Maternal folate and other vitamin supplementation during pregnancy and risk of acute lymphoblastic leukemia in the offspring

Abstract

The Australian Study of Causes of Acute Lymphoblastic Leukemia in Children (Aus-ALL) was designed to test the hypothesis, raised by a previous Western Australian study, that maternal folic acid supplementation during pregnancy might reduce the risk of childhood acute lymphoblastic leukemia (ALL). Aus-ALL was a national, population-based, multicenter case-control study that prospectively recruited 416 cases and 1,361 controls between 2003 and 2007. Detailed information was collected about maternal use of folic acid and other vitamin supplements before and during the index pregnancy. Data were analyzed using logistic regression, adjusting for matching factors and potential confounders. A meta-analysis with the results of previous studies of folic acid supplementation was also conducted. We found weak evidence of a protective effect of maternal folate supplementation before pregnancy against risk of childhood ALL, but no evidence for a protective effect of its use during pregnancy. A meta-analysis including this and 2 other studies, but not the study that raised the hypothesis, also found little evidence that folate supplementation during pregnancy protects against ALL: the summary odds ratios (ORs) for folate supplementation were 1.06 [95% confidence interval (CI): 0.77-1.48] with reference to no folate supplementation and 1.02 (95% CI: 0.86-1.20) with reference to no vitamin supplementation. For vitamin supplementation in general, the summary OR from a meta-analysis of 5 studies-including Aus-ALL-was 0.83 (95% CI: 0.73-0.94). Vitamin supplementation in pregnancy may protect against childhood ALL, but this effect is unlikely to be large or, if real, specifically due to folate.In 2001, a case-control study from Western Australia reported a strong protective effect of maternal folate supplementation (with or without iron) during pregnancy on risk of common acute lymphoblastic leukemia (ALL): odds ratio (OR) ¼ 0.40, 95% CI: 0.21-0.73. 1 Iron supplementation alone was only weakly protective: OR ¼ 0.75, 95% CI: 0.37-1.51, suggesting that if there was a protective effect it lay with folate or the combination of folate and iron. A protective effect of folate is biologically plausible because of its dual roles in methylation and the synthesis and repair of DNA. 2 Folate provides 5-methyltetrahydrofolate for the methylation of homocysteine to methionine, which is converted to S-adenosylmethionine, the principal methyl donor in DNA methylation. DNA methylation affects gene expression, and specific

Folate Pathway Gene Polymorphisms, Maternal Folic Acid Use, and Risk of Childhood Acute Lymphoblastic Leukemia

“…Of the 2,947 eligible control families identified through RDD, 2,071 (70.3%) agreed to take part in the main study (41). In accordance with requirements for age and sex frequency matching, 1,067 control families were asked to provide DNA for the genetic component of the study; of these, 1,027 (96%) agreed.…”

“…We had previously seen weak evidence of an inverse association with ALL risk when mothers took folic acid 300 mg/day in the 3 months prepregnancy (41). We therefore categorized folic acid use for analysis as 300 mg/day versus none prepregnancy.…”

“…The study design and data collection methods have been described elsewhere (41,42). Briefly, incident ALL cases were identified through all 10 Australian pediatric oncology centers, where the large majority of cases are treated.…”

“…However, weak associations were seen with use prepregnancy; ORs were 0.84 [95% confidence interval (CI), 0.55-1.28] for 300.1 to 450 mg per day, and 0.77 (95% CI, 0.52-1.14) for >450 mg per day (41).…”

Informational efficiency of the real estate market: A meta-analysis

“…Although meta-analysis has been widely used in medical research (recent examples are McClaine et al 2010;Milne et al 2010;Visser et al 2010), it has also been used recently in social sciences (e.g., Yang and Lester 2008;Melo et al 2009). Melo et al (2009), for instance, used elasticities that measure the effect of urban agglomeration on productivity, and tried to explain their variations by a set of study characteristics.…”