New Reference Values for Thyroid Volume by Ultrasound in German Children and Adolescents from a Population-Based Study.

CONTEXT: Reliable reference values for thyroid ultrasound measurements are essential to effectively guide individual diagnostics and direct health care measures at the population level, such as iodine fortification programs. However, the latest reference values for total thyroid volume (Tvol) provided by the WHO in 2004 only apply to the 6 to 12-year-old age group and are limited to countries with a long history of iodine sufficiency, which does not reflect the situation in most European countries, including Germany. OBJECTIVE: The present aims to derive up to date thyroid volume ultrasound reference values in German children and adolescents. DESIGN: Data from the baseline assessment of a nationwide study in German children and adolescents (KiGGS) conducted between 2003 and 2006 were used to determine sex-specific reference values for Tvol in thyroid-healthy participants aged 6 to 17 years by age and body surface area (BSA) according to the Lambda-Mu-Sigma (LMS) method. RESULTS: Data from 5559 participants were available for reference chart construction (girls: 2509 (45.1%)). On average, the 97th percentile is 33.4% and 28.5% higher than the corresponding WHO's reference values for boys and girls, respectively. These findings are consistent with most other studies in German and European children and adolescents at a similar time of investigation. Notably, the sample used for this study was iodine-sufficient according to WHO criteria. CONCLUSIONS: The reference values provided by the WHO are overly conservative for this population and could potentially apply to other European countries with a similar history of iodine supply.

Seroprevalence of mucosal and cutaneous human papillomavirus (HPV) types among children and adolescents in the general population in Germany.

BACKGROUND: In Germany, HPV vaccination of adolescent girls was introduced in 2007. Nationally representative data on the distribution of vaccine-relevant HPV types in the pre-vaccination era are, however, only available for the adult population. To obtain data in children and adolescents, we assessed the prevalence and determinants of serological response to 16 different HPV types in a representative sample of 12,257 boys and girls aged 1-17 years living in Germany in 2003-2005. METHODS: Serum samples were tested for antibodies to nine mucosal and seven cutaneous HPV types. The samples had been collected during the nationally representative German Health Interview and Examination Survey for Children and Adolescents in 2003-2006. We calculated age- and gender-specific HPV seroprevalence. We used multivariable regression models to identify associations between demographic and behavioral characteristics and HPV seropositivity. RESULTS: We found low but non-zero seroprevalence for the majority of tested HPV types among children and adolescents in Germany. The overall seroprevalence of HPV-16 was 2.6%, with slightly higher values in adolescents. Seroprevalence of all mucosal types but HPV-6 ranged from 0.6% for HPV-33, to 6.4% for HPV-31 and did not differ by gender. We found high overall seroprevalence for HPV-6 with 24.8%. Cutaneous HPV type seroprevalence ranged from 4.0% for HPV-38 to 31.7% for HPV-1. In the majority of cutaneous types, seroprevalence did not differ between boys and girls, but increased sharply with age, (e.g., HPV-1 from 1.5% in 1-3-years-old to 45.1% in 10-11-years-old). Associations between behavioral factors and type-specific HPV prevalence were determined to be heterogeneous. CONCLUSIONS: We report the first nationally representative data of naturally acquired HPV antibody reactivity in the pre-HPV-vaccination era among children and adolescents living in Germany. These data can be used as baseline estimates for evaluating the impact of the current HPV vaccination strategy targeting 9-14-years-old boys and girls.

The DONALD study as a longitudinal sensor of nutritional developments: iodine and salt intake over more than 30 years in German children.

PURPOSE: Mild-to-moderate iodine deficiency was present in large parts of Germany up to the beginning 1990s and improved from then on. Current epidemiological data on spot urine iodine measurements in German children strongly suggest the re-occurrence of an impaired iodine status. We thus examined whether this re-occurrence is identifiable in more detail, through iodine analyses of 24-h urine samples of a well-characterized cohort of German children in whom samples have been systematically collected from 1985 onward. As iodized salt is a major source for iodine supply, urinary sodium excretion was additionally studied. METHODS: Daily iodine and sodium excretions were measured in 2600 24-h urine samples collected between 1985 and 2018 by 677 healthy children aged 6-12 years (participants of the DONALD study). These data were compared with 24-h iodine and sodium excretion estimates obtained from spot urine samples collected in the representative German Health Interview and Examination Surveys for Children and Adolescents KiGGS-baseline (2003-2006) and KiGGS-wave-2 (2014-2017). RESULTS: Between 1985 and1992, DONALD participants started with a median daily iodine excretion level of 40.1 µg/d. Then, during 1993-2003, iodine excretions mounted up to an approximate plateau (~ 84.8 µg/d). This plateau lasted until 2012. Thereafter, iodine concentrations started to decrease again resulting in a median iodine excretion of only 58.9 µg/d in 2018. Sodium excretion, however, had increased. The marked decrease in iodine status along with an abundant sodium excretion corresponded closely with nationwide KiGGS data. CONCLUSIONS: As exemplified for the clearly worsening iodine status in German children, longitudinal cohort studies collecting detailed biomarker-based prospective data have the potential to reliably capture health-relevant nutritional changes and trends, applicable on a more comprehensive and even representative population level.

