Healthy Danish Children Research Articles

Lipid levels in a cohort of healthy Danish schoolchildren ages 5 to 17 years

It is internationally recognized to use clinical decision limits (CDL) when interpreting the lipid levels in both adults and children, even though the evidence for children is scarce. The purpose of this study is to describe how lipid levels progress in healthy Danish children ages 5 to 17 years. This study is based on the Childhood Health, Activity, and Motor Performance School Study Denmark (CHAMPS-study DK) consisting of 1456 observations of schoolchildren aged 5 to 17 years. Participants have been tested for blood levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and remnant cholesterol levels are calculated. Finally, sex-specific percentile reference curves are presented. Percentile reference curves stratified by sex were generated for all cholesterols and showed that the total cholesterol level peaks at 4.32 mmol/l in 10-year-old boys and 4.46 mmol/l in nine-year-old girls. HDL levels in boys peak at 1.72 mmol/l in nine-year-old boys. HDL levels in girls and LDL levels in both sexes are nearly constant. Triglycerides kept rising to the age of 17 years in both sexes and remnant cholesterol decreased from age 5 to 17 years in both sexes. BMI z-score adjustment revealed no significant association with total cholesterol in both sexes but a significant association between HDL, LDL, triglycerides, and remnant cholesterol. This study is the first to generate percentile reference curves for blood levels of total cholesterol, LDL, HDL, triglycerides, and remnant cholesterol in a cohort of healthy Danish children aged 5 to 17 years.

Decreased Cognitive Function in Danish Children with Epilepsy.

Children with epilepsy have a significantly increased risk of cognitive impairment. EpiTrack Junior is a screening tool developed for fast assessment of cognitive function in children with epilepsy. The tool is validated for German children. This cohort study aims to investigate the differences in cognitive function between healthy Danish children and Danish children diagnosed with epilepsy METHODS: The cognitive function of 204 healthy controls and 90 children and adolescents diagnosed with epilepsy was examined using EpiTrack Junior. The participants of the control group were aged 6 to 16 years. The patients were aged 6 to 20 years. Statistical analyses were performed with the use of SPSS Statistics. The control group showed significantly higher scores than the patient group in three of six subtests and total test scores (p-values ranging from 0.033 to <0.001). When grouped according to the EpiTrack Junior guidelines, more patients showed scores "below average" or "poor" compared to the control group. The age-corrected total score was not associated with antiepileptic drug treatment (p-value of 0.732) nor with a history of focal seizures (p-value of 0.215). A history of generalized tonic-clonic seizures (GTCS) was associated with a higher EpiTrack Junior score (p-value of 0.035). The patient group showed statistically significant lower test scores compared to the control group confirming the relationship between impaired cognitive function and childhood epilepsy. Furthermore, a correlation between a higher EpiTrack Junior score and the presence of GTCS was found. Focal seizures and antiepileptic drug treatment were not associated with the EpiTrack Junior score.

Reference serum percentile values of adiponectin, leptin, and adiponectin/leptin ratio in healthy Danish children and adolescents

The adipokines adiponectin and leptin play key roles in human metabolic regulation and have gained great attention as biomarkers for various metabolic pathologies. Though, pediatric reference values are few and needed. This study aims to establish age- and sex-specific adipokine reference percentiles based on healthy Danish school children. Further, it elucidates sex-specific differences in associations between z-scores of examined adipokines and metabolic variables. Serum adiponectin and serum leptin from 853 observations of healthy Danish schoolchildren aged 8–17 years (median 10.0) were quantified by immunoassays. Age- and sex-specific adipokine reference percentiles were calculated cross-sectionally using the LMS method, and adipokine z-scores were calculated from the fitted model. Multiple linear regression models were used to examine sex-specific differences in associations between adipokine z-scores and various metabolic variables. Girls had a higher median value of adiponectin (11.31 vs. 10.65 μg/mL, p < .001) and leptin (2.30 vs. 1.00 ng/mL, p < .001) and a lower median value of adiponectin/leptin ratio (4.64 vs. 10.76, p < .001) compared to boys. Sex-specific differences were found in associations between adiponectin z-score and HDL (p = .010), between leptin z-score and waist circumference z-score (p = .027) and LDL (p = .048), and between adiponectin/leptin ratio z-scores and waist circumference z-score (p = .044) and LDL (p = .040). Reference percentiles of adiponectin, leptin, and adiponectin/leptin ratio are presented in this paper. To our knowledge, this study is the first to demonstrate sex-specific differences in associations between adipokine z-scores and waist circumference z-score and lipids, respectively in healthy children and adolescents.

