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.

Poor stress resilience in adolescence predicts higher risk of severe COVID-19 and other respiratory infections: A prospective cohort study of 1.4 million Swedish men.

OBJECTIVES: To investigate the associations between stress resilience in late adolescence and later risk of severe COVID-19 and other lower respiratory infections. A secondary aim was to examine potential confounding between low cardiorespiratory fitness (CRF) and stress resilience in relation to respiratory infection. METHODS: We conducted a registry-based cohort study of 1.4 million Swedish men, undergoing military conscription between 1968 and 2005. All were assessed by a psychologist for stress resilience, receiving a score between 1 and 9. The outcomes were hospitalization or death due to COVID-19 from March 2020 to September 2021 and hospitalization due to bacterial or viral pneumonia from conscription until January 2020. A secondary aim was to examine potential confounding between low cardiorespiratory fitness (CRF) and stress resilience in relation to respiratory infection. RESULTS: Poor stress resilience in late adolescence is associated with later risk of severe lower respiratory infections. Using a high resilience score as the reference, the hazard ratio (95 % CI) for death due to COVID-19 for the lowest scores was 1.49 (1.01-2.18) adjusted for CRF and other confounders. The corresponding adjusted hazard ratios for hospitalization due to bacterial pneumonia were 2.28 (2.03-2.57) and for viral pneumonia 1.92 (1.33-2.79). No significant interaction was seen between stress resilience and CRF in the analysis. CONCLUSIONS: Poor stress resilience is a prospective factor for severe COVID-19 as well as for bacterial and viral respiratory pneumonia endpoints, independent of CRF. These findings imply an effect of late adolescent stress resilience on the immune system later in life.

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.

Comparison of associations between alcohol consumption and metabolic syndrome according to three definitions: The Swedish INTERGENE study.

Background: While prevalence estimates differ by definition of metabolic syndrome (MetS), it is less clear how different definitions affect associations with alcohol consumption. Methods: We included 3051 adults aged 25-77 from the baseline examination of the Swedish INTERGENE cohort (2001-2004). Using multiple logistic regression, we investigated cross-sectional associations between ethanol intake and MetS defined according to the Adult Treatment Panel III (ATP III), the International Diabetes Federation (IDF), and the Joint Interim Statement (JIS). Alcohol exposure categories comprised abstinence, and low, medium, and high consumption defined via sex-specific tertiles of ethanol intake among current consumers. Covariates included sociodemographics, health, and lifestyle factors. Results: MetS prevalence estimates varied between 13.9 % (ATP III) and 25.3 % (JIS), with higher prevalence in men than women. Adjusted for age and sex, medium-high alcohol consumption was associated with lower odds of MetS compared to low consumption, while no difference was observed for abstainers. Only the most specific (and thus severe) definition of MetS (ATP III) showed decreasing odds for ethanol intake when adjusted for all covariates. Conclusion: Our study shows that alcohol-related associations differ by definition of MetS. The finding that individuals with the most stringently defined MetS may benefit from alcohol consumption calls for further well-controlled studies.

Longitudinal associations between psychosomatic and emotional status and selected food portion sizes in European children and adolescents: IDEFICS/I.Family study.

This study aims to investigate the influence of psychosomatic and emotional status on food portion sizes (PSs) consumption from high energy-dense food groups in European children and adolescents. We hypothesized that psychosomatic and emotional status would have a significant association with the PS selection of energy-dense food. The study included 7355 children aged between 2 and 9.9 years at baseline (T0) (48.8% females); 3869 after 2 years (T1) (48.2% females), and 2971 (51.8% females) after 6 years of follow-up (T3). Psychosomatic and emotional status were measured using emotional well-being during the last week score (KINDL) and Strengths and Difficulties Questionnaire. PS was calculated from daily food intake recorded in 24-hour dietary recalls. The associations between emotional status indicators and PS from selected energy-dense food groups were assessed by multilevel linear regression models. In the cross-sectional analysis, we observed that higher KINDL scores were linked to lower PS consumption from sweet bakery products and savory snacks in both genders. Moreover, we found that adolescent females with high emotional and peer problem scores tended to consume larger PS of carbohydrate-rich and sugar-fatty food items (P < .017). Longitudinally, higher peer problem scores were associated with increased PS from bread and rolls, margarine and lipids, and dairy products in all genders and age groups (P< .017). In adolescents, psychosomatic and emotional status could be a trigger for consuming large PS from carbohydrate-rich and sugar-fatty energy-dense foods. Thus, nutritional interventions should consider emotional status to decrease unhealthy dietary habits in children and adolescents.

