Folic acid supplementation is not the sole factor in determining neural tube defects: The possible role of autoantibodies

Abstract

Neural tube defects (NTDs) are severe but common congenital malformations. Neonates who suffer from NTDs may experience long-term complications throughout their lives. These NTD complications which have been reduced worldwide are primarily due to environmental and genetic factors. Multicenter NTD studies conducted in Malaysia report a prevalence ranging from 0.79 to 1.29 per 1000 live births based on NTD etiologies, such as anti-epileptic drug consumption and maternal folate levels. In addition, intervention studies concluded that daily consumption of 400 μg of folic acid effectively reduced NTD risk; however, this data has not been robustly tested on the entire population due to the inefficiency of the three interrelated folate transport mechanisms and autoantibody generation. In this review, we evaluated the studies indicating that folic acid supplementation may not be the sole factor in reducing NTD incidence and that autoantibodies may have an important role in the NTD etiological pathway.

Key words: Neural tube defect, folic acid, methylenetetrahydrofolate reductase (MTHFR), Malaysia, anti-epileptic, folate transport mechanisms, autoantibodies