USE OF METHYLFOLATE IN PREGNANCY

Note: This monograph should be read in conjunction with the monograph on use of folic acid in pregnancy.

SUMMARY: Methylfolate (L-methylfolate) is the biologically active form of folate which, unlike folic acid, does not require enzymatic reduction by methylenetetrahydrofolate reductase (MTHFR). It is not a licensed medication and there is limited evidence available relating to efficacy or safety.

UKTIS has received a number of enquiries about whether routine use of methylfolate offers a superior alternative to use of folic acid in pregnancy, on the basis that conversion in the body to the biologically active form is not required. However, to date, no studies have addressed rates of neural tube and other birth defects in infants born to women taking methylfolate in pregnancy, while the population-wide data on the beneficial effects of folic acid are unequivocal.

Routine use of prenatal methylfolate in preference to folic acid cannot currently be recommended. In the UK, current guidelines recommend routine use of 400mcg/day of folic acid preconceptually and until at least 12 weeks of gestation. In women considered to be at increased risk of folate deficiency (family history of neural tube defect, concurrent treatment with drugs which interfere with folate metabolism, or maternal obesity), higher dose folic acid (5mg/day) is recommended. Methylfolate supplementation may, however, be advised in individual cases e.g., women with specific metabolic disorders, where benefit of use is likely to outweigh any theoretical or known risks to mother or fetus.

Exposure to methylfolate at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.