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Side effects of antiepileptic drugs in children
1Département de Pharmacologie Clinique Périnatale et Pédiatrique Hôpital Saint-Vincent de Paul, Paris, France.
Insights
Antiepileptic drugs can increase congenital malformations in children, with risks varying by medication. However, the danger of uncontrolled seizures during pregnancy poses a greater threat to the fetus than potential drug side effects.
Area of Science:
- Pediatric Neurology
- Pharmacology
- Teratology
Background:
- Antiepileptic drug (AED) side effects in children require consideration across all developmental stages, including pregnancy, infancy, and childhood.
- Offspring of mothers treated with AEDs exhibit a higher incidence of congenital malformations compared to controls.
- Prospective studies suggest AEDs, rather than epilepsy itself, are linked to increased teratogenicity.
Purpose of the Study:
- To evaluate the risks of congenital malformations associated with antiepileptic drug use during pregnancy.
- To compare the teratogenic potential of monotherapy versus polytherapy.
- To identify specific AEDs associated with particular birth defects.
Main Methods:
- Review of recent prospective studies examining pregnancy outcomes in women using antiepileptic medications.
- Analysis of associations between specific AEDs (e.g., valproic acid, phenytoin, phenobarbitone) and congenital anomalies.
- Comparison of malformation rates between treated epileptic mothers, untreated epileptic mothers, and normal controls.
Main Results:
- Maternal AED use is associated with increased congenital malformations, with teratogenicity attributed to the drugs themselves.
- Monotherapy may carry a lower risk of facial defects compared to polytherapy.
- Specific associations found: valproic acid with spina bifida; phenytoin and phenobarbitone with facial clefts; polytherapy also linked to facial clefts.
Conclusions:
- While AEDs pose risks, they do not warrant discontinuing treatment for well-controlled epilepsy during pregnancy.
- Avoidance of AED combinations and specific high-risk drugs (valproic acid, diones) is recommended.
- The risk of fetal harm from uncontrolled seizures or status epilepticus outweighs the teratogenic risk of AEDs.
Abstract:
Side effects of antiepileptic drugs in children have to be considered at all stages of maturation: during pregnancy, at birth, during breast feeding and in older children treated for epilepsy. The offspring of drug treated epileptic mothers have a higher incidence of congenital malformations than do those of normal controls or of non treated epileptic mothers. According to recent prospective studies teratogenicity appears to be attributable to antiepileptic drugs rather than to epilepsy since more congenital anomalies have been found among infants of treated epileptic mothers than among untreated epileptic mothers. Monotherapy might be associated with a less pronounced risk for facial defects than is polytherapy. Some studies suggest that the actual drug used is significant for the teratogenic effect: a significant association was seen between maternal use of valproic acid and spina bifida; facial clefts were associated with both phenytoin and phenobarbitone use and also with polytherapy. These side effects do not however justify discouraging a woman on antiepileptic medications from having a child, nor do they perhaps justify changing a satisfactory drug regimen during pregnancy when the epilepsy is well controlled. The use of combinations of anticonvulsants should be avoided as well as anticonvulsants considered as not being safe (valproic acid, diones). However the danger of precipitating severe seizures or status epilepticus by overcautious treatment should be avoided because it poses a greater hazard to the fetus as compared to the low risk of teratogenicity due to anticonvulsants. Infants born to mothers taking either phenytoin or barbiturate derivatives or both may show clinical signs of bleeding and diminished level of coagulation factors, usually during the first 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)