Increased Prevalence of Subclinical Hypothyroidism and Thyroid Autoimmunity in Depressed Adolescents: Results From a Clinical Cross-Sectional Study in Comparison to the General Pediatric Population.

OBJECTIVE: The study was undertaken to determine the prevalence of subclinical and overt thyroid dysfunction as well as thyroid autoimmunity in depressed adolescents in comparison to the general pediatric population. Additionally, the relationship between parameters of thyroid function and Beck Depression Inventory-II (BDI-II) scores was examined. METHODS: Parameters of thyroid function (thyrotropin, free thyroxine, thyroid peroxidase antibodies) and prevalence of thyroid dysfunction and autoimmunity were determined in 360 adolescents (11-19 years) with at least mild depression (BDI-II score > 13) between June 2016 and December 2019 and in a representative reference cohort without evidence of impaired mental health from a nationwide survey (German Health Interview and Examination Survey for Children and Adolescents [KiGGS], 2003-2006). RESULTS: There was a higher prevalence of thyroid peroxidase antibody positivity in depressed adolescents (mean ± SD BDI-II, 30.0 ± 10.4) compared to KiGGS participants (depressed adolescents: 5.8%, 95% CI [3.7-8.6]; odds ratio [OR] 1.9, P = .009, d = 0.36; KiGGS participants: 3.1%, 95% CI [2.5-3.9]). The prevalence of subclinical hypothyroidism was likewise higher in depressed adolescents (9.1%, 95% CI [6.3-12.4] vs KiGGS participants: 2.1%, 95% CI [1.6-2.7]; OR 4.7, P < .001, d = 0.85), but no other types of thyroid dysfunction had a higher prevalence. There was no significant relationship between parameters of thyroid function and BDI-II scores, as examined by multiple regression considering relevant covariates. The positive results were verified in a subsample of patients with a confirmed diagnosis of depression (N = 284). CONCLUSIONS: The prevalence of subclinical hypothyroidism and of thyroid autoimmunity in depressed adolescents is increased. The etiology of these observations is not well understood, and further studies to examine the underlying relationship are required. Moreover, thyroid autoimmunity may constitute an additional risk factor for depression on its own.

Spot urine iodine levels below the WHO recommendation are not related to impaired thyroid function in healthy children and adolescents.

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 < 100 µg/L (57%, 67%, 65% of the age groups 0-5, 6-12 and 13-18 years), the median iodine excretion was 86 µg/L in boys and 80 µg/L in girls. The iodine levels revealed no significant correlation with the thyroid biomarkers TSH, FT4 and FT3. Moreover, iodine values revealed no correlation with levels of antibodies against thyroid peroxidase or thyroglobulin. 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.

The association between thyroid function biomarkers and attention deficit hyperactivity disorder.

The relation between thyroid function biomarkers and attention deficit hyperactivity disorder (ADHD) in children and adolescents is currently unclear. Cross-sectional data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Baseline) was analyzed to assess the association between thyroid function biomarkers and ADHD in a population-based, nationally representative sample. The study cohort included 11,588 children and adolescents with 572 and 559 having an ADHD diagnosis or symptoms, respectively. ADHD symptoms were assessed through the Inattention/Hyperactivity subscale of the Strength and Difficulties Questionnaire. ADHD diagnosis was determined by a physician or psychologist. Serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations were determined enzymatically. Adjusted regression models were used to relate serum TSH, fT3, and fT4 with risk for ADHD diagnosis or symptoms. In children, a 1 mIU/l higher TSH was related to a 10% lower risk (odds ratio [OR] 0.90; 95% confidence interval [CI] 0.81-1.00) of ADHD diagnosis. We found a significant positive association between fT3 and continuously assessed ADHD symptoms in children (ß 0.08; 95% CI 0.03-0.14). Our results suggest that physical maturity may influence the association between thyroid function biomarkers and risk for ADHD.

