Concept for a German Environmental Health Birth Cohort Design and Feasibility Issues

1. Concept for a GermanEnvironmental HealthBirth CohortDesign 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. 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. 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 • Including Human Biomonitoring • Interaction between genesandenvironmental 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.

4. Progress to Date Reviewof existing birth cohort studies First idea for design issues and framework Generating possible research questions1. expert meeting Determining design and main research questions Developing theexposureand outcome assessment 2. expert meeting Elaboration of the overall concept

5. 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 PregnancyandBirthOutcomes 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. Exposure Measurements • 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, …

7. 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. Recruitment Strategy • Recruitment early inpregnancy ( 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 • Incentivesand PR tools needed to make the participant’s benefit clear

9. Study Locations 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 Greifswald Kiel Lübeck Hamburg Neubrandenburg Bremen Berlin Brandenburg Hannover Braunschweig Münster Essen Bochum Halle Düsseldorf Leipzig Bonn Marburg Jena Ludwigshafen Mannheim Saarland Regensburg Heidelberg Augsburg München Freiburg

10. Sample Size 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% Prevalence

11. phone or mail-in questionnaire health care professional or study center home visit 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 samples Home visit 2.Second trimester  22-24 GW * Phone + bring-in biol. specimens 3.Third trimester  34-36 GW * Medical examinations + biol. specimens Birth 4.Birth Medical 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

12. Data Collection Schedule Child Development 6. Age1 Month Questionnaire + bring-in biol. specimens 7. Age 3 Month Questionnaire 8. Age 6 Month Questionnaire + bring-in biol. specimens 9. Age 12 Month Medical examinations + biol. specimens Only in subgroup: Home visit to collect environmental samples Home visit 10. Age 24 Month Questionnaire 11. Age 3 Years Medical examinations + biol. specimens 12. Age 4 Years Questionnaire 13. Age 5 Years Questionnaire 14. Age 6 Years Medical examinations + biol. specimens Follow-up through age 18

13. Feasibility study A Feasibility study B Feasibility study ... Evaluation Update of study plan Developing study protocol Study Timeline 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 throughincentives and public relations Implementation Full study Evaluation Evaluation Update of study protocol Continuing Protocol Development Start 1. year 2. year 3. year 4. year

14. Next Steps • Announcing the study locations • Feasibility studies in the near future • Expert group for Ethicsand Privacy Protection

15. Acknowledgements 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 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 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 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.

17. 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