Similar effects of milk protein and blends of milk and plant-based protein on appetite-related hormones in 7- to 8-year-old healthy Danish children: secondary analyses from the PROGRO randomised trial.

The effect of different protein sources on the appetite-related hormones in children is largely unknown. We investigated the effect of milk protein versus blends of milk and rapeseed protein on plasma leptin and adiponectin in children. We included 88Danish 7- to 8-year-old children randomised to receive 35g protein/day for 4weeks in 2018 as either milk protein or blends of milk and rapeseed protein (ratio 54:46 or 30:70). Outcomes included absolute and fat mass-adjusted adiponectin and leptin measured at baseline, Weeks 1 and 4. There was no difference in changes in absolute and fat mass-adjusted adiponectin and leptin after 1 or 4weeks between the three groups (p≥0.100). Leptin increased within all groups (p≤0.046). Combining the three groups, leptin and fat mass-adjusted leptin increased by 23% (95% CI 11;35) and 17% (6.4;29) during the intervention respectively (both p≤0.001). Adiponectin variables did not change during the intervention period. There were no differences between milk protein and blends of milk and rapeseed protein on absolute and fat mass-adjusted leptin and adiponectin in healthy children with a habitual intake of milk. However, leptin increased within all three groups. Future studies should further investigate effect on appetite-related hormones of rapeseed protein alone.

Reference data for hop tests used in pediatric ACL injury rehabilitation: A cross-sectional study of healthy children.

In rehabilitation, four single‐leg hop tests are frequently used for evaluation of ACL‐injured children. However, reference values on single‐leg hop performance and the corresponding limb symmetry indexes (LSIs) of healthy children younger than 15 years of age are lacking. Thus, the purpose was to describe hop performance and LSIs in healthy Danish children, and to quantify the proportion of participants passing LSI values of ≥85% as well as ≥90%. Healthy children aged 9–15 years were invited to participate in the study. Hop performance (single hop, 6‐m timed hop, triple hop, and cross‐over hop) was assessed for each leg for each hop test and expressed as absolute, normalized (to body height), and LSI values. Descriptive statistics were applied to calculate mean ±SD for all outcomes within age and gender groups. Further, the 95% reference interval was calculated for each age and gender group. A total of 531 healthy children (52% girls) were included in the study, representing seven age groups (9‐15 years). The LSI group means across all participants for the four hop tests ranged between 84 and 95%. Between 70 and 83% of the children had an LSI of ≥85%, while 50 to 65% of the children had an LSI of ≥90%. The present reference material can be used in clinical practice when evaluating hop performance in pediatric ACL patients.

Heritability of pubertal timing: detailed evaluation of specific milestones in healthy boys and girls.

Pubertal timing is highly heritable. Observational studies were inconclusive concerning a potential sex-specific difference in the parental contribution, while genome-wide association studies highlighted a heterogeneity in the genetic architecture of pubertal timing between sexes. Our objectives were to evaluate the association of timing of pubertal milestones in offspring with parental pubertal timing and to identify the genetic basis of the heterogeneity. (1.) Population-based mixed cross-sectional/longitudinal cohort (2006-2014, COPENHAGEN Puberty Study) comprising 1381 healthy Danish children including their parents. (2.) UK Biobank-based summary statistics of genetic data on timing of menarche (n = 188 644), voice-break (n = 154 459) and facial hair (n = 161 470). (1.) Participants underwent clinical examination(s) including blood sampling. Parental pubertal timing was obtained by questionnaire. Timing of milestones were analyzed using SAS-lifereg. (2.) Genetic correlations between pubertal outcomes were estimated using LD Score regression. Genetic heterogeneity was analyzed using METAL. We observed significant associations of relative parental pubertal timing with timing of pubertal milestones in offspring of concordant sex, that is, fathers/sons (e.g. testicular enlargement: P = 0.004, β = 0.34 years per relative category) and mothers/daughters (e.g. thelarche: P < 0.001, β = 0.45 years per relative category). Fewer milestones were associated with relative parental pubertal timing in offspring of discordant sex compared to concordant sex. Large-scale genetic data highlight both moderate to strong genetic correlations between timing of menarche, voice-break and facial hair. Out of 434 lead single-nucleotide polymorphisms significantly associated with at least one outcome, 39 exhibited a significant genetic heterogeneity between sexes (P < 1.15 × 10-4). Our results highlight a distinct genetic heterogeneity of pubertal timing between sexes.