Standardized Map of Iodine Status in Europe.

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 <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

Contribution of iodized salt to total iodine and total salt intake in Germany.

BACKGROUND: Salt reduction campaigns without a parallel increase of iodine fortification will lead to a worsened iodine status in countries with a relevant salt iodization. A decline in iodine supply bears the risk of higher prevalences of goiter, thyroid nodules, and cognitive delay in children. Against this background, we analyzed the contribution of iodized salt to total iodine and salt intake in Germany and compared the results with data from Switzerland. METHODS: Analyses were performed with data of the representative German Health-Interview and Examination-Survey for Adults (DEGS1, 2008-2011) using spot urine measurements of creatinine, iodine, and sodium (n = 6738). Median daily iodine and salt intakes were calculated by estimating 24-h iodine and sodium excretions from urinary analyte/creatinine ratios. Linear regressions were used to deduce iodine intake that originates from iodine containing foods (i.e., salt-independent iodine). From this, ingested iodine originating from salt and the proportion of iodized salt to total salt intake were calculated. Data from Switzerland were obtained from the literature. RESULTS: In Germany, only 42% (52.2 µg/d) of the predicted median total iodine intake (126.2 µg/d), i.e., 12% less than in Switzerland, were found to originate from salt, whereas 73.7 µg/d came from iodine containing foods. 28% (2.6 g/d) of the median salt intake (9.3 g/d) of the German population was calculated to represent iodized salt against 43% in Switzerland. CONCLUSIONS: Along with an almost identical inherent iodine intake in Germany and Switzerland, the average total iodine intake, the contribution of iodized salt to total iodine intake, and the proportion of iodized salt to total salt are higher in Switzerland than in Germany. Despite this, iodine fortification of table salt has recently been increased in Switzerland from 20 to 25 mg/kg to ensure iodine sufficiency in the population, whereas in Germany fortification still remains at a mean level of 20 mg/kg implying a growing risk of increasing iodine deficiency rates if general salt intake drops.

Mucosal and cutaneous Human Papillomavirus seroprevalence among adults in the prevaccine era in Germany - Results from a nationwide population-based survey.

BACKGROUND: Human Papillomavirus (HPV) vaccination of girls was introduced in Germany in 2007. However, data on the distribution of vaccine-relevant HPV types in the general population in Germany in the prevaccine era are limited. METHODS: Serum samples collected during the German National Health Interview and Examination Survey 1998 (GNHIES98), a nationally representative study including men and women aged 18-79 years, were tested for antibodies to 19 mucosal and cutaneous HPV types. Multivariable regression models were developed to identify associations between demographic and behavioral characteristics and HPV seropositivity. RESULTS: Of the 6517 serum samples tested, almost a quarter was seropositive for at least one of the nine HPV vaccine types with no clear age-pattern. HPV-6 and HPV-59 were the most common mucosal types, while HPV-1 and HPV-4 were the most common cutaneous HPV types. Factors independently associated with HPV-16 seroprevalence were seropositive to other sexually transmitted infections and lifetime number of sex partners, as well as urbanity (only among females). CONCLUSIONS: Prevalence of naturally acquired antibodies to HPV types which can be prevented by vaccination is high in both sexes and all age groups. These data can serve as baseline estimates to evaluate the population-level impact of the current vaccination strategy.

Cytomegalovirus (CMV) seroprevalence in the adult population of Germany.

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.

Implications of standardization of serum 25-hydroxyvitamin D data for the evaluation of vitamin D status in Germany, including a temporal analysis.

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 < 30, 30- < 50, and > =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 < 30 nmol/l. Thus, the proportion of deficient vitamin D levels in the German population is still considerable. CONCLUSIONS: The use of standardization of 25(OH)D levels has a substantial impact on estimates of the vitamin D status in Germany. Since clinical diagnostic, therapeutic and public health decision-making require valid and comparable data, standardization and calibration of commercial, clinical and research laboratory assays for 25(OH)D measurement should become common practice. Until then, researchers, health practitioners and policy makers should be aware of the peculiarities of the measurement methods when comparing and interpreting 25(OH)D levels.

Dietary Acid Load and Potassium Intake Associate with Blood Pressure and Hypertension Prevalence in a Representative Sample of the German Adult Population.

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.

Allergic diseases in children and adolescents in Germany. Results of the cross-sectional KiGGS Wave 2 study and trends.

