Case control study of periconceptional folic acid intake and nervous system tumors in children

Childs Nerv Syst. 2010 Dec;26(12):1727-33. doi: 10.1007/s00381-010-1187-x. Epub 2010 May 23.


Purpose: Since 1992, the Centers for Disease Control and Prevention recommends that women of childbearing age consume 400 µg of folic acid per day to reduce the risk of neural tube defects (NTD). It has been speculated that both NTD and nervous system tumors (NST) may share common mechanisms of altered development. It examines the association between folic acid supplementation and the risk for childhood NST.

Methods: Incident cases of children with cancer in Spain registered between 2004 and 2006 were identified through the MACAPE Network Group. Tumors were classified as tumors derived from the neuroectoderm (cases) and those with a mesoderm origin (controls). In a second analysis, NST were further divided into central nervous system tumors (CNST) and sympathetic nervous system tumors (SNST). We compared folic acid supplementation between the groups.

Results: Overall, folic acid supplementation any time during pregnancy was similar between cases and controls (odds ratio (OR)=1.05; 95% confidence interval (CI) 0.92-1.20). However, supplementation before the 21st and 36th days of gestation resulted in significantly lower NST than in children with mesoderm tumors (OR=0.34; 95% CI 0.17-0.69 and OR=0.58; 95% CI 0.37-0.91, respectively). Preconceptional intakes of folic acid were also lower in NST although marginally nonsignificant (OR=0.44; 95% CI 0.10-1.02). When NST were divided into CNST and SNST, significant differences between tumors of mesoderm origin were only found for CNST.

Conclusions: Our results support the hypothesis that folate supplementation reduces the risk of childhood NST, especially CNST. The specific mechanism and cellular role that folate may play in the development of CNST have yet to be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Child, Preschool
  • Female
  • Folic Acid / therapeutic use*
  • Humans
  • Male
  • Nervous System Neoplasms / prevention & control*
  • Pregnancy / drug effects*
  • Prenatal Care / methods*
  • Vitamin B Complex / therapeutic use*


  • Vitamin B Complex
  • Folic Acid