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Purpose Iodine deficiency in childhood and adolescence may lead to later thyroid dysfunction, stunted growth and cognitive impairment. The World Health Organization (WHO) has issued recommended age-dependent urine iodine concentration targets, but a critical threshold beyond which clinical sequelae are to be expected remains undefined. Our study aimed to investigate spot urine iodine concentration in a typical Central European cohort of children and adolescents, and consider the implications of these values in regard to laboratory parameters for evaluating thyroid function. Methods Using the Sandell-Kolthoff method, spot urine iodine concentration was measured cross-sectionally from 1802 healthy children and adolescent in the age range of 0.25–18 years within the LIFE-Child epidemiological study based in and around the city of Leipzig (Germany). Additionally, serum thyroid biomarkers of these subjects were measured and correlated to urine iodine levels. Results In our cohort, 61.39% of boys and 65.91% of girls had an iodine level of Conclusion In our cohort of children and adolescents, the relatively high number of iodine levels below the WHO recommendation appears not to be related to clinical or subclinical thyroid diseases in the respective participants.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from −36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was

Background: Infection with cytomegalovirus (CMV) remains asymptomatic in most immunocompetent hosts, but is the leading cause of congenital viral infection worldwide and can be life-threatening in immunocompromised individuals. We aimed to assess CMV seroprevalence in a nationally representative sample of adults in Germany and to identify sociodemographic factors associated with CMV seropositivity. Methods: Blood samples from 6552 participants (18–79 years) of the “German National Health Interview and Examination Survey 1998”, a population-based sample of the adult population in Germany, were tested for the presence of CMV antibodies using an Ig-multiplex assay. Weighted seroprevalence was calculated and weighted binomial regression was used to identify factors associated with CMV seropositivity. Results: Overall CMV seroprevalence was 56.7% (95%CI: 54.8–58.7%), with a higher seroprevalence in women (62.3%) than in men (51.0%). Seroprevalence increased with age: from 31.8% to 63.7% in men and from 44.1% to 77.6% in women when comparing the 18–29 with the 70–79 year age-group, respectively. CMV seroprevalence in women of childbearing age (18–45 years) was 51.7%. Factors significantly associated with CMV seropositivity were age, country of birth, smoking status, education, living in northern Germany and number of household members. In addition, having attended child care was associated with seropositivity in men, and number of siblings and living in East Germany in women. Conclusion: Our results indicate that half the women of childbearing age were susceptible for primary CMV infection during pregnancy. CMV screening during pregnancy and informing seronegative women about CMV risk reduction measures could prevent congenital CMV infections with its serious consequences.

Diets rich in fruits and vegetables, like the Dietary Approaches to Stop Hypertension (DASH)-diet, are usually characterized by high potassium intake and reduced dietary acid load, and have been shown to reduce blood pressure (BP). However, the relevance of potential renal acid load (PRAL) for BP has not been compared with the relevance to BP of urinary biomarker (K-urine)- and dietary food frequency questionnaire (K-FFQ)-based estimates of potassium intake in a general adult population sample. For 6788 participants (aged 18–79 years) of the representative German Health-Interview and Examination Survey for Adults (DEGS1), associations of PRAL, K-urine, and K-FFQ with BP and hypertension prevalence were cross-sectionally examined in multivariable linear and logistic regression models. PRAL was significantly associated with higher systolic BP (p = 0.0002) and higher hypertension prevalence (Odds ratio [OR] high vs. low PRAL = 1.45, p = 0.0004) in models adjusted for age, sex, body mass index (BMI), estimated sodium intake, kidney function, relevant medication, and further important covariates. Higher estimates of K-FFQ and K-urine were related to lower systolic BP (p = 0.04 and p < 0.0001) and lower hypertension prevalence (OR = 0.82, p = 0.04 and OR = 0.77, p = 0.02) as well as a lower diastolic BP (p = 0.03 and p = 0.0003). Our results show, for the first time in a comparative analysis of a large representative population sample, significant relationships of BP and hypertension prevalence with questionnaire- and biomarker-based estimates of potassium intake and with an estimate of dietary acid load.

