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Altered endothelial nitric oxide synthesis in preterm and small for gestational age infants. BACKGROUND: Preterm infants are often exposed to neuronal and endothelial damage. The aim of the present study was to investigate the correlation between endothelial dysfunction and neuronal injury in preterm infants. METHODS: We compared serum nitric oxide (NO), endothelial nitric oxide synthase (eNOS) and neuron-specific enolase (NSE) concentrations in 33 moderate preterm (MP) and 47 late preterm (LP) infants using standard ELISA. Each group was classified as appropriate for gestational age (AGA) or small for gestational age (SGA). RESULTS: Compared to the AGA infants, the SGA infants had higher NO on day 1 (MP: mean, 72.3 ng/mL, range, 50.9-99.5 ng/mL vs 52.2 ng/mL, range, 28.1-68.2 ng/mL, P < 0.05; LP: mean, 58.4 ng/mL, range, 25.7-66.4 ng/mL vs 43.7 ng/mL, range, 21.2-60.6 ng/mL, P < 0.05), lower eNOS concentration on day 3 in the MP group (mean, 5.8 IU/mL, range, 1.2-7.9 IU/mL vs 8.9 IU/mL, range, 4.2-14.6 IU/mL, P < 0.05), and on day 1 in the LP group (mean, 5.5 IU/mL, range, 1.5-8.1 IU/mL vs 7.7 IU/mL, range, 4.4-13.8 IU/mL, P < 0.05). The NO/eNOS ratio was higher in SGA infants compared with the AGA subgroups (MP: mean, 13.8, range, 9.9-20.2 vs mean, 9.9, range, 4.7-13.1, P < 0.05; LP: mean, 12.2, range, 9.2-19.9 vs mean, 9.9, range, 5.4-14.4, P < 0.05). AGA infants had lower NSE concentration compared with the SGA infants on day 1 in the LP group (mean, 27.4 ng/mL, range, 20-43 ng/mL vs mean, 40.89 ng/mL, range, 34-51 ng/mL, P < 0.05). A positive correlation was found between NO/eNOS ratio and NSE concentration (r = 0.75, P < 0.05 and r = 0.64, P < 0.05 on days 1 and 3, respectively). CONCLUSION: High NO concentration in the context of low eNOS activity suggests a possible role of NO in the development of neuronal injury in SGA infants.