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IJE Advance Access published online on November 9, 2005

International Journal of Epidemiology, doi:10.1093/ije/dyi234
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Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2005; all rights reserved.
Accepted October 5, 2005

Original paper

Congenital structural anomalies in offspring of women with epilepsy--a population-based cohort study in Finland

Miia Artama 1*, Annukka Ritvanen 2, Mika Gissler 3, Jouko Isojärvi 4, and Anssi Auvinen 5

1 Tampere School of Public Health, University of Tampere, Tampere, Finland
2 The Finnish Register of Congenital Malformations, National Research and Development Centre for Welfare and Health, Helsinki, Finland
3 Social Welfare and Health Care Statistics, National Research and Development Centre for Welfare and Health, Helsinki, Finland
4 Department of Neurology, University of Oulu, Oulu, Finland
5 Tampere School of Public Health, University of Tampere, Tampere, Finland; Pediatric Research Center, Tampere University Hospital, Tampere, Finland

* To whom correspondence should be addressed.
Miia Artama, E-mail: miia.artama{at}uta.fi


   Abstract

Background Offspring of women with epilepsy may have an increased risk for congenital malformations, probably attributable to maternal antiepileptic medication. We conducted this population-based study to obtain valid and accurate estimates on major congenital malformations in the offspring of women with epilepsy, based on a large and representative patient cohort.

Methods We identified all women (n = 6535) entitled to full reimbursement for antiepileptic medication indicated for epilepsy for the first time between 1985 and 1994 from the Social Insurance Institution of Finland database. A reference cohort (n = 14 704) was identified from the Finnish Population Register Centre. Information on children born between 1993 and 2000 (patient cohort, n = 2162; reference cohort, n = 5413) was obtained from the Medical Birth Register. Information on children born with malformation (patient cohort, n = 116; reference cohort, n = 151) was obtained from the Finnish Register of Congenital Malformations.

Results The prevalence of major malformation was 54/1000 births among patients with epilepsy and 28/1000 births among mothers without epilepsy, corresponding to a 2-fold overall risk for malformation in the offspring of women with epilepsy. The risk for spina bifida [odds ratio (OR) = 11.3, 95% confidence interval (CI) 2.34-108] and congenital anomalies of genital organs (OR = 8.38, 95% CI 2.15-47.4) was substantially elevated in the offspring of mothers with epilepsy.

Conclusions The absolute excess in the prevalence of major malformations was 26/1000 births in the offspring of mothers with epilepsy in relation to the offspring of reference mothers. The highest relative risk was observed in spina bifida and congenital anomalies of genital organs. However, these malformations cover only a small proportion of all major malformations.

Keywords: Children; cohort studies; congenital anomalies; epilepsy; prevalence.
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