Identification and replication of urine metabolites associated with short-term and habitual intake of sweet and fatty snacks in European children and adolescents.

BACKGROUND: Intake of sweet and fatty snacks may partly contribute to the occurrence of obesity and other health conditions in childhood. Traditional dietary assessment methods may be limited in accurately assessing the intake of sweet and fatty snacks in children. Metabolite biomarkers may aid the objective assessment of children's food intake and support establishing diet-disease relationships. OBJECTIVE: The present study aimed to identify biomarkers of sweet and fatty snack intake in two independent cohorts of European children. METHODS: We used data from the IDEFICS/I.Family cohort from baseline (2007/2008) and two follow-up examination waves (2009/2010 and 2013/2014). In total, n=1788 urine samples from 599 children were analysed for untargeted metabolomics using high-resolution liquid chromatography-mass spectrometry. Short-term dietary intake was assessed by 24-hour dietary recalls, and habitual dietary intake was calculated with the National Cancer Institute method. Data from the DONALD cohort of 24-hour urine samples (n=567) and 3-day weighted dietary records were used for external replication of results. Multivariate modelling with Unbiased Variable selection in R (MUVR) algorithms and linear mixed models were used to identify novel biomarkers. Metabolite features significantly associated with dietary intake were then annotated. RESULTS: In total, 66 metabolites were discovered and found to be statistically significant for "chocolate candy", "cakes, puddings & cookies", "candy & sweets", "ice cream", and "crisps". Most of the features (n=62) could not be annotated. Short-term and habitual chocolate intake were positively associated with theobromine, xanthosine, and cyclo(L-prolyl-L-valyl). These results were replicated in the DONALD cohort. Short-term "candy & sweets" intake was negatively associated with octenoylcarnitine. CONCLUSION: We identified potential metabolite biomarkers of sweet and fatty snacks in children, of which three biomarkers of chocolate intake, namely theobromine, xanthosine, and cyclo(L-prolyl-L-valyl) were externally replicated. However, these potential biomarkers require further validation in children.

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.

Exploring the impact of mental and work-related stress on sick leave among middle-aged women: observations from the population study of women in Gothenburg, Sweden.

OBJECTIVE: To investigate whether mental and work-related stress predicts a one-year incidence of sick leave in a cohort of middle-aged working women. DESIGN: The 2016/17 survey was part of the Population Study of Women in Gothenburg, Sweden, with registry data information on sick leave during one year pre- and post-baseline. SUBJECTS: A cohort of women aged 38 and 50 in 2016/17 (n = 573; 68% participation), of which 504 women were gainfully employed and not on sick leave ± 2 weeks around baseline examination; 493 women had complete data on stress exposure. METHODS: We studied associations between self-assessed mental and work-related stress and incident sick leave of >14 days during the year following the baseline examination. We used multiple logistic regression, adjusting for age and previous sick leave, and additionally for sleep quality, well-being, and physical activity. RESULTS: Overall, 75 women (16%) experienced at least one period of sick leave after baseline. Permanent stress during the last five years almost tripled the risk for incident sick leave, OR = 2.8 (95% CI 1.2-6.3), independent of previous sick leave, OR = 2.3 (95% CI 1.3-4.2). Among 21 specific work-related problems, conflicts at work, OR = 2.2 (95% CI 1.3-3.6), and low decision latitude, OR = 1.7 (95% CI 1.0-2.9), were associated with incident sick leave. The association with conflicts at work remained upon further covariate adjustment. CONCLUSION: Low decision latitude and conflicts at work are risk factors for incident sick leave among working women. The impact of conflicts at work, irrespective of own involvement, may indicate a specific vulnerability among women of interest for future interventions.

About 75% of around 500 middle-aged women reported mental stress in 2016/17. Low decision latitude and conflicts at work predicted incident sick leave independent of general mental stress and previous periods of sick leave. Efforts to improve the work environment may be essential for interventions aiming to reduce absenteeism among working women.

Genetic associations vary across the spectrum of fasting serum insulin: results from the European IDEFICS/I.Family children's cohort.