Effects of oily fish intake on cardiometabolic markers in healthy 8- to 9-y-old children: the FiSK Junior randomized trial

Fish oil improves cardiometabolic markers in adults, but results in children are inconsistent. Few children meet the recommended fish intake and no randomized trials have investigated how fish intake per se affects children's cardiometabolic profile. We investigated whether oily fish consumption modulated serum triacylglycerol and diastolic blood pressure (coprimary outcomes) and other cardiometabolic markers in healthy Danish children and whether effects were sex-specific. In a randomized controlled 12-wk trial, 199 children (aged 8-9 y) received ∼300 g/wk of oily fish or poultry (control). We measured blood pressure, heart rate, and heart rate variability (HRV) via 3-h continuous electrocardiograms and collected fasting blood samples for analysis of erythrocyte EPA [20:5n-3 (ω-3)]+DHA (22:6n-3) and serum triacylglycerol, LDL and HDL cholesterol, glucose, and insulin. One hundred and ninety-seven children (99%) completed the trial. The fish group consumed a median (IQR) of 375 (325-426) g oily fish/wk and the poultry group consumed 400 (359-452) g poultry/wk, which resulted in 2.25 (95% CI: 1.88, 2.62) fatty acid percentage-point higher erythrocyte EPA+DHA in the fish group (P<0.001). In the fish group, serum triacylglycerol decreased by 0.05 mmol/L (95% CI: 0.00, 0.11 mmol/L) (P=0.04) and HDL cholesterol increased by 0.07 mmol/L (95% CI: 0.01, 0.13 mmol/L) (P=0.02); the triacylglycerol effect showed dose-dependency with erythrocyte EPA+DHA (r=-0.15, P=0.04), whereas HDL showed a tendency for such an association(r=0.13, P=0.08). Additional analyses indicated sex-specificity (Pdiet*sex<0.10), because triacylglycerol was reduced by 0.09 mmol/L (95% CI: 0.02, 0.16 mmol/L) in boys only (girls: -0.00; 95% CI: -0.07, 0.07 mmol/L) and heart rate was reduced by 3.4 bpm (95% CI: 0.2, 6.6 bpm) in girls only (boys: 0.6; 95% CI: -2.6, 3.8 bpm). Blood pressure, HRV, and glucose homeostasis were unaffected. Oily fish intake improved serum triacylglycerol and HDL cholesterol in a dose-dependent manner in 8- to 9-y-old children, but had no effect on blood pressure, HRV, or glucose homeostasis. This supports recommendations for fish intake in children and underlines the importance of initiatives to increase children's intake of oily fish. This trial was registered at clinicaltrials.gov as NCT02809508.

Reference limits for GAD65 and IA-2 autoantibodies by chemiluminescence immunoassay in Northern European adults and children

The GAD65 and IA-2 antibodies (Abs) are biomarkers of the development of type 1 diabetes mellitus (T1DM) in both children and adults. The upper reference limit for the autoantibodies made by the manufacture was established on an adult Chinese population. Here, we established upper reference limits for Northern European adults and children in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. Serum samples from healthy Danish children (0–18 years) and adults (18–70 years) were analysed for GAD65Ab and IA-2Ab using MAGLUMI 800 Chemiluminescence Immunoassay (CLIA). The Kruskal–Wallis test was used for evaluating differences between gender and age groups. No gender or age differences were found for neither GAD65Ab nor IA-2Ab, and a combined upper reference limit for both children and adults could be established. An upper reference limit of 5.1 IU/mL was defined for GAD65Ab and 11.5 U/mL for IA-2Ab. Our results showed a substantial discrepancy with the reference limits established by the manufacturer.

