Cohort-Based Reference Values for Serum Ferritin and Transferrin and Longitudinal Determinants of Iron Status in European Children Aged 3-15 Years.

BACKGROUND: Reference values of ferritin and transferrin for European children do not exist. OBJECTIVE: We aimed to provide sex-, age-, and body mass index (BMI)-specific serum ferritin and transferrin reference percentiles of 3-15-y-old children based on cohort data and to investigate determinants of iron status. METHODS: A total of 3390 ferritin and 3416 transferrin measurements from children residing in 8 European countries participating in the IDEFICS/I.Family cohort (https://www.isrctn.com/ISRCTN62310987) at baseline (W0) and 6 y later (W3) were used to estimate percentiles using the generalized additive model for location, scale and shape. Associations of serum ferritin and transferrin concentrations with total iron intake, total iron intake additionally adjusted for vitamin C intake, and iron from heme sources were investigated separately with adjustment for sex, age, country of residence, parental education, usual energy intake and BMI z-score in regression models using cross-sectional and longitudinal data. RESULTS: The age-specific ferritin and transferrin 5th and 95th reference percentiles ranged from 10.9 to 81.1 µg/L and 2.23 to 3.56 g/L, respectively. A deficient iron status was observed in 3% of children at W0 and 7% of children and adolescents at W3, respectively. At both waves, a higher iron intake from heme sources was positively associated with serum ferritin {W0: ß = 3.21 [95% confidence interval (CI): 0.71, 5.71]; W3: ß = 4.48 [95% CI: 2.09, 6.87]}, that is, children consuming one mg more heme iron had a 3.21 and 4.48 µg/L higher ferritin concentration. Adherence to a mainly vegetarian diet was associated with a lower chance for sufficient serum ferritin cross-sectionally at W3 [odds ratio (OR) 0.40 (95% CI: 0.21, 0.81)] and longitudinally [OR 0.35 (95% CI: 0.15, 0.93)]. CONCLUSIONS: Age-, sex-, and BMI-specific reference percentiles of serum ferritin and transferrin concentrations based on cohort data are provided for European children aged 3-15 y and may be used in clinical practice.

Longitudinal associations between vitamin D status and biomarkers of inflammation in a pan-European cohort of children and adolescents.

PURPOSE: To investigate longitudinal associations between the vitamin D status and inflammatory markers in children and adolescents. METHODS: Children from eight European countries from the IDEFICS/I.Family cohort with repeated measurements were included in this study. A linear mixed-effect model was used to model the association of serum 25(OH)D as independent variable and z-scores of inflammatory markers [CRP, cytokines, adipokines, combined inflammation score] as dependent variables, where one level accounts for differences between individuals and the other for changes over age within individuals. RESULTS: A total of 1,582 children were included in the study. In the adjusted model, 25(OH)D levels were positively associated with adiponectin (ß = 0.11 [95% CI 0.07; 0.16]) and negatively with the inflammation score (ß = - 0.24 [95% CI - 0.40; - 0.08]) indicating that the adiponectin z-score increased by 0.11 units and the inflammation score decreased by 0.24 units per 12.5 nmol/l increase in 25(OH)D. In children with overweight or obesity, only a positive association between 25(OH)D and IP-10 was observed while in children with normal weight adiponectin was positively and the inflammation score was negatively associated. Associations of vitamin D with adiponectin and the inflammation score were stronger in girls than in boys and a positive association with TNF-α was observed only in girls. CONCLUSION: Our results suggest that an increase in vitamin D concentrations may help to regulate inflammatory biomarkers. However, it seems to be no benefit of a better vitamin D status in children with overweight/obesity unless their weight is managed to achieve an improved inflammatory marker status.

Disruption of the MICOS complex leads to an aberrant cristae structure and an unexpected, pronounced lifespan extension in Podospora anserina.

