title: Impact of folic acid fortification of flour on neural tube defects: a systematic review.
abstract: OBJECTIVE
  To review the impact of folic acid fortification of flour on the prevalence of neural tube defects (NTD).
  
  
  METHODS
  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.
  
  
  METHODS
  Chile, Argentina, Brazil, Canada, Costa Rica, Iran, Jordan, South Africa and the USA.
  
  
  METHODS
  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.
authors: Research Group on Community Nutrition and Oxidative Stress, University of the Balearic Islands, Palma de Mallorca, Spain. dracastillo@gmail.com
authors: Cecilia
authors: C
authors: Castillo-Lancellotti
authors: Josep A
authors: JA
authors: Tur
authors: Ricardo
authors: R
authors: Uauy
mesh_terms: D001118:Argentina / Q000453:epidemiology; D001938:Brazil / Q000453:epidemiology; D002170:Canada / Q000453:epidemiology; D002677:Chile / Q000453:epidemiology; D003364:Costa Rica / Q000453:epidemiology; D005433:Flour / Q000032:analysis*; D005492:Folic Acid / Q000008:administration & dosage*; D005527:Food, Fortified; D006801:Humans; D007492:Iran / Q000453:epidemiology; D007597:Jordan / Q000453:epidemiology; D050498:Live Birth; D009436:Neural Tube Defects / Q000453:epidemiology / Q000517:prevention & control*; D015995:Prevalence; D012042:Registries; D013019:South Africa / Q000453:epidemiology; D050497:Stillbirth
chemical_list: D005492:Folic Acid