Probiotics and carriage of Streptococcus pneumoniae serotypes in Danish children, a double-blind randomized controlled trial

This study examined the carriage of Streptococcus pneumoniae in healthy Danish children aged 8–19 months and assessed the effect of the probiotics Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis on the pneumococcal carriage during daycare enrolment. Potential risk factors of pneumococcal carriage were analysed and the carriage study was compared with registered invasive pneumococcal disease (IPD) data. This study is a part of the ProbiComp study, which was a double-blind, randomized controlled trial, including 290 children allocated to probiotics or placebo for 6 months and recruited during two autumn seasons (2014/2015). Pneumococci were identified by optochin sensitivity, bile solubility, α-hemolysis and/or capsular reaction. Serotyping was performed by latex agglutination kit and Quellung reaction. The carriage rate of S. pneumoniae was 26.0% at baseline and 67.4% at the end of intervention. No significant difference was observed between the placebo group and the probiotics group (p = 0.508). Children aged 8–19 months were carriers of non-pneumococcal vaccine serotypes causing IPD in children aged 0–4 years. However, serotypes causing most IPD cases in Danish elderly were either not found or found with low prevalence suggesting that children are not the main reservoir of those serotypes and other age groups need to be considered as carriers.

Characterization of Diarrheagenic Enteroaggregative Escherichia coli in Danish Adults-Antibiotic Treatment Does Not Reduce Duration of Diarrhea.

Enteroaggregative Escherichia coli (EAEC) is frequently isolated from sporadic cases of diarrhea and in outbreaks of gastroenteritis in several regions of the world. The pathophysiology of EAEC continues to be enigmatic, and the efficacy of antibiotic treatment in EAEC-associated diarrhea has been discussed. Since the level of antibiotic resistance is increasing, it is essential to restrict the use of antibiotics to prevent further resistance development. We aimed to investigate EAEC strains in adult Danish patients suffering from diarrhea and from healthy controls. We examined the antibiotic resistance in EAEC strains, the clinical response to antibiotic treatment in EAEC diarrheal cases, and the distribution of virulence genes in diarrheal cases. The EAEC strains were collected from patients suffering from diarrhea in a Danish multicenter study. A medical doctor interviewed the patients by using a questionnaire regarding gastrointestinal symptoms, exposures, and use of antibiotic and over-the-counter antidiarrheal drugs. Follow-up was performed after 3–5 months to inquire about differential diagnosis to gastrointestinal disease. A multiplex polymerase chain reaction characterized virulence genes in diarrheal cases. Finally, the level of antibiotic resistance was examined by using the disc diffusion method. Asymptomatic carriage of EAEC in the adult Danish population was rare, in contrast to findings in healthy Danish children. The duration of diarrhea was not shortened by antibiotic treatment, specifically ciprofloxacin treatment, or by over-the-counter antidiarrheal drugs. Follow-up revealed no pathology in diarrheal patients apart from irritable bowel syndrome in two patients. A high number of patients suffered from long-term diarrhea, which was associated with the enterotoxin EAST-1 and a high virulence factor score. A high level of antibiotic resistance was observed and 58% of the EAEC strains were multidrug resistant. Multidrug resistance was most pronounced in cases of travelers' diarrhea, and it was seen that antibiotic treatment did not reduce the duration of diarrhea.

Probiotics and the immunological response to infant vaccinations; a double-blind randomized controlled trial

