Folate Supplementation in Women with Pre-Existing Diabetes

Folate supplementation in the periconceptual period is the standard of care for the prevention of neural tube defects. To support dietary folate intake, some countries have introduced mandatory folic acid fortification of food products. Robust evidence supports the additional use of a low-dose folic acid supplement (0.4 mg/day) in all women from 2-3 months preconception until the end of the 12th week of gestation. For women with pre-existing diabetes, high-dose folic acid supplementation (5 mg/day) is recommended in some, but not all international guidelines. The recommendation is made based on consensus opinion and reflects the increased risk of neural tube defects in pregnant women with pre-existing diabetes. However, there is limited evidence to clarify the high-risk groups that benefit from high-dose folic acid versus those that do not. There are also some data to suggest that high-dose folic acid may be harmful to mothers and offspring, although this issue remains controversial. This narrative review explores the evidence that supports the recommendation for women with pre-existing diabetes to take high-dose folic acid in the periconceptual period. It explores the potential benefits of high-dose supplemental folate beyond the prevention of neural tube defects, and also the potential adverse impacts of high-dose folate use. These topics are considered with a specific focus on the issues that are pertinent to women with pre-existing diabetes. Based on the available evidence, a pragmatic approach to the use of folic acid supplements in women with pre-existing diabetes during the periconception period is suggested. The need for comprehensive preconception care that optimises glycaemic control and addresses other modifiable risk factors before pregnancy is emphasized.