Seizure burden in preterm infants and smaller brain volume at term equivalent age

BACKGROUND: Seizures are underrecognized in preterm infants, and little is known about their impact on brain growth. We aimed to define the association between early seizures and subsequent brain growth. METHODS: Infants <30 weeks’ gestation underwent 72h of prospective aEEG monitoring, term-equivalent age (TEA) MRI, and 2y neurodevelopmental testing. Seizures were defined as trains of sharp waves >10 seconds, evolving in frequency/amplitude/morphology, and identified using automated algorithms with manual review. Using T2-weighted images, cortical surface area (CSA) and gyrification index (GI) were calculated and volumes were segmented into five tissue classes: CSF, gray matter, white matter (WM), deep nuclear gray matter, and cerebellum. Correlations between total seizure burden and tissue-specific volumes were evaluated, controlling for clinical variables of interest. RESULTS: Ninety-nine infants underwent aEEG/MRI assessments (mean GA=26.3 weeks, birthweight=899g). Seizure incidence was 55% with a median of two events; median length=66s and mean burden=285s. Greater seizure burden was associated with smaller CSA and volumes across all tissue types, most prominently in WM (R(2)=−0.603, p<.01), even after controlling for confounders. There was no association with GI. CONCLUSION: Seizures in preterm infants are common and associated with smaller TEA brain volumes. This relationship was strongest for WM and independent of clinical factors.