AIMS/HYPOTHESIS: There is increasing evidence for the existence of shared genetic predictors of metabolic traits and neurodegenerative disease. We previously observed a U-shaped association between fasting insulin in middle-aged women and dementia up to 34 years later. In the present study, we performed genome-wide association (GWA) analyses for fasting serum insulin in European children with a focus on variants associated with the tails of the insulin distribution. METHODS: Genotyping was successful in 2825 children aged 2-14 years at the time of insulin measurement. Because insulin levels vary during childhood, GWA analyses were based on age- and sex-specific z scores. Five percentile ranks of z-insulin were selected and modelled using logistic regression, i.e. the 15th, 25th, 50th, 75th and 85th percentile ranks (P15-P85). Additive genetic models were adjusted for age, sex, BMI, survey year, survey country and principal components derived from genetic data to account for ethnic heterogeneity. Quantile regression was used to determine whether associations with variants identified by GWA analyses differed across quantiles of log-insulin. RESULTS: A variant in the SLC28A1 gene (rs2122859) was associated with the 85th percentile rank of the insulin z score (P85, p value=3×10-8). Two variants associated with low z-insulin (P15, p value <5×10-6) were located on the RBFOX1 and SH3RF3 genes. These genes have previously been associated with both metabolic traits and dementia phenotypes. While variants associated with P50 showed stable associations across the insulin spectrum, we found that associations with variants identified through GWA analyses of P15 and P85 varied across quantiles of log-insulin. CONCLUSIONS/INTERPRETATION: The above results support the notion of a shared genetic architecture for dementia and metabolic traits. Our approach identified genetic variants that were associated with the tails of the insulin spectrum only. Because traditional heritability estimates assume that genetic effects are constant throughout the phenotype distribution, the new findings may have implications for understanding the discrepancy in heritability estimates from GWA and family studies and for the study of U-shaped biomarker-disease associations.

Cardiometabolic risk profile among children with migrant parents and role of parental education: the IDEFICS/I.Family cohort.

BACKGROUND AND AIMS: Evidence shows that migrant children have a higher risk of developing obesity than those with native parents. We aimed to investigate the association between parental migration background and cardiometabolic health in children and adolescents in Europe. METHODS AND RESULTS: We included 8745 children aged 2-17 from the second follow-up of the European IDEFICS/I.Family cohort. Linear regression models were used to investigate the association between parental migration background (one or two migrant parent(s) vs native parents) and body mass index (BMI), metabolic syndrome (MetS) score and its individual components. Outcome variables were parametrized as age and sex-specific z-scores. We adjusted for age, sex, country, and parental education, and additionally for parental income, lifestyle including dietary factors, and maternal BMI. On average, children with two migrant parents had higher z-scores of BMI (+0.24 standard deviation (SD)) and MetS score (+0.30 SD) compared to those with native parents, whereas no significant differences were seen for children with one migrant parent. Associations were attenuated when controlling for maternal BMI and sports club activity. Parental education modified the associations with BMI and MetS z-scores such that they were more pronounced in children with low parental education. CONCLUSION: Children with two migrant parents were at higher risk for adverse cardiometabolic health compared to children with native parents, especially in families with low parental education. These associations were explained by lower physical activity and maternal body weight and encourages early intervention strategies by schools and communities.

Supermarket promotions in Western Sweden are incompatible with Nordic dietary recommendations and differ by area-level socioeconomic index.

