Many antiepileptic medications also seem to be safe for the baby during breast-feeding in that only small amounts are excreted in lactated milk. The degree of penetration into breast milk is dependent on the extent of protein binding. Highly bound drugs do not appear in substantial concentrations and the converse is true. Relatively safe agents include carbamazepine, which is found to be 40 percent of the mother’s serum concentration, resulting in a neonatal blood level that is below the conventionally detectable amount. Phenytoin is excreted at 15 percent of maternal serum concentration, and valproate, being highly protein bound, is virtually absent in breast milk. No adverse effects have been attributed to these small amounts of these drugs. Those that appear in intermediate concentrations include levetiracetam, oxcarbazepine, tiagabine, vigabatrin, gabapentin, and topiramate. Drugs considered risky for the infant because of high concentrations in breast milk include phenobarbital, primidone, ethosuximide, zonisamide, and benzodiazepines. The risks of using this last group of drugs in the postpartum period must be weighed against the sedating effects of the medication on the neonate.
In the past, issues regarding a coagulopathy in the fetus exposed to phenobarbital (now infrequently used for adult seizure disorders) and certain of the other drugs are well known to obstetricians and pediatric specialists and are treated with the oral administration of vitamin K, 20 mg/d during the eighth month or 10 mg IV 4 h before birth and 1 mg IM to the neonate.
Teratogenic Effects of Antiepileptic Medications
Because it is important to prevent major convulsions in the pregnant epileptic woman, antiepileptic medication should not be discontinued or arbitrarily reduced, particularly if there have been recent convulsions. The conventional drugs (phenytoin, carbamazepine, levetiracetam, lamotrigine) are all tolerated in pregnancy comparably to their use before pregnancy. Plasma levels of most of these drugs, both the free and protein-bound fractions, fall slightly in pregnancy in part because they are cleared more rapidly from the blood but there is considerable inter-individual variability. It is important to monitor the drug levels so that adjustments can be made. The main issue, however, pertains to the potential teratogenicity of most of the drugs with valproate having more risk than the others, and a slight reduction in verbal IQ in children born of mothers who had been exposed to valproate during pregnancy.