Mitochondria are dynamic eukaryotic organelles involved in a variety of essential cellular processes including the generation of adenosine triphosphate (ATP) and reactive oxygen species as well as in the control of apoptosis and autophagy. Impairments of mitochondrial functions lead to aging and disease. Previous work with the ascomycete Podospora anserina demonstrated that mitochondrial morphotype as well as mitochondrial ultrastructure change during aging. The latter goes along with an age-dependent reorganization of the inner mitochondrial membrane leading to a change from lamellar cristae to vesicular structures. Particularly from studies with yeast, it is known that besides the F1 Fo -ATP-synthase and the phospholipid cardiolipin also the "mitochondrial contact site and cristae organizing system" (MICOS) complex, existing of the Mic60- and Mic10-subcomplex, is essential for proper cristae formation. In the present study, we aimed to understand the mechanistic basis of age-related changes in the mitochondrial ultrastructure. We observed that MICOS subunits are coregulated at the posttranscriptional level. This regulation partially depends on the mitochondrial iAAA-protease PaIAP. Most surprisingly, we made the counterintuitive observation that, despite the loss of lamellar cristae and of mitochondrial impairments, the ablation of MICOS subunits (except for PaMIC12) leads to a pronounced lifespan extension. Moreover, simultaneous ablation of subunits of both MICOS subcomplexes synergistically increases lifespan, providing formal genetic evidence that both subcomplexes affect lifespan by different and at least partially independent pathways. At the molecular level, we found that ablation of Mic10-subcomplex components leads to a mitohormesis-induced lifespan extension, while lifespan extension of Mic60-subcomplex mutants seems to be controlled by pathways involved in the control of phospholipid homeostasis. Overall, our data demonstrate that both MICOS subcomplexes have different functions and play distinct roles in the aging process of P. anserina.

Longitudinal association of inflammatory markers with markers of glycaemia and insulin resistance in European children.

PURPOSE: Subclinical systemic inflammation may lead to development of type 2 diabetes, but there has been no investigation into its relationship with early progression of glycaemic deterioration and insulin resistance, especially in younger population. In this study we assessed longitudinal associations of pro- and anti-inflammatory markers with markers that evaluate glycaemia and insulin resistance. METHODS: This study includes 6537 initially nondiabetic children (mean age at baseline = 6.2 years) with repeated measurements from the IDEFICS/I.Family cohort study (mean follow-up = 5.3 years) from eight European countries. Markers of inflammation were used as independent variables and markers of glycaemia/insulin resistance as dependent variables. Associations were examined using two-level growth model. Models were adjusted for sex, age, major lifestyle, metabolic risk factors, early life markers, and other inflammatory markers in final model. RESULTS: Children with 6 years of follow-up showed that a one-unit increase in z-score of leptin level was associated with 0.38 (95% CI = 0.32 to 0.44) unit increase in HOMA-IR z-scores. Leptin continued to be associated with HOMA-IR even when analysis was limited to children with no overall obesity, no abdominal obesity, and low to normal triglyceride levels. An inverse association was observed between IL-15 and HOMA-IR (ß = -0.11, 95% CI = -0.15 to -0.07). CONCLUSIONS: IL-15 should be evaluated further in the prevention or treatment of prediabetes whereas leptin may prove to be useful in early detection of prediabetes via their association with markers of insulin resistance in European children.

Towards a harmonized European surveillance for dietary and physical activity indicators in young and adult populations.

BACKGROUND: The Policy Evaluation Network proposes a consolidated approach to measure comparable health indicators across European health surveillance systems to evaluate effectiveness of policy action. METHODS: In a stepwise approach, questionnaire items used by the systems for measuring diet and physical activity data to describe health indicators were identified based on their validity, reliability, and suitability to monitor achievement of health recommendations. They were collated to unified questionnaire modules and discussed bilaterally with representatives of these systems to explore barriers and facilitators for implementation. Also, establishment of a methodological competence platform was proposed, in which the surveillance and monitoring systems agree on the priorities and common quality standards for the harmonization process and to coordinate the integration of questionnaire modules into existing systems. RESULTS: In total, seven questionnaire modules were developed, of which two diet and two physical activity modules were proposed for implementation. Each module allows measurement of data reflecting only partial aspects of national and WHO recommendations related to diet and physical activity. Main barriers were the requirements of systems to monitor temporal trends and to minimize costs. Main facilitator for implementation was the systems' use of questionnaire items that were comparable to the unified modules. Representatives agreed to participate in a methodological competence platform. CONCLUSION: We successfully took first steps in the realization of the roadmap towards a harmonization of European surveillance by introducing unified questionnaire modules allowing the collection of comparable health indicators and by initiating the establishment of a competence platform to guide this process.