Domain-Specific Physical Activity and Stroke in Sweden.

Importance: Associations of domain-specific physical activity with stroke incidence and poststroke outcomes have not been extensively studied using long-term, population-based data. Objective: To investigate associations of leisure time, work time, transport, and household physical activity with stroke incidence and death or dependency in activities of daily living (ADL) 3 months after stroke. Design, Setting, and Participants: The prospective, population-based Interplay Between Genetic Susceptibility and External Factors (INTERGENE) cohort study was conducted among a random sample of individuals from an urban-rural area covering western Sweden; 3614 individuals aged 24 to 77 years were examined in 2001 to 2004, and 1394 individuals were reexamined in 2014 to 2016. The median (range) follow-up was 20.0 years (56 days to 21.9 years). Data were analyzed from September through October 2023. Exposure: Physical activity levels were self-reported for leisure time, work time, transportation, and household domains. The mean number of steps taken over a 6-day period was collected in a subgroup of participants using a sealed pedometer. Main Outcomes and Measures: Follow-up for stroke incidence and mortality rates continued until December 31, 2022. The composite outcome of death or ADL dependency was assessed at 3 months after stroke. Results: Among 3614 individuals (mean [SD] age, 51.4 [13.1] years; 1910 female [52.9%]); 269 individuals (7.4%) developed stroke, of whom 120 individuals (44.6%) were dead or ADL dependent at 3 months. Intermediate (adjusted hazard ratio [aHR], 0.54; 95% CI, 0.38-0.77) and high (aHR, 0.47; 95% CI, 0.31-0.73) levels of leisure time physical activity were associated with a reduced incidence of stroke compared with low levels, as was an intermediate level of physical activity in transportation (aHR, 0.69; 95% CI, 0.52-0.93). High levels of leisure time physical activity were also associated with a reduced risk of poststroke death or ADL dependency (adjusted odds ratio, 0.34; 95% CI, 0.16-0.71) compared with low levels. Work time and household physical activity were not associated with stroke incidence or stroke outcomes. In exploratory subgroup analyses, there were interactions between physical activity and smoking (current smoking or smoking in the past year associated with stroke risk only in participants with low or intermediate physical activity: aHR, 2.33; 95% CI, 1.72-3.15) and family history of stroke (first-degree relative with a history of stroke associated with stroke risk only in participants with low or intermediate physical activity: aHR, 1.73; 95% CI, 1.27-2.38). Conclusions and Relevance: In this study, leisure time and transport-related physical activities were associated with a reduced risk of stroke. A high level of leisure time physical activity was also associated with a lower risk of death or ADL dependency 3 months after stroke.

A longitudinal causal graph analysis investigating modifiable risk factors and obesity in a European cohort of children and adolescents.

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

Body mass index and fitness in late adolescence and risk of cardiovascular disease, respiratory disease, and overall death after COVID-19.

Objective: Since obesity and poor fitness appear to be unfavorable for both cardiovascular health and coping with viral infections such as COVID-19, they are of specific interest in light of the increased risk of cardiovascular and respiratory events now seen after infection with SARS-CoV-2. Therefore, the aim of the present study was to investigate how body mass index (BMI) and cardiorespiratory fitness (CRF) in late adolescence are associated with the risk of cardiovascular disease (CVD), respiratory disease, and mortality after COVID-19. Methods: In this study, 1.5 million 18-year-old Swedish men with BMI and CRF measured during enlistment for military service 1968-2005 were included. Hospitalized and non-hospitalized COVID-19 cases were identified through the Patient Register or positive polymerase chain reaction tests, and age-matched with non-infected controls. CVD, respiratory disease, and mortality after COVID-19 were divided into <60days, 60-180days, >180days post-infection. Cox regression models were used. Results: Hospitalized COVID-19 cases (n = 9839), compared to controls, had >10-fold, 50 to 70-fold, and >70-fold hazards of CVD, respiratory disease, and mortality over the initial 60 days post-infection with little variation across BMI or CRF categories. The elevated risks persisted at declining levels >180 days. For non-hospitalized COVID-19 cases (n = 181,822), there was a 4- to 7-fold increased acute mortality risk, and high CRF was associated with lower risk of post-infectious respiratory disease. Conclusions: The high hazards of adverse outcomes during the first two months after COVID-19 hospitalization, and across BMI and CRF categories, declined rapidly but were still elevated after six months. Adolescent CRF was associated with respiratory disease after COVID-19 without hospitalization, which gives further support to the health benefits of physical activity.

Associations between BMI in youth and site-specific cancer in men-A cohort study with register linkage.

