Vitamin D concentrations from neonatal dried blood spots and the risk of early-onset type 2 diabetes in the Danish D-tect case-cohort study.

AIMS/HYPOTHESIS: The aim of this study was to examine the influence of neonatal vitamin D concentration on the development of early-onset type 2 diabetes in a large population sample. METHODS: We conducted a case-cohort study utilising data from the Danish biobank and registers. Neonatal vitamin D was assessed measuring 25-hydroxyvitamin D3 [25(OH)D3] concentrations on the dried blood spot samples from the Biological Specimen Bank for Neonatal Screening. Cases of type 2 diabetes (n = 731) were retrieved from the Danish National Patient Register for all individuals born in Denmark between 1 May 1981 and 31 December 1992. The sub-cohort (n = 1765) was randomly selected from all children born in the same period. We used a weighted Cox proportional hazard model assessing the hazard of first type 2 diabetes diagnoses by quintiles of 25(OH)D3 and restricted cubic spline. RESULTS: The median 25(OH)D3 concentration (IQR) among cases was 21.3 nmol/l (13.3-34.1) and 23.9 nmol/l (13.7-35.7) in the sub-cohort. There was no indication of a potential lower risk of early-onset type 2 diabetes among individuals in the higher quintile of vitamin D concentration compared with the lowest (HRcrude 0.97 [95% CI 0.71, 1.33] p = 0.85; HRadjusted 1.29 [95% CI 0.92, 1.83] p = 0.14). CONCLUSIONS/INTERPRETATION: The results of this study do not support the hypothesis that higher neonatal vitamin D concentrations are associated with a lower risk of early-onset type 2 diabetes in adulthood.

Exposure to vitamin D from fortified margarine during fetal life and later risk of pre-eclampsia: the D-tect Study.

OBJECTIVE: To examine if fetal exposure to a small dosage of extra vitamin D from food fortification was associated with a decrease in the risk of pre-eclampsia later in life. DESIGN: Cancellation of the mandatory vitamin D fortification of margarine in 1985 created a societal experiment, with entire adjacent birth cohorts exposed or unexposed to extra vitamin D during fetal development. The Danish national medical health registries allowed the identification of pre-eclampsia cases later in life among all exposed and unexposed female individuals. SETTING: Denmark. SUBJECTS: Women born between June 1983 and August 1988, who gave birth to their first child at age 14·5-27·5 years (n 32 621). RESULTS: OR (95 % CI) for pre-eclampsia among women exposed v. unexposed to extra vitamin D from fortification during fetal development was 0·86 (0·76, 0·97). Exposure to extra vitamin D was associated with further reduced odds of pre-eclampsia (0·49 (0·34, 0·72)) among current smokers, but not among former smokers and non-smokers. CONCLUSIONS: Additional vitamin D in fetal life from food fortification seems to reduce the risk of pre-eclampsia later in life. The risk reduction may be particularly strong among women who smoke during pregnancy.

Effects of the Healthy Start randomized intervention on dietary intake among obesity-prone normal-weight children.

OBJECTIVE: The study aimed to evaluate the impact of a 15-month intervention on dietary intake conducted among obesity-prone normal-weight pre-school children. DESIGN: Information on dietary intake was obtained using a 4 d diet record. A diet quality index was adapted to assess how well children's diet complied with the Danish national guidelines. Linear regression per protocol and intention-to-treat analyses of differences in intakes of energy, macronutrients, fruit, vegetables, fish, sugar-sweetened beverages and diet quality index between the two groups were conducted. SETTING: The Healthy Start study was conducted during 2009-2011, focusing on changing diet, physical activity, sleep and stress management to prevent excessive weight gain among Danish children. SUBJECTS: From a population of 635 Danish pre-school children, who had a high birth weight (≥4000 g), high maternal pre-pregnancy BMI (≥28·0 kg/m2) or low maternal educational level (<10 years of schooling), 285 children completed the intervention and had complete information on dietary intake. RESULTS: Children in the intervention group had a lower energy intake after the 15-month intervention (group means: 5·29 v. 5·59 MJ, P=0·02) compared with the control group. We observed lower intakes of carbohydrates and added sugar in the intervention group compared with the control group after the intervention (P=0·002, P=0·01). CONCLUSIONS: The intervention resulted in a lower energy intake, particularly from carbohydrates and added sugar after 15 months of intervention, suggesting that dietary intake can be changed in a healthier direction in children predisposed to obesity.

