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Objective: To evaluate whether early folic acid supplementation during pregnancy prevents diagnosis of autism spectrum disorders in offspring. Methods: Information on autism spectrum disorder diagnosis was obtained from the National Hospital Register and the Central Psychiatric Register. We estimated risk ratios for autism spectrum disorders for children whose mothers took folate or multivitamin supplements from 4 weeks prior from the last menstrual period through to 8 weeks after the last menstrual period (-4 to 8 weeks) by three 4-week periods. Results: We did not find an association between early folate or multivitamin intake for autism spectrum disorder (folic acid--adjusted risk ratio: 1.06, 95% confidence interval: 0.82-1.36; multivitamin--adjusted risk ratio: 1.00, 95% confidence interval: 0.82-1.22), autistic disorder (folic acid--adjusted risk ratio: 1.18, 95% confidence interval: 0.76-1.84; multivitamin--adjusted risk ratio: 1.22, 95% confidence interval: 0.87-1.69), Asperger's syndrome (folic acid--adjusted risk ratio: 0.85, 95% confidence interval: 0.46-1.53; multivitamin--adjusted risk ratio: 0.95, 95% confidence interval: 0.62-1.46), or pervasive developmental disorder--not otherwise specified (folic acid--adjusted risk ratio: 1.07, 95% confidence interval: 0.75-1.54; multivitamin--adjusted risk ratio: 0.87, 95% confidence interval: 0.65-1.17) compared with women reporting no supplement use in the same period. Conclusion: We did not find any evidence to corroborate previous reports of a reduced risk for autism spectrum disorders in offspring of women using folic acid supplements in early pregnancy.

Background: Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD. Methods: An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline. Discussion: Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD. Trial registration: ClinicalTrials.gov NCT04873856. Registered on May 3, 2021. [ABSTRACT FROM AUTHOR]

Purpose: To examine associations between parental occupation and childhood germ cell tumors (GCTs) in offspring while distinguishing by common histologic subtype (i.e., yolk sac tumor and teratoma). Methods: This population-based case–control study included childhood GCT cases in Denmark diagnosed 1968–2015 (< 16 years old at diagnosis) and sex and birth year-matched controls. Demographic information and parental employment histories were obtained from Danish registries. Parental occupation was assessed by industry; job-exposure matrices were used to examine specific occupational exposures (i.e., potentially carcinogenic organic solvents and social contact). Conditional multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Results: Overall, 178 childhood GCT cases (50 yolk sac tumors; 65 teratomas) and 4,355 controls were included for analysis. Maternal employment in education during pregnancy was associated with offspring GCTs (OR 2.45, 95% CI 1.23–4.90), especially yolk sac tumors (OR 5.27, 95% CI 1.94–14.28). High levels of both maternal and paternal occupational social contact were also associated with offspring yolk sac tumors across all exposure periods (ORs 2.30–4.63). No signals were observed for paternal occupational solvent exposure, while imprecise associations were estimated for maternal exposure (e.g., dichloromethane exposure during pregnancy, OR 1.51, 95% CI 0.77–2.95). Conclusion: Our findings suggest that parental occupation is associated with offspring GCTs, with most consistent evidence supporting an association between maternal employment in education or other high social contact jobs and offspring yolk sac tumors. [ABSTRACT FROM AUTHOR]

Several studies have reported associations between prenatal acetaminophen exposure and behavioral outcomes in young children. We aimed to evaluate the associations of prenatal and postnatal exposures to acetaminophen with behavioral problems in children at age 11 years, using behavioral measures reported by parents and children. We studied 40,934 mother-child pairs from the Danish National Birth Cohort enrolled during 1996–2002. Parent-reported and child-reported Strengths and Difficulties Questionnaire (SDQ) responses were collected during the 11-year follow-up. We estimated risk ratios for behavioral problems including total difficulties as well as internalizing or externalizing behaviors following prenatal (during pregnancy) or postnatal (within the first 18 months after birth) acetaminophen exposure. Parent-reported and child-reported SDQ scores were moderately correlated; higher for externalizing (r  = 0.59) than internalizing (r  = 0.49) behaviors. Prenatal acetaminophen exposure was associated with 10%–40% higher risks for total difficulties and internalizing and externalizing problems based on parent- or child-reported SDQ, with the association being stronger for greater cumulative weeks of acetaminophen use. Postnatal exposure was associated with 16%–19% higher risks for parent-reported internalizing behaviors, but the associations were weak or null for child-reported scores except for prosocial behavior. Our study corroborates published associations between prenatal exposures to acetaminophen and behavioral problems and extends the literature to early adolescence. [ABSTRACT FROM AUTHOR]

Spina bifida has been reported to co-occur with pediatric cancer, but comprehensive evaluations remained elusive. We investigated this co-occurrence in two large, population-based studies in Taiwan (N = 1900 cancer cases, 2,077,137 controls) and Denmark (N = 5508 cases, 137,700 controls). Analyses in Denmark were restricted to the period before prenatal diagnostics became available (2004) and pregnancy terminations of fetuses with birth defects became more common. Using national patient and cancer registries, we linked spina bifida and cancer diagnoses among cases and non-cases. The risk of spina bifida among all cancer cases was increased and similar in Denmark [odds ratio (OR)=8.4, 95% confidence interval (CI) 5.1-13.8] and Taiwan (OR = 8.5, 95% CI 4.0-17.8), particularly for central nervous system (CNS) tumors (Denmark: OR = 16.3, 95% CI 8.1-33.0; Taiwan: OR = 26.6, 95% CI 8.5, 83.1), including benign CNS tumors (Denmark: OR = 41.5, 95% CI 21.2, 81.4). These findings suggest the need for comprehensive investigation of shared risk factors in the link between spina bifida and pediatric cancer. [ABSTRACT FROM AUTHOR]

Objective: To examine associations with occupational livestock or other animal dust exposure and offspring cancer risk. Methods: In this population-based case–control study of Danish children aged < 17 years old, 5078 childhood cancer cases diagnosed 1968–2016 were matched to cancer-free controls by birth year and sex (n = 123,228). Occupational livestock or animal dust exposure was identified using a job-exposure matrix. We employed multivariable conditional logistic regression models to estimate associations with offspring cancer for births 1968–2016 and 1989–2016, with the latter timeframe reflecting a period of presumed higher exposure due to changes in Danish farming practices. Sensitivity analyses considered place of birth (urban areas vs. rural areas and small towns). Results: For births 1968–2016, paternal exposure from offspring birth to cancer diagnosis was associated with central nervous system tumors (adjusted odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.04–1.63) and germ cell tumors (OR = 1.82, 95% CI 1.05–3.27), while maternal pregnancy exposure was associated with astrocytoma (OR = 1.89, 95% CI 1.00–3.57). For births 1989–2016, paternal exposure from offspring birth to cancer diagnosis was negatively associated with acute lymphoid leukemia (OR = 0.58, 95% CI 0.33–1.00). For births in rural areas only, maternal exposure from offspring birth to cancer diagnosis was positively associated with acute myeloid leukemia (OR = 2.16, 95% CI 1.09–4.29). Conclusions: This study suggests that paternal occupational animal exposure is associated with offspring germ cell tumors, and maternal pregnancy exposure with astrocytomas. Our results are mixed with respect to leukemia subtypes. [ABSTRACT FROM AUTHOR]

Objective: To compare dietary intake and physical activity (PA) between days of the week in a large sample of the Danish population; furthermore, to investigate the influence of gender and age as determinants for weekly variation.Design: Analysis was based on cross-sectional data from the Danish National Survey of Diet and Physical Activity 2011-2013. Dietary intake and PA were assessed by 7 d of pre-coded food diaries and pedometer-determined step counts. Dietary intake and PA on weekdays (Monday-Thursday), Friday, and weekend days (Saturday and Sunday) were compared using linear mixed models.Setting: Survey with national representation, conducted in Denmark between 2011 and 2013.Participants: A random sample of 4-75-year-old Danes, n 3934 and n 3530 in analysis of dietary intake and PA, respectively.Results: Energy intake during Friday and weekend days was 7-20 % higher compared with weekdays, while step counts were 10 and 17 % lower on Saturday and Sunday, respectively (all P < 0·001). Energy density of liquids and solids, consumption of added sugar, alcohol, discretionary foods, beer, wine and sugar-sweetened beverages were substantially higher, and consumption of dietary fibre, vegetables, fruit and wholegrain products were lower, during Friday and weekend days compared with weekdays (all P < 0·001). The observed patterns were present across gender and age, although weekly variation was most pronounced among children and relatively modest among the elderly.Conclusions: Weekend health behaviours of Danes display less favourable eating and PA behaviour compared with weekdays, making the weekend an important target for public health interventions aiming to improve dietary intake and PA behaviour. [ABSTRACT FROM AUTHOR]

