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Epidemiology. 2014 Nov;25(6):811-22. doi: 10.1097/EDE.0000000000000141.

Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a Childhood Leukemia International Consortium study.

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From the aUniversity of California, School of Public Health, Berkeley, CA; bTelethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, West Perth, Western Australia; cDean's Department and Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; dInserm, CESP Centre for Research in Epidemiology and Population Health, Environmental Epidemiology of Cancer Team, Université Paris-Sud, Villejuif, France; ePediatric Hematology-Oncology Program, Research Program, Instituto Nacional de Cancer, Rio de Janeiro, Brazil; fInstituto Regional de Estudios en Sustancias Tóxicas (IRET), Universidad Nacional, Heredia, Costa Rica; gDivision of Epidemiology Clinical Research, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN; hInternational Agency for Research on Cancer, Section of Environment and Radiation, Lyon, France; iDepartment of Hygiene, Epidemiology, and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; jResearch Department, Children's Cancer Hospital, Cairo, Egypt; kSydney School of Public Health, University of Sydney, New South Wales, Australia; lNational School of Public Health, Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health, Rio de Janeiro, Brazil; mGerman Childhood Cancer Registry, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany; nLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada; and oDepartment of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montréal, Province of Québec, Canada.



Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype.


We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child's age, sex, ethnicity, parental education, and study center.


Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78-0.92) for vitamin use and 0.80 (0.71-0.89) for folic acid use. The reduced risk was more pronounced in children whose parents' education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75-1.14) and 0.68 (0.48-0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester).


Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics.

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