Recent Developments in Neonatal Seizure Interventions

Neonatal seizures, a leading neurological disorder, occur in 1 to 3 per 1000 live births, with higher incidence in premature infants. Despite advancements in neonatal care reducing mortality, long-term morbidity—such as cerebral palsy, developmental delays, and post-neonatal epilepsy—remains a significant concern. Neonatal seizures are predominantly symptomatic of acute brain injury, with common causes including hypoxic-ischemic encephalopathy (HIE) in term infants and intraventricular hemorrhage in preterm infants, along with CNS infections, metabolic disorders, and brain malformations. Recent improvements in seizure detection and classification, through continuous neuromonitoring, neuroimaging, and metabolic/genetic screening, have advanced our understanding. However, treatment options remain limited. Current anticonvulsant therapies, including phenobarbital, are associated with poor efficacy and significant side effects, underscoring the need for alternative therapies. This chapter explores two promising candidates for neonatal seizure management—ganaxolone and levetiracetam. Both have preclinical data supporting their anti-seizure efficacy and potential neuroprotective properties, making them viable alternatives to traditional therapies. Ganaxolone, a GABAA modulator, and levetiracetam, an SV2α ligand, both show promise in reducing seizure activity without the neurotoxic effects seen with other treatments. These therapies offer a potential pathway toward safer, more effective management of neonatal seizures, with the possibility of improving long-term outcomes for affected infants.