OBJECTIVE: This study examined BMI in young men and incident site-specific cancer to estimate population attributable fractions due to BMI based on projected obesity prevalence. METHODS: A population-based cohort study with measured height and weight at age 18. Cox regression models assessed linear associations for BMI and included age, year, and site of conscription as well as parental level of education as covariates. RESULTS: Primary analyses were performed in 1,489,115 men, of whom 78,217 subsequently developed cancer during a mean follow-up of 31 years. BMI was linearly associated with risk of developing all 18 site-specific cancers assessed (malignant melanoma; leukemia; myeloma; Hodgkin lymphoma; non-Hodgkin lymphoma; and cancer in the lungs, head and neck, central nervous system, thyroid, esophagus, stomach, pancreas, liver and gallbladder, colon, rectum, kidney, and bladder), in some instances evident at BMI levels usually defined as normal (20-25 kg/m2 ). Higher BMI was associated with lower risk of prostate cancer. The highest hazard ratios and population attributable fractions were seen for some gastrointestinal cancers. CONCLUSIONS: This study reports linear associations between BMI at age 18 and subsequent site-specific cancers, calling for rapid action to stem the obesity epidemic and to prepare the health care system for steep increases in cancer cases.

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.

Dietary Diversity and Its Association with Diet Quality and Health Status of European Children, Adolescents, and Adults: Results from the I.Family Study.

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

Digital media exposure and cognitive functioning in European children and adolescents of the I.Family study.

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

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.

Cardiorespiratory fitness and BMI measured in youth and 5-year mortality after site-specific cancer diagnoses in men-A population-based cohort study with register linkage.

BACKGROUND: Our aim was to assess associations between cardiorespiratory fitness (CRF) and body mass index (BMI) in youth and 5-year mortality after site-specific cancer diagnoses in men. METHODS: Men with cancer from a population who underwent military conscription at ages 16-25 during 1968-2005 in Sweden were included. CRF was assessed as maximal aerobic workload on a cycle ergometer test and was classified as low, moderate, or high. BMI (kg/m2 ) was classified as underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), or obesity (>30). Conscription data were linked with register data on cancer diagnosis and mortality. Analyses included CRF, BMI, date of diagnosis, and age, year, and center for conscription. RESULTS: A total of 84,621 cancer cases were included. Mean age at diagnosis was 52 years. Follow-up data were available during a mean of 6.5 years. There were linear protective associations between CRF and mortality after any cancer diagnosis (hazard ratio [HR] for high vs. low CRF 0.70), malignant skin cancer (HR 0.80), non-Hodgkin lymphoma (HR 0.78), and cancer in the lungs (HR 0.80), head and neck (HR 0.68), pancreas (HR 0.83), stomach (HR 0.78), liver (HR 0.84), rectum (HR 0.79), and bladder (HR 0.71). Overweight and/or obesity were associated with increased mortality after any cancer (HR for obesity vs. normal weight 1.89), malignant skin cancer (HR 2.03), Hodgkin lymphoma (HR 2.86) and cancer in the head and neck (HR 1.38), thyroid (HR 3.04), rectum (HR 1.53), kidney (HR 1.90), bladder (HR 2.10), and prostate (HR 2.44). CONCLUSION: We report dose-dependent associations between CRF and BMI in youth and mortality after site-specific cancer diagnoses in men. The associations with mortality could be due to both cancer inhibition and an improved tolerance to withstand cancer treatment. These results strengthen the incentive for public health efforts aimed at establishing a high CRF and normal weight in youth.

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.

Maternal vitamin D status and risk of childhood overweight at 5 years of age in two Nordic cohort studies.

Introduction: Maternal vitamin D status during pregnancy has been suggested to have a role in childhood adiposity development, but results are conflicting. Our aims were to investigate [1] the relationships between maternal 25-hydroxyvitamin D (25OHD) during pregnancy and the child's body mass index (BMI) and risk of overweight at 5 years of age, and [2] maternal pre-pregnancy BMI as effect modifier for these associations. Methods: Data sources included a subsample from the Norwegian Mother, Father and Child Cohort Study (MoBa sub-cohort; N = 2,744) and the Swedish GraviD cohort study (N = 891). Maternal 25OHD was analyzed in gestational week 18 in the MoBa sub-cohort and week 10 in the GraviD cohort. In the MoBa sub-cohort, parents reported their child's documented measures of weight and length or height from the health card at routine check-up. In the GraviD cohort, this information was collected directly from medical records. Childhood overweight (including obesity) was identified using the International Obesity Task Force cut-offs. Linear and logistic regression models were used to investigate the association between maternal 25OHD and child's BMI and risk of overweight at 5 years of age in each cohort separately, and in a pooled dataset. Results: In the pooled analysis, maternal 25OHD <30 nmol/L was associated with lower BMI in children at 5 years of age, but not with risk of overweight. Interaction analysis showed that the association was predominant among children of mothers with pre-pregnancy BMI ≥25 kg/m2. Conclusion: Low maternal vitamin D status, particularly in mothers with overweight or obesity, predicted lower BMI in their five-year-old children. However, there was no evidence of an effect on overweight in these children.