Selection of key indicators for European policy monitoring and surveillance for dietary behaviour, physical activity and sedentary behaviour.

BACKGROUND: A pan-European approach to evaluate policy impact on health behaviour requires the employment of a consensus set of established and relevant indicators. METHODS: As part of the Joint Programming Initiative on a Healthy Diet for a Healthy Life, the Policy Evaluation Network PEN identified key indicators of health behaviours and their determinants. These key indicators are already, or have the potential to be, adopted by large European Union surveillance systems for the assessment of policy impact. The iterative selection process included consultations in two rounds via email prior to a 2-days expert workshop. The experts collated a list of dietary behaviour, physical activity and sedentary behaviour indicators for European policy monitoring in young and adult populations based on existing frameworks and literature reviews. The expert panel was composed of researchers, policy makers and representatives of major European surveillance systems and related initiatives, as well as, representatives of organisations providing monitoring data, such as the European Commission and Eurostat. RESULTS: The process provided two lists of key indicators including 37 diet 'policy' indicators and 35 indicators for dietary behaviour and their 'determinants'; as well as 32 physical activity 'policy' indicators and 35 indicators for physical activity, sedentary behaviour and their 'determinants'. CONCLUSION: A total of 139 key indicators related to the individual, the setting and the population level, and suitable for the assessment of dietary behaviour, physical activity and sedentary behaviour were prioritised by policy makers and researchers with the ultimate aim to embed policy evaluation measures in existing surveillance systems across the European Union. In a next step, data sources and suitable instruments will be identified to assess these key indicators.

The role of lifestyle and non-modifiable risk factors in the development of metabolic disturbances from childhood to adolescence.

BACKGROUND: The study aimed to identify the effects of lifestyle, C-reactive protein (CRP) and non-modifiable risk factors on metabolic disturbances in the transition from childhood to adolescence. METHODS: In 3889 children of the IDEFICS/I.Family cohort, latent transition analysis was applied to estimate probabilities of metabolic disturbances based on waist circumference, blood pressure, blood glucose, and lipids assessed at baseline and at 2- and 6-year follow-ups. Multivariate mixed-effects models were used to assess the age-dependent associations of lifestyle, non-modifiable risk factors and CRP, with the transformed probabilities of showing abdominal obesity, hypertension, dyslipidemia, or several metabolic disturbances (reference: being metabolically healthy). RESULTS: Higher maternal body mass index, familial hypertension as well as higher CRP z-score increased the risk for all four metabolic outcomes while low/medium parental education increased the risk of abdominal obesity and of showing several metabolic disturbances. Out of the lifestyle factors, the number of media in the bedroom, membership in a sports club, and well-being were associated with some of the outcomes. For instance, having at least one media in the bedroom increased the risk for showing several metabolic disturbances where the odds ratio (OR) markedly increased with age (1.30 [95% confidence interval 1.18; 1.43] at age 8; 1.18 [1.14; 1.23] for interaction with age; i.e., resulting in an OR of 1.30 × 1.18 = 1.53 at age 9 and so forth). Further, entering puberty at an early age was strongly associated with the risk of abdominal obesity (2.43 [1.60; 3.69] at age 8; 0.75 [0.69; 0.81] for interaction with age) and the risk of showing several metabolic disturbances (2.46 [1.53; 3.96] at age 8; 0.71 [0.65; 0.77] for interaction with age). CONCLUSIONS: Various factors influence the metabolic risk of children revealing the need for multifactorial interventions. Specifically, removing media from children's bedroom as well as membership in a sports club seem to be promising targets for prevention.

Associations of whole blood polyunsaturated fatty acids and insulin resistance among European children and adolescents.