The influence of early exposure to vitamin D for development of diseases later in life.

BACKGROUND: Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status on offspring health later in life has not been widely studied. The present study includes an in-depth examination of the influence of exposure to vitamin D early in life for development of fractures of the wrist, arm and clavicle; obesity, and type 1 diabetes (T1D) during child- and adulthood. METHODS/DESIGN: The study is based on the fact that in 1961 fortifying margarine with vitamin D became mandatory in Denmark and in 1972 low fat milk fortification was allowed. Apart from determining the influences of exposure prior to conception and during prenatal life, we will examine the importance of vitamin D exposure during specific seasons and trimesters, by comparing disease incidence among individuals born before and after fortification. The Danish National databases assure that there are a sufficient number of individuals to verify any vitamin D effects during different gestation phases. Additionally, a validated method will be used to determine neonatal vitamin D status using stored dried blood spots (DBS) from individuals who developed the aforementioned disease entities as adults and their time and gender-matched controls. DISCUSSION: The results of the study will contribute to our current understanding of the significance of supplementation with vitamin D. More specifically, they will enable new research in related fields, including interventional research designed to assess supplementation needs for different subgroups of pregnant women. Also, other health outcomes can subsequently be studied to generate multiple health research opportunities involving vitamin D. Finally, the results of the study will justify the debate of Danish health authorities whether to resume vitamin D supplementation policies.

The Healthy Start project: a randomized, controlled intervention to prevent overweight among normal weight, preschool children at high risk of future overweight.

BACKGROUND: Research shows that obesity prevention has to start early. Targeting interventions towards subgroups of individuals who are predisposed, but yet normal weight, may prove more effective in preventing overweight than interventions towards unselected normal weight subsets. Finally, interventions focused on other factors than diet and activity are lacking. The objectives were to perform a randomized, controlled intervention aiming at preventing overweight in children aged 2-6 years, who are yet normal weight, but have high predisposition for future overweight, and to intervene not only by improving diet and physical activity, but also reduce stress and improve sleep quality and quantity. METHODS/DESIGN: Based on information from the Danish National Birth Registry and administrative birth forms, children were selected based on having either a high birth weight, a mother who was overweight prior to pregnancy, or a familial low socioeconomic status. Selected children (n = 5,902) were randomized into three groups; an intervention group, a shadow control group followed in registers exclusively, and a control group examined at the beginning and at the end of the intervention. Approximately 21% agreed to participate. Children who presented as overweight prior to the intervention were excluded from this study (n = 92). In the intervention group, 271 children were included, and in the control group 272 were included. Information obtained from the shadow control group is on-going, but it is estimated that 394 children will be included. The intervention took place over on average 1½ year between 2009 and 2011, and consisted of optional individual guidance in optimizing diet and physical activity habits, reducing chronic stress and stressful events and improving sleep quality and quantity. The intervention also included participation in cooking classes and play arrangements. Information on dietary intake, meal habits, physical activity, sleep habits, and overall stress level was obtained by 4-7 day questionnaire diaries and objective measurements. DISCUSSION: If the Healthy Start project is effective in preventing excessive weight gain, it will provide valuable information on new determinants of obesity which should be considered in future interventions, and on new strategies to prevent development of overweight and obesity at an early age.

Effects of the healthy start randomized intervention on psychological stress and sleep habits among obesity-susceptible healthy weight children and their parents.