BACKGROUND: Maternal thyroid hormones are essential for fetal brain development in early gestation. Perfluoroalkyl substances (PFASs)—widespread and persistent pollutants—have been suggested to interfere with maternal thyroid hormones in the second or third trimesters, but evidence for an association in the early pregnancy period is sparse. OBJECTIVES: Our goal was to evaluate the gestational-week specific associations of maternal thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels with plasma concentrations of six PFAS chemicals in the first and second pregnancy trimester. METHODS: A cross-sectional analysis was conducted using 1,366 maternal blood samples collected between gestational weeks (GWs) 5 and 19 (median, 8 gestational weeks) in the Danish National Birth Cohort (DNBC) during 1996–2002. We estimated the percentage changes of serum TSH and fT4 levels according to concentrations (in nanograms per milliliter) of six PFAS chemicals modeled as per interquartile range (IQR) increase or by exposure quartiles. Moreover, we contrasted the estimated week-specific TSH or fT4 levels by PFAS quartile and estimated ORs for binary high or low TSH and fT4 status based on the week-specific distribution according to IQR increase of PFAS. RESULTS: TSH levels followed a U-curve trend in early pregnancy with a nadir at GW10, whereas fT4 levels were less fluctuated in the samples. There were no apparent associations between any of the PFASs and changes of average TSH or fT4 levels in total samples. In gestational-week–specific analyses, we found that the estimated TSH values were higher among the highest perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluoroheptane sulfonate (PFHpS) quartiles compared with the lower quartiles from GW5 to GW10, but the difference became null or even reversed after GW10. For binary outcomes, perfluorodecanoic acid (PFDA) was associated with high fT4 status before GW10 [OR=1.46 (95% CI: 1.04, 2.05)]. CONCLUSIONS: We observed some gestational-week-specific associations between high exposure to several PFAS and TSH level in early gestations. Further research of the biology and the potential clinical impact regarding thyroid hormones disruptions in early pregnancy is needed. [ABSTRACT FROM AUTHOR]

Background: Low serum 25-hydroxyvitamin D [25(OH)D] has been associated with unfavorable cardiometabolic risk profiles in many observational studies in children, but very few randomized controlled trials have investigated this.Objective: We explored the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in young, white, 4- to 8-y-old healthy Danish children (55°N) as part of the pan-European ODIN project.Methods: In the ODIN Junior double-blind, placebo-controlled, dose-response trial, 119 children (mean ± SD age: 6.7 ± 1.5 y; 36% male; 82% normal weight) were randomly allocated to 0, 10 or 20 µg/d of vitamin D3 for 20 wk (October-March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, serum triglycerides and cholesterol (total, LDL, HDL, and total:HDL), plasma glucose and insulin, and whole-blood glycated hemoglobin were measured at baseline and endpoint as secondary outcomes together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint adjusted for baseline value of the outcome, and additionally for age, sex, baseline serum 25(OH)D, BMIz, time since breakfast, and breakfast content.Results: Mean ± SD serum 25(OH)D was 56.7 ± 12.3 nmol/L at baseline and differed between groups at endpoint with concentrations of 31.1 ± 7.5, 61.8 ± 10.6, and 75.8 ± 11.5 nmol/L in the 0-, 10-, and 20 µg/d groups, respectively (P < 0.0001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers in analyses adjusted for baseline value of the outcome (all P ≥ 0.05), and additional covariate adjustment did not change the results notably.Conclusions: Preventing the winter decline in serum 25(OH)D with daily vitamin D3 supplementation of 10 or 20 µg had no cardiometabolic effects in healthy 4- to 8-y-old Danish children. This trial was registered at www.clinicaltrials.gov as NCT02145195. [ABSTRACT FROM AUTHOR]

BACKGROUND: Perfluoroalkyl substances (PFASs) are widespread persistent organic compounds that have been suggested to affect neurodevelopment. OBJECTIVE: We aimed to evaluate whether prenatal exposure to PFASs is associated with IQ in children. METHODS: We studied 1,592 pregnancies enrolled in the Danish National Birth Cohort (DNBC) during 1996-2002. Sixteen PFASs were measured in maternal plasma collected in early gestation. Child IQ was assessed at 5 y of age using the Wechsler Primary and Preschool Scales of Intelligence-Revised (WPPSI-R) administered by trained psychologists. Using multivariable linear regression models, we estimated the differences in child IQ scores according to PFAS concentration [per natural-log (ng/mL) unit increase or values categorized in quartiles]. RESULTS: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples, and five additional PFASs were quantified in >80% of the samples. Overall, we found no strong associations between a natural-log unit increase in each of the seven PFASs we evaluated and child IQ scores. A few positive and negative associations were found in the sex-stratified PFAS quartile analyses, but the patterns were inconsistent. CONCLUSION: Overall, we did not find consistent evidence to suggest prenatal exposure to PFASs to be associated with child IQ scores at 5 y of age in the DNBC. Some of the sex-specific observations warrant further investigation. Additional studies should examine offspring IQ at older ages and assess other functional cognitive and neuropsychiatric measures in addition to intelligence. Postnatal exposures to PFASs and mixture effects for PFASs and PFASs with other environmental pollutants should also be considered in future research. [ABSTRACT FROM AUTHOR]

Objective:Recent studies have shown promising effects of physical activity on cognitive function, but there is a need to investigate this link in real-life settings such as schools. Hence, the objective of the present pilot study was to investigate whether the school-based physical activity programme “FIFA 11 for Health” for Europe could improve cognitive performance in preadolescent Danish children.Methods:The pilot study used an 11-week cluster-randomised intervention study design. School classes were randomly assigned to either a control group (CG) (n = 93 children, age = 11.8,s = 0.2 years), which performed the obligatory daily school-based physical activity (5 × 45 minutes per week); or an intervention group (IG) (n = 838 children, age = 11.9,s = 0.4 years), which substituted 2 × 45 minutes per week of the daily school physical activity with the “FIFA 11 for Health” for Europe programme. The programme combines small-sided football games, drills and health education. Cognitive performance was evaluated at baseline and follow-up.Results:The IG improved their cognitive performance compared to the CG for psychomotor function (56,sx– = 22 ms,p < .001), attention (39,sx– = 17 ms,p = .012) and working memory (79,sx– = 35 ms,p = .020).Conclusion:This pilot study provides evidence that the school-based physical activity programme “FIFA 11 for Health” for Europe can improve cognitive performance in preadolescent Danish schoolchildren. Future studies should attempt to disentangle the effects of “FIFA 11 for Health” for Europe on cognitive performance by investigating the characteristics of the programme’s physical activity. [ABSTRACT FROM AUTHOR]

The nutritional supplement ( NS) industry is one of the fastest growing in the world, and NS use in Denmark is among the highest in Europe. However, the exact use in elite athletes and fitness customers targeted for doping control is unknown. Information from 634 doping control forms obtained in 2014 was evaluated (elite athletes: n = 361; fitness customers: n = 273). The majority of female (92.6%) and male (85.0%) elite athletes and female (100.0%) and male (94.0%) fitness customers declared using one or more NS. The use of non-ergogenic NS was more prevalent in women than in men and in younger (15-34 years) compared with older (35-49 years) subjects, but it was less prevalent in intermittent compared with endurance and power/strength sports. Additionally, fitness customers who tested positive for doping also reported using more NS than subjects testing negative, indicating an association between NS and doping abuse. The present results demonstrate a very high prevalence of NS usage in both elite athletes and fitness customers. This highlights the importance of a strong national regulation of NS to avoid contamination of NS with doping substances. [ABSTRACT FROM AUTHOR]

