Antiepileptic drug use, folic acid supplementation, and congenital abnormalities: a population-based case–control study
Article first published online: 12 NOV 2007
RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology
BJOG: An International Journal of Obstetrics & Gynaecology
Volume 115, Issue 1, pages 98–103, January 2008
How to Cite
Kjær, D., Horvath-Puhó, E., Christensen, J., Vestergaard, M., Czeizel, A., Sørensen, H. and Olsen, J. (2008), Antiepileptic drug use, folic acid supplementation, and congenital abnormalities: a population-based case–control study. BJOG: An International Journal of Obstetrics & Gynaecology, 115: 98–103. doi: 10.1111/j.1471-0528.2007.01552.x
- Issue published online: 12 NOV 2007
- Article first published online: 12 NOV 2007
- Accepted 14 September 2007. Published OnlineEarly 12 November 2007.
- congenital abnormalities;
- epidemiological studies;
- folic acid;
Objective To investigate whether folic acid supplementation in early pregnancy modifies the association between the prevalence of congenital abnormalities in the offspring and maternal use of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and primidone (PRI).
Design A population-based case–control study.
Setting The Hungarian Case–Control Surveillance of Congenital Abnormalities (HCCSCA) (1980–1996) and its information on children from the Hungarian Congenital Abnormality Registry and the Hungarian National Birth Registry.
Population Children with congenital abnormalities (cases; n= 20 792, of whom 148 had been exposed to antiepileptic drugs [AEDs]) and unaffected children (controls; n= 38 151, of whom 184 had been exposed to AEDs).
Methods Information on drug exposure and background variables for the mothers were collected from antenatal logbooks, discharge summaries, and structured questionnaires completed by the mothers at the time of HCCSCA registration.
Main outcome measures Congenital abnormalities detected at termination of pregnancy, at birth or until 3 months of age according to CBZ, PB, PHT, or PRI exposure at 5–12 weeks from first day of the last menstrual period (LMP), stratified by folic acid supplementation.
Results Compared with children unexposed to AEDs and folic acid, the odds ratio of congenital abnormalities was 1.47 (95% CI 1.13–1.90) in children exposed to AEDs without folic acid supplementation and 1.27 (95% CI 0.85–1.89) for children exposed to AEDs with folic acid supplementation.
Conclusion The results indicate that the risk of congenital abnormalities in children exposed in utero to CBZ, PB, PHT, and PRI is reduced but not eliminated by folic acid supplementation at 5–12 weeks from LMP. The statistical precision in our study is limited due to rarity of the exposures, and further studies are needed.