Does mandibular bone structure predict subsequent height loss? A longitudinal cohort study of women in Gothenburg, Sweden.

BACKGROUND: Several risk factors for loss of height with increasing age have been identified. OBJECTIVE: To investigate if mandibular bone structure predicts future height loss in middle-aged and elderly Swedish women. DESIGN: Prospective cohort study with longitudinally measured heights, radiographical assessments of the cortical bone using Klemetti's Index (normal, moderate or severely eroded cortex) and classification of the trabecular bone using an index proposed by Lindh et al (sparse, mixed or dense trabeculation). No intervention was performed. SETTING: Gothenburg, Sweden. PARTICIPANTS: A population-based sample of 937 Swedish women born in 1914, 1922 and 1930 was recruited. At the baseline examination, the ages were 38, 46 and 54 years. All had undergone a dental examination with panoramic radiographs of the mandible, and a general examination including height measurements on at least two occasions. MAIN OUTCOME MEASURE: Height loss was calculated over three periods 12-13 years (1968-1980, 1980-1992, 1992-2005). MAIN RESULTS: Mean annual height loss measures were 0.075 cm/year, 0.08 cm/year and 0.18 cm/year over the three observation intervals, corresponding to absolute decreases of 0.9 cm, 1.0 cm and 2.4 cm. Cortical erosion in 1968, 1980 and 1992 significantly predicted height loss 12 years later. Sparse trabeculation in 1968, 1980 and 1992 also predicted significant shrinkage over 12 or 13 years. Multivariable regression analyses adjusting for baseline covariates such as height, birth year, physical activity, smoking, body mass index and education yielded consistent findings except for cortical erosion 1968-1980. CONCLUSION: Mandibular bone structure characteristics such as severe cortical erosion and sparse trabeculation may serve as early risk factors for height loss. Since most individuals visit their dentist at least every 2 years and radiographs are taken, a collaboration between dentists and physicians may open opportunities for predicting future risk of height loss.

Vitamin D intake and determinants of vitamin D status during pregnancy in The Norwegian Mother, Father and Child Cohort Study.

Background: Norwegian data on vitamin D status among pregnant women indicate a moderate to high prevalence of insufficient vitamin D status (25-hydroxyvitamin D (25OHD) concentrations ≤50 nmol/L). There is a lack of population-based research on vitamin D intake and determinants of 25OHD in pregnant women from northern latitudes. The aims of this study were (1) to evaluate total vitamin D intake from both diet and supplements, (2) to investigate determinants of vitamin D status, and (3) to investigate the predicted response in vitamin D status by total vitamin D intake, in pregnant Norwegian women. Methods: In total, 2,960 pregnant women from The Norwegian Environmental Biobank, a sub-study within The Norwegian Mother, Father and Child Cohort Study (MoBa), were included. Total vitamin D intake was estimated from a food frequency questionnaire in gestational week 22. Concentrations of plasma 25OHD was analyzed by automated chemiluminescent microparticle immunoassay method in gestational week 18. Candidate determinant variables of 25OHD were chosen using stepwise backward selection and investigated using multivariable linear regression. Predicted 25OHD by total vitamin D intake, overall and stratified by season and pre-pregnancy BMI, was explored using restricted cubic splines in an adjusted linear regression. Results: Overall, about 61% of the women had a total vitamin D intake below the recommended intake. The main contributors to total vitamin D intake were vitamin D supplements, fish, and fortified margarine. Higher 25OHD concentrations were associated with (in descending order of the beta estimates) summer season, use of solarium, higher vitamin D intake from supplements, origin from high income country, lower pre-pregnancy BMI, higher age, higher vitamin D intake from foods, no smoking during pregnancy, higher education and energy intake. During October-May, a vitamin D intake according to the recommended intake was predicted to reach sufficient 25OHD concentrations >50 nmoL/L. Conclusion: The findings from this study highlight the importance of the vitamin D intake, as one of few modifiable determinants, to reach sufficient 25OHD concentrations during months when dermal synthesis of vitamin D is absent.

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.