Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukaemia in childhood: a case-control study

Lancet. 2001 Dec 8;358(9297):1935-40. doi: 10.1016/S0140-6736(01)06959-8.


Background: Acute lymphoblastic leukaemia is the most common childhood cancer in more-developed countries but it has few recognised risk factors or preventive measures. We aimed to determine and assess the risk factors associated with this disease.

Methods: From 1984 to 1992, we investigated known and suspected risk factors for common acute lymphoblastic leukaemia diagnosed in a population-based case-control study of children aged 0-14 years in Western Australia. 83 children in the study group came from the sole referral centre for paediatric cancer in the state and 166 controls matched for age and sex were recruited through a postal survey of people randomly selected from the state electoral roll. We interviewed mothers of 83 study and 166 control children (82% and 74%, respectively, of those eligible). Fathers completed a self-administered questionnaire.

Findings: We recorded a protective association between iron or folate supplementation in pregnancy and risk of common acute lymphoblastic leukaemia in the child (odds ratio 0.37 [95% CI 0.21-0.65]; p=0.001). For iron alone, the odds ratio was 0.75 (0.37-1.51); only one mother took folate without iron. Further analyses of folate use with or without iron (0.40; 0.21-0.73) showed that the protective effect varies little by time of first use of supplements or for how long they were taken. The association was not weakened by adjustment for potentially confounding variables.

Interpretation: Our results, though unexpected, suggest that folate supplementation in pregnancy reduces the risk of common acute lymphoblastic leukaemia in the child.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Data Collection / methods
  • Dietary Supplements*
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • Infant
  • Infant, Newborn
  • Iron, Dietary / administration & dosage
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / etiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / prevention & control*
  • Pregnancy*
  • Risk Factors
  • Western Australia / epidemiology


  • Iron, Dietary
  • Folic Acid