Poor sleep and psychological stress are obesity determinants that are rarely included in obesity prevention programs. The aim was to report the effects of the Healthy Start randomized intervention on the secondary outcomes psychological stress and sleep duration and onset latency. Data was obtained from the Healthy Start randomized intervention conducted in 2009-2012 among Danish healthy weight children aged 2-6 years, who had either a high birth weight (>4,000 g), high maternal pre-pregnancy body mass index (>28 kg/m2), or low maternal educational level (≤10 years of schooling) and their parents. The intervention was designed to deliver improvements in diet and physical activity habits, optimization of sleep habits, and reduction of psychological family stress. The average intervention period was 15 months. Children with information on a 7-day sleep record, sleep onset latency, Strengths and Difficulties Questionnaire (SDQ), and a modified version of Parenting Stress Index (PSI) were included. The effects of the intervention on sleep habits, PSI scores, SDQ Total Difficulties (SDQ-TD) and Pro-social Behavior scores, and 95% Confidence Intervals (95% CI) were analyzed using linear regression intention-to-treat (n = 543 (intervention group n = 271, control group n = 272)) analyses. No statistically significant effects on sleep duration, sleep onset latency, PSI score, or SDQ Pro-social Behavior score were observed. Values both before and after the intervention were within the normal range both for children in the intervention and children in the control group. Mean change in SDQ-TD was 0.09 points (95% CI -0.57;0.59) in the intervention group, and -0.69 points (95% CI -1.16; -0.23) in the control group (p = 0.06). In conclusion, there were no intervention effects in relation to sleep duration, sleep onset latency, PSI score, or SDQ Pro-social behavior. There was an indication that children in the intervention group had slightly more behavioral problems than the control group after the intervention, but values were within normal range both before and after the intervention, and the difference is not considered to be clinically meaningful.

Vitamin D Concentrations at Birth and the Risk of Rheumatoid Arthritis in Early Adulthood: A Danish Population-Based Case-Cohort Study.

Background: Low vitamin D in pregnancy may impair the development of the fetal immune system and influence the risk of later development of rheumatoid arthritis (RA) in the offspring. The aim was to examine whether lower 25-hydroxyvitamin D3 (25(OH)D) concentrations at birth were associated with the risk of developing RA in early adulthood. Methods: This case-cohort study obtained data from Danish registers and biobanks. Cases included all individuals born during 1981−1996 and recorded in the Danish National Patient Register with a diagnosis of RA with age >18 years at first admission. The random comparison consisted of a subset of Danish children. Vitamin D concentrations were measured in newborn dried blood. In total, 805 RA cases and 2416 individuals from the subcohort were included in the final analysis. Weighted Cox regression was used to calculate hazard ratio (HR). Results: The median (interquartile rage (IQR)) 25(OH)D concentrations among cases were 24.9 nmol/L (IQR:15.4;36.9) and 23.9 nmol/L (IQR:13.6;36.4) among the subcohort. There was no indication of a lower risk of RA among individuals in the highest vitamin D quintile compared with the lowest (HRadj.:1.21 (0.90;1.63)). Conclusion: The risk of RA in early adulthood was not associated with vitamin D concentrations at birth.

Associations between Parental Stress and Subsequent Changes in Dietary Intake and Quality among Preschool Children Susceptible to Obesity.

BACKGROUND: Cross-sectional studies indicate that parental stress may be a barrier for healthy dietary behaviours among children. However, there is a lack of evidence from longitudinal studies on the association between parental stress and changes in dietary intake among toddlers. The aim of this study was to examine the association between parental stress and changes in dietary intake and quality among preschool children susceptible to obesity. METHODS: In the Healthy Start study, parents to 250 preschool children had completed a modified version of the Parental Stress Index and assessed the dietary intake of their children at baseline and after 15 months of follow up. The association between parental stress and changes in dietary intake and quality was examined using multiple linear regression analyses with adjustment for potential confounders. We tested for potential effect modification by group allocation and sex. RESULTS: There were no significant associations between parental stress and subsequent changes in child total energy intake, intake of macronutrients or intake of fruit, vegetables, sugar sweetened beverages, fish or starch, or dietary quality. CONCLUSION: This study provides no evidence to support an association between parental stress and subsequent change in dietary intake and quality of their children. TRIAL REGISTRATION: ClinicalTrials.gov, Trial number: NCT01583335, Registered: 31 March 2012, retrospectively registered.

