Endothelial dysfunction and developmental outcomes of very low birth weight newborns with hypoxic encephalopathy.

OBJECTIVE: To investigate the levels of endothelial constricting and dilating mediators in preterm infants with hypoxic-ischaemic encephalopathy and prospectively evaluate the association between levels measured during the perinatal period and the diagnosis of neurodevelopmental disorders at 3 years of age. METHODS: This regional observational cohort study was conducted at the Azerbaijan Medical University, Baku, Azerbaijan, from November 2011 to January 2013, and comprised very-low-birth-weight infants admitted to the intensive care unit during the perinatal period. Blood concentrations of nitric oxide, endothelin-1 and endothelial nitric oxide synthase were measured on days 1-3 and 5-7 of the neonatal period. Concentrations of neuron-specific enolase and antibodies against N-methyl-D-aspartate glutamate receptors were measured in peripheral blood samples for detection of brain damage in the early neonatal period of life. The infants were divided in 3 different groups: those diagnosed with moderate-to-severe neurodevelopmental disorders or cerebral palsy were included in the first group; those with mild neurologic changes were in the second group; and children without evidence of neurological impairment were in the third group. The fourth group comprised controls. SPSS 20 was used for data analysis. RESULTS: Of the 62 participants, there were 8(12.9%) in the first group, 20(32.3%) in second, 14(22.6%) in third and 20(32.3%) in the control group. The activity of endothelial nitric oxide synthase was reduced and nitric oxide concentrations were increased in the first group compared to those in the third group (p<0.05). Deep endothelial nitric oxide synthase depression and insufficient endothelin-1 synthesis were associated with diagnosis in the first group (p<0.05). No differences in concentrations of neuron-specific enolase and NR2 antibodies were identified among infants with and without a subsequent diagnosis of neurodevelopmental disorders (p>0.05). CONCLUSIONS: The association between depressed endothelial nitric oxide synthase activation and insufficient endothelin-1 synthesis in the early days of life of very-low-birth-weight infants might be one of the causes of more serious and irreversible injury of brain tissue.

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.