This study aims to examine the association of whole blood n-3 and n-6 polyunsaturated fatty acids (PUFA) with insulin resistance (IR) in children. Whole blood fatty acids were measured in 705 children aged 2-9 years of the European IDEFICS/I.Family cohort using gas chromatography in units of weight percentage of all detected fatty acids (%wt/wt). IR was determined by the Homeostasis Model Assessment for IR (HOMA). Mixed effect models were used to assess the associations between selected baseline PUFA and HOMA z-scores at baseline and after 2- and 6-year follow-ups using models with basic and additional confounder adjustment as well as stratified by sex and weight status. In the basic model, α-linolenic (ß = 1.46 SD/%wt/wt, p = 0.006) and eicosapentaenoic acid (ß = 1.17 SD/%wt/wt, p = 0.001) were positively associated with baseline HOMA z-score. In the stratified analyses, α-linolenic acid was positively associated with HOMA z-score in girls only (ß = 1.98 SD/%wt/wt, p = 0.006) and arachidonic acid was inversely associated with baseline HOMA in thin/normal-weight children (ß = - 0.13 SD/%wt/wt, p = 0.0063). In the fully adjusted model, no statistically significant associations were seen.Conclusions: Our overall results do not indicate a protective role of higher blood n-3 PUFA or an adverse role of higher blood arachidonic acid proportion on the risk of IR. What is Known: •Intervention studies reported a beneficial effect of n-3 PUFA supplementation on insulin resistance compared with placebo while observational studies in cildren are inconclusive. •Studies have shown a positive association of n-6 arachidonic acid and insulin resistance indicating an adverse role of arachidonic acid. What is New: •Cross-sectional and longitudinal analyses based on circulating blood fatty acid concentrations in a large cohort of European children and adolescents. •Overall results do not support a protective role of n-3 PUFA or an adverse role of arachidonic acid in insulin resistance.

Development and body mass inversely affect children's brain activation in dorsolateral prefrontal cortex during food choice.

Childhood obesity is a rising problem caused in part by unhealthy food choices. Food choices are based on a neural value signal encoded in the ventromedial prefrontal cortex, and self-control involves modulation of this signal by the dorsolateral prefrontal cortex (dlPFC). We determined the effects of development, body mass (BMI Cole score) and body mass history on the neural correlates of healthy food choice in children. 141 children (aged 10-17y) from Germany, Hungary and Sweden were scanned with fMRI while performing a food choice task. Afterwards health and taste ratings of the foods were collected. In the food choice task children were asked to consider the healthiness or tastiness of the food or to choose naturally. Overall, children made healthier choices when asked to consider healthiness. However, children who had a higher weight gain per year chose less healthy foods when considering healthiness but not when choosing naturally. Pubertal development stage correlated positively while current body mass correlated negatively with dlPFC activation when accepting foods. Pubertal development negatively and current body mass positively influenced the effect of considering healthiness on activation of brain areas involved in salience and motivation. In conclusion, children in earlier stages of pubertal development and children with a higher body weight exhibited less activation in the dlPFC, which has been implicated in self-control during food choice. Furthermore, pubertal development and body mass influenced neural responses to a health cue in areas involved in salience and motivation. Thus, these findings suggest that children in earlier stages of pubertal development, children with a higher body mass gain and children with overweight may possibly be less susceptible to healthy eating interventions that rely on self-control or that highlight health aspects of food.

Prospective associations between dietary patterns and high sensitivity C-reactive protein in European children: the IDEFICS study.

