Background and Aims Neonatal hypoglycemia is a frequent event in small for gestational age (SGA) term newborns. Its clinical significance is a highly controversial issue but in experimental models, hypoglycemia has been reported to cause oxidative stress. Among the reactive species, peroxynitrite is responsible for protein nitration, lipid peroxydation and DNA damage, a process referred to as nitro-oxidative stress which can induce apoptosis. The aim of the present study was to investigate whether hypoglycemia is associated with plasma albumin nitration as a marker of nitro-oxidative stress in SGA term newborns.

Methods Using a highly sensitive ELISA we quantified plasma nitroalbumin (PNA) as a marker of peroxynitrite generation in 26 SGA term newborns with close glucose monitoring. We compared PNA concentrations in 9 normoglycemic (glycemia ≥2.5mmol/L) newborns and in 17 hypoglycemic (glycemia < 2.5 mmol/L) newborns.

Results PNA measured during the first hours of life was inversely correlated with glycemia (r= –0.63, p=0.01) and significantly higher in hypoglycemic compared to normoglycemic patients (7.4ng/mL [5.0–7.9] in normoglycemic patients vs. 20.8ng/mL [9.9–77.7] in hypoglycemic patients, n=14, p<0.01). PNA measured at day 1 of life was significantly higher in patients with recurrent hypoglycemia compared to patients with transient hypoglycemia and normoglycemic patients. We observed significant correlations between PNA at day 1 and the area under the curve of the glycemia measured before PNA sampling for several threshold values of glycemia.

Conclusions These results indicate that recurrent hypoglycemia is associated with systemic protein nitration in SGA term newborns, suggestive of a significant nitro-oxidative stress.