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 72 h of prospective amplitude-integrated electroencephalography (aEEG) monitoring, term-equivalent age (TEA) magnetic resonance imaging (MRI), and 2-year neurodevelopmental testing. Seizures were defined as trains of sharp waves >10 s, 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: cerebrospinal fluid, 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 = 899 g). Seizure incidence was 55% with a median of two events; median length = 66 s and mean burden = 285 s. Greater seizure burden was associated with smaller CSA and volumes across all tissue types, most prominently in WM (R² = −0.603, p < 0.01), even after controlling for confounders. There was no association with GI. Conclusions: Seizures in preterm infants are common and associated with smaller TEA brain volumes. This relationship was strongest for WM and independent of clinical factors. Impact: Seizures in preterm infants are common.Little is known about the association between early seizures and later brain growth.Greater seizure burden is linked with smaller volumes of all brain tissue types, most prominently the WM.This relationship is true even controlling for other factors.Additional study is needed to identify the optimal EEG monitoring and seizure treatment strategy for improved brain growth and neurodevelopmental outcomes.