Sibylle Koletzko

Ludwig-Maximilians-University of Munich, München, Bavaria, Germany

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Publications (308)1358.7 Total impact

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    ABSTRACT: Whether the strength of associations between parental and child allergic diseases differs by whether the first onset of the parental disease is before or after a child's birth has never been examined and is the aim of this study. Yearly childhood asthma, allergic rhinitis and eczema diagnoses were longitudinally regressed against the effect of a parental disease (pre versus post child birth) of the same type separately for each parent using generalized estimation equations. Both a maternal and paternal history of asthma were associated with childhood asthma prevalence up to 15 years of age. Effect estimates were similar for parental asthma with first onset before and after the birth of the child. The results for allergic rhinitis and eczema were less consistent. Parental allergic diseases with first onsets before and after the birth of a child both pose risks to childhood allergic disease in the offspring, especially for asthma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Allergy 03/2015; DOI:10.1111/all.12609 · 6.00 Impact Factor
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    ABSTRACT: To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort. Children from 6 clinical centers in 4 countries positive for HLA-DR3-DQ2 or DR4-DQ8 were annually screened for tissue transglutaminase antibodies (tTGA) and assessed for symptoms by questionnaires. Associations of symptoms with anthropometrics, known risk factors for CD, tTGA levels, and mucosal lesions in those biopsied were examined. Of 6706 screened children, 914 developed persistent positive tTGA, 406 underwent biopsies, and 340 had CD. Compared with age-matched tTGA-negative children, those with persistent tTGA were more likely to have symptoms at 2 (34% vs 19%, P < .001) and 3 years of age (28% vs 19%, P = .009) but not at 4 years (27% vs 21%, NS). Z-scores for height, weight, and BMI did not differ between groups. In children with persistent tTGA, having ≥1 symptom was associated with family history of CD (odds ratio = 2.59, 95% confidence interval, 1.21-5.57) but not with age, gender, or HLA-DR3-DQ2 homozygosity. At seroconversion, tTGA levels were higher in symptomatic than asymptomatic children (P < .001), in those from CD families (P < .001), and in US participants (P < .001) but not associated with age, gender, or HLA genotype. tTGA levels correlated with severity of mucosal lesions both in symptomatic (r = 0.53, P < .001) and asymptomatic children (r = 0.22, P = .01). A majority of children detected with persistent tTGA in screenings are asymptomatic and have normal growth by age 4 years. tTGA levels correlate more strongly with severity of mucosal lesions in symptomatic as compared with asymptomatic children. Copyright © 2015 by the American Academy of Pediatrics.
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    ABSTRACT: Background New evidence emerged on early feeding practices and the risk of coeliac disease.AimTo systematically update evidence on these practices to find out whether there is a need to revise current recommendations.MethodsMEDLINE, EMBASE and the Cochrane Library were searched from July 2012 (end of last search) to February 2015 for studies of any design that assessed the effect of gluten consumption and breastfeeding on the development of coeliac disease and/or coeliac disease-related autoimmunity.ResultsWe identified 21 publications, including two, new, large, randomised controlled trials performed in high-risk infants. Exclusive or any breastfeeding, as well as breastfeeding at the time of gluten introduction, did not reduce the risk of developing coeliac disease during childhood. For infants at high risk of developing coeliac disease, gluten introduction at 4 months of age in very small amounts, or at 6 or 12 months of age, resulted in similar rates of coeliac disease diagnosis in early childhood. Later gluten introduction was associated with later development of coeliac specific autoimmunity and coeliac disease during childhood, but not total risk reduction. Observational studies indicate that consumption of a higher amount of gluten at weaning may increase the risk for coeliac disease development.Conclusions Infant feeding practices (breastfeeding, time of gluten introduction) have no effect on the risk of developing coeliac disease during childhood (at least at specific timeframes evaluated in the included studies), necessitating an update of current European recommendations.
