(Bower and Stanley, 1989; Brown et al., 1997; Cuskelly et al., 1996; Daly et al., 1997), and NTD risk is inversely associated with both folate intake (Bower and Stanley, 1989; Shaw et al., 1995c; Werler et al., 1993) and erythrocyte folate concentration (Daly et al., 1995).

Although it is recognized that there are still uncertainties about the relationships among folate intake, erythrocyte folate, and NTD risk and the extent to which there are differences in the absorption of folate from food compared with supplements, the evidence is still judged sufficient to support a recommendation to reduce the risk of NTD. The recommendation made here for women capable of becoming pregnant is for intake that exceeds the Recommended Dietary Allowance (RDA) for folate. In particular, it is recommended that women capable of becoming pregnant consume 400 µg of folate daily from supplements, fortified foods, or both in addition to consuming food folate from a varied diet. At this time the evidence for a protective effect from folate supplements is much stronger than that for food folate. It is certainly conceivable that, if taken in adequate quantity, food folate will be shown to be as effective as folic acid, but it remains to be demonstrated. When more data are available, this recommendation will be revised.

An even larger dose of folate has been recommended to prevent recurrence in women with a previous NTD-affected pregnancy (CDC, 1991). However, some NTDs are not prevented by increasing folate intake.

To date there is no conclusive evidence to support any population screening for genetic markers of NTD risk. In the event that the correlation between the 5,10-MTHFR T⁶⁷⁷ allele and NTD is confirmed, screening women for the gene that codes for the thermolabile variant would identify only about 15 percent of those at risk for NTD. Thus, recommending consumption of 400 µg folate daily from supplementation or fortified foods for all women capable of becoming pregnant would be a more effective prevention measure than screening for the variant (Mills and Conley, 1996).

Folate may also prevent the occurrence of other types of congenital anomalies. In one randomized trial (Czeizel, 1993) and several case-control studies (Botto et al., 1996; Czeizel et al., 1996; Hayes et al., 1996; Munger et al., 1997; Shaw et al., 1995a, b; Tolarova and Harris, 1995), a reduction in the frequency of orofacial clefts and cardiovascular malformations was observed in women taking vitamin supplements and folate-fortified food. The results, however,