Urinary metabolites of oxidative stress and nitric oxide in preterm and term infants

BACKGROUND: Many neonatal diseases have been associated with oxidative stress and altered nitric oxide status. OBJECTIVE: To determine the effects of clinical interventions on the levels of urinary peroxides, a marker of oxidative stress, and urinary nitrate/nitrites, indices of nitric oxide production and metabolism, in the first 72 h of life in premature infants. METHODS: A single, spot urine sample was collected from 82 premature and 20 healthy term infants within the first 72 h of life. The peroxide levels were quantified using a fluorometric method, and nitrate/nitrite levels were quantified by chemiluminescence. RESULTS: Premature infants had a median peroxide level of 10.0 micromol/mmol creatinine (Cr) (interquartile range 4.8-20.0 micromol/mmol Cr). These values were significantly higher than term infants (median 5.0 micromol/mmol Cr, interquartile range 2.7-10.0 micromol/mmol Cr). Urinary nitrate/nitrite levels were not significantly different between preterm (220.5 micromol/mmol Cr, interquartile range 161-287 micromol/mmol Cr) and healthy term infants (244 micromol/mmol Cr, interquartile range 194-316 micromol/mmol Cr). For urinary peroxides, infants on TPN had significantly higher urinary peroxide levels than infants who were not on TPN at the time of urine collection (p = 0.006). Administration of indomethacin was associated with lower levels of urinary nitrate/nitrites (p = 0.0003). Both effects remained significant after controlling for gestational age, degree of respiratory distress and day of urine collection. CONCLUSION: Monitoring the level of both peroxides and nitrate/nitrite may offer added information about the degree of oxidative stress experienced by a newborn but needs to account for clinical and therapeutic interventions.