Background: Which diet is optimal for weight loss and maintenance remains controversial and implies that no diet fits all patients. Objective: We studied concentrations of fasting plasma glucose (FPG) and fasting insulin (FI) as prognostic markers for successful weight loss and maintenance through diets with different glycemic loads or different fiber and whole-grain content, assessed in 3 randomized trials of overweight participants. Design: After an 8-wk weight loss, participants in the DiOGenes (Diet, Obesity, and Genes) trial consumed ad libitum for 26 wk a diet with either a high or a low glycemic load. Participants in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) Supermarket intervention (SHOPUS) trial consumed ad libitum for 26 wk the New Nordic Diet, which is high in fiber and whole grains, or a control diet. Participants in the NUGENOB (Nutrient-Gene Interactions in Human Obesity) trial consumed a hypocaloric low-fat and high-carbohydrate or a high-fat and low-carbohydrate diet for 10 wk. On the basis of FPG before treatment, participants were categorized as normoglycemic (FPG <5.6 mmol/L), prediabetic (FPG 5.6-6.9 mmol/L), or diabetic (FPG ≥7.0 mmol/L). Modifications of the dietary effects of FPG and FI before treatment were examined with linear mixed models. Results: In the DiOGenes trial, prediabetic individuals regained a mean of 5.83 kg (95% CI: 3.34, 8.32 kg; P < 0.001) more on the high-than on the low-glycemic load diet, whereas normoglycemic individuals regained a mean of 1.44 kg (95% CI: 0.48, 2.41 kg; P = 0.003) more [mean group difference: 4.39 kg (95% CI: 1.76, 7.02 kg); P = 0.001]. In SHOPUS, prediabetic individuals lost a mean of 6.04 kg (95% CI: 4.05, 8.02 kg; P < 0.001) more on the New Nordic Diet than on the control diet, whereas normoglycemic individuals lost a mean of 2.20 kg (95% CI: 1.21, 3.18 kg; P < 0.001) more [mean group difference: 3.84 kg (95% CI: 1.62, 6.06 kg); P = 0.001]. In NUGENOB, diabetic individuals lost a mean of 2.04 kg (95% CI: -0.20, 4.28 kg; P = 0.07) more on the high-fat and low-carbohydrate diet than on the low-fat and high-carbohydrate diet, whereas normoglycemic individuals lost a mean of 0.43 kg (95% CI: 0.03, 0.83 kg; P = 0.03) more on the low-fat and high-carbohydrate diet [mean group difference: 2.47 kg (95% CI: 0.20, 4.75 kg); P = 0.03]. The addition of FI strengthened these associations. Conclusion: Elevated FPG before treatment indicates success with dietary weight loss and maintenance among overweight patients consuming diets with a low glycemic load or with large amounts of fiber and whole grains. [ABSTRACT FROM AUTHOR]

Background: Dietary and endogenously formed long-chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to improve cognitive development, but results are inconclusive, with suggestions of sex specificity. One study suggested that single-nucleotide polymorphisms (SNPs) rs1535 and rs174448 in the fatty acid desaturase (FADS) gene cluster have opposite effects on erythrocyte LCPUFAs at 9 mo. Objective: To explore whether SNPs in FADS and elongase (ELOVL) genes were associated with school performance in a sex-specific manner, we performed a Mendelian randomization study using data from the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study with 765 Danish schoolchildren 8-11 y old. Design: Associations between selected FADS1/2 SNPs (rs1535, rs174448, and rs174468) and ELOVL5 rs2397142, whole-blood fatty acid composition, and performance in the d2 Test of Attention and a reading test were analyzed in multiple regression models including all SNPs, SNP-sex interactions, and covariates related to testing conditions. Results: FADS, rs1535 minor allele carriage associated with lower whole-blood arachidonic acid (P ≤ 0.002), and minor alleles of rs174448 tended to associate with lower docosahexaenoic acid (DHA) (P = 0.052). We identified sex interactions in 50% of the SNP performance sets. Sex-dependent associations were observed for rs174448 and rs1535 on the d2 Test of Attention outcomes (P < 0.03) and for the associations between reading scores and rs174448 and rs2397142 (P < 0.01). All of the sex-specific analyses showed associations in opposite directions in girls and boys. The minor allele carriage of rs174448 was associated with lower d2 Test of Attention performance (P < 0.02) and reading scores (P < 0.001) in boys but with better reading scores in girls (P ≤ 0.002). The associations were consistently the opposite for rs1535 minor allele carriage (P < 0.05). Associations with rs2397142 also appeared to be opposite of those of rs174448, but only for reading and not significant after adjustment for parental educational level and whole-blood DHA. Conclusions: This study showed associations between rs1535 minor allele homozygosity and rs174448 major allele carriage and improved performance in 8-to 11-y-old boys but not in girls, thereby counteracting existing sex differences. This may be a consequence of increased endogenous DHA synthesis in infancy but not at school-age. This trial was registered at clinicaltrials.gov as NCT01457794. [ABSTRACT FROM AUTHOR]

Background: Fertility treatment includes hormonal stimulation of the woman and in vitro manipulation of gametes and embryos that may influence prenatal brain development. We aimed to investigate the association between fertility treatment and childhood epilepsy, including specific types of treatment and indications, as well as subtypes of epilepsy.Methods: In this nationwide birth cohort study, we included all pregnancies in Denmark resulting in live-born singletons, 1995-2003. Children conceived by fertility treatment and children developing epilepsy (until 2013) were identified from Danish national registers.Results: A total of 565,116 pregnancies were included; 8,071 children (1.4%) developed epilepsy. Children conceived after ovulation induction or intrauterine insemination had a slightly higher risk of childhood epilepsy (hazard ratio [HR]: 1.15; 95% confidence interval [CI]: 1.00, 1.31). The association was more pronounced for the subtypes idiopathic generalized and focal epilepsy. Regarding the specific hormonal treatments, only clomiphene citrate was associated with an increased risk of childhood epilepsy, also in a sibling analysis (HR: 2.07; 95% CI: 1.05, 4.08). In vitro fertilization or intracytoplasmic sperm injection was not associated with an overall increased risk of childhood epilepsy but with idiopathic generalized epilepsy (HR: 1.43; 95% CI: 0.99, 2.05). No clear associations were seen regarding other treatment types or indications.Conclusions: Children conceived by ovulation induction or intrauterine insemination with clomiphene citrate may be at slightly increased risk of childhood epilepsy. Furthermore, children conceived by in vitro fertilization or intracytoplasmic sperm injection may be at slightly increased risk of idiopathic generalized epilepsy. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to examine whether occupational and physical activity (PA) at different ages contribute to Parkinson's disease (PD) risk in a large population-based case-control study in Denmark. Methods We identified 1828 PD patients from the Danish National Hospital Register and recruited 1909 gender and year of birth matched controls from the Danish Central Population Register. Occupational and leisure-time PA were determined from a job exposure matrix based on occupational history and self-reported leisure-time information. Results No association was found for occupational PA alone in men, but higher leisure-time PA (≥5 hours/week of strenuous activities) in young adulthood (15-25 years) was associated with a lower PD risk (adjusted odds ratio (ORadj) 0.75, 95% confidence interval (95% CI) 0.62-0.90); men who engaged in high occupational and high leisure-time PA in young adulthood had the lowest PD risk (ORadj 0.58, 95% CI 0.41-0.81). Among women, inverse associations were found for occupation PA before age 50 (highest vs lowest, ORadj 0.75, 95% CI 0.55-1.06) and strenuous leisure-time PA after age 50 (ORadj 0.65, 95% CI 0.87-0.99); no clear pattern was seen for leisure and occupational PA combined. Conclusions We observed gender-specific inverse associations between occupational and leisure-time PA and PD risk; however, we cannot preclude reverse causation especially in older ages since PD has a long prodromal stage that might lead to a reduction of PA years before motor symptom onset and PD diagnosis. [ABSTRACT FROM AUTHOR]

In a longitudinal study including 642 healthy 8–11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August–June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point. In all, eleven SNP in four vitamin D-related genes: Cytochrome P450 subfamily IIR1 (CYP2R1); 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase-1(DHCR7/NADSYN1); group-specific complement (GC); and vitamin D receptor were genotyped. We found minor alleles of CYP2R1 rs10500804, and of GC rs4588 and rs7041 to be associated with lower serum 25(OH)D concentrations across the three seasons (all P<0·01), with estimated 25(OH)D differences of −5·8 to −10·6 nmol/l from major to minor alleles homozygosity. In contrast, minor alleles homozygosity of rs10741657 and rs1562902 in CYP2R1 was associated with higher serum 25(OH)D concentrations compared with major alleles homozygosity (all P<0·001). Interestingly, the association between season and serum 25(OH)D concentrations was modified by GC rs7041 (Pinteraction=0·044), observed as absence of increase in serum 25(OH)D from winter to spring among children with minor alleles homozygous genotypes compared with the two other genotypes of rs7041 (P<0·001). Our results suggest that common genetic variants are associated with lower serum 25(OH)D concentrations across a school year. Potentially due to modified serum 25(OH)D response to UVB sunlight exposure. Further confirmation and paediatric studies investigating vitamin D-related health outcomes of these genotypic differences are needed. [ABSTRACT FROM AUTHOR]