Associations between Child Mental Well-Being or Conflicts during Mealtime and Picky Eating Behaviour.

Pickiness is an eating behavior that many families with young children face. Having joint family meals may impact the child's pickiness, for instance by influencing their willingness to try novel foods. Moreover, picky children have been shown to display greater emotionality. The aim of this study was to investigate if children's mental well-being and parent-reported conflicts during mealtime were associated with pickiness among obesity-prone children. Data was obtained from the baseline examination of the Healthy Start intervention study, the Danish Medical Birth registry and the Danish Health Visitor's Child Health Database, and included 635 children aged 2-6 years that were all at high risk for becoming overweight later in life. Children's mental well-being was measured by the strengths and difficulties questionnaire. Crude and adjusted ordinal logistic regressions were used to investigate the cross-sectional associations. Children had a higher odds associated with changing from a category of less pickiness to a category of more pickiness for each one point higher SDQ score (ORadj. = 1.35, 95% CI = 1.14; 1.61) and lower odds (ORadj. = 0.57, 95% CI = 0.38; 0.86) associated with changing pickiness category towards more pickiness for each one point higher SDQ prosocial score. Moreover, children with conflicts during mealtime had higher odds of being in a worse pickiness category compared to children without conflicts (ORadj. = 3.37, 95% CI = 2.27; 5.01). This study showed that among obesity-prone children, behavioral problems, as well as conflicts during mealtime, were associated with more picky behaviors. Further longitudinal studies are needed to confirm the findings, as are studies including general child population subsets.

How to screen for social withdrawal in primary care: An evaluation of the alarm distress baby scale using item response theory.

Background: Early identification of infants at-risk is imperative for proper referral to intervention programs. The Alarm Distress Baby Scale (ADBB) is an eight-item observer-rated screening tool detecting social withdrawal in infants. Previously, a shortened five-item version of the scale (m-ADBB) has been proposed. To date, few studies have examined the validity of the two scales, and no studies have examined the validity of the ADBB after implementation as a universal screening tool in primary care. Objective: The aim of this study is to use Item Response Theory (IRT) to examine the construct validity of the ADBB when used by public health visitors in primary care. Methods: Participants were 24,752 infants (aged: 2-12.9 months) screened by public health visitors using the ADBB. Screenings were categorized into three waves according to the infant's age at the screening time (2-3.9 months, 4-7.9 months, and 8-12.9 months). Analyses were conducted separately on each wave. We checked IRT assumptions: (a) Unidimensionality, (b) Monotonicity, (c) Local independence, and (d) No DIF in relation to infant sex and gestational age. The 2PLM was used to assess model fit and estimate model parameters. Results: Items fulfilled assumptions regarding unidimensionality, monotonicity, and no clinical and significant DIF. Local independence was not present for all items (i.e. 2, 7, and 8). The items showed moderate to good discriminatory abilities (alpha values ≥ 1.11) and discriminated best above average levels of social withdrawal (theta values ≥ 1.33). Items 7 and 8 showed nearly identical ICC suggesting that the two items discriminate equally well at the same level of social withdrawal. In addition, items 4 and 6 discriminated best at very high levels of social withdrawal, which might be of limited interest for screening purposes. Finally, the items showed similar patterns in terms of discrimination and location parameters across the three waves. Conclusions: The ADBB shows several psychometric strengths when used by public health visitors in primary care, and the items show good discriminatory abilities at the levels of social withdrawal of interest for screening purposes. Yet, the results also suggest that for first-line screening, the validity of the scale might be improved with the removal of items 4, 6, and 8 as suggested in the m-ADBB. However, before recommending implementation of the m-ADBB, studies comparing the criterion-related validity of the two scales are needed.

Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project.