    Alimentary Pharmacology & Therapeutics 03/2015; DOI:10.1111/apt.13163 · 4.55 Impact Factor
  • Pneumologie 02/2015; 69(S 01). DOI:10.1055/s-0035-1544620
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    ABSTRACT: Background: IgA- and IgG-antibodies against deamidated gliadin peptides (DGP) specifically bind the disease-inducing antigen and might be superior to transglutaminase type 2 (TG2) IgA in monitoring patients on a gluten-free diet (GFD). The aim of this study was to compare the performance of DGP-IgG and DGP-IgA with TG2-IgA of four manufacturers in pediatric celiac patients at diagnosis and during follow-up under a GFD. Patients and Methods: In total 411 sera of 91 IgA competent children with biopsy proven celiac disease were analyzed at diagnosis and during follow-up on a GFD. Ninety-eight children with normal duodenal histology served as controls. The tests (TheBindingSite, Euroimmun, Phadia, part of Thermo Fisher Scientific, INOVA) for detection of TG2-IgA, DGP-IgG and DGP-IgA were used according to the manufacturers' instructions. Results: Sensitivity to diagnose CD was high for TG2-IgA (100 %) and DGP-IgG (90 - 100 %), but lower for DGP-IgA (67 - 86 %). Specificity was high for all tests (97 - 100 %). The frequency of TG2-IgA titers > 10 × upper limit of normal at diagnosis ranged from 47 - 90 %. Under a GFD DGP-IgA became negative more rapidly than DGP-IgG and TG2-IgA. Non-adherence to GFD was best indicated by positive TG2-IgA. Conclusions: Combined testing for TG2-IgA and DGP-IgG does not increase the detection rate of CD in IgA competent children compared to TG2-IgA only. There are significant differences with respect to proportions of celiac children with titers > 10 × ULN between the manufacturers. This calls for harmonization of tests. TG2-IgA showed the highest titer rise with non-adherence to the GFD, independent of the manufacturer. © Georg Thieme Verlag KG Stuttgart · New York.
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    ABSTRACT: ZUSAMMENFASSUNG Hintergrund: Chronisch-entzündliche Darmerkrankungen (CED) treten in jedem Alter auf, der Erkrankungsgipfel liegt aber im Jugend-und jungen Erwachsenenalter. Eine Erfassung pädiatrischer Patienten bietet die Möglichkeit, Diagnose und Therapie zu dokumentieren und so zu optimieren. Methoden: Zwischen 2004–2014 wurden 3 991 CED-Patienten unter 18 Jahren im Register CEDATA-GPGE erfasst. Patienten mit Registrierung bei Diagnose und dokumen-tiertem Verlauf > 3 Monate (N = 1 257) wurden bezüglich der Dauer und Art der Symp-tomatik bis zur Diagnose, der Vollständigkeit der Diagnostik, des Erkrankungsphänotyps sowie der initialen Therapie getrennt nach Alter unter und über 10 Jahre ausgewertet. Ergebnisse: Von 958 vollständig dokumentierten Patienten hatten 616 (64,3 %) einen M. Crohn (MC), 278 (29 %) eine Colitis ulcerosa (CU), 64 (6,7 %) eine unklassifizierte chronisch-entzündliche Darmerkrankung und 23,2 % waren jünger als 10 Jahre. Die diagnostische Latenz war bei Morbus Crohn länger als bei Colitis ulcerosa (0,5 versus 0,3 Jahre), unabhängig vom Alter. Einen ileo kolonischen Befall hatten 62,5 %, eine Be-teiligung im oberen Gastrointestinaltrakt > 50 % der Crohn-Patienten. Eine subtotale oder Pankolitis betraf 71 % der Patienten mit CU. Die den Leitlinien entsprechende Di-agnostik verbesserte sich kontinuierlich. So wurden 2004/2005 etwa 69 % endosko-pisch mit Ileo koloskopie und Ösophagogastroduodenoskopie untersucht, 2013/2014 fast 100 %, auch der Anteil der empfohlen Dünndarmdiagnostik stieg von 41,2 % auf 60,9 %. Bei der initialen Therapie dominierten 5-Aminosalizylate (86,8 % MC, 100 % CU) und Glukokortikoide (60,6 % MC, 65,6 % CU). Eine enterale Ernährungstherapie er-hielten 32 % der Morbus-Crohn-Patienten.