Methods: We studied 1491 mothers and children enrolled in the Danish National Birth Cohort (DNBC; 1996-2002). Prenatal paracetamol use was prospectively recorded in three telephone interviews. Trained psychologists assessed child's attention function using the Test of Everyday Attention for Children at Five (TEACh-5). Parents and preschool teachers completed Behaviour Rating Inventory of Executive Function (BRIEF) to assess executive functions. We estimated the differences of composite mean outcome scores, and odds ratios (OR) for subnormal attention or executive function (defined as 1 standard deviation below the mean), adjusting for maternal IQ, maternal mental health, indications for paracetamol use and other potential confounders.Results: First trimester use of paracetamol was associated with poorer attention scores in childhood [mean difference -0.34, 95% confidence interval (CI) -0.63, -0.05 for overall attention, and -0.25, 95% CI -0.50, 0.01 for selective attention]. Children prenatally exposed to paracetamol were also at a higher risk for subnormal overall attention (OR = 1.5, 95% CI 1.0, 2.5), selective attention difficulties (OR = 1.5, 95% CI 1.0, 2.4), and parent-rated subnormal executive function (metacognition index, OR = 1.5, 95% CI 0.9, 2.3). The risks for subnormal overall attention or executive function were elevated with longer duration of paracetamol use in pregnancy.Conclusions: We found some evidence that maternal paracetamol use during pregnancy was associated with poorer attention and executive function in 5-year-olds. [ABSTRACT FROM AUTHOR]

Background: Children in northern latitudes are at high risk of vitamin D deficiency during winter because of negligible dermal vitamin D3 production. However, to our knowledge, the dietary requirement for maintaining the nutritional adequacy of vitamin D in young children has not been investigated. Objective: We aimed to establish the distribution of vitamin D intakes required to maintain winter serum 25-hydroxyvitamin D [25(OH)D] concentrations above the proposed cutoffs (25, 30, 40, and 50 nmol/L) in white Danish children aged 4-8 y living at 55°N. Design: In a double-blind, randomized, controlled trial 119 children (mean age: 6.7 y) were assigned to 0 (placebo), 10, or 20 μg vitamin D3/d supplementation for 20 wk. We measured anthropometry, dietary vitamin D, and serum 25(OH)D with liquid chromatography- tandem mass spectrometry at baseline and endpoint. Results: The mean ± SD baseline saum 25(OH)D was 56.7 ± 12.3 nmol/L (range: 28.7-101.4 nmol/L). Serum 25(OH)D increased by a mean ± SE of 4.9 ± 1.3 and 17.7 ± 1.8 nmol/L in the groups receiving 10 and 20 mg vitamin D3/d, respectively, and decreased by 24.1 ± 1.2 nmol/L in the placebo group (P < 0.001). A nonlinear model of serum 25(OH)D as a function of total vitamin D intake (diet and supplements) was fit to the data. The estimated vitamin D intakes required to maintain winter serum 25(OH)D >30 (avoiding deficiency) and >50 nmol/L (ensuring adequacy) in 97.5% of participants were 8.3 and 19.5 μg/d, respectively, and 4.4 μg/d was required to maintain serum 25(OH)D >40 nmol/L in 50% of participants. Conclusions: Vitamin D intakes between 8 and 20 μg/d are required by white 4- to 8-y-olds during winter in northern latitudes to maintain serum 25(OH)D >30-50 nmol/L depending on chosen serum 25(OH)D threshold. This trial was registered at clinicaltrials. gov as NCT02145195. [ABSTRACT FROM AUTHOR]

Objective: To explore whether socio-economic differences exist in cardiometabolic risk markers in children and whether lifestyle-related factors potentially mediate these differences. Design: Cross-sectional study including measurements of fasting blood lipids, glucose, homeostasis model assessment of insulin resistance (HOMA-IR), blood pressure and heart rate. Potential mediators examined were fat mass index (FMI); intakes of fruit, vegetables, dietary fibre and added sugar; whole-blood n-3 longchain PUFA (LCPUFA) as a biomarker of fish intake; and physical activity and sedentary time. Setting: Nine primary schools in Denmark. Subjects: Children aged 8-11 years (n 715). Results: Children of parents with the shortest compared with longest education had higher TAG by 0·12 (95% CI 0·04, 0·21) mmol/l and HOMA-IR by 0·36 (0·10, 0·62), whereas children of parents with a vocational education had higher total cholesterol by 0·14 (0·02, 0·27) mmol/l and LDL cholesterol by 0·14 (0·03, 0·25) mmol/l compared with children of parents with the longest education; all P <0·05. FMI explained 25% of the difference in TAG, 64% of the difference in HOMA-IR and 21-29% of the differences in cholesterols. FMI and whole-blood n-3 LCPUFA combined explained 42% of the difference in TAG, whereas FMI, whole-blood n-3 LCPUFA and dietary fibre explained 89% of the difference in HOMA-IR. Conclusions: Socio-economic differences were present in blood lipids and insulin resistance among 8- to 11-year-olds and were mediated by body fatness, wholeblood n-3 LCPUFA and dietary fibre. These lifestyle factors may be targets in public initiatives to reduce socio-economic differences. Confirmation in longitudinal studies and trials is warranted. [ABSTRACT FROM AUTHOR]

Purpose: We recently showed that provision of Nordic school meals rich in fish, vegetables and potatoes and with reduced intakes of fat improved blood pressure, insulin resistance assessed by the homeostatic model (HOMA-IR), and plasma triacylglycerol despite increasing waist circumference in Danish 8-11-year-olds. This study explored whether intake or biomarkers of key dietary components in the schools meals were associated with these metabolic syndrome (MetS) markers during the 6-month intervention. Methods: Data from 7-day dietary records and measurements of whole-blood docosahexaenoic acid (DHA, 22:6n-3), blood pressure, fasting blood MetS markers, waist circumference and android/total fat mass assessed by dual-energy X-ray absorptiometry collected at baseline, 3 and 6 months from 523 children were analyzed in linear mixed-effects models adjusted for puberty, growth and fasting. Results: After adjustment for multiple testing, whole-blood DHA was negatively associated with HOMA-IR ( P < 0.001) and triacylglycerol ( P < 0.0001). Potato intake was positively associated with waist circumference ( P < 0.01), but not with android/total fat mass ( P = 0.94). Intakes of whole-grain as well as dietary fiber, protein and fat were not associated with any of the MetS markers. Conclusions: DHA in whole-blood, an indicator of DHA and fish intake, seemed to be the main diet-related predictor of the beneficial effects of the school meals on MetS markers. Increased potato intake was associated with increased waist circumference, but this may not only be due to an increase in abdominal fat, as no association was seen with fat distribution. [ABSTRACT FROM AUTHOR]

BACKGROUND: Very little is currently known about air pollutants' adverse effects on neuro-degenerative diseases even though recent studies have linked particulate exposures to brain pathologies associated with Parkinson's and Alzheimer's disease. OBJECTIVE: In the present study, we investigated long-term exposure to traffic-related air pollution and Parkinson's disease. METHODS: In a case-control study of 1,696 Parkinson's disease (PD) patients identified from Danish hospital registries and diagnosed 1996--2009 and 1,800 population controls matched by sex and year of birth, we assessed long-term traffic-related air pollutant exposures (represented by nitrogen dioxide; NO2) from a dispersion model, using residential addresses from 1971 to the date of diagnosis or first cardinal symptom for cases and the corresponding index date for their matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for matching factors and potential confounders. RESULTS: We found ambient air pollution from traffic sources to be associated with risk of PD, with a 9% higher risk (95% CI: 3, 16.0%) per interquartile range increase (2.97 µg/m³) in modeled NO2. For participants living for ≥ 20 years in the capital city, ORs were larger (OR = 1.21; 95% CI: 1.11, 1.31) than in provincial towns (OR = 1.10; 95% CI: 0.97, 1.26), whereas there was no association among rural residents. CONCLUSIONS: Our findings raise concerns about potential effects of air pollution from traffic and other sources on the risk of PD, particularly in populations with high or increasing exposures. [ABSTRACT FROM AUTHOR]