BACKGROUND: Large supermarket chains produce weekly advertisements to promote foods and influence consumer purchases. The broad consumer reach of these ads presents an opportunity to promote foods that align with dietary recommendations. Thus, the aim of this study was to investigate the health quality of supermarkets' weekly food promotions in a large region of Sweden with attention to more and less advantaged socioeconomic index areas. METHODS: Analysis of weekly advertisements from 122 individual stores, representing seven chains, was carried out in a large region of Sweden from 2-29 March in 2020. Food promotions were divided into categories according to the Nordic Nutrition Recommendations and World Health Organization Regional Office for Europe's nutrient profile model, and defined as 'most healthy', 'healthy', 'unhealthy' and 'most unhealthy'. A mean socioeconomic index was used to classify each store location to determine whether proportions of the 'most unhealthy' foods differed between more advantaged and more disadvantaged socioeconomic index areas. RESULTS: In total, 29,958 food items were analyzed. Two-thirds of promotions belonged to the food groups considered 'most unhealthy' and 'unhealthy'. In the 'most unhealthy' food group 'sugar-rich beverages and foods' constituted approximately 23.0% of the promotions. Food promotions had 25% increased odds to be from the 'most unhealthy' group (odds ratio 1.25, confidence interval 1.17, 1.33) in more disadvantaged socioeconomic index areas. This association could be explained by the supermarket chain the stores belonged to. CONCLUSIONS: Our findings indicate that Swedish supermarkets promote a large proportion of unhealthy foods as classified by the Nordic Nutrition Recommendations. We also observe that certain national supermarket chains tend to locate their stores in more disadvantaged areas and promote a greater proportion of unhealthy foods in their weekly advertisements compared to the more advantaged areas. There is an urgent need for supermarkets to shift promotions toward healthier food items.

Associations between cardiorespiratory fitness in youth and the incidence of site-specific cancer in men: a cohort study with register linkage.

OBJECTIVES: To assess the associations between cardiorespiratory fitness (CRF) in young men and the incidence of site-specific cancer. METHODS: A Swedish population-based cohort study with register linkage of men who underwent military conscription in 1968-2005 was undertaken. CRF was assessed by maximal aerobic workload cycle test at conscription. Cox regression models assessed linear associations and included CRF, age, year and site of conscription, body mass index and parental level of education. CRF was also categorised into low, moderate and high for facilitated interpretation and results comparing high and low CRF are reported. RESULTS: Primary analyses were performed in 1 078 000 men, of whom 84 117 subsequently developed cancer in at least one site during a mean follow-up of 33 years. Higher CRF was linearly associated with a lower hazard ratio (HR) of developing cancer in the head and neck (n=2738, HR 0.81, 95% CI 0.74 to 0.90), oesophagus (n=689, HR 0.61, 95% CI 0.50 to 0.74), stomach (n=902, HR 0.79, 95% CI 0.67 to 0.94), pancreas (n=1280, HR 0.88, 95% CI 0.76 to 1.01), liver (n=1111, HR 0.60, 95% CI 0.51 to 0.71), colon (n=3222, HR 0.82, 95% CI 0.75 to 0.90), rectum (n=2337, HR 0.95, 95% CI 0.85 to 1.05), kidney (n=1753, HR 0.80, 95% CI 0.70 to 0.90) and lung (n=1635, HR 0.58, 95% CI 0.51 to 0.66). However, higher CRF predicted a higher hazard of being diagnosed with prostate cancer (n=14 232, HR 1.07, 95% CI 1.03 to 1.12) and malignant skin cancer (n=23 064, HR 1.31, 95% CI 1.27 to 1.36). CONCLUSION: We report a number of protective associations between higher CRF in healthy young men and the subsequent hazard of site-specific cancers. These results have implications for public health policymaking, strengthening the incentive to promote health through improving CRF in youth.

Improving cardiorespiratory fitness protects against inflammation in children: the IDEFICS study.

BACKGROUND: Muscular and cardiorespiratory fitness (MF and CRF) have been related to inflammation. Thus, the aim of this study was to assess the relationship between fitness and high-sensitivity C-reactive protein (hs-CRP) in European children both in the cross-sectional and longitudinal analysis. METHODS: Three hundred and fifty-seven children (46.2% males) aged 2-9 years with hs-CRP measured, data from MF and CRF, diet quality, objectively measured physical activity (PA) and screen time at baseline and follow-up after 2 years were included. Body mass index z-score (zBMI), waist circumference (WC) and fat mass index (FMI) were assessed. MF and CRF were also dichotomized as follows: low-medium quartiles (Q1-Q3) and highest quartile (Q4). RESULTS: At follow-up, children with the highest CRF (Q4) showed a lower probability of having high hs-CRP. In the longitudinal analysis, children who improved their CRF over time showed a significantly lower probability (p < 0.05) of being in the highest hs-CRP category at follow-up, independently of the body composition index considered: odds ratio (OR) = 0.22 for zBMI, OR = 0.17 for WC, and OR = 0.21 for FMI. CONCLUSIONS: Improving CRF during childhood reduces the odds of an inflammatory profile, independently of body composition and lifestyle behaviours. These highlight the importance of enhancing fitness, especially CRF, to avoid an inflammatory state in children. IMPACT: Improvements in the cardiorespiratory profile during childhood could reverse an unfavourable inflammatory status. There is a longitudinal and inverse association between CRF and inflammation in children. This is the first longitudinal study assessing the relationship between fitness and inflammation during childhood that takes also into account the lifestyle behaviours. Results from the present study suggest a protective role of fitness already in childhood. Efforts to improve fitness in children should be aimed at as inflammation could trigger future cardiovascular disease.

