across Europe. The body mass index was categorized in “normal weight” and “overweight/obesity”. Two non-consecutive 24-h dietary recalls were collected with a computerized self-reported software. Principal component factor analysis was used to identify DP. Mixed-effect logistic regression models were used to evaluate the association between the sex-specific DP and overweight/obesity outcome. As a result, we found three DP in boys (snacking and bread, Mediterranean diet, and breakfast) and four DP in girls (convenience, plant-based and eggs, Western, and breakfast). The association between DP and overweight/obesity highlights that those adolescents with higher adherence to the breakfast DP had lower odds for overweight/obesity, even after the inclusion of covariables in the adjustments. In European adolescents, the breakfast DP positively characterized by breakfast cereals, fruit, milk, and dairy and negatively characterized by sugar-sweetened beverages in boys and negatively characterized by cereals (pasta, rice, and others) in girls, was inversely associated with overweight/obesity.

Abstract Background Studies on aggregation of taste preferences among children and their siblings as well as their parents are scarce. We investigated the familial aggregation of taste preferences as well as the effect of sex, age, country of residence and education on variation in taste preferences in the pan- European I.Family cohort. Method Thirteen thousand one hundred sixty-five participants from 7 European countries, comprising 2,230 boys

Digital media (DM) influences children’s food choice. We aim to investigate associations between DM use and taste preferences (TP) for sweet, fatty, bitter, and salty in European children and adolescents. Individuals aged 6–17 years (N = 7094) providing cross-sectional data for DM use: television (TV), computer/game console (PC), smartphone and internet, were included. Children (6 to 2 h/day was associated with sweet (OR = 1.27, 95% CI = 1.02–1.57) and fatty preference (OR = 1.37; 95% CI = 1.10–1.70). Internet exposure was inversely associated with bitter preference, notably in male adolescents (OR = 0.65, 95% CI = 0.50–0.84), but positively associated with salty preference (OR = 1.29, 95% CI = 1.02–1.64). DM exposure was associated with sweet, fatty, salty and bitter TP in children and adolescents, serving as the basis for future longitudinal studies to shed light on the underlying mechanism by which DM exposure may determine eating habits.

Abstract Background The negative impact of childhood overweight on psychosocial well-being has been demonstrated in a number of studies. There is also evidence that psychosocial well-being may influence future overweight. We examined the bidirectional association between childhood overweight and psychosocial well-being in children from a large European cohort. The dual aim was to investigate the chronology of associations between overweight and psychosocial health indicators and the extent to which these associations may be explained by parental education. Methods Participants from the IDEFICS study were recruited from eight countries between September 2007 and June 2008 when the children were aged 2 to 9.9 years old. Children and families provided data on lifestyle, psychosocial well-being, and measured anthropometry at baseline and at follow-up 2 years later. This study includes children with weight, height, and psychosocial well-being measurements at both time points (n = 7,831). Psychosocial well-being was measured by the KINDL® and Strengths and Difficulties Questionnaire respectively. The first instrument measures health-related quality of life including emotional well-being, self-esteem, parent relations and social relations while the second measures well-being based on emotional symptoms, conduct problems and peer-related problems. Logistic regression was used for modeling longitudinal associations. Results Children who were overweight at baseline had increased risk of poor health-related quality of life (odds ratio (OR) = 1.23; 95 % confidence interval (CI):1.03–1.48) measured 2 years later; this association was unidirectional. In contrast to health-related quality of life, poor well-being at baseline was associated with increased risk of overweight (OR = 1.39; 95 % CI:1.03–1.86) at 2 year follow-up; this association was also only observed in one direction. Adjustment for parental education did not change our findings. Conclusion Our findings indicate that the association between overweight and psychosocial well-being may be bidirectional but varies by assessment measures. Future research should further investigate which aspects of psychosocial well-being are most likely to precede overweight and which are more likely to be consequences of overweight.

BACKGROUND:We investigated the association between the consumer attitudes of European parents and their children's taste preferences and food choice. Furthermore, we studied whether the parental consumer attitudes were related to education level. METHODS:This analysis included 1,407 IDEFICS study children aged 6.0 to 11.8 years and from 7 European countries, who participated in the sensory taste perception module between 2007 and 2010. Parental consumer attitude was operationalized as 'trusting in foods known from advertisements' (trusting advertisements) and as 'not avoiding additives in food' (not avoiding additives). Parents reported their educational attainment and completed a food frequency questionnaire for their children. Consumption frequencies of sweet, fatty and processed foods as well as a healthy diet adherence score were calculated. Children performed fat, sweet and umami taste preference tests. Multivariable logistic models were used to analyse the association between parental consumer attitudes and their children's taste preference frequencies as well as parental education. Linear regression models were used to analyse the association between parental consumer attitudes and their children's food consumption. RESULTS:Parental consumer attitudes were not associated with children's fat, sweet and umami taste preferences. Children of parents trusting advertisements consumed more frequently processed foods (β = 1.21, 95% CI: 0.49; 1.93). Children of parents not avoiding additives consumed more often sweet, fatty and processed foods and had a lower healthy diet adherence score (β = 2.37, 95% CI: 1.03; 3.70; β = 2.27, 95% CI: 1.12; 3.43; β = 0.91, 95% CI: 0.22; 1.59; β = -2.87, 95% CI: -3.89; -1.85, respectively). Unfavourable parental consumer attitudes were associated with a lower parental education level across Europe (Compared to high education: Odds Ratio (OR) of trusting advertisements with medium education: 1.04, 95% CI: 0.77; 1.40; OR with low education: 2.01, 95% CI: 1.15; 3.54; OR of not avoiding additives with medium education: 1.91, 95% CI: 1.44; 2.54; OR with low education: 1.76, 95% CI: 0.96; 3.24). CONCLUSIONS:Across Europe, unfavourable parental consumer attitudes are associated with a lower diet quality of their children. Parental consumer attitudes in turn were associated with their own level of education. This has implications for policy makers, interventions and health promotion programmes that aim to promote healthy eating.

