For the B vitamins the developmental disorder of greatest concern is neural tube defect (NTD). Major gaps in knowledge include the mechanisms by which maternal folate sufficiency reduces the occurrence of NTD in the infant (e.g., evaluation of whether increased NTD risk is due to folate deficiency or to the mode of action of folate sufficiency [does it act on mother, embryo, or both?]); the relative efficacy of food folate, folate added to food, and folate supplements in reducing NTD risk; the process, if any, by which folate influences the embryonic process of neurulation; and the genes that are responsible for the heritability and folate-responsiveness of NTD. This latter area could include (1) linkage analyses in suitable genetically homogeneous human populations to assess the etiologic relationship between NTD and a variety of genetic alterations (including the thermolabile variant of 5,10-methylenetetrahydrofolate reductase) and in the genes responsible for NTD in the curly tail mouse; (2) investigation of whether alterations in any of these genes produce NTD when induced in mouse models, yield folate-responsive NTD in mouse models, and provide suitable markers for assessing NTD risk in human populations; and (3) identification of an animal model for common human NTDs that is responsive to relevant levels of folate.

Although interest is high and numerous studies have been conducted, there are still serious gaps in knowledge of the relationship of B vitamin intake to risk of vascular disease and other chronic degenerative diseases. With the new U.S. regulations on the fortification of cereal grains with folate, it is now possible to investigate the health effects, both positive and negative, of folate fortification on folate intake and health status by life stage and gender.

For B vitamins and choline as a group, only a few studies have been conducted that were explicitly designed to address adverse effects of chronic high intake. Thus, information on which to base Tolerable Upper Intake Levels (ULs) is extremely scanty. Because it appears that vitamin B₁₂ deficiency greatly increases the potential