Longitudinal association of childhood physical activity and physical fitness with physical activity in adolescence: insights from the IDEFICS/I.Family study.

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.

Associations between alcohol and liver enzymes are modified by coffee, cigarettes, and overweight in a Swedish female population.

PURPOSE: To examine whether positive associations between alcohol and liver enzymes were modified by coffee consumption, smoking, or weight status in a female population. METHODS: Regular consumption of beer, wine, and spirits was assessed in a representative cohort of 1462 Swedish women aged 38-60 in 1968, and re-assessed in 1974. In 1980, gamma-glutamyltransferase (GGT) and aspartase transaminase (AST) were measured in 1130 women. Exposures were averaged over values obtained in 1968 and 1974. Multivariable linear regression linked total ethanol intake to log-transformed enzyme values, including interactions by coffee, smoking, and overweight in mutually adjusted models. RESULTS: Coffee consumption significantly modified the association between ethanol intake and liver enzymes. One g/day higher ethanol intake was associated with 5.5 (3.5, 7.5)% higher values of GGT, and 1.2 (0.4, 2.1)% higher values of AST in women consuming 0-1 cups of coffee per day, while smaller or no effects were observed in women consuming ≥2 cups/day. Synergistic interactions were observed for ethanol and smoking, and for ethanol and overweight. Average alcohol-related effects on GGT in smokers and non-smokers were given by 3.8 (2.7, 4.9)% and 2.1 (0.9, 3.2)% per g ethanol/day, and by 0.9 (0.4, 1.4)% and 0.2 (-0.3, 0.7)% for AST. Similarly, in overweight women, 1 g/day higher ethanol intake was associated with 4.3 (3.0, 5.6)% higher GGT compared to 1.6 (0.7, 2.5)% in non-overweight women. CONCLUSIONS: The results suggest that coffee consumption reduces the enzyme-raising effect of ethanol in the presence of synergistic interactions with smoking and overweight, specifically in women.

Interactions between dietary patterns and genetic factors in relation to incident dementia among 70-year-olds.

PURPOSE: To investigate potential interactions between dietary patterns and genetic factors modulating risk for Alzheimer's disease (AD) in relation to incident dementia. METHODS: Data were derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden, including 602 dementia-free 70-year-olds (examined 1992-93, or 2000-02; 64% women) followed for incident dementia until 2016. Two factors from a reduced rank regression analysis were translated into dietary patterns, one healthy (e.g., vegetables, fruit, and fish) and one western (e.g., red meat, refined cereals, and full-fat dairy products). Genetic risk was determined by APOE ε4 status and non-APOE AD-polygenic risk scores (AD-PRSs). Gene-diet interactions in relation to incident dementia were analysed with Cox regression models. The interaction p value threshold was < 0.1. RESULTS: There were interactions between the dietary patterns and APOE ε4 status in relation to incident dementia (interaction p value threshold of < 0.1), while no evidence of interactions were found between the dietary patterns and the AD-PRSs. Those with higher adherence to a healthy dietary pattern had a reduced risk of dementia among ε4 non-carriers (HR: 0.77; 95% CI: 0.61; 0.98), but not among ε4 carriers (HR: 0.86; CI: 0.63; 1.18). Those with a higher adherence to the western dietary pattern had an increased risk of dementia among ε4 carriers (HR: 1.37; 95% CI: 1.05; 1.78), while no association was observed among ε4 non-carriers (HR: 0.99; CI: 0.81; 1.21). CONCLUSIONS: The results of this study suggest that there is an interplay between dietary patterns and APOE ε4 status in relation to incident dementia.

