What dose of folic acid should be used for pregnant diabetic women?

I t 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 (NTDs). Offspring of women with pregestational diabetes mellitus have an increased risk of congenital anomalies, including NTDs (1). In animal models, folic acid supplementation reduces glucose-induced congenital anomalies with a threshold effect (2). In humans, the protection afforded by folic acid supplementation against diabetesassociated birth defects is not clear: mult ivitamin supplements have 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 (3). In recent years, several academic societies (4,5) have recommended high doses of folic acid (4–5 mg/day) to diabetic pregnant women, based on their risk of congenital malformations. As folic acid–tolerable upper intake level is 1 mg/day, the aforementioned recommendations should be considered in the pharmacological range. High doses of folic acid can aggravate B12 vitamin deficiency and promote neoplasia (6), with diabetic women being at high risk (7). On the other hand, most diabetic women, even when planning pregnancy, do not take any folic acid supplement (8). We suggest that large efforts be made to ensure that, as one of the interventions of comprehensive prepregnancy care, diabetic women receive at least the folic acid dose recommended for the general population. When using high doses, we must take into account that they are in the pharmacological range, that there is no evidence of their benefit as a primary prevention strategy in diabetic pregnancy, and that side effects are potentially serious.