The recent obesity epidemic in children also showed an increase in the prevalence of hypertension. As blood pressure (BP) is associated with (long-chain) polyunsaturated fatty acids (LC PUFA), genetic variation in desaturase enzymes being involved in the synthesis of LC PUFA may be associated with BP. This study aimed to investigate the direct effects (independent of mediating variables) and indirect effects (mediated through intermediate variables) of a common variant in the FADS1 gene, rs174546, known to affect delta-5 desaturase (D5D) activity on PUFA level, body mass index (BMI) and BP.A subsample of the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) baseline survey including 520 children aged 2 to

BACKGROUND AND AIMS:Neuromedin U (NMU) is a hypothalamic neuropeptide with important roles in several metabolic processes, recently suggested as potential therapeutic target for obesity. We analysed the associations between NMU gene variants and haplotypes and body mass index (BMI) in a large sample of European children. METHODS AND RESULTS:From a large European multi-center study on childhood obesity, 4,528 children (2.0-9.9 years, mean age 6.0±1.8 SD; boys 52.2%) were randomly selected, stratifying by age, sex and country, and genotyped for tag single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653,C:T) of NMU gene, then haplotypes were inferred. Regression models were applied to estimate the associations between SNPs or haplotypes and BMI as well as other anthropometric measures. BMI was associated with all NMU SNPs (p

BACKGROUND:Starting from birth, this explorative study aimed to investigate between-country differences in body mass index (BMI) trajectories and whether early life factors explain these differences. METHODS:The sample included 7,644 children from seven European countries (Belgium, Cyprus, Germany, Hungary, Italy, Spain, Sweden) participating in the multi-centre IDEFICS study. Information on early life factors and in total 53,409 repeated measurements of height and weight from 0 to

BACKGROUND:Polyunsaturated n-3 and n-6 polyunsaturated fatty acids (PUFA) are precursors of biologically active metabolites that affect blood pressure (BP) regulation. This study investigated the association of n-3 and n-6 PUFA and BP in children and adolescents. METHODS:In a subsample of 1267 children aged 2-9 years at baseline of the European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort whole blood fatty acids were measured by a validated gas chromatographic method. Systolic and diastolic BP was measured at baseline and after two and six years. Mixed-effects models were used to assess the associations between fatty acids at baseline and BP z-scores over time adjusting for relevant covariables. Models were further estimated stratified by sex and weight status. RESULTS:The baseline level of arachidonic acid was positively associated with subsequent systolic BP (β = 0.08, P = 0.002) and diastolic BP (β = 0.07, P

Genetic variability in the FADS1-FADS2 gene cluster [encoding delta-5 (D5D) and delta-6 (D6D) desaturases] has been associated with plasma long-chain PUFA (LCPUFA) and lipid levels in adults. To better understand these relationships, we further characterized the association between FADS1-FADS2 genetic variability and D5D and D6D activities in adolescents. Thirteen single nucleotide polymorphisms (SNPs) were genotyped in 1,144 European adolescents (mean ± SD age: 14.7 ± 1.4 y). Serum phospholipid fatty acid levels were analyzed using gas chromatography. D5D and D6D activities were estimated from the C20:4n-6/C20:3n-6 and C20:3n-6/C18:2n-6 ratios, respectively. Minor alleles of nine SNPs were associated with higher 18:2n-6 levels (1.9E-18 ≤ P ≤ 6.1E-5), lower C20:4n-6 levels (7.1E-69 ≤ P ≤ 1.2E-12), and lower D5D activity (7.2E-44 ≤ P ≤ 4.4E-5). All haplotypes carrying the rs174546 minor allele were associated with lower D5D activity, suggesting that this SNP is in linkage disequilibrium with a functional SNP within FADS1. In contrast, only the rs968567 minor allele was associated with higher D6D activity (P = 1.5E-6). This finding agrees with an earlier in vitro study showing that the minor allele of rs968567 is associated with a higher FADS2 promoter activity. These results suggest that rare alleles of several SNPs in the FADS gene cluster are associated with higher D6D activity and lower D5D activity in European adolescents.

