Evaluation of Food Fortification with Folic Acid for the Primary Prevention of Neural Tube Defects

Background

NEURAL TUBE DEFECTS (NTDS) ARE BIRTH DEFECTS RESULTING FROM THE FAILURE OF NEURAL TUBE closure during early development of the human embryo. The 1997 Canadian national NTD rate was 0.75 per 1,000 births (live births and stillbirths), down from 1.16 per 1,000 in 1989 (Health Canada, 2000). The rates tend to be higher in the eastern provinces than in the west (Persad et al. 2002; Gucciardi et al. 2002; Crane et al. 2001). Historically, Newfoundland has had one of the highest rates in North America with a reported average yearly incidence rate for 1976-1997 of 3.4 per 1,000 births (including live births, stillbirths and fetuses from pregnancies terminated after a prenatal diagnosis of an NTD) (Crane et al. 2001).

Evidence from a number of studies has demonstrated that periconceptional use of vitamin supplements containing folic acid reduces the risk of NTDs (Laurence et al. 1981; Smithells et al. 1983; MRC Vitamin Study Research Group 1991; Czeizel and Dudas 1992). Although the mechanism of action of this nutrient in influencing the risk of NTDs is poorly understood, the evidence of the benefit of folic acid has led many health organizations since late 1992 to recommend periconceptional folic acid supplementation, at a level of 400 mg/day for low risk women (CDC 1992; Health Canada 1993; Canadian Task Force on the Periodic Health Examination 1994).

Because of concern that public education campaigns alone would not be effective in achieving optimal periconceptional folic acid intake for the majority of women, food fortification with folic acid was proposed as a strategy to ensure that all women of childbearing age increase their dietary intake of this vitamin. In March 1996 the US Food and Drug Administration (FDA) announced that it would permit addition of folic acid to enriched flour and other enriched cereal grain products, and that this addition would be mandatory as of January 1998. The level of fortification was set at 0.14 mg folic acid per 100 g of cereal grain product. It was determined that at this level of fortification, the intake of folate (from all sources) for the target and the general population would be kept below 1,000 mg/day, which was deemed to be the safe upper limit. This level of fortification was estimated to increase the average daily intake of folic acid in women of childbearing age by about 100 mg (Food and Drug Administration 1996).

Subsequent to the US decision, Canada followed suit, permitting folic acid fortification at an equivalent level in December 1996 (addition of folic acid to white flour and enriched pasta and cornmeal at 0.15 mg folic acid per 100 g of flour and 0.20 mg folic acid per 100 g of pasta). In Canada, fortification became mandatory in November 1998 (Canada Gazette 1998).

The question of whether folic acid fortification of grain products poses any serious health risk has been controversial. The main concern has been the potential masking of vitamin B₁₂ deficiency, a condition that affects 10-15% of the population over age 60 (Institute of Medicine 1998; Balk and Russell 1999). Increased folic acid intake may correct the haematologic signs of vitamin B₁₂ deficiency, thus delaying diagnosis and treatment of the condition while its attendant neurologic manifestations progress. Seniors may be at particular risk since the incidence of vitamin B₁₂ deficiency increases with age.

Thus, Health Canada undertook a population based study to evaluate the effectiveness of the public health strategy of food fortification with folic acid and to determine possible adverse effects resulting from fortification.