Abstract LB-31: Maternal supplementation with folic acid and other vitamins before and during pregnancy and risk of leukemia in the offspring: A childhood leukemia international consortium (CLIC) study.
Authors: Metayer Catherine , Milne Elizabeth , Dockerty John D. , Clavel Jacqueline , Pombo-de-Oliveira Maria S. , Wesseling Catharina , Spector Logan G. , Schüz Joachim , Petridou Eleni , Ezzat Sameera , Armstrong Bruce K. , Rudant Jérémie , Koifman Sergio , Kaatsch Peter , Moschovi Maria , Rashed Wafaa , Selvin Steve , McCauley Kathryn , Kang Alice Y. , Hung Rayjean J. , Buffler Patricia A. , Infante-Rivard Claire 
Published: August 2014

Abstract
Background: Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemias (ALL) and 17% acute myeloid leukemias (AML). The early onset of the disease is suggestive of genetic predisposition and critical exposures occurring before birth. Maternal prenatal supplementation with folic acid and other vitamins, known to maintain DNA integrity and limit oxidative stress, could play a role in the prevention of childhood leukemia. However, reduced risks of childhood ALL following prenatal supplementation have been reported inconsistently. As for childhood AML, a rarer subtype, little is known regarding the effect of prenatal vitamins. Methods: We pooled original data on socio-demographic characteristics and maternal intake of folic acid, vitamins, and alcohol from 12 case-control studies (1980-2012) participating in CLIC (clic.berkeley.edu). The standardized data included the use of any vitamins, and use of folic acid, given anytime (before and/or during pregnancy) or during a specific period. The pooled analyses included 6,970 cases of ALL, 585 cases of AML, and 19,617 controls. Subgroup analyses were undertaken for vitamin type, period of use, and leukemia subtype. Logistic regression was used to estimate the odds ratios (OR) and 95 % confidence interval (CI), adjusted for age, sex, ethnicity, and other confounders including parental education, and study center. Results: Maternal intake of vitamins and folic acid anytime prenatally was associated with reduced risks of childhood ALL and AML. For ALL, the ORs for vitamin and folic acid intake during pregnancy specifically were 0.78 (95% CI: 0.71-0.85) and 0.82 (95% CI: 0.72-0.94), respectively, and 0.85 (95% CI: 0.64-1.13) and 0.52 (95% CI: 0.31-0.88), respectively, for AML. The observed reduction in ALL risk associated with prenatal vitamin intake was stronger in households where parents had no formal education or a primary education (OR=0.68, 95% CI: 0.56-0.83) and a secondary education (OR=0.75, 95% CI: 0.66-0.85), compared to those with a tertiary education (OR=0.96, 95% CI: 0.86-1.09). A similar trend across education levels was reported for maternal folic acid intake. The association between childhood ALL and maternal vitamin and folic acid intake also appeared stronger among women who did not consume alcohol. Conclusions: Our analyses based on the largest number of childhood ALL and AML cases to date suggest that maternal vitamin and folic acid intake reduces the risk of acute childhood leukemias. The risk seems modified by surrogate markers of nutritional status such as socio-economic status and alcohol consumption. Alternatively, participant selection, recall, access to prenatal care, or genetic susceptibility may vary in low vs. high income populations, therefore possibly contributing to this observation.
Citation Format: Catherine Metayer, Elizabeth Milne, John D. Dockerty, Jacqueline Clavel, Maria S. Pombo-de-Oliveira, Catharina Wesseling, Logan G. Spector, Joachim Schüz, Eleni Petridou, Sameera Ezzat, Bruce K. Armstrong, Jérémie Rudant, Sergio Koifman, Peter Kaatsch, Maria Moschovi, Wafaa Rashed, Steve Selvin, Kathryn McCauley, Alice Y. Kang, Rayjean J. Hung, Patricia A. Buffler, Claire Infante-Rivard. Maternal supplementation with folic acid and other vitamins before and during pregnancy and risk of leukemia in the offspring: A childhood leukemia international consortium (CLIC) study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-31. doi:10.1158/1538-7445.AM2013-LB-31
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.