By utilizing historical changes in Danish legislation related to mandatory vitamin D fortification of margarine, which was implemented in the mid 1930s and abruptly abandoned in June 1985, the studies in the D-tect project investigated the effects of vitamin D on health outcomes in individuals, who during gestation were exposed or unexposed to extra vitamin D from fortified margarine. This paper reviews and narratively summarizes the analytic approaches alongside the results of the societal fortification experiment studies from the D-tect project and addresses the challenges in designing societal experiment studies and evaluating their results. The latter are discussed as lessons learned that may be useful for designers of similar studies, expected to be extensively utilized while researching the health consequences of the COVID-19 pandemic by comparing individuals born before and after the epidemic. In the D-tect project, 16 articles based on the societal fortification experiment were published analyzing 10 different outcomes and using different statistical approaches. Lessons learned included the detail of the analysis of the historical information on the exposure, availability and validity of the outcome data, variety of analytical approaches, and specifics concerning vitamin D effect evaluation, such as consideration of the influence of sunshine or season. In conclusion, the D-tect project clearly demonstrated the cost-effectiveness and research potential of natural- or societal-experiment-based studies.

Neonatal Vitamin D Status and Risk of Asthma in Childhood: Results from the D-Tect Study.

BACKGROUND: low vitamin D status in pregnancy can influence the offspring's lung function and contribute to childhood asthma development. The objective of this study was to examine the influence of neonatal vitamin D status on the development of asthma among children age 3-9 years in a large population sample. METHOD: in a case-cohort study utilizing a Danish biobank and register data we examined the association between neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentrations and incidence of asthma among children aged 3-9 years. Cases of asthma (n = 911) were randomly selected among all cases of asthma in the Danish National Patient Register from children born between 1992 and 2002. The sub-cohort (n = 1423) was randomly selected among all children born in the same period. We used a weighted Cox proportional hazard model assessing the hazard of first asthma diagnoses by quintiles of 25(OH)D3. RESULTS: the median 25(OH)D3 (interquartile range) for asthma cases was 23 nmol/L (14-35) and the sub-cohort 25 nmol/L (14-40). The hazard ratio for developing asthma between ages 3 and 9 years was lower for children in the fifth quintile of neonatal 25(OH)D3 compared to children in the first quintile, both in the unadjusted (0.61 95% CI: 0.46-0.80) and adjusted (0.55 95% CI: 0.39-0.77) analyses. CONCLUSION: the results from our study suggest that higher neonatal vitamin D concentration may reduce the risk of developing childhood asthma at ages 3-9 years, indicating that neonatal vitamin D status as a proxy of vitamin D status during the prenatal period is important for normal immune- and lung development.

Choice of foods and ingredients for moderately malnourished children 6 months to 5 years of age.

There is consensus on how to treat severe malnutrition, but there is no agreement on the most cost-effective way to treat infants and young children with moderate malnutrition who consume cereal-dominated diets. The aim of this review is to give an overview of the nutritional qualities of relevant foods and ingredients in relation to the nutritional needs of children with moderate malnutrition and to identify research needs. The following general aspects are covered: energy density, macronutrient content and quality, minerals and vitamins, bioactive substances, antinutritional factors, and food processing. The nutritional values of the main food groups--cereals, legumes, pulses, roots, vegetables, fruits, and animal foods--are discussed. The special beneficial qualities of animal-source foods, which contain high levels of minerals important for growth, high-quality protein, and no antinutrients or fibers, are emphasized. In cereal-dominated diets, the plant foods should be processed to reduce the contents of antinutrients and fibers. Provision of a high fat content to increase energy density is emphasized; however, the content of micronutrients should also be increased to maintain nutrient density. The source of fat should be selected to supply optimal amounts of polyunsaturated fatty acids (PUFAs), especially n-3 fatty acids. Among multiple research needs, the following are highlighted: to identify the minimum quantity of animal foods needed to support acceptable child growth and development, to examine the nutritional gains of reducing contents of antinutrients and fibers in cereal- and legume-based diets, and to examine the role of fat quality, especially PUFA content and ratios, in children with moderate malnutrition.

