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Background The generalized additive model for location, scale and shape (GAMLSS) is a flexible regression model with a wide range of applications. In particular, it is the standard method to estimate age-specific percentile curves for clinical parameters for children and adolescents. Deriving international percentile curves requires large datasets that cover a diverse population. Such datasets are typically obtained by pooling data from multiple studies. However, due to ethical and legal constraints, physically sharing and pooling sensitive individual-level data might not always be permitted. Therefore, we aimed to develop a privacy-enhancing method to fit a GAMLSS. Methods We developed a federated version of the GAMLSS algorithm which allows to co-analyze data from different sources, without physically transferring the data. Instead, data are analyzed locally within their secure home environments and only non-disclosive analysis results are shared. We implemented our method in DataSHIELD, an open-source software infrastructure for federated analysis in R, and investigated its theoretical properties. Considering two different use cases, we applied our algorithm to physically separated epidemiological study data and compared its results with the ones obtained by fitting a GAMLSS to the physically-pooled data. Furthermore, we evaluated the runtime of the federated GAMLSS against the original GAMLSS algorithm for varying number of observations and DataSHIELD servers. Results We proved that, in theory, the federated GAMLSS yields identical results as the original GAMLSS algorithm, using the additivity of matrix multiplication in the fitting algorithm. Furthermore, we provided an implementation of the proposed algorithm and demonstrated that the federated GAMLSS implementation yielded the same results as the pooled GAMLSS in our examples, with only minor differences attributable to numerical computation. However, the runtime was more than 1000 times higher for fitting the federated compared to the pooled GAMLSS. Conclusions In this paper, we propose a privacy-enhancing federated GAMLSS that yields virtually identical results as the original GAMLSS algorithm, without the need to physically pool the data.

Background The Latin American (LA) region is still facing an ongoing epidemiological transition and shows a complex public health scenario regarding non-communicable diseases (NCDs). A healthy diet and consumption of specific food groups may decrease the risk of NCDs, however there is a lack of dietary intake data in LA countries. Objective Provide updated data on the dietary intake of key science-based selected food groups related to NCDs risk in LA countries. Design ELANS (Latin American Study of Nutrition and Health) is a multicenter cross-sectional study assessing food consumption from an urban sample between15 to 65 years old from 8 LA countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela). Two 24-HR were obtained from 9,218 individuals. The daily intake of 10 food groups related to NCDs risk (fruits; vegetables; legumes/beans; nuts and seeds; whole grains products; fish and seafood; yogurt; red meat; processed meats; sugar-sweetened beverages (ready-to-drink and homemade)) were assessed and compared to global recommendations. Results Only 7.2% of the overall sample reached WHO’s recommendation for fruits and vegetables consumption (400 grams per day). Regarding the dietary patterns related to a reduced risk of NCDs, among the overall sample legumes and fruits were the food groups with closer intake to the recommendation, although much lower than expected (13.1% and 11.5%, respectively). Less than 3.5% of the sample met the optimal consumption level of vegetables, nuts, whole grains, fish and yogurt. Largest country-dependent differences in average daily consumption were found for legumes, nuts, fish, and yogurt. Mean consumption of SSB showed large differences between countries. Conclusion Diet intake quality is deficient for nutrient-dense food groups, suggesting a higher risk for NCDs in the urban LA region in upcoming decades. These data provide relevant and up-to-date information to take urgent public health actions to improve consumption of critically foods in order to prevent NCDs.

