Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States

Background:
In 1992, the United States Public Health Service recommended that all women of childbearing age consume 400 g of folic acid daily. The Food and Drug Administration authorized the addition of synthetic folic acid to grain products in March 1996 with mandatory compliance by January 1998. The impact of these public health policies on the prevalence of neural tube defects needs to be evaluated. We sought to determine the prevalences of spina bifida and anencephaly during the transition to mandatory folic acid fortification.

Methods:
Twenty-four population-based surveillance systems were used to identify 5,630 cases of spina bifida and anencephaly from 1995-99. Cases were divided into three temporal categories depending on whether neural tube development occurred before folic acid fortification (January 1995 to December 1996), during optional fortification (January 1997 to September 1998), or during mandatory fortification (October 1998 to December 1999). Prevalences for each defect were calculated for each time period. Data were also stratified by programs that did and did not ascertain prenatally diagnosed cases.

Results:
The prevalence of spina bifida decreased 31% (prevalence ratio [PR] = 0.69, 95% confidence interval [CI] = 0.63-0.74) from the pre- to the mandatory fortification period and the prevalence of anencephaly decreased 16% (PR = 0.84, 95% CI = 0.75-0.95). Stratification by prenatal ascertainment did not alter results for spina bifida but did impact anencephaly trends.

Conclusions
The decline in the prevalence of spina bifida was temporally associated with folic acid fortification of US grain supplies. The temporal association between fortification and the prevalence of anencephaly is unclear.

Journal Reference:
L.J. Williams et al. Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States. Teratology 66:33-39, 2002


Excerpt:
It is also possible that because these defects have multiple etiologies, and thus, may follow the multifactorial/threshold model (Fraser, ’98), the combination of factors that results in the development of spina bifida may differ from that for anencephaly. Given differing etiologies, two possible conclusions could be drawn about the relationship between folic acid consumption and these defects. First, the amount of folic acid needed to prevent anencephaly may be higher than the amount needed to prevent spina bifida. The MRC (’91) and Czeizel and Dudas studies (’92) administered 4,000 g and 800 g of folic acid to subjects, respectively. The current level of folic acid fortification mandated by the FDA may not be high enough to prevent cases of anencephaly. Second, there may be a smaller percentage of folic acid-preventable anencephaly cases compared to spina bifida and additional fortification would not contribute to the further prevention of this birth defect.