Tramadol prescribed use in general and chronic noncancer pain: a nationwide register-based cohort study of all patients above 16 years.

Background and aims In the Western world, it has become clear that we are facing a crisis of overuse, abuse and improperly prescribed use of opioids. As part of the ongoing discussion on opioid use, the use and prescription of tramadol have been addressed in recent years. A significant portion of this discussion should adequately address the risk factors for the use of weak opioid products such as tramadol. The risk factors which characterise the long-term tramadol use are still incompletely understood. Thus, we aimed to describe the characteristics of Danish patients using tramadol in more detail, under different scenarios and determinants of subsequent usage patterns. Methods We conducted a nationwide cohort study to identify individuals purchasing tramadol from 01/01/2004 to 31/12/2015 who are age 16 + years old by using data from The Danish National Databases; these databases consist of unique information for all citizens in Denmark. Logistic regression analyses were used to assess the potential risk factors for repeated tramadol use. Results The final cancer-free cohort consisted of N = 941,839 tramadol users: 54.4% women, with a mean age of 53.2 years. The number of chronic noncancer pain (CNCP) was 430,641 individuals, and 56% of the total third who repeated the use of tramadol with two + purchased prescriptions were CNCP patients. The increased risk of repeated use for CNCP was, among others, associated with: male sex (HR 1.21), age 69-110 (HR 1.72), back/spine pain men (HR 1.47), women (HR 1.46), spondylopathies (HR 1.24), male osteoporosis (HR 1.22), multimorbid ulcer/skin (HR 1.28), region of municipality Northern Jutland (HR 1.74), Central Jutland (HR 1.75), number of co-medication 4-9 (HR 1.33), dementia (HR 1.27). Factors associated with decreased risk: co-medication ischemic heart disease (HR 0.85), diagnosis headache (HR 0.70), household income highest tertile (HR 0.81), unknown (HR 0.70), single women (HR 0.96). Conclusions This study proved a widespread prescribed use of tramadol in Denmark, and, as know from the literature, weak opioid use may lead to long-term use of high potent opioids, this usage is inappropriate, in general, but especially for the treatment of CNCP. Implications When striving to reduce the overuse of opioids, focus on the extensive use of tramadol may be essential. The current study indicates an excessive and not appropriately prescribed use of tramadol among Danish CNCP patients. In addition to being inappropriate, such use may also have an impact on the growing problem of an illicit Internet market for this drug. Thus, the situation must be taken seriously. The current study confirms the recent clinical guideline and the National Recommendations in Denmark, which emphasises the risks of problematic use of tramadol. The research may also be relevant in other comparable countries. Caution must especially be taken with CNCP patients with comorbidities like diabetes, lung disease, dementia, and osteoporosis.

Association between hair cortisol concentration and dietary intake among normal weight preschool children predisposed to overweight and obesity.

BACKGROUND: The association between chronically elevated cortisol, as measured by hair cortisol concentration (HCC), and dietary intake among children has generally not been explored. Moreover, it is unknown whether there is an association between parental HCC and dietary intake among their children. OBJECTIVE: To examine associations between HCC and dietary intake among children, and to explore the association between parental HCC and dietary intake among their children. METHODS: We conducted a cross-sectional study based on 296 children predisposed to overweight and obesity who participated in the Healthy Start study. Multiple Linear regression analyses were conducted to assess the association between HCC and total energy intake, macronutrients, fruit and vegetables, added sugar, sugar-sweetened beverages (SSB), and a diet quality index (DQI). RESULTS: Among the children, we found that higher HCC was associated with a lower consumption of dietary fat (ß: -0.7 g/day [95% CI: -1.3, -0.0] per 100 pg/mg HCC). We found no statistically significant association between HCC and intake of total energy, protein, carbohydrate, fruit and vegetables, added sugar, SSB or DQI. We found no association between parental HCC and intake of total energy, added sugar, selected food groups or DQI among their children. However, stratified analyses showed that paternal HCC was associated with a borderline significant lower total energy intake and significantly lower protein intake, but only among daughters (adjusted ß: -42 kcal/day [95% CI: -85, 0] and -2.6 g/day [95% CI: -4.4, -0.8] per 100 pg/mg HCC, respectively). CONCLUSION: Among children, chronic stress as measured by HCC may be associated with a lower fat consumption, and paternal HCC may be associated with a lower intake of energy and protein among their daughters. However, the associations observed were weak, and any clinical relevance of these findings remains questionable.

