Currently used treatment protocols for neonatal seizures vary among centers with limited evidence to support the choice of a given antiseizure medication. Because of concerns about the potential negative impact of phenobarbital on long-term neurodevelopment outcomes, our unit transitioned to fosphenytoin as the first-line antiseizure medication. A retrospective observational cohort study was conducted to compare the acute and long-term outcomes of fosphenytoin and phenobarbital as first-line antiseizure medication for neonatal seizure treatment. The 2 study groups had similar baseline characteristics for neonatal variables as well as maternal antenatal complications. We did not find any differences in the acute outcomes between the 2 groups. However, significantly fewer infants in the fosphenytoin group had moderate-to-severe neurodevelopmental delay at the 18- and 24-month assessments. In conclusion, although both medications were equally efficacious for acute neonatal seizure control, fosphenytoin had the potential for significantly better neurodevelopmental outcomes at 18-24 months of age.
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