PURPOSE: This prospective study explores high sensitivity C-reactive protein (hs-CRP) levels in relation to dietary patterns at two time points in European children. METHODS: Out of the baseline sample of the IDEFICS study (n = 16,228), 4020 children, aged 2-9 years at baseline, with available hs-CRP levels and valid data from a food frequency questionnaire (FFQ) at baseline (T0) and 2 years later (T1) were included. K-means clustering algorithm based on the similarities between relative food consumption frequencies of the FFQ was applied. hs-CRP was dichotomized according to sex-specific cutoff points. Multilevel logistic regression was performed to assess the relationship between dietary patterns and hs-CRP adjusting for covariates. RESULTS: Three consistent dietary patterns were found at T0 and T1: 'animal protein and refined carbohydrate', 'sweet and processed' and 'healthy'. Children allocated to the 'protein' and 'sweet and processed' clusters at both time points had significantly higher odds of being in the highest category of hs-CRP (OR 1.47; 95% CI 1.03-2.09 for 'animal protein and refined carbohydrate' and OR 1.44; 95% CI 1.08-1.92 for 'sweet and processed') compared to the 'healthy' cluster. The odds remained significantly higher for the 'sweet and processed' pattern (OR 1.39; 95% CI 1.05-1.84) when covariates were included. CONCLUSIONS: A dietary pattern characterized by frequent consumption of sugar and processed products and infrequent consumption of vegetables and fruits over time was independently related with inflammation in European children. Efforts to improve the quality of the diet in childhood may prevent future diseases related with chronic inflammation.

Association of desaturase activity and C-reactive protein in European children.

BACKGROUND: Desaturase enzymes influence the fatty acid (FA) composition of body tissues and their activity affects the conversion rate of saturated to monounsaturated FA and of polyunsaturated FA (PUFA) to long-chain PUFA. Desaturase activity has further been shown to be associated with inflammation. We investigate the association between delta-9 (D9D), delta-6 (D6D) and delta-5 desaturase (D5D) activity and high-sensitive C-reactive protein (CRP) in young children. METHODS: In the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort study children were examined at baseline (T0) and after 2 y (T1). D9D, D6D, and D5D activities were estimated from T0 product-precursor FA ratios. CRP was measured at T0 and T1. In a subsample of 1,943 children with available information on FA, CRP, and covariates, the cross-sectional and longitudinal associations of desaturase activity and CRP were analyzed. RESULTS: Cross-sectionally, a D9D increase of 0.01 units was associated with a 11% higher risk of having a serum CRP ≥ Percentile 75 (P75) (OR, 99% CI: 1.11 (1.01; 1.22)) whereas D6D and D5D were not associated with CRP. No significant associations were observed between baseline desaturase activity and CRP 2 y later. CONCLUSION: Cross-sectionally, our results indicate a positive association of D9D and CRP independent of weight status. High D9D activity may increase the risk of subclinical inflammation which is associated with metabolic disorders. As D9D expression increases with higher intake of saturated FA and carbohydrates, dietary changes may influence D9D activity and thus CRP. However, it remains to be investigated whether there is a causal relationship between D9D activity and CRP.

Cross-sectional and longitudinal associations between energy intake and BMI z-score in European children.

BACKGROUND: Evidence for the effect of dietary energy on BMI z-scores in young children is limited. We aim to investigate cross-sectional and longitudinal effects of daily energy intake (EI) on BMI z-scores of European boys and girls considering growth-related height dependencies of EI using residual EI. METHODS: To investigate cross-sectional and longitudinal effects of daily energy intake (EI) on BMI z-scores of European boys and girls considering growth-related height dependencies of EI using residual EI. METHODS: Subjects were children aged 2- < 10 y old (N = 2753, 48.2% girls) participating in the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) baseline and follow-up examination. Usual EI (kcal/day) was calculated based on the National Cancer Institute-method excluding subjects with implausible reported EI. Effect of age, height and sex-adjusted residuals of EI on BMI z-score was investigated stratified by baseline age -group (2- < 4 y, 4- < 6 y, 6- < 8 y and 8- < 10 y) cross-sectionally using linear regression models adjusted for relevant confounders (crude model: age, sex, country; fully adjusted model: plus parental ISCED level, parental BMI, screen time; subgroup analysis: plus objectively measured physical activity). Longitudinal associations were estimated between changes in (Δ) residual EI per year and ΔBMI z-score per year with adjustments analogously to the cross-sectional models but with additional adjustment for residual EI at baseline. RESULTS: Cross-sectionally, positive associations were observed between residual EI and BMI z-score for the full study sample, for boys and in older (≥6 years) but not in younger children in the crude and fully adjusted model. Longitudinally, small positive associations were observed between Δresidual EI per y on ΔBMI z-score per y for the full study sample and in 4- < 6 y olds in the crude and fully adjusted model. CONCLUSION: In conclusion, EI above the average intakes for a certain sex, age and height are weakly associated with BMI z-scores in European children. Residual EI may be considered as a useful exposure measure in children as it accounts for growth-related changes in usual EI during childhood.

