Neural-Tube Defects Decline After Folic Acid Fortification

QUEBEC CITY, Quebec, July 11 -- Folic acid supplementation of white flour and cereal products in Canada reduced neural-tube defects by 46%, researchers reported.

The rate reduction was greatest for spina bifida, down 53%, Philippe De Wals, Ph.D., of Laval University here, and colleagues reported in the July 12 issue of the New England Journal of Medicine.

In the U.S., fortification of many cereal products with folic acid became mandatory on January 1, 1998. On November 11, 1998, the Canadian government followed suit, requiring folic acid fortification of all types of white flour, enriched pasta, and cornmeal.

The goal was to increase by approximately 30% to 70% the average intake of folic acid among women of childbearing age without posing a risk to the general public.

Higher levels of fortification were not adopted, the researchers said, because of concern about exceeding the recommended daily intake of 1,000 ?g for adults.

The study included live birth, stillbirths, and pregnancy terminations among women living in seven of the 10 Canadian provinces 1993 to 2002. On the basis of published results for red-cell folate levels, the study period was divided into prefortification and full-fortification periods.

During the study period, a total of 2,446 children with neural-tube defects were recorded among 1.9 million births.

In Canada, the prevalence of neural-tube defects has been historically higher in the eastern provinces than in the western provinces, the authors noted.

They found that after folic acid fortification, the reduction in rates was greater in regions with a higher baseline prevalence of neural-tube defects at the outset than in regions with a lower prevalence.

For example, the greatest reduction was observed in Newfoundland and Labrador -- in the east -- which had a rate difference before versus after fortification of 3.80 per 1,000 births, compared with British Columbia -- in the west -- with a rate difference of 0.21 per 1,000 births.

Geographical differences almost disappeared after fortification began, the researchers said.

The observed reduction in rates was greatest for spina bifida (53%) going from 0.86 per 1,000 births to 0.40 per 1,000 births, the researchers reported. For anencephaly and encephalocele the decreases were 38% and 31%, respectively.

A previous study, which assessed the effect of folic acid fortification in the U.S., used eight population-based surveillance systems that identified infants with neural-tube defects diagnosed prenatally, the researchers wrote.

In that study, the combined prevalence rate of anencephaly and spina bifida was 1.06 per 1,000 births before fortification (1995-1996) and 0.76 per 1,000 births after fortification (1999-2000), for a 28% reduction.

This decrease was less than that of the Canadian results, which included a 46% decline for all neural tube defects, and 48% for anencephaly and spina bifida combined, the researchers said.

The higher baseline rate in Canada may have contributed to the difference, they said, but other factors could also have played a role, including differences in ethnic distribution, eating habits, use of vitamin supplements, and the prevalence of other risk factors for neural tube defects, such as maternal obesity and diabetes.

In Canada, the researchers said, the current rate of neural-tube defects ranges from 0.7 to 1.3 per 1,000 births, with an average of 0.9 per 1,000 births.

Since not all cases of neural tube defects can be prevented, the potential for further improvement would be smaller than that reported in this study, but might be as much as 30% for a residual risk of 0.6 per 1,000 births. Validation of this model is warranted in other settings, Dr. De Wals said.

"Decisions regarding the optimal level of food fortification and the types of foods to be enriched must take into account both safety, especially for seniors who may have unrecognized B₁₂ deficiency, and the goal of maximizing the reduction in neural-tube defects," the Canadians concluded.