Folic acid food fortification is associated with a decline in neuroblastoma

Clin Pharmacol Ther. 2003 Sep;74(3):288-94. doi: 10.1016/S0009-9236(03)00200-5.


Background: Neuroblastoma, an embryonic tumor, is the second most common pediatric tumor and is the most prevalent extracranial solid tumor in children. Results of previous studies have suggested that maternal vitamin intake may decrease the risk of several childhood cancers. In January 1997, Canada began fortifying flour with folic acid for the prevention of neural tube defects. The effect of folic acid fortification on the rate of neuroblastoma in offspring is not known.

Methods: We investigated the rates of neuroblastoma (<1 year), acute lymphoblastic leukemia, and hepatoblastoma registered by the Pediatric Oncology Group of Ontario, which captures 95% of all pediatric cancers in Ontario, before and after the introduction of folate fortification.

Results: An interventional time series analysis showed that the incidence of neuroblastoma declined from 1.57 cases per 10,000 births before to 0.62 case per 10,000 births after folic acid fortification (P <.0001). The crude incidence rate ratio (0.40; 95% confidence interval, 0.25-0.64) remained significant after adjustment for both age and disease stage at diagnosis (adjusted incidence rate ratio, 0.38; 95% confidence interval, 0.23-0.62). In contrast, there was no significant change in the rate of infant acute lymphoblastic leukemia (incidence rate ratio, 0.97; 95% confidence interval, 0.41-2.27) or hepatoblastoma (incidence rate ratio, 0.81; 95% confidence interval, 0.35-1.89).

Conclusions: Folic acid fortification was associated with a 60% reduction in neuroblastoma but was not associated with any change in the rate of infant acute lymphoblastic leukemia or hepatoblastoma. Further investigation is needed into the role of metabolism in the formation and prevention of neuroblastoma and other embryonically determined cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Canada / epidemiology
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Databases, Factual
  • Folic Acid / pharmacology*
  • Food, Fortified*
  • Hepatoblastoma / epidemiology
  • Humans
  • Liver Neoplasms / epidemiology
  • Neuroblastoma / epidemiology*
  • Neuroblastoma / prevention & control
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology
  • Retrospective Studies


  • Folic Acid