Associations between social vulnerabilities and dietary patterns in European children: the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) study.

Socio-economic inequalities in childhood can determine dietary patterns, and therefore future health. This study aimed to explore associations between social vulnerabilities and dietary patterns assessed at two time points, and to investigate the association between accumulation of vulnerabilities and dietary patterns. A total of 9301 children aged 2-9 years participated at baseline and 2-year follow-up examinations of the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS study. In all, three dietary patterns were identified at baseline and follow-up by applying the K-means clustering algorithm based on a higher frequency of consumption of snacks and fast food (processed), sweet foods and drinks (sweet), and fruits and vegetables (healthy). Vulnerable groups were defined at baseline as follows: children whose parents lacked a social network, children from single-parent families, children of migrant origin and children with unemployed parents. Multinomial mixed models were used to assess the associations between social vulnerabilities and children's dietary patterns at baseline and follow-up. Children whose parents lacked a social network (OR 1·31; 99 % CI 1·01, 1·70) and migrants (OR 1·45; 99 % CI 1·15, 1·83) were more likely to be in the processed cluster at baseline and follow-up. Children whose parents were homemakers (OR 0·74; 99 % CI 0·60, 0·92) were less likely to be in the processed cluster at baseline. A higher number of vulnerabilities was associated with a higher probability of children being in the processed cluster (OR 1·78; 99 % CI 1·21, 2·62). Therefore, special attention should be paid to children of vulnerable groups as they present unhealthier dietary patterns.

[Safety of folic acid]. / Sicherheit von Folsäure. Fakten und Fiktionen.

Improving dietary folate intake is a central public health goal. However, critical voices have become louder warning of too high intake of folic acid. Safety concerns of a high folic acid exposure are usually limited to synthetic folic acid contained in drugs and food supplements. Against this background, the present article focuses on two matters: (a) How do the absorption and metabolism of synthetic folic acid differ from that of other folates? (b) How has the longterm safety of folic acid to be judged, especially regarding the risk of colorectal cancer, autism, asthma, impaired immune defence, masking vitamin B12 deficiency and interactions with the methotrexate metabolism?

Mapping the existing evidence of the effects of school food policies on health, acceptance and affordability of secondary school children in Europe: a scoping review protocol.

INTRODUCTION: Unhealthy diets pose a significant public health risk among European children, contributing to the increasing prevalence of overweight and non-communicable diseases. Children spend a substantial amount of time at school daily, including lunchtime, so the school setting becomes crucial for promoting healthy diets and lifestyle habits. While there is a large body of literature on the impact of school food policies on health and non-health outcomes, it is essential to identify which policies are effective and can be recommended for implementation to ensure the efficient use of resources. This article presents a protocol for a scoping review that aims to map the current published literature on the effects of school food policies on health outcomes, acceptance and affordability in secondary school children in Europe. Moreover, the scoping review will map the measurements used to assess health outcomes, acceptance and affordability. METHODS AND ANALYSIS: The scoping review protocol and review follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review. To identify eligible studies, we will search MEDLINE, PsycINFO, CINAHL and Web of Science. The reference lists of the included articles will be checked for additional studies. In addition, country-specific ministry reports from Member States of the European Union, the UK, Norway, Iceland and Switzerland will be identified. The WHO and European Commission websites will also be searched for relevant reports. The scoping review will include literature published until 20 September 2023. No restrictions to study design and language will be applied. Screening and data extraction will be carried out independently by three reviewers. Disagreements will be resolved by discussion. A pretested data charting table will be used to extract key information. Findings will be presented in tabular and visualised summaries and a narrative summary. ETHICS AND DISSEMINATION: This scoping review does not require ethical approval. Our dissemination strategy comprises peer-reviewed publications, conference presentations and recommendations to policy-makers.