    Deutsches Ärzteblatt International 01/2015; 2015(112):121-7. DOI:10.3238/arztebl.2015.0121 · 3.61 Impact Factor
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    ABSTRACT: Background Vitamin D is well recognized for its role in skeletal health and its involvement in the modulation of the immune system. In the literature, controversial results are reported for atopic diseases. Thus, we investigated the association between vitamin D status and the prevalence of atopic diseases.Methods Serum 25-hydroxy-vitamin D (25(OH)D) concentrations were measured in a sample of 2815 10-years old children from two German birth cohort studies. Self-reported physician-diagnosed eczema, hay fever or allergic rhinitis, and asthma were used as outcome variables as well as specific IgE positivity against common allergens. We applied logistic regression models, deriving adjusted odds ratio estimates (aOR) and 95% confidence intervals (CI).ResultsFor asthma and hay fever or allergic rhinitis, no associations existed with serum 25(OH)D concentrations. We observed a significant positive relationship between serum 25(OH)D levels and eczema at age 10 (aOR¿=¿1.09, CI¿=¿1.01-1.17, per 10 nmol/l increase in serum 25(OH)D levels) and for the lifetime prevalence of eczema (aOR¿=¿1.05, CI¿=¿1.01-1.09). Specific IgE positivity for food allergens (aOR¿=¿1.07, CI¿=¿1.02-1.11) and aeroallergens (aOR¿=¿1.05, CI¿=¿1.01-1.08) at age 10, as well as lifetime prevalence, was significantly related to the vitamin D status.Conclusion In this study we found no indication that higher blood 25(OH)D levels are associated with decreased risk for any of the atopic outcomes in children. However, we observed a positive association of serum 25(OH)D concentrations with eczema and detectable specific IgE. Due to the given limitations of our study, the clinical relevance of these findings needs further clarification.
    BMC Pediatrics 11/2014; 14(1):286. DOI:10.1186/s12887-014-0286-3 · 1.92 Impact Factor
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    ABSTRACT: Aim Residential mobility during childhood has been associated with several adverse health outcomes. The present study investigates the influence of residential mobility during childhood measured by the frequency of moves, the child’s age at the time of the move and the total distance moved on the development of behavioural problems in school-age children. Subject and methods Data (N = 2,933) of two German population-based, prospective birth-cohort studies were used. Measurement of children’s residential mobility is based on the addresses at birth, 2, 6 and 10 years, which were collected by questionnaires and subsequently geocoded. Behavioural outcomes were assessed using the Strengths and Difficulties Questionnaire applied at 10-year follow-up. Multiple logistic regression analyses controlling for sex and age of the child, study centre, parental educational level, mother’s age at birth, single parent status and child’s time spent in front of a screen were applied. Results Children with two or more relocations—odds ratio (OR) = 1.95, 95 % confidence interval (CI) = 1.23–3.11—who moved at school age (OR = 1.97, CI = 1.17–3.31) or who moved more than 50 km in total (OR = 1.76, CI = 1.03–3.00) showed a significantly increased risk for the development of behavioural problems measured by the Total Difficulties Score compared to children who have never moved. Moving during early childhood and moving only short distance (less than 10 km in total) were not associated with behavioural problems. Conclusion Increased residential mobility during childhood and especially moves at school age may negatively affect children’s later behaviour. Prevention may consist in parental or teacher’s support of children to cope with moving.
    Journal of Public Health 10/2014; 21(1). DOI:10.1007/s10389-012-0522-y · 2.06 Impact Factor
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    ABSTRACT: Background A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. Methods We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. Results Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. Conclusions As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children. (Funded by the European Commission and others; PreventCD Current Controlled Trials number, ISRCTN74582487 .).
    New England Journal of Medicine 10/2014; 371(14):1304-1315. DOI:10.1056/NEJMoa1404172 · 54.42 Impact Factor
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    ABSTRACT: Background and aims Measurement of 7 alpha-hydroxy-4-cholesten-3-one (C4) in serum is a semiquantitative test for bile acid malabsorption (BAM). We have previously established pediatric normal values for C4 with an upper limit of normal of 66.5 ng/mL, independent of age and sex. Here we performed the C4 test in 58 pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). Methods C4 was measured using high performance liquid chromatography (HPLC) in fasting serum samples of 44 patients with CD (range 7–19 years) and 14 with UC (4–18 years). Disease activity was assessed by the pediatric CD and UC activity indices (PCDAI and PUCAI, respectively) plus serum (CRP, ESR) and fecal inflammatory markers (calprotectin). Results C4 concentrations were increased in 10 CD (23%) (range: 70.8–269.3 ng/mL) but only one UC patient (72.9 ng/mL). CD patients with diarrhea (n = 12) had higher C4-values compared to those without (76.9 vs. 30.4 ng/mL; p = 0.0043). Ileal resection in CD patients (n = 10) was associated with increased C4 concentrations (81.2 vs. 24.3 ng/mL, p = 0.0004). No correlation was found between C4 values and inflammatory markers. Six of 7 CD patients with persistent diarrhea but quiescent disease (PCDAI ≤ 12.5) had C4 values indicating BAM. Conclusion Elevated C4 concentrations indicating BAM are common in children with CD. They are associated with ileal resection and non-bloody diarrhea in the absence of active disease or elevated inflammatory markers. The C4-test identifies a subgroup of CD patients with persistent diarrhea in spite of clinical remission which may benefit from bile acid binding therapy.
