1. Concept for a German Environmental Health Birth Cohort Design and Feasibility Issues Schmidt B, Moebus S, Lösch C, Pieper C, Hoffmann B, Andrich S, Schulz C, Seiwert M, Kolossa-Gehring M, Jöckel K-H Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011

2. 2 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Objectives Developing a concept for a German Environmental Health Birth Cohort for the Federal Environment Agency (Umweltbundesamt)  Broad range of environmental health problems  With regard to socioeconomic aspects and migration  Individual exposure assessment, e.g. human biomonitoring  Detection of gene x environment interactions  Current German birth cohorts are medium-sized and focus on special aspects of child health

3. 3 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Developing a concept for a German Environmental Health Birth Cohort for the Federal Environment Agency (Umweltbundesamt)  Broad range of environmental health problems  With regard to socioeconomic aspects and migration  Including Human Biomonitoring  Interaction between genes and environmental risk factors  Current German birth cohorts are medium-sized and focus on special aspects of child health Large scale birth cohort study needed, 100 000 to 200 000 participants, build as a platform for future research. Objectives

4. 4 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Review of existing birth cohort studies First idea for design issues and framework Generating possible research questions 1. expert meeting Determining design and main research questions Developing the exposure and outcome assessment 2. expert meeting Elaboration of the overall concept Progress to Date

5. 5 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Main Research Issues 1. The Impact of Environmental Pollutants and Noise on Neurodevelopment and Cognitive Abilities 2. The Impact of Endocrine Disruptors on Reproductive Development 3. The Impact of Environmental Pollutants on Pregnancy and Birth Outcomes 4. The Impact of Indoor/Outdoor Air Pollution and Inhalation Allergens on Asthma, Allergy and Wheezing 5. The Impact of Environmental Pollutants on Obesity, Insulin Resistance and Diabetes

6. 6 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011  Chemical exposures: e.g., organic/inorganic chemicals, air pollutants, …  Physical exposures: e.g., housing/neighborhood characteristics, noise, …  Biological exposures: e.g., allergens, bacteria, infections, …  Genetics: e.g., DNA, gene expression,...  Psychosocial exposures: e.g., demographics, family support, health behavior, … Exposure Measurements

7. 7 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Exposure Measurements biospecimens: blood, urine, breast milk, cord blood, placenta, meconium, nails/hair, …  Pilot study for perinatal sample collection and biobanking indoor/outdoor air pollution: allergens, particulate matter, volatile organic compounds, …  Detailed exposure assessment in subgroup via home visits noise: noise maps, models and questionnaires, …  Detailed noise assessment in subgroup

8. 8 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Recruitment Strategy  Recruitment early in pregnancy (  1st trimester)  Also: Enrollment at different stages during pregnancy and even shortly after delivery  Therefore: Multimodal approach via gynecologists, prenatal care providers, maternity wards… …but also pharmacies or public institutions  Incentives and PR tools needed to make the participant’s benefit clear

9. 9 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Selection of study locations should be based on:  socioeconomic characteristics  environmental characteristics  demographic characteristics Also needed:  Study centers with experience in recruitment  taking The German National Cohort into account Study Locations Jena Marburg Augsburg Regensburg Saarland Bochum Münster Essen Heidelberg Mannheim Freiburg Leipzig Halle Berlin Brandenburg Neubrandenburg Bremen Hamburg Hannover Braunschweig Kiel Bonn Lübeck Düsseldorf München Ludwigshafen Greifswald

10. 10 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Sample Size Prevalence Autism, Thyroid Dysfunction, Metabolic Syndrome ADHD, Asthma Impaired Neurodevelopment, Atopic Dermatitis, Obesity Design: nested case-control study (case:controls = 1:4) Frequency of environmental exposure: 10%

