Seizure-associated brain injury in term newborns with perinatal asphyxia

Background: There is controversy over whether seizures, the most common manifestation of neonatal brain injury, may themselves damage the developing brain. Objective: To determine if neonatal seizures are independently associated with brain injury in newborns with perinatal asphyxia. Methods: Ninety term neonates were studied with MRI and single-voxel H-1-MRS on median day of life 6 (range 1 to 13 days). The severity of MR abnormality in the H-1-MRS regions of interest was scored using a validated scale. Seizure severity was scored based on seizure frequency and duration, EEG findings, and anticonvulsant administration. Multivariable linear regression tested the independent association of seizure severity with impaired cerebral metabolism measured by lactate/choline and compromised neuronal integrity measured by N-acetylaspartate/choline in both regions. Results: Clinical seizures occurred in 33 of 90 infants (37%). Seizure severity was associated with increased lactate/choline in both the intervascular boundary zone (p < 0.001) and the basal nuclei (p = 0.011) when controlling for potential confounders of MRI abnormalities and amount of resuscitation at birth. Each increase in seizure score was independently associated with a 21% increase in lactate/choline in the intervascular boundary zone (95% CI, 5.1-38.2%) and a 15% increase in the basal nuclei (95% CI, 0.1-31.7%). Seizure severity was independently associated with diminished N-acetylaspartate/choline in the intervascular boundary zone (P = 0.034). Conclusion: The severity of seizures in human newborns with perinatal asphyxia is independently associated with brain injury and is not limited to structural damage detectable by MRI.