Population trajectories and age-dependent associations of obesity risk factors with body mass index from childhood to adolescence across European regions: A two-cohort study.

OBJECTIVE: To investigate population trajectories of behavioural risk factors of obesity from childhood to adolescence and their associations with body mass index (BMI) in children across European regions. METHODS: Data were harmonised between the European multi-centre IDEFICS/I.Family and the Amsterdam Born Children and their Development Cohort. Participants were aged 2.0-9.9 and 5.0-7.5 years at baseline, respectively, and were followed until age 18 years. Behavioural risk factors of interest included diet, physical activity, media use and sleep. Mixed effects models were used for statistical analyses to account for repeated measurements taken from the same child. RESULTS: The study included a total of 14 328 individuals: 4114, 4582, 3220 and 2412 participants from Northern, Southern, Eastern Europe and Amsterdam, respectively. Risk factor means and prevalences changed with age, but the trajectories were mostly similar across regions. Almost no associations between behavioural factors and BMI were found at the age of 6 years. At 11 years, daily sugar-sweetened foods consumption, use of active transport, sports club membership and longer nocturnal sleep duration were negatively associated with BMI in most regions; positive associations were found with media use. Most associations at 11 years of age persisted to 15 years. CONCLUSIONS: Whilst population trajectories of media use and nocturnal sleep duration are similar across European regions, those of other behavioural risk factors like active transport and daily vegetable consumption differ. Also, associations between behavioural risk factors and BMI become stronger with age and show similar patterns across regions.

Establish a noninvasive model to screen metabolic dysfunction-associated steatotic liver disease in children aged 6-14 years in China and its applications in high-obesity-risk countries and regions.

Background: The prevalence of metabolic-associated steatotic liver disease (MASLD) is rising precipitously among children, particularly in regions or countries burdened with high prevalence of obesity. However, identifying those at high risk remains a significant challenge, as the majority do not exhibit distinct symptoms of MASLD. There is an urgent need for a widely accepted non-invasive predictor to facilitate early disease diagnosis and management of the disease. Our study aims to 1) evaluate and compare existing predictors of MASLD, and 2) develop a practical screening strategy for children, tailored to local prevalence of obesity. Methods: We utilized a school-based cross-sectional survey in Beijing as the training dataset to establish predictive models for screening MASLD in children. An independent school-based study in Ningbo was used to validate the models. We selected the optimal non-invasive MASLD predictor by comparing logistic regression model, random forest model, decision tree model, and support vector machine model using both the Beijing and Ningbo datasets. This was followed by serial testing using the best performance index we identified and indices from previous studies. Finally, we calculated the potential MASLD screening recommendation categories and corresponding profits based on national and subnational obesity prevalence, and applied those three categories to 200 countries according to their obesity prevalence from 1990 to 2022. Findings: A total of 1018 children were included (NBeijing = 596, NNingbo = 422). The logistic regression model demonstrated the best performance, identifying the waist-to-height ratio (WHtR, cutoff value ≥0.48) as the optimal noninvasive index for predicting MASLD, with strong performance in both training and validation set. Additionally, the combination of WHtR and lipid accumulation product (LAP) was selected as an optimal serial test to improve the positive predictive value, with a LAP cutoff value of ≥668.22 cm × mg/dL. Based on the obesity prevalence among 30 provinces, three MASLD screening recommendations were proposed: 1) "Population-screening-recommended": For regions with an obesity prevalence ≥12.0%, where MASLD prevalence ranged from 5.0% to 21.5%; 2) "Resources-permitted": For regions with an obesity prevalence between 8.4% and 12.0%, where MASLD prevalence ranged from 2.3% to 4.4%; 3) "Population-screening-not-recommended": For regions with an obesity prevalence <8.4%, where MASLD prevalence is difficult to detect using our tool. Using our proposed cutoff for screening MASLD, the number of countries classified into the "Population-screening-recommended" and "Resources-permitted" categories increased from one and 11 in 1990 to 95 and 28 in 2022, respectively. Interpretation: WHtR might serve as a practical and accessible index for predicting pediatric MASLD. A WHtR value ≥0.48 could facilitate early identification and management of MASLD in areas with obesity prevalence ≥12.0%. Furthermore, combining WHtR ≥0.48 with LAP ≥668.22 cm × mg/dL is recommended for individual MASLD screening. Moreover, linking these measures with population obesity prevalence not only helps estimate MASLD prevalence but also indicates potential screening profits in regions at varying levels of obesity risk. Funding: This study was supported by grants from Capital's Funds for Health Improvement and Research (Grant No. 2022-1G-4251), National Natural Science Foundation of China (Grant No. 82273654), Major Science and Technology Projects for Health of Zhejiang Province (Grant No. WKJ-ZJ-2216), Cyrus Tang Foundation for Young Scholar 2022 (2022-B126) and Sino-German Mobility Programme (M-0015).

