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Glutathione synthesis rates after amino acid administration directly after birth in preterm infants^1,2,3

¹ From the Department of Pediatrics, Division of Neonatology (FWJtB, HS, KdG, and JBvG), and Department of Clinical Pharmacy (AV) Erasmus MC–Sophia Children's Hospital, Rotterdam, Netherlands; the Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy (ML and GB)

Background: The availability of glutathione, the main intracellular antioxidant, is compromised in preterm neonates. A possible explanation is the low availability of substrate for synthesis, because many neonatologists are reluctant to administer amino acids in the direct postnatal period for fear of intolerance.

Objective: The objective of the study was to determine the effects of amino acid administration directly after birth on glutathione synthesis rates and markers of oxidative stress.

Design: Premature infants (<1500 g) received from birth onward either dextrose (control group; n = 10) or dextrose plus 2.4 g amino acids · kg ^{– 1} · d^–1 (intervention group; n = 10). On postnatal day 2, [1-¹³C]glycine was administered to determine glutathione fractional synthesis rates (FSR_GSH) and absolute synthesis rates (ASR_GSH) in erythrocytes. In plasma, advanced oxidized protein products and dityrosine, both markers of oxidative stress, were measured. The results are expressed as means ± SDs.

Results: The FSR_GSH was not different between groups: 44 ± 6 and 48 ± 9%/d in the control and intervention groups, respectively (P = 0.28). The concentration of erythrocyte glutathione was higher (P < 0.001) in the intervention group (2.28 ± 0.35 mmol/L) than in the control group (1.73 ± 0.37 mmol/L). ASR_GSH values were 6.5 ± 1.5 and 11.3 ± 1.9 mg · kg^–1 · d^–1 in the control and intervention groups, respectively (P < 0.001). Advanced oxidized protein products and dityrosine concentrations were not significantly different between groups.

Conclusions: Amino acid administration directly after birth increases ASR_GSH in preterm infants. Our data are consistent, however, with higher glutathione concentrations rather than a higher FSR_GSH. Greater availability of glutathione, nevertheless, did not decrease markers of oxidative stress.