Background: Comparability of 25-hydroxyvitamin D (25(OH)D) measurements is hampered by method-related differences in measurement values. International standardization of laboratory assays has been suggested to solve this problem. Methods: As part of the European Commission–funded project ‘Food-based solutions for optimal vitamin D nutrition and health through the life cycle’ (ODIN), original measurements of serum 25(OH)D of three German national health surveys conducted between 1998 and 2011 have been standardized retrospectively. In these representative population-based samples including persons aged between 1 and 79 years, the original 25(OH)D values were compared with those after standardization. Mean values and prevalences of vitamin D deficiency, insufficiency, and sufficiency (25(OH)D levels =50 nmol/l, respectively) were calculated by sex and age groups based on original and standardized 25(OH)D data. Results: In comparison to the original 25(OH)D levels, the standardized levels showed higher means overall and in age- and sex-specific analyses. After standardization, the prevalence of vitamin D deficiency was lower in all surveys while the prevalence of vitamin D sufficiency was higher. Nevertheless, even after standardization ~ 15% of adults and 12.5% of children had serum 25(OH)D levels

Lyme borreliosis, the most common tickborne disease in the Northern Hemisphere, is caused by infection with spirochetes of the Borrelia burgdorferi sensu lato (s.l.) complex. Five genospecies are known to be pathogenic for humans: B. burgdorferi sensu stricto (s.s.), B. afzelii, B. garinii, B. bavariensis, and B. spielmanii (1). In Europe, the bacterium is transmitted to humans through the bite of Ixodes ricinus ticks; in eastern Europe, I. persulcatus ticks can also transmit the bacterium. In Europe, where the most common clinical manifestation of Lyme borreliosis is erythema migrans, followed by Lyme neuroborreliosis and Lyme arthritis (2), data are sparse regarding B. burgdorferi s.l. infection rates and risk factors (3). Persons of all ages are at risk for infection; however, surveillance data and prospective studies in Europe and the United States suggest that children and the elderly are particularly at risk (4–6). Population-based surveillance data suggest that Lyme borreliosis is endemic in eastern Germany: annual incidence is 20–35 cases/100,000 inhabitants (7). Regional differences in incidence are observed, but data cannot be easily compared because of reporting biases and differences in infection awareness. The limited representativeness and comparability of Lyme borreliosis surveillance data are well documented (8). Under such conditions, population-based serosurveys with high representativeness can provide valid estimates of the force of infection (rate at which susceptible persons acquire Lyme borreliosis) and the lifetime risk for infection; however, seroprevalence estimates do not necessarily represent cases of clinical disease. In a population-based seroprevalence study among 1- to 17-year-old children in Germany, seroprevalence increased cumulatively by age (9). We present data on the prevalence and determinants of B. burgdorferi s.l. seropositivity among adults in Germany during 2008–2011.

The association between selenium status and risk of acute myocardial infarction was examined in a multicenter case-control study in 10 centers from Europe and Israel in 1991-1992. Selenium in toenails was assessed for 683 nonfatal male cases with first acute myocardial infarction and 729 controls less than 70 years of age. Median toenail selenium content was 0.553 microgram/g for cases and 0.590 microgram/g for controls. After adjustment for age, center, and smoking, the odds ratio for myocardial infarction in the highest quintile of selenium as compared with the lowest was 0.63 (95 percent confidence interval 0.37-1.07, p for trend = 0.08). The observed inverse trend was somewhat stronger when the authors adjusted for vitamin E status (p = 0.05). Analysis stratified for smoking habits showed an inverse association in former smokers (odds ratio for the 75th-25th percentile contrast = 0.63 (95 percent confidence interval 0.43-0.94)), but not in current smokers (odds ratio = 0.97 (0.71-1.32)) or in those who had never smoked (odds ratio = 1.55 (0.87-2.76)). Analysis stratified by center showed a significant inverse association between selenium levels and risk of myocardial infarction for Germany (Berlin) only (75th to 25th percentile odds ratio = 0.62 (95 percent confidence interval 0.42-0.91)), which was the center with the lowest selenium levels. It appears that the increased risk of acute myocardial infarction at low levels of selenium intake is largely explained by cigarette smoking; selenium status does not appear to be an important determinant of risk of myocardial infarction at the levels observed in a large part of Europe.

Background Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality. Methods In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488. Findings We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and, This project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement 613977 for the ODIN Integrated Project [Food-based solutions for optimal vitamin D nutrition and health through the life cycle http://www.odin-vitd.eu/]. Funding for the individual studies contributing data to this effort can be found in Appendix (S1 File), section 11.

