The Japan Environment and Children's Study (JECS)

1. The Japan Environment and Children's Study (JECS) Ayano Takeuchi, PhD National Core Center of the Japan Environment and Children’s Study, National Institute for Environmental Studies, Japan 5th International Childhood Cancer Cohort Consortium (I4C) Workshop on November 12-13, 2012in Lyon, France

2. Overview of the Japan Environment & Children’s Study (JECS) Chemical exposure during the fetal and infant stages adversely effects children’s health Core Hypothesis (Exposure) (Outcome) ○ The Environment / Chemicals POPs(dioxins, PCBs, organofluoric compounds, flame retardants, etc.), heavy metals (mercury, lead, arsenic, cadmium, etc.), endocrine disruptors (bisphenol A, etc.), agrichemicals, VOC (benzene, etc.), etc. ○ Physical Development: Low birth weight, development after birth, etc. ○ Congenital Anomalies: Hypospadias, Cryptochidism,cleft lops, cleft palate, Spina Bifida, digestive tract obstruction, ventricular septal defects,Down’s Syndrome, etc. ○ Sexual Differentiation Abnormalities: Sex ratio, genital development impairment, sexual differentiation of the brain, etc. ○ Psychoneuro DevelopmentDisorders: Autism, learning disorders, AHDH (attention-deficit hyperactivity disorder), etc. ○ Genetics ○ Immune System Disorders: Pediatric allergies, atrophy, asthma, etc. ○ Socioeconomics ○ Cancers: Leukaemia, solid cancers, etc. ○ Lifestyle ○ Endocrine / Metabolic Abnormalities: Lowered glucose tolerance, obesity, etc. JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

3. JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012 Overview of the Japan Environment & Children’s Study (JECS) • Pilot Study: evaluates the feasibility, acceptability and cost of the proposed outcome and exposure measurement procedures as well as Study administration protocols to be used in the Main Study • Main Study: 100,000 mother–child pairs (+ fathers when accessible) from 15 locations • 3 years recruitment period from 2011, Jan. • Following the participants until children become 13 years of age • Sub-study: A sub-cohort (n = 5,000) will be formed within Main Study to examine extended exposure–outcome relationships • Indoor exposure vs. medical examination • Case-Cohort or Nested Case-Control studies using Sub and Main Study • Adjunct Studies: conducted on a portion of the Main Study cohort, of which protocols are reviewed and approved by the Steering Committee • JECS is a flexible and developing study, learning from other studies

4. Study Locations (JECS) (15) JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

5. JECS road map and budget Main Study Recruitment Main Study FY 2009 2010 2011 2012 2013 2014 2015 Biological sample analysis Sub Study b yen ca. m USD 7 87.5 ? Case-Cohort Nested Case-Control 6 75 5 62.5 Adjunct Studies* 4 50 3 37.5 Pilot Study 2 25 sequential data management and data cleaning FY: Fiscal year starting April, * Funding not provided by JECS 1 12.5 provisional data fix, and start to analysis 0 0 Now, we are here JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

6. Overview of the JECS Main Study Schedule Hair Blood Data from Questionnaires Urine Cord Blood, DBS Milk JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

7. Transitions of the Number of Recruitment JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

8. Follow up status As of 28 September 2012 JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

9. Data Cleaning and Statistical Analysis Plan • Connect provisional fixed data every year, and connect outcome information as the occasion demands • Sequential Data Cleaning • Within certain questionnaire • Within certain period: • consistency between questionnaire Within certain period (1yr) provisional data fix Within questionnaire Recruit • Statistical Analysis Plan • After data fixed provisionally… • Adjust missing data • Adjust measurement errors • After data fixed • Life course epidemiology • Adjust correlation between repeated measured covariate T1 T2 0m 1m 6m 2011 12 13 14 15 16 17 JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

