Chinese Children and Families Cohort StudyChinese Children and Families Cohort Study

中国儿童与家庭队列研究

I4C Workshop Barcelona, SpainSeptember 20,2011

Peng Yin

Chinese Center for Disease Control and PreventionBeijing, China

China-U.S. Collaboration on Folic Acid Studies

1993 - Began enrollment of women in 27 cities/counties 1993 - Began enrollment of women in 27 cities/counties

1996 - Completed enrollment of CIP mothers giving birth 1996 - Completed enrollment of CIP mothers giving birth

2001 - First follow-up completed 2001 - First follow-up completed

1999 - Folic acid - NTD findings published 1999 - Folic acid - NTD findings published

2011 - Second follow-up of CIP cohort 2011 - Second follow-up of CIP cohort

1991 - Started RCT pilot study in Hebei province 1991 - Started RCT pilot study in Hebei province

1997 - CIP data checking and cleaning 1997 - CIP data checking and cleaning

1992 - RCT changed to Community Intervention Program (CIP) 1992 - RCT changed to Community Intervention Program (CIP)

Folic Acid Community Intervention Program, 1993-1996

ZhejiangZhejiang

JiangsuJiangsu ShanxiShanxi

Beijing Beijing

HebeHebeii

ShanghaiShanghai SouthNTD rate1/1,000

NorthNTD rate5-6/1,000

US – China Collaborative NTD Prevention Project

• Intervention:Intervention: 400μg folic acid daily, 400μg folic acid daily, contact thru1contact thru1stst trimester trimester

• Evaluation:Evaluation: N=247,831 in 1994-96 N=247,831 in 1994-96

• Result:Result: ↓↓↓↓neural tube defectsneural tube defects• Publication:Publication: Berry RJ, Li Z, et al.

N Engl J Med 1999;341:485-90

0.00.0

1.01.0

2.02.0

3.03.0

4.04.0

5.05.0

NorthNorth SouthSouth

40% 40%

NTD

Rat

e/10

00N

TD R

ate/

1000

85%85%

No Folic AcidNo Folic AcidFolic AcidFolic Acid

First follow up of cohort children in 2000

Goal:Goal: Complete follow-up of Complete follow-up of offspring (4-6 years old)offspring (4-6 years old)

Participation:Participation: 93% of families 93% of families

Source of Source of information information

Health care records and Health care records and examination of childrenexamination of children

Findings:Findings: No effects on weight or No effects on weight or height or cognitive status by height or cognitive status by mothers’ use of folic acidmothers’ use of folic acid

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

• 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).

Specific aims

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

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

Community Intervention Program (CIP) Study 1993-1996247,000 Mother + Child pairs and Fathers

Pilot Study #3Test 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)

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)

Pediatric Cancer Risk FactorsProspective 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)

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 #2Test procedures for collecting diet, physical activity, UV (n = 100 mother/child pairs, subset of 500 families)

Pilot Study #1Locate subjects, interview and obtain permission for routine health record access for health records of mothers and offspring (n = 500 families)

Inter-relationship of Pilot Studies (Green Background) that will Test Procedures for Three Planned Main (Blue Background) Studies carried out in the CIP Population

Progress of CFCS

Pilot study in two field sites: Task 1follow-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 3Identify all pediatric cancers diagnosed/treated since 1994 in 5

hospitals serving the CIP countiesVisited the hospitals, started liaising with local government and

Ministry of Health to get access to the medical records in the hospitals

• 200 - 236 cases of pediatric leukemias <15yrs

• 600 - 800 total pediatric cancers <15 yrs

• Birth weight and childhood cancer

• Occupational exposure and childhood cancer

Potential contribution of CFCS to I4C

• 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

Acknowledgements