In industrialized countries atopic diseases have been reported to be less likely in children and adolescents with a migrant background compared to non-migrants. This paper aimed at both examining and comparing prevalence of asthma, allergic rhinoconjunctivitis and atopic dermatitis and allergic sensitization to specific IgE antibodies in children and adolescents with and without a migrant background. Using data of the population-based German Health Interview and Examination Survey for children and adolescents (KiGGS; n = 17,450; 0–17 years), lifetime and 12-month prevalence of atopic diseases and point prevalence of 20 common allergic sensitizations were investigated among migrants compared to non-migrants. Multiple regression models were used to estimate the association of atopic disease and allergic sensitization with migrant background. In multivariate analyses with substantial adjustment we found atopic dermatitis about one-third less often (OR 0.73, 0.57–0.93) in participants with a two-sided migrant background. Statistically significant associations between allergic sensitizations and a two-sided migrant background remained for birch (OR 0.73, 0.58–0.90), soybean (OR 0.72, 0.54–0.96), peanut (OR 0.69, 0.53–0.90), rice (OR 0.64, 0.48–0.87), potato (OR 0.64, 0.48–0.85), and horse dander (OR 0.58, 0.40–0.85). Environmental factors and living conditions might be responsible for the observed differences.

Celiac disease is an immune-mediated systemic disorder triggered by gluten-containing grains in genetically predisposed individuals (1– 3). Its defining characteristics are enteropathy and evidence of celiac disease–specific autoantibodies to tissue transglutaminase (3). Celiac disease is usually lifelong but with a gluten-free diet it is very treatable: the mucosa of the small intestine return to their normal condition and subsequent tests for celiac disease–specific autoantibodies are negative. Celiac disease can develop at any age. Symptoms range from the classic signs of malabsorption syndrome—diarrhea, weight loss, growth failure, osteoporosis, and anemia—to nonspecific symptoms such as chronic constipation or abdominal pain (1, 2). Screening examinations in children have revealed that 50 to 70% of those affected are asymptomatic (4, 5). Celiac disease cannot develop without a genetic predisposition to HLA markers DQ2 or DQ8. Approximately one-third of the Caucasian population is DQ2-positive or DQ8-positive. If celiac disease is suspected, the first step should be to determine serum levels of IgA autoantibodies to tissue transglutaminase IgA (tTG-IgA) or to endomysium (EmA-IgA), in addition to determining total IgA to rule out IgA deficiency (2, 3). The highly sensitive and specific autoantibody tests identify patients with celiac disease and make it possible to document its prevalence and incidence, regardless of whether patients suffer any clinical complaints. The frequency of classic celiac disease with malabsorption is approximately 1 in 1000 children (6, 7). The prevalence of celiac disease that has been established using antibody screening in various European countries and North America is estimated at approximately 1% (8, 9). Incidence seems to have increased in recent decades (10). There are no current figures on the prevalence of celiac disease in children in Germany. A cross-sectional study conducted 20 years ago, involving 3004 children, found celiac disease confirmed by biopsy in one in 500 (0.2%) of the children (6). In the southern German KORA/MONICA population cohort, 63 of 4633 (1.4%) and 18 of 4173 (0.43%) of adults respectively were found to have tTG-IgA levels above the cut-off value in two cross-sectional studies (9, 11). When compared to seronegative individuals of the same ages, there was an approximately twofold increase in the risk of dying within nine years for seropositive men (217/2289 versus 11/44) and an approximately fourfold increase in risk for seropositive women (91/2281 versus 4/19) (11). Even when clinical symptoms are absent, celiac disease that remains untreated in the long term entails numerous health risks including lymphoproliferative diseases (12– 19). In children identified via screening there is increasing evidence that growth and bone quality can be adversely affected (15, 19). Because the complaints of celiac disease are so nonspecific, it often takes years before symptomatic patients are diagnosed (20). By then, symptoms and organic complications of celiac disease that has remained untreated for many years, such as pancreatic failure or atrophy of the spleen, are often no longer reversible (20– 22). We used retained samples from KiGGS study participants. The KiGGS study was a study conducted by the Robert Koch Institute in Berlin as part of German nationwide health monitoring of child and adolescent health. The retained samples were used to establish the prevalence of celiac disease–specific autoantibodies in children and adolescents in Germany and to compare the anthropometric and various laboratory parameters of seropositive and seronegative individuals.

We assessed hepatitis E virus (HEV) antibody seroprevalence in a sample of the adult population in Germany. Overall HEV IgG prevalence was 16.8% (95% CI 15.6%–17.9%) and increased with age, leveling off at >60 years of age. HEV is endemic in Germany, and the lifetime risk for exposure is high.

