PREconception Folic Acid Clinical Efficacy (PREFACE) Trial

A multisite randomized controlled trial to determine whether supplementation with (6S)-5-methyltetrahydrofolic acid (5-MTHF) is at least as effective as synthetic folic acid in increasing maternal folate status for protection against neural tube defects (NTDs).

Inclusion criteria

• Non-pregnant females who are:
• Currently trying to become pregnant;
• Aged 19-42 years;
• Low risk for an NTD-affected pregnancy

Exclusion criteria

• Trying to conceive for ≥6 months (as ~90% of pregnancies occur after 6 months of trying);
• Diagnosed ovulatory disorders (polycystic ovary syndrome, endometriosis, or menstrual irregularity);
• More than 2 miscarriages in the past year;
• Undergoing fertility assistance (including current IVF or intrauterine insemination);
• Pre-existing medical condition known to impact maternal folate status (malabsorptive and inflammatory bowel diseases, active celiac disease, gastric bypass surgery, type 1 or 2 diabetes mellitus);
• Lifestyle factors known to impact maternal folate status (current smoking, >6 alcoholic drinks per week, recreational drug use);
• On the female or male side of those trying to conceive: personal NTD history, previous NTD-affected pregnancy, or personal or family history of other folate sensitive congenital anomalies;
• Use of folate-inhibiting medications (Chloramphenicol, Methotrexate, Metformin, Sulfasalazine, Phenobarbital, Phenytoin, Primidone, Triamterene, Barbiturates).