Impact of red meat, processed meat and fibre intake on risk of late-onset chronic inflammatory diseases: prospective cohort study on lifestyle factors using the Danish 'Diet, Cancer and Health' cohort (PROCID-DCH): protocol.

INTRODUCTION: Chronic inflammatory diseases (CIDs) (Crohn's disease, ulcerative colitis, psoriasis, psoriatic arthritis, rheumatoid arthritis and multiple sclerosis) are diseases of the immune system that have some shared genetic and environmental predisposing factors, but still few studies have investigated the effects of lifestyle on disease risk of several CIDs. The primary aim of this prospective cohort study is to investigate the impact of fibre, red meat and processed meat on risk of late-onset CID, with the perspective that results of this study can contribute in supporting future diet recommendations for effective personalised prevention. METHODS AND ANALYSIS: The study will use data from 57 053 persons from the prospective Danish cohort study 'Diet, Cancer and Health' together with National Health Registry data. The follow-up period is from December 1993 to December 2018. Questionnaire data on diet and lifestyle were collected at entry to the Diet, Cancer and Health study. The outcome CID is defined as having a diagnosis of one of the CIDs registered in the National Patient Registry or, for multiple sclerosis, in the Danish Multiple Sclerosis Registry during follow-up and being treated with a drug used for the specific disease. The major outcome of the analyses will be to detect variability in risk of late onset of any CID and, if power allows, disease risk of late onset of each CID diagnosis between persons with different fibre and red meat, and processed meat intake. The outcome will be adjusted for age, sex, body mass index, physical activity, energy, alcohol, fermented dairy products, education, smoking status, hormone replacement therapy and comorbidity. ETHICS AND DISSEMINATION: The study is approved by the Danish Data Protection Agency (2012-58-0018). The core study is an open register-based cohort study. The study does not need approval from the Ethics committee or Institutional Review Board by Danish law. Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT03456206; Post-results.

Extra vitamin D from fortification and the risk of preeclampsia: The D-tect Study.

The objective of the study was to examine if exposure to extra vitamin D from food fortification was associated with a decrease in the risk of preeclampsia. The study was based on a natural experiment exploring the effect of the abolition of the Danish mandatory vitamin D fortification of margarine in 1985. The effect of the extra vitamin D (1.25µg vitamin D/100 g margarine) was examined by comparing preeclampsia risk in women who have been exposed or unexposed to extra vitamin D from the fortified margarine during pregnancy, and who gave birth in the period from June 1983 to August 1988. The Danish National Patient Registry allowed the identification of pregnancies complicated by preeclampsia. The study included 73,237 women who gave birth during 1983-1988. We found no association between exposure to vitamin D fortification during pregnancy and the risk of any of the pregnancy related hypertensive disorders, including preeclampsia: Odds ratios (OR, 95%) for all hypertensive pregnancy related disorders among exposed vs. unexposed women was (OR 1.04, 95%CI: 0.98,1.10). In conclusion, the extra vitamin D from the mandatory vitamin D fortification did not influence the risk of preeclampsia.

Joining Parents' Bed at Night and Overweight among 2- to 6-Year-Old Children - Results from the 'Healthy Start' Randomized Intervention.