    Journal of Crohn s and Colitis 09/2014; 8(9). DOI:10.1016/j.crohns.2014.02.027 · 3.56 Impact Factor
  • Journal of Crohn s and Colitis 09/2014; 8:S406. DOI:10.1016/S1873-9946(14)50046-3 · 3.56 Impact Factor
  • Journal of Crohn s and Colitis 09/2014; 8:S412. DOI:10.1016/S1873-9946(14)50068-2 · 3.56 Impact Factor
  • Journal of Crohn s and Colitis 09/2014; 8:S422. DOI:10.1016/S1873-9946(14)50096-7 · 3.56 Impact Factor
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    ABSTRACT: Patients with a diverse spectrum of rare genetic disorders can present with inflammatory bowel diseases (monogenic IBD). Patients with these disorders often develop symptoms during infancy or early childhood, along with endoscopic or histologic features of Crohn's disease, ulcerative colitis or IBD unclassified. Defects in interleukin 10 signaling have a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Several genetic defects that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the IBD-like phenotype. Several of these monogenic conditions do not respond to conventional therapy and are associated with high morbidity and mortality. Due to the broad spectrum of these extremely rare diseases, a correct diagnosis is frequently a challenge and often delayed. In many cases, these diseases cannot be categorized based on standard histologic and immunologic features of IBD. Genetic analysis is required to identify the cause of the disorder and offer the patient appropriate treatment options, which include medical therapy, surgery, or allogeneic hematopoietic stem cell transplantation. In addition, diagnosis based on genetic analysis can lead to genetic counseling for family members of patients. We describe key intestinal, extra-intestinal, and laboratory features of 50 genetic variants associated with IBD-like intestinal inflammation. We provide approaches for identifying patients likely to have these disorders. We discuss classical approaches to identify these variants in patients, starting with phenotypic and functional assessments that lead to analysis of candidate genes. As a complementary approach, we discuss parallel genetic screening using next-generation sequencing followed by functional confirmation of genetic defects.
    Gastroenterology 07/2014; 147(5). DOI:10.1053/j.gastro.2014.07.023 · 12.82 Impact Factor
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    ABSTRACT: The presence of HLA haplotype DR3-DQ2 or DR4-DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG).
    New England Journal of Medicine 07/2014; 371(1):42-9. DOI:10.1056/NEJMoa1313977 · 54.42 Impact Factor
  • Zeitschrift für Gastroenterologie 07/2014; 52(7):711-743. DOI:10.1055/s-0034-1366687 · 1.67 Impact Factor
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    ABSTRACT: AIM: We investigated whether objectively measured access to urban green spaces is associated with behavioural problems in 10-year old children living in Munich and its surrounding areas. METHODS: Behavioural problems were assessed in the GINIplus and LISAplus 10-year follow-up between 2006 and 2009 using the Strengths and Difficulties Questionnaire. Access to green spaces was defined using the distance from a child's residence to the nearest urban green space. Associations between access to urban green spaces and behavioural problems were assessed using proportional odds and logistic regression models in 1932 children with complete exposure, outcome and covariate data. RESULTS: The distance between a child's residence and the nearest urban green space was positively associated with the odds of hyperactivity/inattention, especially among children with abnormal values compared to children with borderline or normal values (odds ratio (OR)=1.20 (95% confidence interval (CI)=1.01-1.42) per 500m increase in distance). When stratified by sex, this association was only statistically significant among males. Children living further than 500m away from urban green spaces had more overall behavioural problems than those living within 500m of urban green spaces (proportional OR=1.41 (95% CI=1.06-1.87)). Behavioural problems were not associated with the distance to forests or with residential surrounding greenness. CONCLUSION: Poor access to urban green spaces was associated with behavioural problems in 10-year old children. Results were most consistent with hyperactivity/inattention problems.