Sufficient summer/autumn vitamin D status appears important to mitigate winter nadirs at northern latitudes. We conducted a cross-sectional study to evaluate autumn vitamin D status and its determinants in 782 Danish 8–11-year-old children (55°N) using baseline data from the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study, a large randomised controlled trial. Blood samples and demographic and behavioural data, including 7-d dietary recordings, objectively measured physical activity, and time spent outdoors during school hours, were collected during September–November. Mean serum 25-hydroxyvitamin D (25(OH)D) was 60·8 (SD 18·7) nmol/l. Serum 25(OH)D levels ≤50 nmol/l were found in 28·4% of the children and 2·4% had concentrations <25 nmol/l. Upon multivariate adjustment, increasing age (per year) (β −2·9; 95% CI −5·1, −0·7 nmol/l), female sex (β −3·3; 95% CI −5·9, −0·7 nmol/l), sampling in October (β −5·2; 95% CI −10·1, −0·4 nmol/l) and November (β −13·3; 95% CI −17·7, −9·1), and non-white ethnicity (β −5·7; 95% CI −11·1, −0·3 nmol/l) were negatively associated with 25(OH)D (all P<0·05). Likewise, immigrant/descendant background was negatively associated with 25(OH)D, particularly in females (β −16·3; 95% CI −21·9, −10·7) (P<0·001) (Pinteraction=0·003). Moderate-to-vigorous physical activity (MVPA) (min/d) (β 0·06; 95% CI 0·01, 0·12), outdoor walking during school hours (min/week) (β 0·4; 95% CI 0·1, 0·6) and intake of vitamin D-containing supplements ≥3 d/week (β 8·7; 95% CI 6·4, 11·0) were positively associated with 25(OH)D (all P<0·05). The high proportion of children with vitamin D status below the recommended sufficiency level of 50 nmol/l raises concern as levels expectedly drop further during winter months. Frequent intake of vitamin D supplements was strongly associated with status. MVPA and outdoor activity during school hours should be investigated further in interventions to improve autumn vitamin D status in children at northern latitudes. [ABSTRACT FROM AUTHOR]

Background: Death of a close family member such as a parent or a sibling can cause prolonged stress and changes in the family structure that may have extensive social and health effects on a young child. The aim of this paper is to examine the rate of type 1 diabetes following bereavement due to death of a first-degree family member in early life.Methods: We used data from the Danish Civil Registration System (CRS) to identify singleton births in Denmark born 1 January 1980 through 31 December 2005, n = 1 740 245 and their next of kin. We categorised children as exposed to bereavement if they lost a mother, father or sibling from age 5 years onwards, the remaining children were considered unexposed. Children were followed until first diagnosis of diabetes, death, emigration, or 31 December 2010. We estimated incidence rate ratios (IRRs) from birth using log-linear Poisson regression models with person-years as an offset variable. Exposed children were followed up for an average of 9.1 years [standard deviation (SD) 6.7] and unexposed children were followed up for an average of 12.3 years (SD 7.3).Results: In our sample 94 943 children were exposed to bereavement, and 6110 cases of type 1 diabetes were identified. Bereavement was associated with an increased rate of type 1 diabetes when exposure onset began after 11 years of age (adjusted IRR 1.28, 95% confidence interval 1.08, 1.51).Conclusion: We found some evidence to indicate an increase in the rate of type 1 diabetes among children exposed to bereavement when exposure occurred after 11 years of age. [ABSTRACT FROM AUTHOR]

Vitamin D status has been associated with cardiometabolic markers even in children, but the associations may be confounded by fat mass and physical activity behaviour. This study investigated associations between vitamin D status and cardiometabolic risk profile, as well as the impact of fat mass and physical activity in Danish 8–11-year-old children, using baseline data from 782 children participating in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. We assessed vitamin D status as serum 25-hydroxyvitamin D (25(OH)D) and measured blood pressure, fasting plasma glucose, homoeostasis model of assessment-insulin resistance, plasma lipids, inflammatory markers, anthropometry and fat mass by dual-energy X-ray absorptiometry, and physical activity by 7 d accelerometry during August–November. Mean serum 25(OH)D was 60·8 (sd 18·7) nmol/l. Each 10 mmol/l 25(OH)D increase was associated with lower diastolic blood pressure (−0·3 mmHg, 95 % CI −0·6, −0·0) (P=0·02), total cholesterol (−0·07 mmol/l, 95 % CI −0·10, −0·05), LDL-cholesterol (−0·05 mmol/l, 95 % CI −0·08, −0·03), TAG (−0·02 mmol/l, 95 % CI −0·03, −0·01) (P≤0·001 for all lipids) and lower metabolic syndrome (MetS) score (P=0·01). Adjustment for fat mass index did not change the associations, but the association with blood pressure became borderline significant after adjustment for physical activity (P=0·06). In conclusion, vitamin D status was negatively associated with blood pressure, plasma lipids and a MetS score in Danish school children with low prevalence of vitamin D deficiency, and apart from blood pressure the associations were independent of body fat and physical activity. The potential underlying cause–effect relationship and possible long-term implications should be investigated in randomised controlled trials. [ABSTRACT FROM PUBLISHER]

BackgroundThe number of studies on electronic self-monitoring in affective disorder and other psychiatric disorders is increasing and indicates high patient acceptance and adherence. Nevertheless, the effect of electronic self-monitoring in patients with bipolar disorder has never been investigated in a randomized controlled trial (RCT). The objective of this trial was to investigate in a RCT whether the use of daily electronic self-monitoring using smartphones reduces depressive and manic symptoms in patients with bipolar disorder.MethodA total of 78 patients with bipolar disorder according to ICD-10 criteria, aged 18–60 years, and with 17-item Hamilton Depression Rating Scale (HAMD-17) and Young Mania Rating Scale (YMRS) scores ≤17 were randomized to the use of a smartphone for daily self-monitoring including a clinical feedback loop (the intervention group) or to the use of a smartphone for normal communicative purposes (the control group) for 6 months. The primary outcomes were differences in depressive and manic symptoms measured using HAMD-17 and YMRS, respectively, between the intervention and control groups.ResultsIntention-to-treat analyses using linear mixed models showed no significant effects of daily self-monitoring using smartphones on depressive as well as manic symptoms. There was a tendency towards more sustained depressive symptoms in the intervention group (B = 2.02, 95% confidence interval −0.13 to 4.17, p = 0.066). Sub-group analysis among patients without mixed symptoms and patients with presence of depressive and manic symptoms showed significantly more depressive symptoms and fewer manic symptoms during the trial period in the intervention group.ConclusionsThese results highlight that electronic self-monitoring, although intuitive and appealing, needs critical consideration and further clarification before it is implemented as a clinical tool. [ABSTRACT FROM AUTHOR]

Early excessive weight gain is positively associated with later obesity, and yet the effect of weight gain during specific periods and the impact of infant feeding practices are debated. The objective of the present study was to examine the impact of weight gain in periods of early childhood on body composition at 3 years, and whether infant feeding modified the relationship between early growth and body composition at 3 years. We studied 233 children from the prospective cohort study, SKOT (in Danish: Småbørns Kost og Trivsel). Birth weight z-scores (BWZ) and change in weight-for-age z-scores (WAZ) from 0 to 5, 5 to 9, 9 to 18 and 18 to 36 months were analysed for relations with body composition (anthropometry and bioelectrical impedance) at 3 years by multivariate regression analysis. BWZ and change in WAZ from 0 to 5 months were positively associated with BMI, fat mass index (FMI) and fat-free mass index (FFMI) at 3 years. Full breastfeeding for 6 months (compared to less than 1 month) eliminated the effect of early growth (P= 0·01). Full breastfeeding for 6 months (compared to less than 1 month) also eliminated the positive relation between BWZ and FMI (P= 0·009). No effect modification of infant feeding was found for FFMI. In conclusion, high birth weight and rapid growth from 0 to 5 months were associated with increased FMI and FFMI at 3 years. Longer duration of full breastfeeding reduced the effect of birth weight and early weight gain on fat mass. [ABSTRACT FROM AUTHOR]