OBJECTIVE: Parental and child co-sleeping has been suggested as a risk factor for short sleep duration and poor sleep quality that may lead to overweight. We examined if joining parent's bed during night was associated with child overweight. METHODS: Cross-sectional data from the 'Healthy Start' study including 635 2- to 6-year-old Danish children, who were all considered obesity prone. Of these, 496 children had complete information on BMI and whether the child joined parents' bed during night and if so, how frequently. International cut-offs for overweight according to age and gender were applied, and logistic regression was used to estimate odds ratio (OR) and 95% Confidence Intervals (CI). Analyses were adjusted for the child's age and gender, overall family stress, parental educational level, and parental BMI. RESULTS: Children who did not join their parent's bed were more likely to be overweight compared to children who did (OR 1.75 (95% CI 0.99-3.10)). Children who rarely joined their parents' bed had OR 2.74 of being overweight (95% CI 1.01-7.44) compared to children who joined every night. CONCLUSION: Children who rarely joined parents' bed during night were almost three times more likely to be overweight than those who joined every night.

Effects of the Healthy Start randomized intervention trial on physical activity among normal weight preschool children predisposed to overweight and obesity.

BACKGROUND: There is limited evidence to support the effectiveness of primary interventions aiming to prevent excess weight gain among young children. Evaluating behavioral changes, such as physical activity (PA), may add to future development of efficient interventions. The objective was to evaluate the effect on PA outcomes of the 15 month Healthy Start intervention that focused on changing diet, PA, sleep and stress management among normal weight but obesity-prone preschool children. Children were defined as obesity-prone if they had a birth weight > 4,000 g, mothers with a pre-pregnancy body mass index of > 28 kg/m2, or mothers with ≤ 10 years of schooling. METHOD: From a baseline study population of 635 normal weight 2-6 year old preschool children from the greater Copenhagen area, parents of 307 children had given information on PA at both the baseline and follow-up examinations. PA was obtained from a 7 days recording in the Children's Physical Activity Questionnaire. Time used for sport activities were combined with outdoor playing time to achieve a proxy of total PA level of moderate to vigorous intensity. RESULTS: Linear regression analyses revealed that at follow-up the intervention group spent more time on sports and outdoor activities combined per week than the control group (ITT analyses: intervention: 400 min/week; 95% confidence interval (CI): 341, 459 versus control: 321 min/week; 95% CI: 277, 366; p = 0.02), although no significant intervention effects were seen for each of the subcategories, e.g. sports participation, outdoor activities, screen time, or commuting frequency. CONCLUSION: Our results suggest that the overall time spent on sports and outdoor activities combined was increased at follow-up among normal weight obesity-prone children, as a result of the Healthy Start intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01583335.

Relationship between pickiness and subsequent development in body mass index and diet intake in obesity prone normal weight preschool children.

BACKGROUND: Most children have periods in their life where they reject familiar as well as non-familiar food items and this is often referred to as pickiness. The consequences of pickiness may be malnutrition and, if prolonged, potentially lower body weight. However, studies investigating the consequence of pickiness on subsequent changes in diet intake and weight are limited. OBJECTIVES: To examine whether pickiness influences body mass index as well as diet intake over subsequent 15 months among obesity prone normal weight children aged 2-6 years. METHODS: Data was obtained from the "Healthy Start" intervention study which included 271 children aged 2-6 years susceptible to overweight later in life. Information on pickiness was obtained from a parental questionnaire. Dietary habits were collected by 4-day dietary records filled in by the parents and height and weight were measured by trained health professionals and both measured twice over a 15 month period. Linear regression models were performed to assess the influence of pickiness on body mass index and diet with adjustments for possible confounders. RESULTS: No differences in mean BMI Z-score were seen between picky/non-picky (P = 0.68) and little picky/non-picky (P = 0.68) children at 15 month follow-up. Picky children had a lower intake of protein (P = 0.01) than non-picky children despite no differences in total energy intake (P = 0.74), or in the other macronutrients, or the intake of fruit and vegetables, though children being a little picky had a lower intake of starch compared to non-picky children (P = 0.05). Results were essentially similar before and after adjustment for key covariates. CONCLUSION: Our study showed that BMI Z-score after 15 months follow-up was similar for picky and non-picky children. Picky children seemed to develop a lower protein intake despite similar total energy intake and diet composition.