Impact of folic acid fortification of flour on neural tube defects: a systematic review

Public Health Nutr. 2013 May;16(5):901-11. doi: 10.1017/S1368980012003576. Epub 2012 Jul 31.


Objective: To review the impact of folic acid fortification of flour on the prevalence of neural tube defects (NTD).

Design: Systematic review of the literature on MEDLINE via PubMed, Scopus, OvidSP and LILACS (Latin American and Caribbean Health Sciences Literature) reporting the impact of folic acid fortification of flour on the prevalence of NTD in 2000-2011. Focusing on Santiago of Chile's birth defects registry (1999-2009) and the monitoring of flour fortification, we analysed the prevalence (NTD cases/10 000 births) pre and post flour fortification and the percentile distribution of folic acid content in flour (2005-2009). We explored the potential association between median folic acid in flour (mg/kg) and the prevalence of NTD.

Setting: Chile, Argentina, Brazil, Canada, Costa Rica, Iran, Jordan, South Africa and the USA.

Subjects: Live births and stillbirths.

Results: Twenty-seven studies that met inclusion criteria were evaluated. Costa Rica showed a significant reduction in NTD (∼60 %). Prevalence in Chile decreased from 18·6 to 7·3/10 000 births from 1999 to 2007 and showed a slight increase to 8·5 in 2008-2009, possibly due to changes in fortification limits. When we related the prevalence of NTD with levels of flour fortification, the lowest prevalence was observed at a folic acid level of 1·5 mg/kg.

Conclusions: Fortification of flour with folic acid has had a major impact on NTD in all countries where this has been reported. Chile showed a 55 % reduction in NTD prevalence between 1999 and 2009. There is a need to constantly monitor the levels of flour fortification to maximize benefits and prevent the potential risk of folic acid excess, moreover to be vigilant for any new adverse effects associated with excess.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Argentina / epidemiology
  • Brazil / epidemiology
  • Canada / epidemiology
  • Chile / epidemiology
  • Costa Rica / epidemiology
  • Flour / analysis*
  • Folic Acid / administration & dosage*
  • Food, Fortified*
  • Humans
  • Iran / epidemiology
  • Jordan / epidemiology
  • Live Birth
  • Neural Tube Defects / epidemiology
  • Neural Tube Defects / prevention & control*
  • Prevalence
  • Registries
  • South Africa / epidemiology
  • Stillbirth


  • Folic Acid