It is well established that folate requirements increase during pregnancy and that supplementing 0.4 mg folic acid/day to the general pregnant population is beneficial in terms of reducing the risk of neural tube defects. It is also well established that offspring of women with pregestational diabetes mellitus have an increased risk of congenital anomalies. In animal models, both in vivo and in vitro, folic acid supplementation reduces glucose-induced congenital anomalies. In recent years, several academic societies have included diabetic women in the high-risk category for neural tube defects, so that the supplementation applying for them would be 4-5 mg/day, the dose recommended for secondary prevention in women with a former fetus affected with a neural tube defect. The protection afforded by folic acid supplementation in diabetic pregnant women is not clear: multivitamin supplementation has been reported to reduce the risk of congenital anomalies but the composition of the supplements was unknown and the benefit probably included that of overall prepregnancy care. In addition, in real life, most diabetic women even when planning pregnancy do not take folic acid supplements. To complicate things further, folic acid supplementation has potential deleterious effects, with promotion of neoplasia being among them. Folic acid tolerable upper intake level is set at 1 mg/day, so that the aforementioned recommendations should be considered in the pharmacological range. After reviewing these issues, we conclude that big efforts should be made to ensure that diabetic women receive periconceptionally a folic acid supplementation of 0.4 mg/day, as one of the interventions of comprehensive prepregnancy care. Until a favourable risk-benefit ratio is documented, we propose that higher doses are restricted to women not achieving adequate blood glucose regulation, and that long periods of supplementation are avoided. In recent years there are multiple patents including methods of detection of abnormalities in folate metabolism and trying to improve the supplementation of this micronutrient. Only one of them would be specific for diabetes.
folic acid, neural tube defects, congenital anomalies, pregestational diabetes, tumorigenesis, B12
Servei d'Endocrinologia I Nutricio, Hospital de la Santa Creu i Sant Pau, Sant Antoni M. Claret, 167,08025 Barcelona, Spain.