To describe the design of the Feel4Diabetes-intervention and the baseline characteristics of the study sample. School- and community-based intervention with cluster-randomized design, aiming to promote healthy lifestyle and tackle obesity and obesity-related metabolic risk factors for the prevention of type 2 diabetes among families from vulnerable population groups. The intervention was implemented in 2016-2018 and included: (i) the 'all-families' component, provided to all children and their families via a school- and community-based intervention; and (ii) an additional component, the 'high-risk families' component, provided to high-risk families for diabetes as identified with a discrete manner by the FINDRISC questionnaire, which comprised seven counselling sessions (2016-2017) and a text-messaging intervention (2017-2018) delivered by trained health professionals in out-of-school settings. Although the intervention was adjusted to local needs and contextual circumstances, standardized protocols and procedures were used across all countries for the process, impact, outcome and cost-effectiveness evaluation of the intervention. Primary schools and municipalities in six European countries. Families (primary-school children, their parents and grandparents) were recruited from the overall population in low/middle-income countries (Bulgaria, Hungary), from low socio-economic areas in high-income countries (Belgium, Finland) and from countries under austerity measures (Greece, Spain). The Feel4Diabetes-intervention reached 30 309 families from 236 primary schools. In total, 20 442 families were screened and 12 193 'all families' and 2230 'high-risk families' were measured at baseline. The Feel4Diabetes-intervention is expected to provide evidence-based results and key learnings that could guide the design and scaling-up of affordable and potentially cost-effective population-based interventions for the prevention of type 2 diabetes.

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. The investigation of pre-, peri- and postpartum risk factors on the risk of obesity at age 2 to 9. 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. 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. 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.

Understanding factors influencing clinical biomarkers is important for the prevention of chronic disease. This study aimed to estimate transitions of biomarker status from childhood to adolescence and to identify determinants of biomarker status in early life in a prospective children cohort. Our sample comprised 1295 children participating in the baseline (2007/08) and second follow-up examination (2013/14) of the multi-center IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS)/I.Family study. Clinical blood biomarkers including glycated hemoglobin A1c (HbA1c), high-density lipoprotein cholesterol (HDL-cholesterol), triglycerides, C-reactive protein (CRP), interleukin 6, ferritin, leptin and insulin-like growth factor 1 (IGF-1) were repeatedly measured in 2007/2008 (age range: 3.0 to <10.0 years) and in 2013/2014. Latent transition analysis was used to estimate biomarker statuses and transition probabilities; determinants of biomarker status were estimated using mixed-effects models. Four distinct biomarker statuses were identified: (1) \"normal\" (all biomarkers low/medium; except HDL-cholesterol; reference), (2) \"low leptin/IGF-1/HbA1c\", (3) \"dyslipidemia/high leptin\" and (4) \"inflammation\". Children classified as \"low leptin/IGF-1/HbA1c\" at baseline were most likely to stay in this status (89.8%) or to change to the \"normal\" status (10%) during follow-up. Compared to \"normal\" children, children classified as \"low leptin/IGF-1/HbA1c\" were less likely to have a family history of diabetes (0.26 [0.08;0.86]; odds ratio (OR) and 95% confidence interval) or hypertension (0.53 [0.29;0.99]) and the children (0.32 [0.27;0.38]) as well as their mothers (0.93 [0.88;0.98]) had a lower BMI. Children from families with low/medium education had a 55% [9%-119%] higher risk of being in the \"dyslipidemia/high leptin\" and 49% [1%-121%] higher risk of being in the \"inflammation\" status as compared to children in the \"normal\" status. Membership in a sports club reduced the latter risks by 28% [2%-47%] and 40% [17%-56%], respectively. European children showed distinct phenotypes for the investigated biomarkers. Especially parental characteristics like a family history of diabetes or hypertension, a high maternal BMI, or low/medium education were associated with unfavorable biomarker status in children.

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 < 0.01, Limma test) in less physically active children were identified, including the down-regulation of genes related to cardiometabolic benefits and improved skeletal function ( KLB , NOX4 , and SYPL2 ), and the up-regulation of genes whose elevated expression levels are associated with metabolic complications ( IRX5 , UBD , and MGP ). The analysis of the enriched pathways significantly affected by PA levels were those associated with protein catabolism, skeletal morphogenesis, and wound healing, among others, which may suggest a differential impact of low PA on these processes. Microarray analysis comparing children according to their usual PA has revealed potential PBC transcript-based biomarkers that may be useful in early discerning children expending high sedentary time and its associated negative consequences.

