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Food fortification with folic acid and neural tube defects


Based on findings that folic acid supplementation before conception and during the first trimester reduces the occurrence of neural tube defects, it is now recommended that women take a daily supplement of 400 µg of folic acid as soon as they stop using contraception and for the first three months of pregnancy. In addition, grain products are now fortified with folic acid (e.g. breakfast cereals and breads) to help reduce the occurrence of folate-preventable neural tube defects. This paper aims to assess the impact of fortifying food with folic acid on the prevalence of neural tube defects.


Women are currently advised to try to increase their folate from dietary sources to 300 µg a day (in addition to taking a daily supplement of 400 µg of folic acid). Current fortification is estimated to add approximately 100 µg of folic acid to the average daily diet. This study found a 19% reduction in neural tube defect prevalence following folic acid fortification, highlighting the impact and importance of additional dietary folate which can be consumed with little effort (e.g. two slices of fortified bread and a 90 g serving of Brussels sprouts each contain 100 µg of folate).


MA Honein et al. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. Journal of the American Medical Association 2001 285: 2981-2986.


In 1992 the US Public Health Service issued the recommendation that women, capable of becoming pregnant, should take a 400 µg supplement of folic acid a day. A survey indicated that only 29% of women were following this recommendation in 1998. To increase folic acid intake, the addition of folic acid to the grain supply was authorised in 1996 and made compulsory in 1998.


The prevalence of neural tube defects (specifically spina bifida and anencephaly) was assessed by examining birth certificates from 45 US states and Washington, DC. The number of cases before folic acid fortification (from 1995 to 1996) was compared with the number of cases after fortification became compulsory (from 1998 to 1999).


The birth prevalence of neural tube defects decreased from 37.8 per 100,000 live births before fortification to 30.5 per 100,000 live births after fortification. This represents a 19% decline (prevalence ratio 0.81, 95% confidence interval 0.75 to 0.87). Table 1 shows the number of live births and neural tube defect cases contributing to this result.

Table 1. Estimated decline in neural tube defects following US folic acid fortification.


Number of live births

Number of neural tube defect cases

Prevalence ratio








0.81 (0.75-0.87)

The occurrence of neural tube defect births, unaffected by prenatal diagnosis and termination, was also examined among women who either had no prenatal care or began it in the third trimester. The observed decline (from 53.4 per 100,000 before fortification to 46.5 per 100,000 after fortification) was not significant (prevalence ratio 0.87, 95% confidence interval 0.64 to 1.18). The number of live births contributing this analysis was 159,322 (with 74 neural tube defect cases) pre-fortification and 166,718 (with 89 neural tube defect cases) post-fortification due to only 3.9% of women in this sub-group.


This study illustrates the complexity of assessing the impact of food fortification. For example:

  1. the results are reliant upon consistent and accurate reporting on birth certificates;
  2. although fortification did not appear to make a difference in neural tube defect prevalence among women receiving either no or only third-trimester prenatal care, this result may be due to considerably fewer women and cases in this sub-analysis;
  3. consumption of fortified products (e.g. breads and cereals) will vary among women;
  4. the percentage of women taking additional folic acid supplementation is unknown.

Despite the insurmountable difficulties with this type of study, a reduction was nevertheless found in neural tube defect birth prevalence following folic acid fortification of the grain supply.