[Celiac disease--the chameleon among the food intolerances]. / Zöliakie. Das Chamäleon unter den Nahrungsmittelintoleranzen.

Celiac disease is an autoimmune disorder resulting from gluten intolerance and is based on a genetically predisposition. Symptoms occur upon exposure to prolamin from wheat, rye, barley and related grain. The pathogenesis of celiac disease has not yet been sufficiently elucidated but is being considered as an autoimmune process. At its core are the deamidation of prolamin fragments, the building of specific antibodies and the activation of cytotoxic T-cells. The immunological inflammatory process is accompanied by structural damages of the enterocytes (villous atrophy, colonization and crypt hyperplasia). The symptoms and their extent depend on the type of the celiac disease; classic and non-classic forms are being distinguished (atypical, oligosymptomatic, latent and silent celiac disease). Characteristics of the classic presentation are malabsorption syndrome and intestinal symptoms such as mushy diarrhea and abdominal distension. The diagnosis of celiac disease is based on four pillars: Anamnesis and clinical presentation, serological evidence of coeliac specific antibodies (IgA-t-TG; IgA-EmA), small intestine biopsy and improvement of symptoms after institution of a gluten-free diet. The basis of the therapy is a lifelong gluten-free diet, i. e. wheat, rye, barley, spelt, green-core, faro-wheat, kamuth and conventional oats as well as food items obtained therefrom. Small amounts of up to 50 mg gluten per day are usually tolerated by most patients; amounts of > or = 100 mg/day lead mostly to symptoms. Gluten-free foods contain < or = 20 ppm or 20 mg/kg (Sign: symbol of the 'crossed ear' or label 'gluten-free'). At the beginning of the therapy the fat and lactose intake may need to be reduced; also the supplementation of single micronutrients (fat-soluble vitamins, folic acid, B12, iron, and calcium) may be required. Alternative therapies are being developed but have not yet been clinically tested.

[Nutrient supplements--possibilities and limitations: part 2]. / Nährstoffsupplemente--Möglichkeiten und Grenzen Teil 2: Ausgewählte Risikogruppen--Supplemente in der Schwangerschaft.

Pregnant women are at greater risk of an insufficient vitamin and mineral supply. Based on hemodynamic, endocrine and metabolic changes due to pregnancy, the body weight and blood volume increase. These changes result in an increased requirement of most vitamins and minerals while the energy requirement increases by about 10%. Besides iodine (recommended intake as supplement 150 microg/d), iron (recommended intake 30-40 mg/d), vitamin D (recommended intake as supplement 20-50 microg/d), and docosahexaenoic acid (recommended intake 200 mg/d), folic acid is one of the critical micronutrients during pregnancy. Food folate and synthetic folic acid differ in their bioavailability. About 50% of the food folate is absorbed whereas almost 100% of folic acid from supplements is bioavailable. The contents are thus indicated as folate equivalents. In the form ofTHF, folic acid functions as coenzyme for the transfer of C1 units in the metabolism of amino acids, purines and pyrimidines. Folic acid (isolated or in combination with other vitamins and minerals) reduces the total risk for neural tube defects by 72%. For primary prevention it is recommended that all women who are planning to become pregnant take 400-800 microg synthetic folic acid along with a diet rich in folate. The additional intake should be continued at least until the end of the first trimester. For secondary prevention of neural tube defects an intake of 4 mg/d is recommended.