Objectives: We investigated whether working night shifts was associated with the risk of Parkinson's disease (PD). Methods: Between January 2008 and December 2010, we recruited 1808 patients with a confirmed diagnosis of idiopathic PD from Denmark and 1876 population controls matched by year of birth and gender. Information on lifelong occupational history, including information on night work, smoking, caffeine and alcohol consumption habits, and family history of PD was collected through structured telephone interviews. Results Overall, there was no association between a history of night shift work and PD [odds ratio (OR) for any type of night work (ie, either permanent or rotating night work) 1.01, 95% confidence interval (95% CI) 0.86-1.21]. Compared with persons who never worked night shifts, risks of those with longer durations of night work did not appear to differ (OR<10 years = 0.95, 95% CI 0.75-1.19, OR10-19 years = 1.09, 95% CI 0.77-1.53, OR≥20 years = 1.05, 95% CI 0.81-1.37, P for trend = 0.23). Associations were similar among men and women. Conclusions: These data suggest that working night shifts is not associated with PD or that low tolerance for night shift work is an early marker of PD. Due to the novel and exploratory nature of these findings, confirmation is needed. [ABSTRACT FROM AUTHOR]

The relationship between Parkinson disease (PD) and smoking has been examined in several studies, but little is known about smoking in conjunction with other behaviors and a family history of PD. Using unconditional logistic regression analysis, we studied individual and joint associations of these factors with idiopathic PD among 1,808 Danish patients who were diagnosed in 1996-2009 and matched to 1,876 randomly selected population controls. Although there was a downward trend in duration of smoking, this was not observed for daily tobacco consumption. A moderate intake of caffeine (3.1-5 cups/day) was associated with a lower odds ratio for PD (0.45, 95% confidence interval: 0.34, 0.62), as was a moderate intake of alcohol (3.1-7 units/week) (odds ratio = 0.60, 95% confidence interval: 0.58, 0.84); a higher daily intake did not reduce the odds further. When these behaviors were studied in combination with smoking, the odds ratios were lower than those for each one alone. Compared with never smokers with no family history of PD, never smokers who did have a family history had an odds ratio of 2.81 (95% confidence interval: 1.91, 4.13); for smokers with a family history, the odds ratio was 1.60 (95% confidence interval: 1.15, 2.23). In conclusion, duration of smoking seems to be more important than intensity in the relationship between smoking and idiopathic PD. The finding of lower risk estimates for smoking in combination with caffeine or alcohol requires further confirmation. [ABSTRACT FROM AUTHOR]

It is widely assumed that nutrition can improve school performance in children; however, evidence remains limited and inconclusive. In the present study, we investigated whether serving healthy school meals influenced concentration and school performance of 8- to 11-year-old Danish children. The OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet) School Meal Study was a cluster-randomised, controlled, cross-over trial comparing a healthy school meal programme with the usual packed lunch from home (control) each for 3 months (NCT 01457794). The d2 test of attention, the Learning Rating Scale (LRS) and standard tests on reading and mathematics proficiency were administered at baseline and at the end of each study period. Intervention effects were evaluated using hierarchical mixed models. The school meal intervention did not influence concentration performance (CP; primary outcome, n 693) or processing speed; however, the decrease in error percentage was 0·18 points smaller (P< 0·001) in the intervention period than in the control period (medians: baseline 2·03 %; intervention 1·46 %; control 1·37 %). In contrast, the intervention increased reading speed (0·7 sentence, P= 0·009) and the number of correct sentences (1·8 sentences, P< 0·001), which corresponded to 11 and 25 %, respectively, of the effect of one school year. The percentage of correct sentences also improved (P< 0·001), indicating that the number correct improved relatively more than reading speed. There was no effect on overall math performance or outcomes from the LRS. In conclusion, school meals did not affect CP, but improved reading performance, which is a complex cognitive activity that involves inference, and increased errors related to impulsivity and inattention. These findings are worth examining in future trials. [ABSTRACT FROM PUBLISHER]

Background: With the increasing focus on obesity, growth patterns in infancy and early childhood have gained much attention. Although the adiposity rebound has been in focus because of a shown association with adult obesity, not much has been published about the infant peak in body mass index (BMI). Objective: This study links age and BMI at infant peak to duration of breastfeeding and body composition at 3 y of age. Design: Frequent weight and height measurements for 311 Danish children in the SKOT (Complementary and Young Child Feeding -- Impact on Short and Long Term Development and Health; in Danish) cohort were used to estimate BMI growth curves for the age span from 14 d to 19 mo by using a nonlinear mixed-effects model. BMI growth velocity before peak and age and BMI at peak were derived from the subject-specific models. Information about pregnancy and breastfeeding was assessed from background questionnaires. Assessment of body composition at age 3 y was made based on bioelectrical impedance, weight, and height. Results: A longer duration of exclusive breastfeeding was associated with an earlier peak in infant BMI (P = 0.0003) and a lower prepeak velocity (P < 0.0001). BMI level at peak and prepeak velocity was positively associated with fat and fat-free mass at age 3 y (all P < 0.0001), whereas a later age at peak was associated with a lower fat mass, fat mass index, and fat-free mass index at age 3 y (all P < 0.001). Conclusions: BMI peak characteristics are strongly associated with both duration of exclusive breastfeeding and body composition at 3 y of age. Thus, a better knowledge of characteristics and determinants of the early BMI peak is likely to improve our understanding of early development of obesity. [ABSTRACT FROM AUTHOR]

An increasing number of children are exhibiting features of the metabolic syndrome (MetS) including abdominal fatness, hypertension, adverse lipid profile and insulin resistance. Healthy eating practices during school hours may improve the cardiometabolic profile, but there is a lack of evidence. In the present study, the effect of provision of school meals rich in fish, vegetables and fibre on a MetS score (primary outcome) and on individual cardiometabolic markers and body composition (secondary outcomes) was investigated in 834 Danish school children. The study was carried out as a cluster-randomised, controlled, non-blinded, cross-over trial at nine schools. Children aged 8–11 years received freshly prepared school lunch and snacks or usual packed lunch from home (control) each for 3 months. Dietary intake, physical activity, cardiometabolic markers and body composition were measured at baseline and after each dietary period. The school meals did not affect the MetS score (P= 1·00). However, it was found that mean arterial pressure was reduced by 0·4 (95 % CI 0·0, 0·8) mmHg (P= 0·04), fasting total cholesterol concentrations by 0·05 (95 % CI 0·02, 0·08) mmol/l (P= 0·001), HDL-cholesterol concentrations by 0·02 (95 % CI 0·00, 0·03) mmol/l, TAG concentrations by 0·02 (95 % CI 0·00, 0·04) mmol/l (both P< 0·05), and homeostasis model of assessment-insulin resistance by 0·10 (95 % CI 0·04, 0·16) points (P= 0·001) compared with the control diet in the intention-to-treat analyses. Waist circumference increased 0·5 (95 % CI 0·3, 0·7) cm (P< 0·001), but BMI z-score remained unaffected. Complete-case analyses and analyses adjusted for household educational level, pubertal status and physical activity confirmed the results. In conclusion, the school meals did not affect the MetS score in 8–11-year-olds, as small improvements in blood pressure, TAG concentrations and insulin resistance were counterbalanced by slight undesired effects on waist circumference and HDL-cholesterol concentrations. [ABSTRACT FROM PUBLISHER]

Perfluoroalkyl substances (PFASs) are persistent pollutants and endocrine disruptors that may affect fetal brain development. We investigated whether prenatal exposure to PFASs increases the risk of congenital cerebral palsy (CP). The source population for this study includes 83,389 liveborn singletons and mothers enrolled in the Danish National Birth Cohort during 1996–2002. We identified 156 CP cases by linking the cohort to the Danish National Cerebral Palsy Register, and we randomly selected 550 controls using a case-cohort design. We measured 16 PFASs in maternal plasma collected in early or midpregnancy, and 6 PFASs were quantifiable in more than 90% of the samples. We found a higher risk of CP in boys with higher maternal PFAS levels; per 1-unit (natural-log ng/mL) increase, the risk ratios were 1.7 (95% confidence interval: 1.0, 2.8) for perfluorooctane sulfonate and 2.1 (95% confidence interval: 1.2, 3.6) for perfluorooctanoic acid. We also observed a dose-response pattern of CP risk in boys per quartile of maternal level of perfluorooctane sulfonate and perfluorooctanoic acid (P for trend < 0.01). PFASs were associated with both unilateral and bilateral spastic CP subphenotypes. No association between PFASs and CP was found in girls. Prenatal exposures to PFASs may increase the risk of CP in boys, but the finding is novel and replication is needed. [ABSTRACT FROM PUBLISHER]

