Does periconceptional folic acid supplementation increase the risk of miscarriage or pregnancy loss?

The short version: the best evidence shows no increased risk of miscarriage from periconceptional folic acid supplementation, but the data is not definitive.

The question of miscarriage risk was raised by early signals from the Hungarian and MRC randomized trials, which initially reported a possible increase [1]. Later analysis of those same trials found a relative risk of about 1.06, which was not statistically significant [1]. The large China folic acid intervention study, which followed about 250,000 women, found a miscarriage relative risk of 0.97 (95% CI 0.84–1.12), meaning no increase at all [1]. That Chinese study used 400 mcg per day of folic acid alone, started before conception and continued through early pregnancy [1].

The evidence here is limited in important ways. The Chinese study is observational, not a randomized trial, and the Hungarian trial was designed for neural tube defect prevention, not miscarriage detection. No study in this retrieval was designed with miscarriage as the primary endpoint. The confidence intervals in the Chinese study are wide enough that a modest increase or decrease in risk cannot be ruled out. The 2005 review notes that the early miscarriage signal was "not consistently reproduced" and that overall there was "no strong evidence of harm" [1].

What this means for you: the available data, from the largest study ever done on this question, does not show that folic acid supplementation around conception increases the risk of miscarriage. The evidence is not airtight—no long-term randomized trial with miscarriage as the primary outcome exists—but the signal from the best available data is neutral.

My call: periconceptional folic acid supplementation does not appear to increase miscarriage risk based on the largest and most relevant study, but the evidence base is not definitive. Confidence: moderate.