The Chinese Center for Disease Control and Prevention (China CDC), U.S. National Cancer Institute (NCI), and U.S. Centers for Disease Control and Prevention (USCDC) investigators will evaluate prospectively the role of periconceptional folic acid supplements and other postulated risk factors in risk of developing pediatric leukemia and other pediatric cancers. This study, the Children and Families Cohort Study (CFCS), will be carried out in a unique population of offspring of Chinese mothers who were enrolled during 1993-95 in a large (N=247,831) Community Intervention Program (CIP) of periconceptional folic acid supplements for the prevention of neural tube defects (NTD). The CIP demonstrated notably reduced risk of NTD in newborns whose mothers regularly took (“exposed”) versus did not take (“unexposed”) folic acid supplements during the periconceptional/early first trimester period. NCI, the China CDC and the U.S. CDC are currently conducting pilot investigations to evaluate possible late health effects of periconceptional folic acid in three studies in the CIP population. These investigations will provide unique data and each has important public health implications for the health of CIP mothers and their offspring. This population is unique internationally because the exact timing, dose, and duration of in utero exposure to folic acid (without other vitamins) through supplementation was measured and recorded, and there has been no folic acid fortification in the Chinese food supply, and use of vitamin supplements during the periconception and prenatal period was nonexistent at the time of study. Moreover, the two generations of CIP mothers and children each experienced enormous changes in lifestyle and environmental exposures during the past two decades of rapid transformation of the Chinese society. The three components of the study include: (1) A record linkage cohort and nested case-control study of periconceptional folic acid and other postulated risk factors for pediatric leukemia and other pediatric cancers to test the hypothesis that periconceptional folic acid may reduce risk of pediatric leukemia and total pediatric cancer and to evaluate prospectively this and other postulated risk factors from data collected in 1993-96; (2) a planned follow-up study (including questionnaire administration, validation of reported serious diseases outcomes, anthropometric measures) in 22,000 mothers and children in the 247,000+ families (to be expanded to all families pending funding) to evaluate a broad range of serious chronic disease outcomes and risk factors in relation to periconceptional folic acid supplementation (including specific cancers, circulatory diseases, autism in the children, asthma and others); and (3) a detailed assessment in 3,000 mother-offspring pairs of dietary, physical activity, body mass index and other relevant measures of obesity, ultraviolet radiation, folic acid, other B vitamins, homocysteine, vitamin D, and methylation differences in specific genes to characterize these important determinants of several serious chronic diseases and to evaluate the influence of nutritional status and physical activity on any observed methylation differences. A pilot study for the first component is in progress and pilot studies have been successfully completed for the second and third components. Analysis of the pilot data will be completed by the end of calendar year 2013.