Background and purpose Parkinson's disease is more common in men than women by a ratio of about 1.5:1 and yet there is no consensus to date as to whether female reproductive factors including hormone use affect Parkinson's disease risk. Our objective was to examine the relationship between Parkinson's disease and female reproductive factors in the largest population-based Parkinson's disease case−control study to date. Methods Seven hundred and forty-three female Parkinson's disease cases diagnosed between 1996 and 2009 were selected from the Danish National Hospital Register, diagnoses confirmed by medical record review, and the cases were matched by birth year to 765 female controls randomly selected from the Danish Civil Registration System. Covariate information was collected in computer-assisted telephone interviews covering an extensive array of topics including reproductive and lifestyle factors. Results After adjusting for smoking, caffeine and alcohol use, education, age, and family Parkinson's disease history, inverse associations between Parkinson's disease and early menarche (first period at ≤11 years), oral contraceptives, high parity (≥4 children) and bilateral oophorectomy were found; adjusted odds ratios and 95% confidence limits were respectively 0.68 (0.45-1.03) for early menarche, 0.87 (0.69-1.10) for oral contraceptives, 0.79 (0.59-1.06) for high parity and 0.65 (0.45-0.94) for bilateral oophorectomy. Little support for associations between Parkinson's disease and fertile life length, age at menopause or post-menopausal hormone treatment was found. Conclusions Reproductive factors related to women's early- to mid-reproductive lives appear to be predictive of subsequent Parkinson's disease risk whereas factors occurring later in life seem less important. [ABSTRACT FROM AUTHOR]

For 3-year-old children suitable methods to estimate body composition are sparse. We aimed to develop predictive equations for estimating fat-free mass (FFM) from bioelectrical impedance (BIA) and anthropometry using dual-energy X-ray absorptiometry (DXA) as reference method using data from 99 healthy 3-year-old Danish children. Predictive equations were derived from two multiple linear regression models, a comprehensive model (height2/resistance (RI), six anthropometric measurements) and a simple model (RI, height, weight). Their uncertainty was quantified by means of 10-fold cross-validation approach. Prediction error of FFM was 3.0% for both equations (root mean square error: 360 and 356 g, respectively). The derived equations produced BIA-based prediction of FFM and FM near DXA scan results. We suggest that the predictive equations can be applied in similar population samples aged 2-4 years. The derived equations may prove useful for studies linking body composition to early risk factors and early onset of obesity. [ABSTRACT FROM AUTHOR]

Background: Infant docosahexaenoic acid (DHA) status is supported by the DHA content of breast milk and thus can decrease once complementary feeding begins. Furthermore, it is unclear to what extent endogenous DHA synthesis contributes to status. Objective: We investigated several determinants, including FAD genotypes on DHA status at 9 mo and 3 y. Design: This was a cross-sectional study with Danish infants from 2 prospective studies [Essentielle Fedtsyrer i OvergangskosteN (EFiON) and the Småørns Kost Og Trivsel (SKOT) cohort] in which we measured red blood cell (RBC) DHA status at 9 mo (n = 409) and 3 y (n = 176) and genotyped 4 FADS tag single nucleotide polymorphisms (SNPs): rs3834458, rs1535, rs174575, and rs174448 (n = 401). Information about breastfeeding was obtained by using questionnaires, and fish intake was assessed by using 7-d precoded food diaries. Results: FADS genotype, breastfeeding, and fish intake explained ;5% of the variation in infant RBC DHA status [mean ± SD: 6.6 ± 1.9% of fatty acids (FA%)]. Breastfeeding explained most of the variation (~ 20%), and still being breastfed at 9 mo was associated with a 0.7 FA% higher DHA compared with no longer being breastfed (P < 0.001). The FADS SNPs rs1535 and rs3834458 were highly correlated (r = 0.98). Homozygous carriers of the minor allele of rs1535 had a DHA increase of 1.8 FA% (P = 0.001) relative to those with the wild-type allele, whereas minor allele carriers of rs174448 and rs174575 had a decrease of 1.1 FA% (P = 0.005) and 2.0 FA% (P = 0.001), respectively. Each 10-g increment in fish intake was associated with an increased DHA status of 0.3 FA%. At 3 y, fish intake was the only significant determinant of DHA status (0.2 FA%/10 g). Conclusion: Breastfeeding, FADS genotype, and fish intake are important deternainants of DHA status in late infancy. The EFiON study was registered at clinicaltrials.gov as NCT 00631046. [ABSTRACT FROM AUTHOR]

Background: Effects of protein intake on appetite-regulating hormones and their dynamics are unclear. Objectives: We investigated the satiating effects of meals with varying protein contents and whether there was an effect of dose on appetite-regulating hormones and appetite ratings. Design: Twenty-five men [mean ± SD age: 30.0 ± 8.7 y; body mass index (BMI; in kg/m²): 25.9 ± 4.7] participated in the 3-way, randomized, double-blind crossover study. Test meals were iso-caloric with 30% of energy from fat and protein content adjusted at the expense of carbohydrate. Test meals were normal protein (NP; 14% of energy from protein), medium-high protein (MHP; 25% of energy from protein), and high protein (HP, 50% of energy from protein). Appetite ratings and blood samples were assessed every 0.5 h for 4 h. An ad libitum lunch was served 4 h after the meat. Results: Protein increased dose-dependently glucagon-like peptide-1 (GLP-1), peptide YY (PYY) 3-36, and glucagon; MHP produced 10%, 7%, and 47% greater responses, respectively; and HP produced 20%, 14%, and 116% greater responses, respectively, than did NP (P < 0.03). Compared with NP, HP increased insulin and cholecystokinin and decreased ghrelin and glucose-dependent insulinotropic polypeptide (P < 0.05). Satiety and fullness dose-dependently increased by 7% and 6% for MHP and 16% and 19% for HP compared with NP (P < 0.001). Hunger and prospective consumption dose-dependently decreased by 15% and 13% for MHP and by 25% and 26% for HP compared with NP (P < 0.0003). There was a combined effect of GLP-1 and PYY 3-36 (P = 0.03) next to the additive effect of GLP- (P = 0.006) on the composite appetite score. No difference was shown in ad libitum energy intake. Conclusion: Protein dose-dependently increased satiety and GLP-1, PYY 3-36, and glucagon, which may, at least in part, be responsible for the satiety-stimulating effect of protein. This trial was registered at clinicaltrials.gov as NCT01561235. [ABSTRACT FROM AUTHOR]

Background and purpose: It has been speculated that gastrointestinal infection with Helicobacter pylori (HP) contributes to the development of Parkinson's disease (PD). We used nationwide Danish registers to investigate this hypothesis. Methods: We identified 4484 patients with a first time PD diagnosis between 2001 and 2008 from the Danish National Patient Register (DNPR) and 22 416 population controls from the Danish Civil Registration System (CRS). Information on drug use was obtained from the National Prescription Registry (NPR). We used logistic regression to compute odds ratios (OR) for the association between treatment for HP and risk of PD. Results: Prescriptions for HP-eradication drugs and proton pump inhibitors (PPI) 5 or more years prior to the diagnosis of PD were associated with a 45% and 23% increase in PD risk, respectively. Hospitalizations and outpatient visits for gastritis and peptic/duodenal ulcers, however, were not associated with PD. Conclusions: Our population-based study suggests that chronic HP infections and/or gastritis contribute to PD or that these are PD-related pathologies that precede motor symptoms. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Insulin contributes to normal brain function. Previous studies have suggested associations between midlife diabetes and neurodegenerative diseases, including Parkinson's disease. Using Danish population registers, we investigated whether a history of diabetes or the use of antidiabetes drugs was associated with Parkinson's disease. RESEARCH DESIGN AND METHODS--From the nationwide Danish Hospital Register hospital records, we identified 1,931 patients with a first-time diagnosis of Parkinson's disease between 2001 and 2006. We randomly selected 9,651 population control subjects from the Central Population Registry and density matched them by birth year and sex. Pharmacy records comprising all antidiabetes and anti-Parkinson drug prescriptions in Denmark were available. Odds ratios (ORs) were estimated by logistic regression models. RESULTS--Having diabetes, as defined by one or more hospitalizations and/or outpatient visits for the condition, was associated with a 36% increased risk of developing Parkinson's disease (OR 1.36 [95% CI 1.08-1.71]). Similarly, diabetes defined by the use of any antidiabetes medications was associated with a 35% increased Parkinson's disease risk (1.35 [1.10-1.65]). When diabetes was defined as the use of oral antidiabetes medications, effect estimates were stronger in women (2.92 [1.34-6.36]), whereas when diabetes was defined as any antidiabetes drug prescription, patients with early-onset Parkinson's disease were at highest risk (i.e., Parkinson's disease diagnosed before the age of 60 years; 3.07 [1.65-5.70]). CONCLUSIONS--We found that a diagnosis of, or treatment received for, diabetes was significantly associated with an increased risk of developing Parkinson's disease, especially younger-onset Parkinson's disease. Our results suggest a common pathophysiologic pathway between the two diseases. Future studies should take age at Parkinson's disease onset into account. [ABSTRACT FROM AUTHOR]

