Antiepileptic drug use of women with epilepsy and congenital malformations in offspring.
OBJECTIVE
To compare the risk for congenital malformations in offspring between women with epilepsy being treated with antiepileptic drugs (AEDs) during pregnancy and those who discontinued their antiepileptic medication before pregnancy in a population-based cohort of female patients with epilepsy.


METHODS
All patients with epilepsy (n = 20,101) eligible for AED reimbursement for the first time during 1985 to 1994 were identified from the Social Insurance Institution of Finland. Information on births during 1991 to 2000 was obtained from the National Medical Birth Registry. Information on AED use during pregnancy and on pregnancy outcomes was abstracted from medical records.


RESULTS
Congenital malformations were more common among offspring of women on antiepileptic medication (65/1,411; 4.6%) than among offspring of untreated patients (26/939; 2.8%) (p = 0.02). The risk of malformations was substantially higher in the offspring of patients using valproate as monotherapy (OR = 4.18; 95% CI: 2.31, 7.57) or valproate as polytherapy (OR = 3.54; 95% CI: 1.42, 8.11) than of untreated patients. Polytherapy without valproate was not associated with increased risk of malformations.


CONCLUSIONS
Excess risk was confined to patients using valproate during pregnancy. The risk for malformations was not elevated in offspring of mothers using carbamazepine, oxcarbazepine, or phenytoin (as monotherapy or polytherapy without valproate).
Artama
M
M
Tampere School of Public Health, University of Tampere, FIN-33014, Finland. miia.artama@uta.fi
Auvinen
A
A
Raudaskoski
T
T
Isojärvi
I
I
Isojärvi
J
J
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology* / Q000473:pathology / Q000503:physiopathology; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D018376:Cardiovascular Abnormalities / Q000139:chemically induced / Q000453:epidemiology; D002972:Cleft Palate / Q000139:chemically induced / Q000453:epidemiology; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005835:Genitalia / Q000002:abnormalities; D006801:Humans; D009139:Musculoskeletal Abnormalities / Q000139:chemically induced / Q000453:epidemiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000139:chemically induced / Q000453:epidemiology; D014635:Valproic Acid / Q000009:adverse effects
D000927:Anticonvulsants; D014635:Valproic Acid