ObjectivesTo examine the independent and combined association of physical activity (PA) and sedentary behavior (SB) on both systolic (SBP) and diastolic blood pressure (DBP) in adolescents from two observational studies.MethodsParticipants from two cross-sectional studies, one conducted in Europe (n = 3,308; HELENA study) and the other in Brazil (n = 991; BRACAH study), were selected by complex sampling. Systolic and diastolic blood pressure (outcomes), PA and SB, both independently and combined, and potential confounders were analyzed. Associations were examined by multilevel linear regression.ResultsPerforming the recommended amount of PA (≥ 60 min/d) attenuated the effect of SB on DBP in BRACAH study girls and in boys from both studies. In contrast, PA did not attenuate the effects of SB on the SBP of girls in the HELENA study. The combination of less than recommended levels of PA with 2-4 h/d of sedentary behavior was found to be associated with increased SBP in boys from both studies.ConclusionsMeeting current PA recommendations could mediate the association between SB and DBP in both sexes. In boys, the joint effect of low levels of PA and excessive sedentary activity increases SBP levels. Longitudinal studies are required to confirm these findings.

Neuromedin U, encoded by the NMU gene, is a hypothalamic neuropeptide that regulates both energy metabolism and bone mass. The beta-2 adrenergic receptor, encoded by the ADRB2 gene, mediates several effects of catecholamine hormones and neurotransmitters in bone. We investigated whether NMU single nucleotide polymorphisms (SNPs) and haplotypes, as well as functional ADRB2 SNPs, are associated with bone stiffness in children from the IDEFICS cohort, also evaluating whether NMU and ADRB2 interact to affect this trait. A sample of 2,274 subjects (52.5% boys, age 6.2 ± 1.8 years) from eight European countries, having data on calcaneus bone stiffness index (SI, mean of both feet) and genotyping (NMU gene: rs6827359, rs12500837, rs9999653; ADRB2 gene: rs1042713, rs1042714), was studied. After false discovery rate adjustment, SI was significantly associated with all NMU SNPs. rs6827359 CC homozygotes showed the strongest association (recessive model, Δ= -1.8, p=0.006). Among the five retrieved haplotypes with frequencies higher than 1% (range 2.0-43.9%), the CCT haplotype (frequency=39.7%) was associated with lower SI values (dominant model, Δ= -1.0, p=0.04) as compared to the most prevalent haplotype. A non-significant decrease in SI was observed in in ADRB2 rs1042713 GG homozygotes, while subjects carrying SI-lowering genotypes at both SNPs (frequency = 8.4%) showed much lower SI than non-carriers (Δ= -3.9, p

BACKGROUND: The association between objectively assessed sedentary time and metabolic risk factors in childhood have rarely been studied. Therefore, we examined the independent relationship between objectively assessed and self-rated sedentary time and indicators of metabolic health in Dutch and Hungarian 10-12 year olds. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional survey in primary schools. Participants were Dutch and Hungarian girls (n = 73, aged 12.2 ± 0.6 years, 18% overweight/obese) and boys (n = 69, aged 12.2 ± 0.7 years, 38% overweight/obese). Sedentary time and physical activity were assessed by the Actigraph accelerometer. TV and PC time were assessed by self-report. Adiposity indicators included body weight, height, and waist circumference (WC). Fasting plasma glucose, C-peptide, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides were determined in capillary blood and summed into a metabolic risk score. Linear regression analyses were adjusted for physical activity, number of sedentary bouts and WC. Children spent on average 7.6 hours of their daily waking time in sedentary behavior and self-reported 116 ± 64 min/day watching TV and 85 ± 57 min/day using the computer. Comparing the 1(st) and 4(th) quartile of objectively assessed sedentary time, C-Peptide levels, WC and BMI were significantly higher in the most sedentary quartile, while the difference in metabolic risk score was borderline significant (p = 0.09). Comparing the 1(st) and 4(th) quartile of TV time, BMI was significantly higher in the most sedentary quartile, while the difference in WC score was borderline significant (p = 0.06). In the adjusted linear regression analysis we found no significant association of sedentary time with metabolic risk. CONCLUSIONS/SIGNIFICANCE: Although BMI and WC were higher in the most sedentary versus the least sedentary children; we found no further evidence that more sedentary children were at increased metabolic risk.

The mass splitting of elliptic anisotropy (ν2) at low transverse momentum is considered as a hallmark of hydrodynamic collective flow. We investigate a multiphase transport (AMPT) model where the ν2 is mainly generated by an anisotropic escape mechanism, not of the hydrodynamic flow nature, and where mass splitting is also observed. We demonstrate that the ν2 mass splitting in AMPT is small right after hadronization (especially when resonance decays are included); the mass splitting mainly comes from hadronic rescatterings, even though their contribution to the overall charged hadron ν2 is small. These findings are qualitatively the same as those from hybrid models that combine hydrodynamics with a hadron cascade. We further show that there is no qualitative difference between heavy ion collisions and small system collisions. Our results indicate that the ν2 mass splitting is not a unique signature of hydrodynamic collective flow and thus cannot distinguish whether the elliptic flow is generated mainly from hydrodynamics or the anisotropic parton escape. [ABSTRACT FROM AUTHOR]