Ivermectin resistance has recently been described in Parascaris equorum and there have been reports from several countries of a shortened egg reappearance period (ERP) following ivermectin treatment for cyathostomins. This study was aimed at determining the efficacy of ivermectin in treating cyathostomins and P. equorum in Danish horses. A total of 196 animals were selected from 52 farms, all of which were using a selective anthelmintic treatment strategy. ERP was investigated with weekly samples from 96 horses from nine farms. Horses were treated with ivermectin oral paste by their owners at an estimated dose rate of 0.2 mg/kg. Overall, faecal egg counts were reduced 10-14 days after treatment by 96.9% and 100% for P. equorum and cyathostomins, respectively. Mean faecal egg count reductions at 4 and 6 weeks post treatment were 99.5% and 96.9%, respectively. No signs of developing ivermectin resistance were found in either cyathostomins or P. equorum in the studied horses. [ABSTRACT FROM AUTHOR]

Background: Immigrant studies offer insights into the relative importance of environment and genes in disease etiology. There is considerable variation in testicular cancer incidence worldwide. We investigated testicular cancer risk in first- and second-generation immigrants to Denmark, a high-incidence country, to evaluate the relative influence of genes and environment and the potential timing of action of environmental factor(s). Methods: A cohort of 2.1 million men who were born since 1930 and lived in Denmark between 1968 and 2003 was established based on information in the Danish Civil Registration System, which included their immigration histories. Cancer histories were obtained from the Danish Cancer Registry. Testicular cancer risk was estimated as rate ratios (RRs) with 95% confidence intervals (CIs) based on log-linear Poisson regression. Results: Overall, 4216 testicular cancer cases occurred during 43 million person-years of follow-up in 2.1 million men. These included 166 cases among 344444 direct immigrants to Denmark and 13 cases among 56189 men born in Denmark to immigrant parents. These first- and second-generation immigrants had RRs of testicular cancer of 0.37 (95% Cl = 0.31 to 0.43) and 0.88 (95% Cl = 0.51 to 1.53), respectively, compared with men born in Denmark of parents born in Denmark. The rate in first-generation immigrants was not modified by age at immigration or duration of stay and reflected that in the country of origin. Conclusion: The testicular cancer risk in first-generation immigrants was lower than that in native-born Danes and reflected that in the countries of origin, whereas the risk in second-generation immigrants was similar to that in natives of Denmark. Together these findings argue for a substantial influence of environmental factors limited to the period early in life, most probably to the period in utero. [ABSTRACT FROM AUTHOR]

This study attempts to predict plant-based yogurt consumers' intention to consume plant-based yogurt alternatives in Denmark employing Ajzen's theory of planned behaviour as a theoretical framework. An online survey was conducted among 265 consumers recruited through convenience (snowball) sampling. The results from structural equation modelling analysis show that attitude (β = 0.216, p < 0.001), perceived behavioural control (self-efficacy) (β = 0.229, p < 0.001) and perceived sensory attributes (β = 0.324, p < 0.001) positively and significantly influenced consumers' intention to consume plant-based yogurt alternatives. However, subjective norms (β = 0.106, p = 0.087) and perceived barriers (β = −0.051, p = 0.414) did not influence consumers' intention to consume plant-based yogurt alternatives. Further, objective knowledge showed no significant influence on attitudes (β = 0.077, p = 0.242) and intention (β = −0.029, p = 0.603) towards plant-based yogurt alternatives. The intention (β = 0.677, p < 0.001) to consume plant-based yogurt alternatives showed a strong positive correlation with the behaviour to consume plant-based yogurt alternatives. The results from logistic regression indicated that socio-demographic characteristics, gender, education, income and region of residence were significantly associated with consumption of plant-based yogurt alternatives. Thus, focusing on consumers' attitudes and self-efficacy and improving the organoleptic characteristics might promote the consumption of plant-based yogurt alternatives in Denmark and similar countries. [ABSTRACT FROM AUTHOR]

Objective: Retinoblastoma is the most common primary intraocular tumor affecting children. We examine the role of parental occupational exposures and risk of retinoblastoma among offspring. Methods: Our population-based case-control study linked data from four nationwide Danish registries and included all cases of retinoblastoma diagnosed in Danish children (<5 y, n = 144) between 1975 and 2014. We focused on two biologically relevant acquirtime periods: 90 days preconception to conception for fathers; conception to birth for mothers. Parents were grouped into major industry headings created from Danish industry codes. Results: We observed increased risk of all retinoblastoma for children of fathers in the food and drink industry and iron and metal industry. Bilateral disease was associated with paternal work in manufacturing and land transportation. Conclusion: Our results suggest that some occupational exposures may increase the risk of childhood sporadic retinoblastoma. [ABSTRACT FROM AUTHOR]

• Hemoglobin A1c (HbA1c) declined after initiating elexacaftor/tezacaftor/ivacaftor. • HbA1c declined irrespective of age, sex, and baseline glucose tolerance status. • Insulin use was unchanged after initiation with elexacaftor/tezacaftor/ivacaftor. • In those with diabetes, continuous glucose monitoring measures were also unaltered. Elexacaftor/tezacaftor/ivacaftor (ETI) has improved the clinical status of individuals with cystic fibrosis (CF), however, whether ETI impacts glucose tolerance remains unknown. We aimed to study the change in glycated hemoglobin (HbA1c) and CF related diabetes (CFRD) status after initiation of ETI. We included individuals ≥12 years treated with ETI in Denmark in a longitudinal observational study. HbA1c was measured at baseline, 3, 6, 9 and 12 months after treatment initiation. Change in HbA1c was assessed in mixed models adjusted for age, sex, glucose tolerance and prior CFTR modulator treatment. In a sub-population with CFRD, we assessed the change in insulin usage, hypoglycemic events and the 30-day continuous glucose monitoring (CGM) parameters (i.e., average blood glucose, time below (≤3.9 mM) and above (>10.0 mM) normal range, and the variation in glucose) after 12 months of treatment. Among 321 individuals with CF, HbA1c declined by 2.1 mmol/mol [95 % confidence interval (CI): -2.6; -1.5 mmol/mol] after 3 months and by 2.3 mmol/mol [95 %CI: -2.8; -1.9 mmol/mol] after 12 months of ETI treatment. The decline was independent of glucose tolerance status at baseline. In 26 individuals with CFRD at baseline, the mean decline in HbA1c was 3.6 mmol/mol [95 %CI: -6.9; -0.4 mmol/mol] after 12 months, but we did not observe any change in insulin usage, weekly number of hypoglycemic events or CGM parameters. In the Danish CF cohort, HbA1c declined over 12 months of ETI treatment, however, among a subset with CFRD, we observed no change in insulin usage and CGM glucose levels. [ABSTRACT FROM AUTHOR]

• Infant BCG immunisation induces M. ulcerans -specific immune responses. • M. ulcerans - and M. tuberculosis -specific immune responses are qualitatively similar. • Magnitude of M. ulcerans -specific immune responses was not influenced by BCG strain. • These in-vitro findings support the protective effect observed epidemiologically. Bacillus Calmette–Guérin (BCG) vaccine provides partial protection against Buruli ulcer caused by Mycobacterium ulcerans in epidemiological studies. This study aimed to quantify M. ulcerans -specific immune responses induced by BCG immunisation. Intracellular cytokine analysis of in-vitro experiments done 10 weeks after BCG immunisation in 130 Australian infants randomised to one of three BCG vaccine strains given either at birth (BCG-Denmark, BCG-Japan, or BCG-Russia) or at two months of age (BCG-Denmark). Proportions of polyfunctional CD4+ T-cells were higher in M. ulcerans -stimulated compared to unstimulated control samples. These proportions were not influenced by the vaccine strain or timing of the immunisation. The M. ulcerans -specific immune responses showed similar patterns to those observed in M. tuberculosis -stimulated samples, although they were of lower magnitude. Our data show that BCG immunisation induces M. ulcerans -specific immune responses in infants, likely explaining the cross-protective effect observed in epidemiological studies. (ACTRN12608000227392) [ABSTRACT FROM AUTHOR]