Non-communicable diseases are growing at an alarming rate in Latin America. We assessed total and added sugar intake in Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela, to verify the adequacy of the World Health Organization’s recommendations, considering gender, socioeconomic level (SEL) and age. A total of 9218 non-institutionalized individuals living in urban areas (age range 15–65 years) were assessed in the Latin American Study of Nutrition and Health (ELANS), a multicenter household population-based cross-sectional survey. Socio-demographic data were collected. Total and added sugar intakes were measured using twonon-consecutive 24-h dietary recalls. The prevalence of excessive sugar intake was estimated. A large proportion of individuals showed high consumption of total and added sugar intake, which reflected in the high prevalence of excessive sugar intake. With minimal differences across countries, in general, women, individuals with high SEL, and younger people had higher percentages of total energy intake from total and added sugar intake, and of contribution of carbohydrates from total and added sugars. Thus, there is high consumption of total and added sugar intake in the Latin American countries with some peculiarities considering socio-demographic variables, which should be considered in each country’s health intervention proposals.

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.

An adequate vitamin D status is essential during childhood and adolescence, for its important role in cell growth, skeletal structure and development. It also reduces the risk of conditions such as CVD, osteoporosis, diabetes mellitus, infections and autoimmune disease. As comparable data on the European level are lacking, assessment of vitamin D concentrations was included in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. Fasting blood samples were obtained from a subsample of 1006 adolescents (470 males; 46·8 %) with an age range of 12·5–17·5 years, selected in the ten HELENA cities in the nine European countries participating in this cross-sectional study, and analysed for 25-hydroxycholecalciferol (25(OH)D) by ELISA using EDTA plasma. As specific reference values for adolescents are missing, percentile distribution were computed by age and sex. Median 25(OH)D levels for the whole population were 57·1 nmol/l (5th percentile 24·3 nmol/l, 95th percentile 99·05 nmol/l). Vitamin D status was classified into four groups according to international guidelines (sufficiency/optimal levels ≥ 75 nmol/l; insufficiency 50–75 nmol/l; deficiency 27·5–49·99 nmol/l and severe deficiency < 27·5 nmol/l). About 80 % of the sample had suboptimal levels (39 % had insufficient, 27 % deficient and 15 % severely deficient levels). Vitamin D concentrations increased with age (P < 0·01) and tended to decrease according to BMI. Geographical differences were also identified. Our study results indicate that vitamin D deficiency is a highly prevalent condition in European adolescents and should be a matter of concern for public health authorities.

PurposeTo examine the adherence to the Mediterranean dietary pattern (MDP) in metabolically healthy overweight or obese (MHO) and metabolically unhealthy obese (MUO) European adolescents.MethodsIn this cross-sectional study, 137 overweight/obese adolescents aged 12–17 years old from the HELENA study were included. Height, weight, waist circumference and skinfold thickness were measured and body mass index and body fat percent were calculated. Systolic and diastolic blood pressure, glucose, HDL cholesterol, triglycerides and cardiorespiratory fitness (20 m shuttle run test) were measured. MHO and MUO phenotypes were categorized following the Jolliffe and Janssen criteria. Two non-consecutive 24 h recalls were used for dietary intake assessment and the adherence to the MDP was calculated using the Mediterranean dietary pattern score (MDP score) (range 0–9).ResultsA total of 45 (22 girls) adolescents (32.8%) were categorized as MHO. The adherence to the MDP was significantly higher in MHO than in MUO adolescents regardless of age, sex, body fat percentage, energy intake and center (MDP score: 4.6 ± 1.6 vs. 3.9 ± 1.5, p = 0.036), but this difference became non-significant after further adjustment for cardiorespiratory fitness. Participants who had a low adherence to the MDP (MDP score ≤ 4) had a higher likelihood of having MUO phenotype regardless of sex, age, energy intake, center and body fat percentage (OR 2.2; 95% CI 1.01–4.81, p = 0.048).ConclusionsAdherence to the MDP might be beneficial to maintain metabolic health in overweight/obese adolescents, yet cardiorespiratory fitness seems to play a key role on the metabolic phenotype.