ObjectivesTo examine the effect of a combination of probiotics on the antibody response to pneumococcal and pertussis vaccination in healthy Danish children, aged 8–14 months, at the time of starting day care. Moreover, the cytokine response to lipopolysaccharide of whole blood was assessed. MethodsA total of 290 children were randomly allocated to receive a combination of Bifidobacterium animalis ssp. lactis and Lactobacillus rhamnosus GG daily for a 6-month intervention period, and blood samples were drawn at the start and end of the study. Specific antibody response towards Streptococcus pneumoniae serotypes and Bordetella pertussis toxin, as well as endotoxin-induced interleukin-6 (IL-6) and interferon-γ (IFN-γ) production in blood were analysed by Luminex and ELISA. ResultsThere was no significant difference between the average individual changes from baseline to end of study in antibody concentrations for S. pneumoniae for both the probiotics (340.4% ± 11.2%) and the placebo group (382.9% ± 10.4%) (p 0.525), nor for B. pertussis toxin in the two groups (probiotics 190.1% ± 12.6% versus placebo 238.8% ± 1.1%, p 0.340). The average individual change in IL-6 concentration was significantly lower in the probiotics versus the placebo group (2.9% ± 10.3% versus 33.7% ± 9.0%, p 0.024), whereas there was no difference in IFN-γ concentration (0.0% ± 0.2% versus –0.2% ± 0.1%, p 0.279). ConclusionsThe probiotic intervention did not affect the antibody response against S. pneumoniae and B. pertussis toxin in healthy Danish children.

Winter Cholecalciferol Supplementation at 55°N Has No Effect on Markers of Cardiometabolic Risk in Healthy Children Aged 4–8 Years

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. 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. 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. 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. 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.

Winter cholecalciferol supplementation at 55°N has little effect on markers of innate immune defense in healthy children aged 4-8years: a secondary analysis from a randomized controlled trial.

We explored the effect of winter cholecalciferol (vitamin D3) supplementation on innate immune markers in healthy Danish children (55°N). In the double-blind, placebo-controlled trial, ODIN Junior, 119 healthy, white, 4-8year-olds were randomized to 0 (placebo), 10 or 20µg/day of vitamin D3 for 20weeks (October-March). Cheek mucosal swabs, blood samples, and questionnaires on acute respiratory infections the previous month were collected at baseline and endpoint. Innate immune markers were measured as secondary outcomes including in vivo oral mucosal gene expression of calprotectin (S100A9), lipocalin-2 (LCN2), beta-defensin-4 (DEFB4), interleukin-8 (IL-8), viperin (RSAD2), and the cathelicidin-antimicrobial-peptide (CAMP); ex vivo whole-blood lipopolysaccharide (LPS)-induced cathelicidin, IL-8, and IL-6; and plasma cathelicidin, together with serum 25-hydroxyvitamin D [25(OH)D]. Serum 25(OH)D was 56.7 ± 12.3nmol/L at baseline and 31.1 ± 7.5, 61.8 ± 10.6, and 75.8 ± 11.5nmol/L at endpoint after placebo, 10 and 20µg/day of vitamin D3 (P < 0.0001), respectively. A decreased oral mucosal S100A9 expression with placebo [- 18 (95% CI - 1; - 32)%] was marginally avoided with 20µg/day [6 (- 13; 28)%] (P = 0.06). Likewise, a decreased LPS-induced IL-8 with placebo [- 438 (95% CI - 693; - 184) ng/L] was marginally avoided with 20µg/day [- 109 (- 374; 157) ng/L] (P = 0.07). All other immune markers and respiratory infection episodes were unaffected by vitamin D3 supplementation (all P > 0.11). Winter vitamin D3 supplementation of 10µg/day did not affect innate immune markers, whereas 20µg/day tended to maintain the capacity to produce a few markers in healthy children.

Antimicrobial resistance in the Bacteroides fragilis group in faecal microbiota from healthy Danish children.

The Bacteroides fragilis group constitute a significant portion of the human gut microbiota and comprise a major proportion of anaerobic bacteria isolated in human infections. We established a baseline of antimicrobial susceptibility rates in the B. fragilis group in the intestinal tract of relatively antibiotic-naive healthy Danish children. From 174 faecal samples collected from children attending day care, 359 non-duplicate isolates were screened for antimicrobial susceptibility. Of these, 0.0%, 1.9%, 5.0% and 21.2% of isolates were intermediate-susceptible or resistant to metronidazole, meropenem, piperacillin/tazobactam and clindamycin, respectively. Eighteen additional studies reporting susceptibility rates in the B. fragilis group bacteria were identified by conducting a literature search. Heterogeneity among results from studies of B. fragilis group antimicrobial susceptibility rates in faecal microbiota exists.

UV filters analyzed by isotope diluted TurboFlow-LC-MS/MS in urine from Danish children and adolescents.