Consumption of foods with the Keyhole front-of-pack nutrition label: potential impact on energy and nutrient intakes of Swedish adolescents.

OBJECTIVE: The Keyhole is an internationally recognised front-of-pack nutrition label, guiding consumers to healthier food options. It indicates products in accordance with specific criteria for dietary fats, sugars, fibres, salt and wholegrains. The objective of this study was to simulate the potential impact of the Keyhole on adolescents' energy and nutrient intakes by modelling a shift from reported food intakes to foods meeting the Keyhole criteria. DESIGN: Self-reported dietary intake data were derived from a cross-sectional survey. Multiple replacement scenarios were calculated, where foods meeting the Keyhole criteria replaced reported non-compliant foods with varying proportions of replacement. SETTING: Dietary survey 'Riksmaten Adolescents 2016-2017' in schools across Sweden. PARTICIPANTS: A nationally representative sample of 3099 adolescents in school years 5, 8 and 11 (55 % girls). RESULTS: Overall, replacement with foods meeting the Keyhole criteria led to more adolescents meeting nutrition recommendations. Largest median intake improvements were seen for wholegrains (+196 %), SFA (-13 %), PUFA (+17 %) and fibres (+15 %). Smallest improvements were seen for free sugars (-3 %) and salt (-2 %), partly explained by the ineligibility of main food sources of free sugars for the Keyhole, and non-inclusion of ready meals that are often high in salt. Most micronutrient intakes were stable or improved. Unintentional effects included decreases in vitamin A, MUFA and energy intakes. Largest potential improvements in fat and fibre sources were observed in the youngest age group. CONCLUSIONS: A shift to Keyhole alternatives for everyday foods would improve adolescents' nutrient intakes, even with smaller exchanges.

Correlates of bitter, sweet, salty and umami taste sensitivity in European children: Role of sex, age and weight status - The IDEFICS study.

We aimed to describe differences in taste sensitivity in children according to age across 7- to 11-year-old children from eight European countries. We further compared taste sensitivity between boys vs. girls and under-/normal weight vs. overweight/obese children. Within the European multicentre IDEFICS (Identification and prevention of dietary and lifestyle-induced health effects in children and infants) study, 1938 school children participated in sweet, bitter, salty and umami detection threshold tests between 2007 and 2010, using the paired comparison staircase method. The lowest concentration at which the child was able to detect a difference to water was determined as taste detection threshold as a proxy of taste sensitivity. Mean taste thresholds were calculated stratified for sex, age groups, weight groups and country. BMI was calculated using measured height and weight; socio-demographic information was collected using questionnaires. Ordinal logistic regressions were conducted to investigate the association between sex, weight status (as categorical exposure variable) and age (as continuous exposure variable) and the taste sensitivity for the four taste modalities (as outcome), separately. Older children were more taste sensitive for sweet and salty and less taste sensitive for umami and bitter than younger children. Girls were more sensitive to sweet taste than boys. Overweight or obese children were less sensitive to sweet and salty taste compared to normal weight children This was the first study comparing taste sensitivity by measuring taste thresholds in children across different European countries. We conclude that taste thresholds are associated with weight status, children become more sensitive to sweet and salty tastes with increasing age, and girls might be more sensitive to sweet than boys.

Forty-four-year longitudinal study of stroke incidence and risk factors - the Prospective Population Study of Women in Gothenburg.

