Abstract
BACKGROUND: Neurological complications remain the most common cause of long-term disability among preterm infants despite progress made in neonatal intensive care. Cranial ultrasound (CUS) is the first-line imaging modality for early diagnosis of periventricular leukomalacia (PVL) and peri-/intraventricular hemorrhage (PIVH), but is less sensitive in the detection of subtle damage in the white matter. Consequently, there is increasing interest in the role of biochemical biomarkers that could be useful to complement bedside neuroimaging for early diagnosis of brain injury in preterm infants. Neuron-specific enolase (NSE), a neuronal cytoplasmic enzyme released after neuronal damage, has been proposed as a potential biomarker of neonatal brain injury. However, the exact role of NSE for the diagnosis of brain injury in preterm newborns has still to be explored. The objective of this study was to evaluate the association between early serum NSE levels and CUS-detected brain injury, and to assess the diagnostic accuracy of NSE in identifying PVL and/or PIVH in preterm infants. METHODS: In this prospective cohort study, 55 preterm neonates (<37 weeks gestation) admitted to a tertiary neonatology center were enrolled. NSE concentrations were measured using chemiluminescent microparticle immunoassay, and serial CUS examinations were used to classify brain injury. Mann-Whitney U tests, Spearman correlation, and receiver operating characteristic (ROC) analyses were applied. RESULTS: NSE values were significantly higher in infants with abnormal CUS findings compared with those with normal CUS (median 78.9 vs. 39.1 µg/L; P<0.001). At the exploratory, ROC-derived cut-off of 43.2 µg/L (Youden's index), discrimination was high in this cohort [area under the curve 0.911; 95% confidence interval (CI): 0.817-0.981], with sensitivity 91.4% (95% CI: 76.9-98.2%) and specificity 85.0% (95% CI: 62.1-96.8%). NSE correlated with PVL severity (ρ=0.685; P=0.002) and showed an upward trend with PIVH severity. CONCLUSIONS: Serum NSE measured on day 3 of life was associated with CUS-detected brain injury (PVL or PIVH) in preterm infants. In this single-center cohort, NSE demonstrated promising diagnostic accuracy for identifying ultrasound-detectable brain injury. The proposed cut-off is exploratory and requires validation in larger, preferably multicenter cohorts before clinical application.