Treatment of epilepsy in pregnancy.
Pregnant women with epilepsy constitute 0.5% of all pregnancies. Proper seizure control is the primary goal in treating women with epilepsy. The commonly used anticonvulsants are established human teratogens. Factors such as epilepsy, anticonvulsant-induced teratogenicity, patient's genetic predisposition and the severity of convulsive disorder may attribute to adverse pregnancy outcome for the children of women with epilepsy. Anticonvulsant interaction with folic acid and phytomenadione (vitamin K) metabolism may lead to an increased risk for neural tube defect and early neonatal bleeding. Psychological, hormonal and pharmacokinetic changes in pregnancy may escalate seizure activity. Preconceptional counselling should include patient education to ensure a clear understanding of risks of uncontrolled seizures and possible teratogenicity of anticonvulsants. Genetic counselling should be performed if both parents have epilepsy or the disease is inherited. Seizure control should be achieved at least 6 months prior to conception and, if clinically possible, by the lowest effective dose of a single anticonvulsant according to the type of epilepsy. The new anticonvulsants are not recommended in pregnancy and require further research to prove their safety in humans. Folic acid 5 mg/day should be administered 3 months before conception and during the first trimester to prevent folic acid deficiency-induced malformations. Antenatal management should include assessment of patients for anticonvulsant-associated birth defects through detailed ultrasound examination and levels of maternal serum alpha-fetoproteins. Therapeutic drug monitoring should be performed monthly, or as clinically indicated. If phenobarbital, carbamazepine or phenytoin is administered, maternal phytomenadione supplementation should begin 4 weeks before the expected date of delivery. In order to prevent convulsions during labour, proper seizure control should be achieved during the third trimester. Benzodiazepines or phenytoin are found to be effective for seizure cessation during labour and delivery. Phytomenadione should be administered immediately after birth to the newborn. The neonate should be assessed carefully for epilepsy and anticonvulsant-associated dysmorphology. Advising the patient on postpartum management regarding contraception and breast-feeding will help maximise the best possible outcome for the newborn and mother. With proper preconceptional, antenatal and postpartum management up to 95% of these pregnancies have been reported to have favourable outcomes.
Nulman
I
I
Hospital for Sick Children, University of Toronto, Ontario, Canada. inulman@sickkids.on.ca
Laslo
D
D
Koren
G
G
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000378:metabolism
D000927:Anticonvulsants