11. 11 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Data Collection Schedule Pregnancy 1. First trimester  10-12 GW *Medical examinations + diaries + contacting father + biol. specimens Only in subgroup: Home visit to collect environmental samplesHome visit 2. Second trimester  22-24 GW *Phone + bring-in biol. specimens 3. Third trimester  34-36 GW *Medical examinations + biol. specimens Birth 4. BirthMedical examinations + medical records + biol. specimens 5. First week of life *Questionnaire + Medical records * Handing out questionnaires, diaries and contacting father in the case of late enrollment phone or mail-in questionnaire health care professional or study center home visit

12. 12 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Data Collection Schedule Child Development 6. Age 1 MonthQuestionnaire + bring-in biol. specimens 7. Age 3 Month Questionnaire 8. Age 6 MonthQuestionnaire + bring-in biol. specimens 9. Age 12 MonthMedical examinations + biol. specimens Only in subgroup: Home visit to collect environmental samplesHome visit 10. Age 24 MonthQuestionnaire 11. Age 3 YearsMedical examinations + biol. specimens 12. Age 4 YearsQuestionnaire 13. Age 5 YearsQuestionnaire 14. Age 6 YearsMedical examinations + biol. specimens Follow-up through age 18

13. 13 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Implementation Evaluation Full study Evaluation Continuing Protocol Development Evaluation Update of study plan Developing study protocol Feasibility study A Feasibility study B Feasibility study... Feasibility studies to explore, e.g., … …effective strategies to recruit and retain participants. …cooperation with local health care providers and community-based organizations …improving response through incentives and public relations Study Timeline Start 1. year 2. year 3. year 4. year Update of study protocol

14. 14 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Next Steps  Announcing the study locations  Feasibility studies in the near future  Expert group for Ethics and Privacy Protection

15. 15 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Acknowledgements N. Berger, U. of Würzburg K. Birmingham, U. of Bristol T. Dwyer, MCRI R. Fehr, LIGA.NRW M. Flechtner-Mors, U. of Ulm J. Genuneit, University of Ulm W. Göpel, University of Lübeck J. Golding, University of Bristol D. Grabow, Kinderkrebsregister E. Hamelmann, Ruhr-U. Bochum T. Harder, UM Berlin J. Heinrich, Helmholtz C. Munich S. Hirschfeld, ENICHD U. Ranft, University of Düsseldorf U. Ravens-Sieberer, UMC Hamburg-E. O. Razum, University of Bielefeld M. Schlaud, Robert-Koch Institute C. Sommerfeld, BfR K. Stark, Robert-Koch Institute R. Thyrian, University of Greifswald H.-E. Wichmann, Helmholtz C. Munich A. Wiesel, University of Mainz G. A. Wiesmüller, U. of Münster B. Wolz, BMU M. Wilhelm, Ruhr-U. Bochum I. Zöllner, LGA Ba.-Wü. A. Hofman, EMC Rotterdam C. Hornberg, U. of Bielefeld M. Kersting, FKE Dortmund W. Kiess, University of Leipzig F. Klasen, UMC Hamburg-Eppend. U. Krämer, U. of Düsseldorf M. Kreuzer, BfS B.-M. Kurth, Robert Koch Institute K. von Mühlendahl, GAPAM M. Nieuwenhuijsen, CREAL A.-M. Nybo Andersen, U. of Copenhagen H. Pohlabeln, BIPS Federal Environment Agency of Germany (Umweltbundesamt): A. Gieß, M. Kolossa-Gehring, C. Schulz, M. Seiwert Exposure and outcome assessment for main research issues: R. von Kries, University of Munich W. Ahrens & T. Behrens, University of Bremen M. Schmidt, University of Duisburg-Essen S. Lau, University Medicine Berlin A.-G. Ziegler & C. Winkler, Helmholtz Center Munich

16. 16 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011

17. 17 Institute for Medical Informatics, Biometry and Epidemiology University Hospital of Essen, 2011 Sample Size Autism, Thyroid Dysfunction, Metabolic Syndrome ADHD, Asthma Impaired Neurodevelopment, Atopic Dermatitis, Obesity Design: embedded case-control study (case:controls = 1:4), interaction on multiplicative scale Risk allele frequency: 10% Environmental exposure: 10% Genetic OR = 1.2 Environmental OR = 1.5