OBJECTIVE: To assess stroke incidence over 44 years and association with risk factors. To study total stroke incidence at 60-82 years of age and risk factors. DESIGN: Prospective population study. SETTING: Gothenburg, Sweden, with ∼450,000 inhabitants. SUBJECTS: A representative sample of a general population of women (1462 in total) in 5 age strata aged 38-60 years in 1968-1969 (the Population Study of Women in Gothenburg, PSWG) were followed up to the ages of 82-104 years in 2012. Further, analysis was also performed for the age interval 60-82 years. MAIN OUTCOME MEASURES: Incidence of total stroke (TS), ischaemic (IS), haemorrhagic (HS), non-specified (NS) and fatal (FS) strokes and association with baseline classic risk factors (such as hypertension, atrial fibrillation, low physical activity, diabetes, high waist-hip-ratio, hyperlipidaemia, smoking), low education, mental stress, pre-eclampsia and oral health as expressed by loss of teeth and bone score. Blood pressure in levels 1-3 according to modern guidelines. Associations with atrial fibrillation, diabetes and myocardial infarction shown in survival analyses. The five cohorts contributed to risk time data concerning associations with TS in the 60-82 age interval from the examination performed when they were 60. RESULTS: Three hundred and thirty-seven (23%) women had a first-ever stroke, 64 (19%) fatal. TS was associated with physical inactivity, high triglycerides and low education in multivariable analysis. The main sub-type IS was associated with systolic blood pressure, physical inactivity and low education. Pre-eclampsia showed association with IS only in the univariable analysis. FS was associated with systolic blood pressure and smoking. During 60-82 years of age, having <20 teeth (HR 1.74, CI 1.25-2.42), diabetes (HR 2.28 CI 1.09-4.76), WHR (HR 1.29 per 0.1 units CI 1.01-1.63), systolic blood pressure (HR 1.11 per 10 units CI 1.04-1.18) and smoking (HR 1.57, CI 1.14-2.16), were associated with TS in the combined five cohorts. CONCLUSIONS: Several classic risk factors showed independent associations with stroke. Vulnerability factors as low education and oral health, reflected by loss of teeth, also showed association with stroke. All these factors are possible to target in primary care preventive interventions.Key PointsStroke is a common disease and the risk of stroke is a key issue demanding preventive strategies in primary health care. The present prospective population study of women showsOut of 1460 women, almost a quarter got a stroke. The stroke incidence 60-82 years of age was rather stable between the first four age cohorts but somewhat lower in the latest cohort, born 1930.Hypertension, low physical activity, low education and high triglyceride levels but not cholesterol were associated with stroke in women.Low education and loss of teeth are vulnerability factors that should need particular attention.

Polygenic risk for obesity and its interaction with lifestyle and sociodemographic factors in European children and adolescents.

BACKGROUND: Childhood obesity is a complex multifaceted condition, which is influenced by genetics, environmental factors, and their interaction. However, these interactions have mainly been studied in twin studies and evidence from population-based cohorts is limited. Here, we analyze the interaction of an obesity-related genome-wide polygenic risk score (PRS) with sociodemographic and lifestyle factors for BMI and waist circumference (WC) in European children and adolescents. METHODS: The analyses are based on 8609 repeated observations from 3098 participants aged 2-16 years from the IDEFICS/I.Family cohort. A genome-wide polygenic risk score (PRS) was calculated using summary statistics from independent genome-wide association studies of BMI. Associations were estimated using generalized linear mixed models adjusted for sex, age, region of residence, parental education, dietary intake, relatedness, and population stratification. RESULTS: The PRS was associated with BMI (beta estimate [95% confidence interval (95%-CI)] = 0.33 [0.30, 0.37], r2 = 0.11, p value = 7.9 × 10-81) and WC (beta [95%-CI] = 0.36 [0.32, 0.40], r2 = 0.09, p value = 1.8 × 10-71). We observed significant interactions with demographic and lifestyle factors for BMI as well as WC. Children from Southern Europe showed increased genetic liability to obesity (BMI: beta [95%-CI] = 0.40 [0.34, 0.45]) in comparison to children from central Europe (beta [95%-CI] = 0.29 [0.23, 0.34]), p-interaction = 0.0066). Children of parents with a low level of education showed an increased genetic liability to obesity (BMI: beta [95%-CI] = 0.48 [0.38, 0.59]) in comparison to children of parents with a high level of education (beta [95%-CI] = 0.30 [0.26, 0.34]), p-interaction = 0.0012). Furthermore, the genetic liability to obesity was attenuated by a higher intake of fiber (BMI: beta [95%-CI] interaction = -0.02 [-0.04,-0.01]) and shorter screen times (beta [95%-CI] interaction = 0.02 [0.00, 0.03]). CONCLUSIONS: Our results highlight that a healthy childhood environment might partly offset a genetic predisposition to obesity during childhood and adolescence.

