Women taking antiseizure medication for epilepsy, have around a 45% reduced risk of major congenital anomalies in their children—if they initiate high-dose folic acid before pregnancy.
This is the finding of a large Nordic register-based study (SCAN-AED) involving Aarhus University Hospital. The study also finds that starting folic acid supplementation after pregnancy onset is not associated with any protective effect.
– We observe a clear association between the timing of initiation of high dose folic acid supplementation and the risk of congenital anomalies. The critical window of starting high-dose folic acid supplementation appears to be before pregnancy, says Jakob Christensen, consultant neurologist at Aarhus University Hospital and professor at Aarhus University.
The paper has been published in the scientific journal JNNP ( Journal of Neurology, Neurosurgery & Psychiatry ) . Free to access link to the article and a 4-minute video abstract: https://jnnp.bmj.com/content/early/2026/03/27/jnnp-2025-337395.full
The study includes data from more than 13,000 pregnancies among women treated with antiseizure medications in Denmark, Norway, Sweden, and Iceland.
The results show that:
This corresponds to an absolute risk reduction of 22 cases per 1000 pregnancies and a relative reduction of 45%.
No reduction in risk of congenital anomalies was observed when folic acid supplementation was initiated after pregnancy onset.
The association was even stronger among women taking medications associated with a higher risk of fetal harm, including valproate, where subgroup analyses showed up to an 86% relative reduction in risk.
High-dose folic acid has been recommended for pregnant women with epilepsy for many years, but the evidence has been limited and inconsistent.
– Previous studies of folic acid have not adequately accounted for timing of the treatment. Our study shows that this is a crucial factor, says Dr. Yuelian Sun, who is the first author on the paper and Senior researcher at Aarhus University Hospital and the University of Bergen in Norway.
The researchers emphasize that the findings do not mean women should change treatment on their own.
– The key message is that planning before pregnancy is essential. Women should always discuss both medication and folic acid supplementation with their doctor, says Julie Werenberg Dreier, Professor at the Department of Public Health at Aarhus University.
The study is based on nationwide register data from four Nordic countries over more than 20 years and uses an advanced method known as target trial emulation , which mimics a clinical trial.
However, it remains an observational study, and the findings should be interpreted with caution due to the possibility of unmeasured confounding factors with potential impact on child outcome.
Study type : Register-based observational study (target trial emulation)
Collaborators: Aarhus University Hospital and Aarhus University, University of Bergen, Karolinska Institutet and others
Funding : NordForsk, Trond Mohn Foundation, Research Council of Norway
Conflicts of interest : Declared in the article (including research funding and honoraria from pharmaceutical companies)
Scientific publication :
Sun Y, Alvestad S, Cohen JM, et al.
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 & Psychiatry , 2026
DOI: 10.1136/jnnp-2025-337395
Free to access link: http://jnnp.bmj.com/cgi/rapidpdf/jnnp-2025-337395?ijkey=hytaVpkgAxMZUs7&keytype=ref
Yuelian Sun
Senior Researcher, Aarhus University Hospital and University of Bergen
Tel. +45 2559 6425
Email: ys@clin.au.dk
Jakob Christensen
Consultant neurologist, Aarhus University Hospital
Professor, Department of Clinical Medicine, Aarhus University
Tel: +45 6086 5899
Email: jakob@farm.au.dk
Julie Werenberg Dreier
Professor, National Centre for Register-based Research, Department of Public Health Aarhus University
Tel: +45 2562 1178
Email: jwdreier.ncrr@ph.au.dk
Journal of Neurology Neurosurgery & Psychiatry
Observational study
People
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
20-Jan-2026