Comparing the observed and predicted effectiveness of folic acid fortification in preventing neural tube defects.

Abstract

In 1992, the US Public Health Service recommended that all women of childbearing age consume 400 μg of folic acid daily to reduce their risk of having a pregnancy affected with a neural tube defect. In 1999, we reported a complete ascertainment of open neural tube defects that occurred in Maine during 1991–1996, including diagnoses made prenatally and after birth. That study showed no reduction in the incidence of open neural tube defects. According to published reports, relatively few women were taking supplements prior to conception during that time period. During 1997, folic acid fortiŽcation of grain products was undertaken in the United States and Canada at a level of 140 μg/100 g. Using the same methodology as before, we now extend the time period of ascertainment of pregnancies with open neural tube defects through the year 2000 (Table 1). Results from the years 1993–1996 are from our earlier work (column 1). These are the four years immediately preceding fortiŽcation. The data from 1997, when fortiŽcation was being introduced (second column), are separated from the 1998–2000 time period because the potential full impact of fortiŽcation would not have been felt until late in that year. The prevalence of all open neural tube defects in 1998–2000 was 10.7 per 10,000, as opposed to 12.3 per 10,000 in 1993–1996. This represents a reduction of 13% (95% conŽdence interval –41 to +27%). The effect was similar for both open spina biŽda and anencephaly. Although no formal methods for collecting reports of adverse health consequences associated with fortiŽcation exist in Maine, the Department of Human Services, Bureau of Health has received no anecdotal reports of adverse events (E Mulcahy, personal communication). Several other studies from North America report the effect of folic acid fortiŽcation on the incidence of open neural tube defects. These are summarised in Table 2. One study encompassing 45 states in the United States that relied entirely on birth certiŽcate data found a 19% decline. A study from Nova Scotia which identiŽed defects both prenatally and at birth reported a reduction of 54%. The most reliable report contained data from nine states that included cases ascertained both through prenatal diagnosis and at birth. That study reported a reduction of 32%. A unifying approach to interpreting the impact of folic acid fortiŽcation on neural tube defect incidence has been proposed. That approach takes into account both the serum folate levels prior to fortiŽcation and the increase of folic acid intake due to fortiŽcation. None of the studies in Table 2 measured serum folate, but the reported incidence of neural tube defects in each of the study populations prior to fortiŽcation can be used to crudely estimate those average levels. Table 2 shows the pre-fortiŽcation incidence, the estimated serum folate levels, and the expected percentage reduction in incidence post-fortiŽcation, according to the proposed model. The last column contains the actual reduction in incidence reported by each study. These reductions are generally in line with expectations. The higher than expected Žndings in some studies may be related to higher actual doses of folic acid due to increased efforts to encourage supplementation, more than the prescribed amount of folic acid being routinely added by manufacturers, and the availability of a wider choice of folate-fortiŽed food products. The greater the level of folic acid in a population, the lower will be the baseline incidence of neural tube defects. In order for further impact to be achieved on an already low incidence, incrementally higher doses of folic acid will be necessary. Because of the relatively high incidence of neural tube defects in Nova Scotia prefortiŽcation, the small amount of folic acid added via fortiŽcation would be expected to provide a 2–3 times greater reduction in incidence than the same level of fortiŽcation, overall, in the United States. These Žndings underscore the need for even further increases in folic acid intake. For example, were women of child-bearing age to ingest 5000 μg per day, the