Allergic diseases are among the most common health issues children and adolescents face. Allergic reactions occur when the immune system becomes allergically sensitised and are detected by measuring levels of specific immunoglobulin E antibodies (IgE antibodies) in the blood. This article discusses the prevalences of bronchial asthma, hay fever, atopic dermatitis and allergic contact dermatitis for 0- to 17-year-olds, as well as the prevalence of allergic sensitisation to a mix of frequent inhalant allergens (SX1) among 3- to 17-year-olds based on data from the second wave of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2, 2014-2017). 12-month prevalence trends between KiGGS Wave 2 and the KiGGS baseline study (2003-2006) are shown according to gender and age group. There were no significant changes in the 12-month prevalence of hay fever (8.8%) atopic dermatitis (7.0%) and bronchial asthma (3.5%) compared to the KiGGS baseline study, which indicates a stabilisation at a high level. More than one in six children (16.1%) currently suffer from at least one of these three diseases. 37.1% of 3- to 17-year-olds are sensitised to the multiple allergen mix SX1. Similar to the development of disease prevalence, SX1 sensitisation too has remained stable at a high level over the course of the past ten years.

Interlaboratory variability of urinary iodine measurements.

BACKGROUND: The iodine status of populations is usually assessed by median urinary iodine concentrations (UIC) in population-based studies, but it is unclear to which extent UIC are comparable across different laboratories. The aim of our study was to investigate the variability of UIC measurements across three well-established German laboratories with long-term clinical-chemical expertise in iodine measurements and to compare these results to the gold standard inductively coupled plasma mass spectrometry (ICP-MS). METHODS: UIC levels were measured from 303 urine samples derived from the "Dortmund Nutritional and Anthropometric Longitudinally Designed Study" and from volunteers of the University Medicine Greifswald at four different German laboratories. Three of these laboratories used Sandell-Kolthoff reaction with different digestion methods for UIC measurement (Lab1-Lab3), whereas one laboratory used ICP-MS as gold standard. RESULTS: Median UIC levels were significantly different across the four laboratories (ICP-MS: 77 µg/L; Lab1: 69 µg/L; Lab2: 73 µg/L; Lab3: 111 µg/L). Linear regressions associating UIC levels of Lab1-Lab3 with UIC levels of ICP-MS showed intercepts significantly different from 0 and slopes significantly different from 1. Intraclass correlations (ICC) in comparison to ICP-MS were 0.91 for Lab1, 0.98 for Lab2, and 0.69 for Lab3. Using the digestion method of Lab2 in Lab3 improved the comparison of UIC levels of Lab3 with those from the ICP-MS (ICC=0.89). CONCLUSIONS: We have demonstrated larger interlaboratory variations across high-quality laboratories with long-lasting experience in iodine measurements indicating a relevant non-comparability of UIC measurements in iodine monitoring studies. Therefore, standardization of UIC measurements has to be expedited.

Baseline Assessment of 25-Hydroxyvitamin D Assay Performance: A Vitamin D Standardization Program (VDSP) Interlaboratory Comparison Study.

The Vitamin D Standardization Program (VDSP) coordinated an interlaboratory study to assess the comparability of measurements of total 25-hydroxyvitamin D [25(OH)D] in human serum, which is the primary marker of vitamin D status. A set of 50 individual donor samples were analyzed by 15 different laboratories representing national nutrition surveys, assay manufacturers, and clinical and/or research laboratories to provide results for total 25(OH)D using both immunoassays (IAs) and LC tandem MS (MS/MS). The results were evaluated relative to bias compared with the target values assigned based on a combination of measurements at Ghent University (Belgium) and the U.S. National Institute of Standards and Technology using reference measurement procedures for the determination of 25(OH)D2 and 25(OH)D3. CV and mean bias for each laboratory and assay platform were assessed and compared with previously established VDSP performance criteria, namely CV ≤ 10% and mean bias ≤ 5%. Nearly all LC-MS/MS results achieved VDSP criteria, whereas only 50% of IAs met the criterion for a ≤10% CV and only three of eight IAs achieved the ≤5% bias. These results establish a benchmark for the evaluation of 25(OH)D assay performance and standardization activities in the future.

Baseline Assessment of 25-Hydroxyvitamin D Reference Material and Proficiency Testing/External Quality Assurance Material Commutability: A Vitamin D Standardization Program Study.

