Neonatal seizures are relatively common, occurring in 0.07-.27% of live term births and 5.8-13.2% of live premature births. Neonatal seizures can be difficult to diagnose, especially without EEG, as they are not typically generalized tonic-clonic events. In addition, not all seizures require treatment. When an anticonvulsant is indicated, phenobarbital is the most commonly administered drug followed by phenytoin.
Mechanism of Action
Phenobarbital is often used in concert with another nonbenzodiazepine antiepileptic drug (NBAED) such as phenytoin. Benzodiazepines such as midazolam, lorazepam, or diazepam are more rarely used. Diazepam's long half-life in babies makes it unsuitable for use in prolonged infusions. Studies have shown that phenobarbital is effective in controlling seizures in less than 50% in infants; when used in concert with phenytoin, this number rises to about two thirds. Phenobarbital depresses the nervous system and is a sedative at high doses; neonates may require respiratory assistance during treatment.
Current Use in High-Resource Settings
While phenobarbital is the preferred first-line treatment for neonatal seizures, there is considerable controversy as to whether seizures are enough of a health risk to the neonate to warrant the use of anticonvulsants. There are no large-scale studies comparing the effectiveness of antiepileptic drugs against a placebo. When used, therapeutic serum concentrations of phenobarbital are typically 20-40 mg/l. This can be achieved using a loading dose of 40 mg/kg for infants on ventilation, or split between two doses of 20 mg/kg for infants without ventilators. A 10-15 minute infusion IV is most common, but IM and oral dosing is possible. Phenytoin is administered as a 15 mg/kg IV 'push' at a rate no greater than 1 mg/kg per min. Oral dosing is possible as well.
Application in Low-Resource Settings
Neonatal seizures are particularly common in low-resource nations, possibly due to higher rates of infection, asphyxia, meningitis, and stroke. The incidence of seizures may be higher in developing locations with higher rates of infants resuscitated due to birth asphyxia. The treatment of choice is still phenobarbital, due to its availability and low cost.