Early Serum S100B and Neurophysiological and Structural Brain Abnormalities in a Prospective Cohort of Preterm Infants

Background: Early identification of brain dysfunction in preterm infants remains challenging because cranial ultrasonography (CUS) may not capture early neurophysiological abnormalities. Serum S100B has been proposed as a marker of neonatal brain injury, but its relationship with electroencephalographic (EEG) abnormalities in preterm infants remains unclear. Objectives: Our objectives were to evaluate the association between early neonatal serum S100B concentrations and EEG abnormality severity in preterm infants and to determine whether similar associations are observed with structural brain injury detected by CUS. Methods: This prospective observational cohort included 116 preterm infants from 281 prospectively enrolled neonates. Serum S100B was measured within the first 24 h of life. Conventional multichannel EEG was performed at 10–14 days of life, and CUS was performed serially to assess intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL). Associations with EEG severity were evaluated using correlation analysis and ordinal logistic regression. A sensitivity analysis was restricted to infants with a postmenstrual age (PMA) ≤ 36 weeks at EEG and used a preterm-specific EEG grading system. Results: Higher log10(S100B) concentrations were associated with greater EEG abnormality severity (Spearman’s ρ = 0.49, p < 0.001) and remained independently associated after adjustment for gestational age and Respiratory Distress Syndrome (RDS) (adjusted OR 19.95, 95% CI 4.97–80.16; p < 0.001). No significant associations were observed between S100B concentrations and IVH or PVL severity. In the PMA-restricted sensitivity analysis (n = 89), the association between S100B and EEG abnormality severity remained significant using the preterm-specific grading system (ρ = 0.54, p < 0.001). Conclusions: During the early neonatal period, higher serum S100B concentrations were associated with greater neurophysiological abnormality severity in preterm infants, whereas associations with ultrasound-defined IVH or PVL were not demonstrated. The persistence of the S100B–EEG association in the PMA-specific sensitivity analysis supports the robustness of this finding across EEG grading approaches.