Chinese Children and Families Cohort Study

1. Chinese Children and Families Cohort Study 中国儿童与家庭队列研究 Peng Yin Chinese Center for Disease Control and Prevention Beijing, China I4C Workshop Barcelona, Spain September 20,2011

2. China-U.S. Collaboration on Folic Acid Studies 2011 - Second follow-up of CIP cohort 2001- First follow-up completed 1999 - Folic acid - NTD findings published 1997 - CIP data checking and cleaning 1996- Completed enrollment of CIP mothers giving birth 1993 - Began enrollment of women in 27 cities/counties 1992- RCT changed to Community Intervention Program (CIP) 1991 - Started RCT pilot study in Hebei province

3. Folic Acid Community Intervention Program, 1993-1996 North NTD rate 5-6/1,000 Beijing Hebei Shanxi Jiangsu South NTD rate 1/1,000 Shanghai Zhejiang

4. 5.0 85% 4.0 3.0 40% NTD Rate/1000 2.0 1.0 0.0 North South US – China Collaborative NTD Prevention Project • Intervention: 400μg folic acid daily, contact thru1st trimester • Evaluation: N=247,831 in 1994-96 • Result:↓↓neural tube defects • Publication:Berry RJ, Li Z, et al. • N Engl J Med 1999;341:485-90 No Folic Acid Folic Acid

5. First follow up of cohort children in 2000

6. Unique Opportunity to Assess Risk Factors Pediatric and Adult Chronic Diseases > Community Intervention Population is unique worldwide in exposure and in size > Epidemiologic studies in China have yielded many new and important clues about causes of serious chronic diseases

7. Background and Hypotheses Background • Several scientific reports that periconception folic acid may reduce risk of pediatric leukemia • Some evidence that periconceptional folic acid supplements may be related to other rapidly increasing serious childhood diseases • Dietary studies suggest that early life folic acid may reduce risk of cardiovascular diseases and certain cancers in adults

8. Objectives and Key Questions Does Periconceptional Folic Acid: • Reduce risks of pediatric leukemia or other pediatric cancers in offspring • Affect risk of pediatric asthma, autism or other chronic diseases of children • Have a protective effect on risk factors (BMI, blood pressure) for cardiovascular disease or cancer in mothers

9. Specific aims • To re-establish contact with ~241,000 mothers who enrolled in the original Community Intervention Program (CIP) in 1993-1996 to study the prevention of neural tube defects using folic acid supplementation. • To ascertain and verify all occurrences of pediatric cancers, deaths from any causes. • To examine growth and development, and developmental disabilities in this population of adolescents (ages 14-16).

10. Approach: CFCS Feasibility Study • Task 1: Follow-up of Late Effects of Periconceptional Folic Acid in CIP Mothers and Offspring • Task 2: Assessment of Diet, Nutrition, Physical Activity, Ultraviolet Radiation (UV), and Associated Biomarkers in CIP Mothers and Offspring • Task 3: Record Linkage Cohort & Nested Case-Control Study of Postulated Risk Factors for Pediatric Cancer

11. Record linkage for Pediatric Cancer Risk Factors Objective: - compare incidence of pediatric leukemia and other pediatric cancers in offspring of mothers who took vs did not take periconceptional folic acid supplements - assess prospective risk factors for pediatric leukemia and other pediatric cancers Methods - seek hospital records for all pediatric cancers in hospitals serving the population among children born 1994-96 and match these back to the CIP population - prospective assessment of pediatric leukemia risks in exposed vs. unexposed - case-cohort study of risk factors for pediatric cancer

12. Inter-relationship of Pilot Studies (Green Background) that will Test Procedures for Three Planned Main (Blue Background) Studies carried out in the CIP Population Community Intervention Program (CIP) Study 1993-1996 247,000 Mother + Child pairs and Fathers Pilot Study #3 Test procedures for identifying and abstracting medical records for diagnostic validation of pediatric cancer 1994 and later in children born 1993-96 in catchment area (n + 5 hospitals) Pilot Study #1 Locate subjects, interview and obtain permission for routine health record access for health records of mothers and offspring (n = 500 families) Follow-Up Folic Acid Late Effects - Follow-up mother/child pairs for late effects of folic acid - Interview fathers for cofounders (n = 20,000 families) Pilot Study #2 Test procedures for collecting diet, physical activity, UV (n = 100 mother/child pairs, subset of 500 families) Pediatric Cancer Risk Factors Prospective investigation of risk factors for pediatric cancer - folic acid (periconceptional) and risk of pediatric leukemia in offspring - case-cohort study of risk factors for pediatric cancer (based on routine health records and maternal interviews 1993-96) Diet, Nutrition, Physical Activity Feasibility study to assess diet, physical activity, UV and biomarkers: determinants of risk factors for adult cancers (n = 3,000 mother/child pairs, subset of 20,000 families)

13. Progress of CFCS Pilot study in two field sites: Task 1 follow-up a sample of 500 CIP families - obtained national, provincial, and local government approval and support - carried out training workshop - tracing of CIP families underway - launched data collection Pilot study of task 3 Identify all pediatric cancers diagnosed/treated since 1994 in 5 hospitals serving the CIP counties Visited the hospitals, started liaising with local government and Ministry of Health to get access to the medical records in the hospitals

14. Potential contribution of CFCS to I4C • 200 - 236 cases of pediatric leukemias <15yrs • 600 - 800 total pediatric cancers <15 yrs • Birth weight and childhood cancer • Occupational exposure and childhood cancer

15. Acknowledgements • Investigators • - China CDC: Wang Yu, Liang Xiaofeng, Wang Linhong, Yin Peng, Wang Ning • - NCI: Martha Linet, Nancy Potischman, Ann Chao • - US CDC: RJ Berry, Hao Ling • Local investigators in Taicang (Yang Ruilan) and Laoting (Meng Fanwen) • All participating CIP families