Background The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue. Methods Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants). Results The range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks. Conclusions These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated.

Abstract —Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and Israel. Cases (n=639) included patients with a first myocardial infarction admitted to coronary care units within 24 hours from the onset of symptoms. Controls (n=700) were selected to represent the populations originating the cases. Adipose tissue levels of fatty acids were determined by capillary gas chromatography. The mean (±SD) proportion of α-linolenic acid was 0.77% (±0.19) of fatty acids in cases and 0.80% (±0.19) of fatty acids in controls ( P =0.01). The relative risk for the highest quintile of α-linolenic acid compared with the lowest was 0.42 (95% confidence interval [CI] 0.22 to 0.81, P -trend=0.02). After adjusting for classical risk factors, the relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P -trend=0.38). The mean proportion of docosahexaenoic acid was 0.24% (±0.13) of fatty acids in cases and 0.25% (±0.13) of fatty acids in controls ( P =0.14), with no evidence of association with risk of myocardial infarction. In this large case-control study we could not detect a protective effect of docosahexaenoic acid on the risk of myocardial infarction. The protective effect of α-linolenic acid was attenuated after adjusting for classical risk factors (mainly smoking), but it deserves further research.

The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991 -1992) was used to explore the hypothesis that fatty acids of the omega-3 family inhibit breast cancer and that the degree of inhibition depends on background levels of omega-6 polyunsaturates. Considered in isolation, the level of omega-3 or omega-6 fat in adipose tissue displayed little consistent association with breast cancer across study centers. The ratio of long-chain omega-3 fatty acids to total omega-6 fat showed an inverse association with breast cancer in four of five centers. In Malaga, Spain, the odds ratio for the highest tertile relative to the lowest reached 0.32 (95% confidence interval 0.13-0.82). In this center, total omega-6 fatty acid was strongly associated with breast cancer. With all centers pooled, the odds ratio for long-chain omega-3 to total omega-6 reached 0.80 for the second tertile and 0.65 for the third tertile, a downward trend bordering on statistical significance (p for trend = 0.055). While not definitive, these results provide evidence for the hypothesis that the balance between omega-3 and omega-6 fat may play a rolein breast cancer. Am J Epidemiol 1998; 147: 342-52

A multicenter case-control study was conducted to evaluate the relations between antioxidant status assessed by biomarkers and acute myocardial infarction. Incidence cases and frequency matched controls were recruited from 10 European countries to maximize the variance in exposure within the study. Adipose tissue needle aspiration biopsies were taken shortly after the infarction and analyzed for levels of carotenoids and tocopherols. An examination of colinearity including all covariates and the three carotenoids, alpha-carotene, beta-carotene, and lycopene, showed that the variables were sufficiently independent to model simultaneously. When examined singularly, each of the carotenoids appeared to be protective. Upon simultaneous analyses of the carotenoids, however, using conditional logistic regression models that controlled for age, body mass index, socioeconomic status, smoking, hypertension, and maternal and paternal history of disease, lycopene remained independently protective, with an odds ratio of 0.52 for the contrast of the 10th and 90th percentiles (95% confidence interval 0.33-0.82, p = 0.005). The associations for alpha- and beta-carotene were largely eliminated. We conclude that lycopene, or some substance highly correlated which is in a common food source, may contribute to the protective effect of vegetable consumption on myocardial infarction risk.

BACKGROUND: Population sodium intake and its impact on public health has been a subject of a critical scientific debate for many years. The German Health Interview and Examination Survey for Adults (DEGS1) facilitate the biomarker-based estimation of sodium intake of the German population, although using spot urine concentrations to extrapolate to daily excretion estimates is associated with uncertainties that should be considered. METHODS: Casual spot urine samples of 6910 German adults collected in DEGS1 were used to representatively estimate sodium intake of the German population. To extrapolate from spot urine concentrations to daily sodium excretion, five published equations were applied, and the results were compared to recommended sodium intake values. RESULTS: The estimated means range from 166–230 mmol/d (men) and from 124–194 mmol/d (women). The variability of results also differs between applied equations; interquartile ranges vary between 41 and 133 mmol (men) and 21 and 118 mmol (women). CONCLUSIONS: Regardless of the applied equation, most German adults consume much more sodium than recommended by several institutions. To reduce uncertainty and to fully exploit the potential of biomarker-based estimates of sodium intake, either the sampling strategy should be expanded or the extrapolation from spot urines to daily intake should be refined.