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Timing of high-dose folic acid supplementation in the periconceptional period among women taking antiseizure medications and risk of major congenital anomalies: a target trial emulation

We have conducted a sequential target trial emulation using nationwide register data from Denmark, Iceland, Norway, and Sweden (1997–2020). We observe a clear association between the timing of initiation of high dose folic acid supplementation and the risk of congenital anomalies. Initiation of high-dose folic acid supplementation 1–12 weeks before pregnancy was associated with an absolute risk reduction of 2.2 percentage points and a 45% relative risk reduction of MCAs in offspring. In contrast, initiation of high-dose folic acid supplementation 1–12 weeks after pregnancy onset was not associated with a reduced risk of MCAs. 

This achievement was the result of a massive collaboration across five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). I’m proud to have contributed significantly at every stage: from proposing the methodology and leading the analysis to presenting these findings at international conferences and drafting the final manuscript.

Sun, Y., Alvestad, S., Cohen, J. M., Igland, J., Gilhus, N. E., Vegrim, H. M., Tomson, T., Christensen, J., Leinonen, M. K., Gissler, M., Zoega, H., Razaz, N., Dreier, J. W., & Bjørk, M. H. Timing of high-dose folic acid supplementation in the periconceptional period among women taking antiseizure medications and risk of major congenital anomalies: a target trial emulation. Journal of neurology, neurosurgery, and psychiatry 2026 doi: 10.1136/jnnp-2025-337395 [published Online First: 20260324]