    Environment International 06/2014; 71C:29-35. DOI:10.1016/j.envint.2014.06.002 · 5.66 Impact Factor
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    ABSTRACT: Crohn disease is an inflammatory bowel disease (IBD) with a complex mode of inheritance. Although nucleotide binding and oligomerization domain containing 2 (NOD2) is the strongest risk factor, the cause of Crohn disease remains unknown in the majority of the cases. X-linked inhibitor of apoptosis (XIAP) deficiency causes X-linked lymphoproliferative syndrome type 2. IBD has been reported in some XIAP-deficient patients.
    Journal of Allergy and Clinical Immunology 06/2014; DOI:10.1016/j.jaci.2014.04.031 · 11.25 Impact Factor
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    ABSTRACT: Background: Although rotavirus (RV) vaccination was licensed in 2006, it was not included into the officially recommended German childhood vaccination schedule until 2013. Local differences in health policies in the past led to large differences in vaccination coverage rate among the federal states of Germany. This enables an ecologic study of RV vaccine effectiveness. Methods: We performed a population-based retrospective analysis of RV vaccination use, RV notification and hospitalization among 0 to 5-year-old children in Germany during 2006 to 2011/2012. We compared effectiveness of the 2 RV vaccines, Rotateq and Rotarix, in an ambulatory setting and analyzed potential side effects. Results: We observed a significant reduction in RV notifications since introduction of RV vaccination. In areas attaining vaccine coverage of 64%, RV-related hospital admissions of 0 and 1-year-old children decreased by 60% compared with 19% reduction in the low vaccination coverage area. Decrease in RV-related hospitalizations of 0 and 1-year-old children was specific and significantly associated with vaccination coverage of the individual federal state (P < 0.0001, r = -0.68). There was no overall increase in intussusception rate or Kawasaki disease-related hospital admissions since introduction of RV vaccination. The 2 licensed RV vaccines had similar effectiveness in the ambulatory setting. Conclusions: Postmarketing data suggest that RV vaccination is efficient in reducing RV-related hospitalizations. There is no apparent difference in effectiveness for Rotarix and Rotateq.
    The Pediatric Infectious Disease Journal 06/2014; 33(11). DOI:10.1097/INF.0000000000000441 · 3.14 Impact Factor
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    ABSTRACT: Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.

Publication Stats

6k Citations
1,358.70 Total Impact Points

Institutions

  • 1998–2015
    • Ludwig-Maximilians-University of Munich
      • • Children in the Department of Surgery, Dr. von Hauner Children's Hospital
      • • Department of Internal Medicine II
      München, Bavaria, Germany
  • 2001–2014
    • Technische Universität München
      München, Bavaria, Germany
  • 2013
    • University of Groningen
      Groningen, Groningen, Netherlands
    • University of British Columbia - Vancouver
      • School of Population and Public Health
      Vancouver, British Columbia, Canada
    • Max Planck Institute of Psychiatry
      München, Bavaria, Germany
  • 2012
    • Medical University of Warsaw
      Warszawa, Masovian Voivodeship, Poland
    • Helmholtz Zentrum München
      • Institut für Epidemiologie
      München, Bavaria, Germany
  • 1995–2012
    • University Hospital München
      München, Bavaria, Germany
  • 2010
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
  • 2009
    • Fudan University
      Shanghai, Shanghai Shi, China
    • University of Wuerzburg
      • Department of Internal Medicine II
      Würzburg, Bavaria, Germany
  • 2008
    • St. Marien- und St. Annastiftskrankenhaus
      Ludwigshafen, Rheinland-Pfalz, Germany
  • 2006–2007
    • Max von Pettenkofer-Institut
      München, Bavaria, Germany
    • University of Southampton
      • Institute of Human Nutrition
      Southampton, ENG, United Kingdom
  • 2003
    • Marien-Hospital Wesel
      Wesel, North Rhine-Westphalia, Germany
    • Pathologisches Institut Bremerhaven
      Bremerhaven, Bremen, Germany
  • 1993
    • University of Toronto
      • Hospital for Sick Children
      Toronto, Ontario, Canada
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany