Clinical trials conducted almost three decades ago proved that folic acid taken before and during early pregnancy can reduce a woman’s chance of having a neural tube defect (NTD) affected pregnancy by up to 80%. Public health authorities worldwide have advised that women planning a pregnancy take a folic acid-containing supplement (400-600 µg/d) before trying to conceive to the end of the first trimester. Because many pregnancies are unplanned and NTDs occur in the first month of pregnancy, many countries, including Australia, have mandated the addition of folic acid to a food staple such as wheat flour. Both strategies have markedly reduced the incidence of NTDs globally.

One area of debate is whether women with pre-existing diabetes or a prior history (or at higher risk, i.e., obese) of gestational diabetes mellitus (GDM) require more folic acid. In Australia, most professional organisations recommend that women with diabetes or a prior history of GDM take 5000 µg/day of folic acid.   While women with existing diabetes are at higher risk of NTD-affected pregnancies, no high-quality evidence supports a higher folic acid supplement dose to prevent NTDs. Further clinical trials to establish the dose of folic acid required to reduce NTDs in women with diabetes would be unethical. Thus, recommendations for women with diabetes to take a higher dose of folic acid are and will remain primarily based on consensus opinion.

The question then becomes, does taking high-dose folic acid pose any risk? The only proven benefit of taking folic acid during pregnancy is the prevention of NTDs. These birth defects occur in the first month of pregnancy, and there is no other proven benefit of taking folic acid. Yet many women with and without diabetes take folic acid throughout pregnancy. Worryingly observational evidence suggests that continued folic acid use may increase the risk of adverse pregnancy and child outcomes such as GDM, prematurity, large for gestational age, and adverse increased risk of food allergy, obesity, and other metabolic disease in the offspring.

In this presentation, I will review the evidence supporting the higher folic acid supplementation dose to prevent NTDs in women with diabetes during pregnancy. I will also explore the risks and benefits of the higher dose of folic acid periconceptionally and continued use throughout pregnancy.