Experimental studies indicate that some chemicals with UV blocking properties (known as UV filters) can act as endocrine disruptors. UV filters are used in sunscreens and other cosmetic- and personal care products, as well as in other consumer products such as food packaging, clothing and furniture textiles to protect the products against UV radiation. Here we present the urinary excretion of suspected endocrine active UV filters in Danish children and adolescents recruited from the general population. The content of benzophenone (BP), benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), 5-chloro-2- hydroxybenzophenone (BP-7), 4-hydroxybenzophenone (4-HBP), 4-methyl-benzophenone (4-MBP), 3-(4- methylbenzylidene)-camphor (4-MBC) and 3-benzylidene camphor (3-BC) were monitored in 24h urine and two consecutive first morning samples from 129 healthy Danish children and adolescents (6-21 yrs). All 387 samples were collected during the autumn (Nov. 2007) and were analyzed by a new on-line TurboFlow-LC-MS/MS method developed for simultaneous biomonitoring of these nine UV filters in urine. BP-3 and BP-1 were detected in more than 80% of the 24h samples and were significantly correlated (R2=0.815). BP, 4-HBP and BP-2 were found in 43, 15 and 5% of the samples, respectively. The median (range) concentrations of the UV-filters in 24-h urine were as follows: BP-3, 0.92 (LOD-115); BP-1, 0.54 (LOD-44.6); BP,<LOD (LOD-48.5); 4-HBP,<LOD (LOD-10.5); and BP-2,<LOD (LOD-8.43) ng/mL. In general BP-1 and BP-3 were higher in girls compared to boys and were also higher in the group of adolescent girls (16-21 yrs) compared to the younger age groups of girls. None of the other UV filters; BP-7, 4-MBP, 4-MBC or 3-BC were detected in urine. A highly significant correlation between first morning and 24h urine levels of BP-3, BP-1 and 4-HBP from the same day was observed. Our project on UV filters analyzed by a new robust and sensitive LC-MS/MS method in Danish children and adolescents showed that almost all individuals were exposed to UV filters. Sun protection products have been claimed to be a major source of exposure to sunscreens. However since all children in the present study were exposed during autumn where sunscreens are not needed in Denmark our study also indicates that other sources and routes of exposure might be of relevance.

Polychlorinated biphenyl exposure and glucose metabolism in 9-year-old Danish children.

Human exposure to polychlorinated biphenyls (PCBs) has been associated to type 2 diabetes in adults. We aimed to determine whether concurrent plasma PCB concentration was associated with markers of glucose metabolism in healthy children. Cross-sectional study of 771 healthy Danish third grade school children ages 8-10 years in the municipality of Odense were recruited in 1997 through a two-stage cluster sampling from 25 schools stratified according to location and socioeconomic character; 509 (9.7 ± 0.8 y, 53% girls) had adequate amounts available for PCB analyses. Fasting serum glucose and insulin were measured and a homeostasis assessment model of insulin resistance (HOMA-IR) and β-cell function (HOMA-B) calculated. Plasma PCB congeners and other persistent compounds were measured and ΣPCB calculated. PCBs were present in plasma at low concentrations, median, 0.19 μg/g lipid (interquartile range, 0.12-0.31). After adjustment for putative confounding factors, the second, third, fourth, and fifth quintiles of total PCB were significantly inversely associated with serum insulin (-14.6%, -21.7%, -18.9%, -23.1%, P trend < .01), compared with the first quintile, but not with serum glucose (P = .45). HOMA-IR and HOMA-B were affected in the same direction due to the declining insulin levels with increasing PCB exposure. Similar results were found for individual PCB congeners, for βHCB (hexachlorobenzen) and pp-DDE (dichlorodiphenyldichloroethylene). A strong inverse association between serum insulin and PCB exposure was found while fasting glucose remained within the expected narrow range. Our findings suggest that PCB may not exert effect through decreased peripheral insulin sensitivity, as seen in obese and low-fit children, but rather through a toxicity to β-cells. It remains to be demonstrated whether lower HOMA-B is caused by destruction of β-cell-reducing peripheral insulin resistance and thereby increase fasting glucose as previously found.

