BACKGROUND: The clinical significance of early transient hypoglycemia (ETH), a frequent event in preterm newborns, is a highly controversial issue. In experimental models, hypoglycemia has been reported to cause oxidative stress. Among the reactive species, early generated peroxynitrite is responsible for protein nitration and lipid peroxidation, a process referred to as nitrative stress. OBJECTIVES: The aim of the present study is to investigate whether ETH is associated with protein nitration in the preterm newborn. METHODS: Using a novel highly sensitive ELISA, we quantified plasma nitroalbumin (PNA) as a marker of peroxynitrite generation in 72 preterm newborns (28-36 weeks), among which 25 had a glycemia level of <2.5 mmol/l during the first hour of life (H1). RESULTS: PNA was significantly higher in ETH than in normoglycemic infants at H1 [median = 6.3 (3.8-8.8) vs. 3.4 ng/ml (2.1-5.1), p = 0.027] and at day 1 [median = 6.6 (5.6-15.3) vs. 3.9 ng/ml (2.3-4.6), p = 0.014]. PNA was inversely correlated with glycemia at H1 (r = -0.30, p = 0.01) and at day 1 (r = -0.63, p = 0.001). In ETH infants, lactatemia was inversely correlated with PNA. At day 1, PNA was higher in ETH infants treated by gavage than in those treated with intravenous dextrose [median = 8.9 ng/ml (7.1-10.4) vs. 4.4 ng/ml (2.6-5.7), p = 0.008]. CONCLUSIONS: These results indicate that ETH is associated with increased peroxynitrite generation resulting in systemic protein nitration in premature newborns. Treatment of ETH with intravenous dextrose is associated with lower PNA levels than gavage.