High-intensity activity is more strongly associated with metabolic health in children compared to sedentary time: a cross-sectional study of the I.Family cohort.

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 (R2 = 2.8%), while vigorous intensity physical activity was associated with lower body mass index (R2 = 3.6%), MetS score (R2 = 3.1%) and higher high-density lipoprotein cholesterol (R2 = 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 (R2 = 1.5% and R2 = 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.

Media use trajectories and risk of metabolic syndrome in European children and adolescents: the IDEFICS/I.Family cohort.

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: ß = 0.54, 95%CI = 0.20-0.88; intercept: ß = 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.

The temporal relationship between parental concern of overeating and childhood obesity considering genetic susceptibility: longitudinal results from the IDEFICS/I.Family study.

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 (ß = 0.16, 95% CI: 0.10, 0.21) and baseline z-WC (ß = 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 (ß = 0.10, 95% CI: 0.07, 0.13) and z-WC at wave 3 (ß = 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.

Ultra-processed foods consumption and diet quality of European children, adolescents and adults: Results from the I.Family study.

BACKGROUND AND AIMS: Food processing has been indicated as a factor capable of negatively affecting the global food system, including the profile of consumers' diets. The objectives of the present study were to provide a description of the consumption of ultra-processed foods (UPFs) in the large population of children, adolescents and adults from eight European countries participating to the I.Family study, and to investigate the association between UPFs intake and nutritional quality of the diet. METHODS AND RESULTS: Dietary intake was assessed using a 24-h dietary recall. The quality of the diet was evaluated by the Healthy Dietary Adherence Score (HDAS) using an FFQ. UPFs were classified according to the NOVA classification. Almost half of the daily energy intake of the 7073 participants came from UPFs, and this trend decreased progressively with age. UPFs contributed more than 50 % of the daily intake of total and saturated fat, carbohydrates and about 70 % of sugars intake in children and adolescents. No differences in UPFs consumption were found according to the educational and socio-economic status of the population. Energy intake increased across the quintiles of UPFs intake, while HDAS decreased. The frequency of consumption of fruit and vegetable, fish, and fibre rich foods was low in the fifth quintile of UPFs intake, both in adolescents and in adults. The consumption of foods rich in calories and low in nutritional content, operationally defined as "junk food", was significantly higher in the fifth quintile. CONCLUSIONS: In the population of the European I.Family study, UPFs contributed a large proportion of the daily energy intake, especially in children and adolescents. Higher consumption of UPFs was associated with a lower quality of the diet. REGISTRATION NUMBER FOR CLINICAL TRIALS: ISRCTN62310987.

Secular trends in diet-related greenhouse gas emission estimates since 2000 - a shift towards sustainable diets in Sweden.

OBJECTIVE: This study examines secular changes in diet-related greenhouse gas emissions (GHGE) in younger and older Swedish adults, since the turn of this century. DESIGN: Two cross-sectional health examination surveys were conducted in 2001-2004 (T1) and 2014-2018 (T2). At both times, an eighty-six-item FFQ was embedded in the survey. From the food frequencies and age-standardised portion sizes, GHGE estimates (kg CO2e/year) were calculated. GHGE was modelled as a function of time period and covariates, for five distinct age groups. SETTING: The municipality of Gothenburg, in western Sweden. PARTICIPANTS: Women and men aged 25-34, 35-44, 45-54, 55-64 and 65-75 years were randomly selected from the population registry and recruited for examinations. After exclusion of participants with incomplete dietary data, the analytic sample consisted of 2569 individuals at T1 and 2119 at T2. RESULTS: Lower dietary GHGE scores were observed at T2 compared with T1, in each age group, adjusting for sex, BMI and education. The largest differences in GHGE were observed in the youngest age group (approximately 30 % reduction). Decreasing trends in GHGE from animal-based foods were observed at all ages and were accompanied by smaller increases from plant-based sources in younger groups only. At all ages, GHGE from discretionary foods decreased, and prevalence of overweight remained stable. CONCLUSIONS: Optimal dietary trends should support both human health and planetary health. Our results suggest that Swedish adults have moved in this direction, e.g. through less intake of red meat products and stable weight status.