10. Acknowledgement • Participating Families • Staffs at Regional Centres • International Working Group Members • Taxpayers • Toshihiro Kawamoto, MD. PhD, PI of JECS • Shoji Nakayama, MD. PhD, I4C Steering Committee member • JECS website: • http://www.env.go.jp/en/chemi/hs/jecs • Contact: • hoken-risuku@env.go.jp • takeuchi.ayano@nies.go.jp JECS website je vous remercie de votre écoute

11. preliminary materials

12. JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012 Overview of the Japan Environment & Children’s Study (JECS) • Method: Multilayered prospective birth cohort study • Core Hypothesis: Chemical exposure during infant stages adversely affects children • The goal of the Study is to better understand the impact of environmental exposures on children’s health and development and to improve their health and future environment • “Environment” includes indoor and outdoor air, water, soil and dust, diet, noise, socio-economic status, education, occupation, lifestyles, mental and social support • Genetic factors will also be examined • Anticipated Results • (1) Identify environmental factors impacting children's health • (2) Develop risk management systems that address vulnerabilities in children • (3) Ensure a sound environment where future generations are able to grow up in good health

13. JECS Expected Scientific Output JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

14. Health outcomes of priority interest JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

15. Exposures of concern JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

16. Prevalence of High Exposure Group Cases in Disease 100,000 1% 3% 5% 10% 25% Obesity 10% 10,000 6,970 2,390 1,470 790 390 Atopic Dermatitis (5 yr) 3.8% 3,770 20,420 7,000 4,320 2,310 1,160 Early or Late Puberty 3% 3,000 25,960 8,890 5,490 2,940 1,480 ADHD (5 yr) 3% 3,000 25,960 8,890 5,490 2,940 1,480 Asthma（5 yr） 2.4% 2,400 32,740 11,220 6,920 3,710 1,860 Autism 1% 1,000 80,210 27,480 16,960 9,100 4,570 Cryptorchidism 0.7% 700 115,080 39,430 24,330 13,060 6,560 Gender Identity Disorder 0.2% 200 405,670 139,010 85,770 46,050 23,140 Down's Syndrome 0.1% 100 812,500 278,430 171,790 92,230 46,350 Hypospadias 0.05% 50 1,626,160 557,260 343,820 184,590 92,780 Type１Diabetes 0.001% 1 81,364,610 27,882,380 17,203,340 9,236,040 4,642,460 Needed Sample Size (JECS), why 100,000 subjects? Conditions:χ2test Assumption. Significance Level 5%, Statistical Power 80%, Risk Ratio 2.0 Prevalence of Disease Diseases with low prevalence (>0.1%) can be analyzed. JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

17. JECS Expected Scientific Output ■Direct Results ■■ Indirect Results ■ Provide broad-scoped and shared research foundation for children’s health not limited to environmental factors Identify environmental factors impacting children’s health 　　⇒Eliminate hazardous environments ● Promote regulatory measures covering the manufacture, import and use of chemical substances as well as self-led compliance initiatives ● Amend and establish new environmental standards Provide function as a biological specimen bank Respond to the broad research needs of industry, government and academia after a scientific and ethical review Identify genes relating to chemical substance sensitivity, diseases, and disorders ⇒ Prevention ● Genetic diagnosis at birth ● Specialized countermeasures for at-risk children Provide function as a data archive Cultivate / strengthen competencies of the nation’s environmental epidemiologic researchers Reduce childhood diseases Ensure safe and sound environment for children’s development Address Japan’s declining birthrate JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

18. Implementation Framework (JECS) JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012

19. Recruitment Methods (JECS) 100k participants over 3 years →3% of newborns in Japan 1,092,674 (2006) 1. Diverse nationwide mix 15 Regional Unit Centers(Hokkaido to Okinawa) 2. Study zones Population per unit ranges from 0.2 to 1 million(farming villages to major metropolitan centers) 3. Number to recruit 2k to 9k per unit over a 3-year period 4. Population-base Conduct outreach to encourage participation by most expectant mothers in each zone. Goal to achieve a coverage ratio in excess of 50% 5. Emphasis on regional exposure characteristics JECS, 5th I4C workshop in Lyon France, Nov. 12-13, 2012