Public Health Nutrition

Nutrition and health

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

Cecilia Castillo-Lancellottia1 c1 p1, Josep A Tura1 and Ricardo Uauya2

a1 Research Group on Community Nutrition and Oxidative Stress, University of the Balearic Islands, Palma de Mallorca, Spain

a2 Public Health and Nutrition Unit, Laboratory of Molecular Epidemiology, Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile


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.

(Received February 21 2012)

(Revised June 05 2012)

(Accepted June 20 2012)

(Online publication July 31 2012)


  • Folic acid;
  • Neural tube defects;
  • Spinal dysraphism;
  • Food fortification;
  • Systematic review


c1 Corresponding author: Email

p1 Correspondence address: Fleming 6711 Las Condes Santiago, Chile.