The utilization, safety, and effectiveness of periconceptional high dose folic acid supplementation

Neural tube defects are one of the most common congenital anomalies encountered in Canada. They can result in fetal deaths, newborn and child deaths, and life-long disability. Folic acid supplementation is an important intervention to prevent neural tube defects. While Health Canada has consistently recommended 0.4 mg per day (standard dose) for women at low risk, Canadian guidelines for high doses (5 mg per day) have varied considerably over time. These variations are due, in part, to a lack of strong evidence of additional benefits of 5 mg per day folic acid. Folic acid doses higher than 1.0 mg per day are only available by prescription and are therefore exclusively initiated by physicians. Following over seven years where high-dose folic acid was recommended widely for many potential risk factors, revised 2015 Society of Obstetricians and Gynaecologists of Canada (SOGC) guidelines considerably restricted the recommended indications for 5 mg per day folic acid. However, the impact of these more restrictive guidelines on physician prescribing practices is unclear. Furthermore, given that many women in Canada and around the world have taken high doses of folic acid, evidence is urgently required on any potential risks and benefits associated with the use of 5 mg per day folic acid. We will use prescription claims data from British Columbia and Manitoba to study the effect of revised 2015 guidelines on 5 mg per day folic acid use among pregnant women. We will use electronic health record data from the United Kingdom to compare women who receive high and standard dose folic acid with regards to their chances of developing breast cancer later in life or having a baby with neural tube defects. This study will provide information to help inform the public and the medical community about the use of high-dose folic acid to prevent neural tube defects in Canada and the risks and benefits of high-dose folic acid supplementation.