Common Variants in CYP2R1 and GC Genes Predict Vitamin D Concentrations in Healthy Danish Children and Adults

Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are known to influence serum vitamin D concentrations. Genetic epidemiology of vitamin D is in its infancy and a better understanding on how genetic variation influences vitamin D concentration is needed. We aimed to analyse previously reported vitamin D-related polymorphisms in relation to serum 25(OH)D concentrations in 201 healthy Danish families with dependent children in late summer in Denmark. Serum 25(OH)D concentrations and a total of 25 SNPs in GC, VDR, CYP2R1, CYP24A1, CYP27B1, C10or88 and DHCR7/NADSYN1 genes were analysed in 758 participants. Genotype distributions were in Hardy–Weinberg equilibrium for the adult population for all the studied polymorphisms. Four SNPs in CYP2R1 (rs1562902, rs7116978, rs10741657 and rs10766197) and six SNPs in GC (rs4588, rs842999, rs2282679, rs12512631, rs16846876 and rs17467825) were statistically significantly associated with serum 25(OH)D concentrations in children, adults and all combined. Several of the SNPs were in strong linkage disequilibrium, and the associations were driven by CYP2R1-rs10741657 and rs10766197, and by GC-rs4588 and rs842999. Genetic risk score analysis showed that carriers with no risk alleles of CYP2R1-rs10741657 and rs10766197, and/or GC rs4588 and rs842999 had significantly higher serum 25(OH)D concentrations compared to carriers of all risk alleles. To conclude, our results provide supporting evidence that common polymorphisms in GC and CYP2R1 are associated with serum 25(OH)D concentrations in the Caucasian population and that certain haplotypes may predispose to lower 25(OH)D concentrations in late summer in Denmark.

Body fat throughout childhood in 2647 healthy Danish children: agreement of BMI, waist circumference, skinfolds with dual X-ray absorptiometry

Total body fat percentage (%BF) evaluated by dual energy X-ray absorptiometry (DXA) scans (DXA %BF) is widely recognized as a precise measure of fatness. We aimed to establish national reference curves for DXA %BF, %BF calculated from skinfolds (SF %BF) and waist circumference (WC) in healthy children, and to compare agreement between the different methods. Based on 11 481 physical examinations (anthropometry) and 1200 DXA scans from a longitudinal cohort of Danish children (n=2647), we established reference curves (LMS-method) for SF %BF, WC (birth to 14 years) and DXA %BF (8-14 years). Age- and sex-specific Z-scores for body mass index (BMI), WC and SF %BF were compared. Sensitivity and specificity were calculated for agreement of WC, SF %BF and BMI with DXA %BF to identify obese children (>+1 s.d.). %BF differed with age, sex, pubertal stage and social class. SF %BF correlated strongly with DXA %BF (r=0.86). BMI and WC also correlated positively with DXA %BF (Z-scores; r= 0.78 and 0.69). Sensitivity and specificity were 79.5 and 93.8 for SF %BF, 75.9 and 90.3 for BMI and 59.2 and 95.4 for WC. SF %BF showed the highest correlation and best agreement with DXA %BF in identifying children with excess fat (+1 s.d.).

Physical Activity in Children Attending Preschools

To identify correlates of objectively measured moderate and vigorous physical activity (MVPA) in children during preschool attendance. This cross-sectional study included data from 426 apparently healthy Danish children (49.5% boys), 5 to 6 years of age enrolled in 42 randomly selected preschools. The percentage of time spent in MVPA (≥ 574 counts/15 second) during preschool attendance was measured using ActiGraph accelerometers over 4.3 preschool days in May and June in 2009. Thirty-seven potential correlates across the child, preschool staff, and preschool environment domains were tested for associations with MVPA. The final multivariate model identified 9 significant correlates of MVPA. Preterm birth, vegetation on the playground, and rainy days were negatively associated with MVPA, whereas child motor coordination, location of preschool building on the playground, gender (boys), percentage afternoon hours, and size of indoor area per child were positively associated with MVPA. The direction of the significant association with the parental mean education level was unclear. We identified a number of new modifiable correlates of MVPA during preschool attendance. The positive association with size of indoor area per child and location of the preschool building on the playground seem important correlates to be targeted in future studies.

Bone mineral content in healthy danish children assessed by DXA-scanning and by computerised determination from hand radiographs

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)