The Vitamin D Standardization Program (VDSP) coordinated a study in 2012 to assess the commutability of reference materials and proficiency testing/external quality assurance materials for total 25-hydroxyvitamin D [25(OH)D] in human serum, the primary indicator of vitamin D status. A set of 50 single-donor serum samples as well as 17 reference and proficiency testing/external quality assessment materials were analyzed by participating laboratories that used either immunoassay or LC-MS methods for total 25(OH)D. The commutability test materials included National Institute of Standards and Technology Standard Reference Material 972a Vitamin D Metabolites in Human Serum as well as materials from the College of American Pathologists and the Vitamin D External Quality Assessment Scheme. Study protocols and data analysis procedures were in accordance with Clinical and Laboratory Standards Institute guidelines. The majority of the test materials were found to be commutable with the methods used in this commutability study. These results provide guidance for laboratories needing to choose appropriate reference materials and select proficiency or external quality assessment programs and will serve as a foundation for additional VDSP studies.

Decreasing seroprevalence of herpes simplex virus type 1 and type 2 in Germany leaves many people susceptible to genital infection: time to raise awareness and enhance control.

BACKGROUND: Herpes simplex infections (HSV1/2) are characterized by recurrent symptoms, a risk of neonatal herpes, and the facilitation of HIV transmission. In Germany, HSV1/2 infections are not notifiable and data are scarce. A previous study found higher HSV1/2 seroprevalences in women in East Germany than in women in West Germany. We assessed changes in the HSV1/2 seroprevalences over time and investigated determinants associated with HSV1/2 seropositivity to guide prevention and control. METHODS: The study was based on the German Health Interview and Examination Survey for Adults (DEGS; 2008-2011) and the German National Health Interview and Examination Survey (GNHIES; 1997-1999). We tested serum samples from DEGS participants for HSV1 and HSV2 immunoglobulin G. We used Pearson's χ2 test to compare the HSV1/HSV2 seroprevalences in terms of sex, age, and region of residence (East/West Germany) and investigated potential determinants by calculating prevalence ratios (PR) with log-binomial regression. All statistical analyses included survey weights. RESULTS: In total, 6627 DEGS participants were tested for HSV1, and 5013 were also tested for HSV2. Overall, HSV1 seroprevalence decreased significantly from 1997-1999 (82.1%; 95%CI 80.6-83.6) to 2008-2011 (78.4%; 95%CI 77.8-79.7). In the same period, overall HSV2 seroprevalence decreased significantly from 13.3% (95%CI 11.9-14.9) to 9.6% (95%CI 8.6-10.8), notably in 18-24-year-old men (10.4 to 0%) in East Germany. Women were more likely than men to be seropositive for HSV1 (PR 1.1) or HSV2 (PR 1.6). A lower level of education, smoking, and not speaking German were associated with HSV1 in both sexes. Women of older age, who smoked, or had a history of abortion and men of older age or who had not attended a nursery school during childhood were more often seropositive for HSV2. CONCLUSION: The reduced seroprevalences of HSV1 and HSV2 leave more people susceptible to genital HSV1/2 infections. Practitioners should be aware of HSV infection as a differential diagnosis for genital ulcers. We recommend educational interventions to raise awareness of the sexual transmission route of HSV1/2, possible consequences, and prevention. Interventions should especially target pregnant women, their partners, and people at risk of HIV.

Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium.

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 <30 nmol/L were 1.15 (1.00-1.29), 1.33 (1.16-1.51), and 1.67 (1.44-1.89), respectively. We observed similar results for cardiovascular mortality, but there was no significant linear association between 25(OH)D and cancer mortality. There was also no significantly increased mortality risk at high 25(OH)D levels up to 125 nmol/L. INTERPRETATION: In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths.

12-Month prevalence of allergies in Germany.

The prevalence of allergies has increased dramatically during recent decades, and thus, got into the focus of public health. As part of the 2014 German Health Update (GEDA 2014/2015-EHIS), 28.1% of respondents reported that they were affected by an allergic disease other than asthma. Reports of allergies are more common among women than men and among younger and middle-aged adults than people over the age of 65. Adults with higher levels of education stated more frequently that they are affected by allergies than adults with lower levels of education. Allergic reactions occur in various organ systems, but the skin, mucous membranes, respiratory tract and the intestines are most commonly affected. As allergic reactions often significantly restrict people's quality of life, early diagnosis and appropriate care for sufferers is essential.

Lower Prevalence of Atopic Dermatitis and Allergic Sensitization among Children and Adolescents with a Two-Sided Migrant Background.

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.