- J Korean Neurol Assoc. 2010;28(4):249-256.
- Effect of Antiepileptic Drugs on Fetal Congenital Malformation and Cognitive Function
- Se-Jin Lee
- Department of Neurology, Yeungnam University College of Medicine, Daegu, Korea
- 항간질제가 태아의 선천기형 및 인지기능에 미치는 영향
- 영남대학교 의과대학 신경과학교실
- Abstract
- Although the majority of women with epilepsy give birth to healthy children, intrauterine exposure to antiepileptic
drugs (AEDs) increases the risk of fetal major congenital malformations (MCMs), a two-to threefold increase in risk with
older AEDs. Several prospective pregnancy registries demonstrated a consistent pattern of increased risk for MCMs with
valproate (VPA) used as monotherapy, compared to unexposed populations and to other AEDs. Polytherapy likely
increases risk for MCMs, but the risk is more pronounced if VPA was included. There are dose-effect relationships in
some AEDs and specific MCMs associated with specific AEDs. Dose-dependent risk for MCMs has been demonstrated
with VPA above 800 to 1000 mg. Carbamazepine and VPA have been reported to be associated with a significant increase
in the risk of spina bifida. For newer AEDs other than lamotrigine, data are still too limited to determine the risks for
MCMs. Fetal exposure to AEDs can produce cognitive deficits. VPA and AED polytherapy probably reduces cognitive
outcomes and monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. If possible,
avoidance of VPA and AED polytharapy during the first trimester should be considered to decrease the risk of MCMs,
and avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive
outcomes. However these risks must be balanced against potentially grave risks to both mother and fetus posed by
seizures. Further studies are needed to compare risks for MCMs and reduced cognitive outcomes of each AEDs at
different dosages and combination. Key Words: Epilepsy, Pregnancy, Teratogenesis, Congenital malformation, Cognitive function, Antiepileptic drugs
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