Trends of selected malformations in relation to folic acid recommendations and fortification: an international assessment

Birth Defects Res A Clin Mol Teratol. 2006 Oct;76(10):693-705. doi: 10.1002/bdra.20307.


Background: Two crucial issues relative to the benefits and impact of folic acid in the prevention of birth defects are whether supplementation recommendations alone, without fortification, are effective in reducing the population-wide rates of neural tube defects (NTDs), and whether such policies can reduce the occurrence of other birth defects. Using data from 15 registries, we assessed rates and trends of 14 major defects, including NTDs, in areas with official recommendations or fortification to assess the effectiveness of recommendations and fortification on a wide range of major birth defects.

Methods: We evaluated surveillance data through 2003 on major birth defects from population-based registries from Europe, North America, and Australia. All included ascertainment of pregnancy terminations (where legal). Trends before and after policies or fortification were assessed via Poisson regression and were compared via rate ratios.

Results: Significant changes in trends were seen for NTDs in areas with fortification but not in areas with supplementation recommendations alone. For other major birth defects, there was an overall lack of major trend changes after recommendations or fortification. However, some significant declines were observed for select birth defects in individual areas.

Conclusions: Recommendations alone remain an ineffective approach in translating the known protective effect of folic acid in population-wide decline in NTD rates. Fortification appears to be effective in reducing NTDs. The effect on other birth defects remains unclear.

Publication types

  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Dietary Supplements / standards
  • Evaluation Studies as Topic
  • Female
  • Folic Acid*
  • Food, Fortified* / standards
  • Guidelines as Topic*
  • Humans
  • International Cooperation
  • Male
  • Neural Tube Defects / epidemiology*
  • Neural Tube Defects / etiology
  • Neural Tube Defects / prevention & control*
  • Pregnancy
  • Pregnancy Complications / epidemiology
  • Pregnancy Complications / etiology
  • Pregnancy Complications / prevention & control
  • Registries*
  • Retrospective Studies


  • Folic Acid