Published online August 3, 2009
PEDIATRICS Vol. 124 No. 3 September 2009, pp. e439-e449 (doi:10.1542/peds.2009-0434)
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ARTICLE

Preterm Resuscitation With Low Oxygen Causes Less Oxidative Stress, Inflammation, and Chronic Lung Disease

Maximo Vento, PhD, MDa, Manuel Moro, MDb, Raquel Escrig, MDa, Luis Arruza, MDb, Gema Villar, MDb, Isabel Izquierdo, MDa, L. Jackson Roberts, II, MDc, Alessandro Arduini, PhDd, Justo Javier Escobar, PhDd, Juan Sastre, PhDd and Miguel A. Asensi, PhDd

a Division of Neonatology, University Hospital La Fe, Valencia, Spain
b Division of Neonatology, University Hospital San Carlos, Madrid, Spain
c Department of Pharmacology, Vanderbilt University, Nashville, Tennessee
d Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain

OBJECTIVE: The goal was to reduce adverse pulmonary adverse outcomes, oxidative stress, and inflammation in neonates of 24 to 28 weeks of gestation initially resuscitated with fractions of inspired oxygen of 30% or 90%.

METHODS: Randomized assignment to receive 30% (N = 37) or 90% (N = 41) oxygen was performed. Targeted oxygen saturation values were 75% at 5 minutes and 85% at 10 minutes. Blood oxidized glutathione (GSSG)/reduced glutathione ratio and urinary o-tyrosine, 8-oxo-dihydroxyguanosine, and isoprostane levels, isofuran elimination, and plasma interleukin 8 and tumor necrosis factor {alpha} levels were determined.

RESULTS: The low-oxygen group needed fewer days of oxygen supplementation (6 vs 22 days; P < .01) and fewer days of mechanical ventilation (13 vs 27 days; P < .01) and had a lower incidence of bronchopulmonary dysplasia at discharge (15.4% vs 31.7%; P < .05). GSSG/reduced glutathione x 100 ratios at day 1 and 3 were significantly higher in the high-oxygen group (day 1: high-oxygen group: 13.36 ± 5.25; low-oxygen group: 8.46 ± 3.87; P < .01; day 3: high-oxygen group: 8.87 ± 4.40; low-oxygen group: 6.97 ± 3.11; P < .05). Urinary markers of oxidative stress were increased significantly in the high-oxygen group, compared with the low-oxygen group, in the first week after birth. GSSG levels on day 3 and urinary isofuran, o-tyrosine, and 8-hydroxy-2'-deoxyguanosine levels on day 7 were correlated significantly with development of chronic lung disease.

CONCLUSIONS: Resuscitation of preterm neonates with 30% oxygen causes less oxidative stress, inflammation, need for oxygen, and risk of bronchopulmonary dysplasia.

Key Words: prematurity • resuscitation • oxygen • oxidative stress biomarkers • inflammatory cytokines • bronchopulmonary dysplasia

Abbreviations: ELGAN—extremely low gestational age neonate • DR—delivery room • BPD—bronchopulmonary dysplasia • ROS—reactive oxygen species • FIO2—fraction of inspired oxygen • SpO2—pulse oxygen saturation • GSH—reduced glutathione • GSSG—oxidized glutathione • TNF-{alpha}—tumor necrosis factor {alpha} • IL-8—interleukin 8 • HR—heart rate

Accepted Apr 14, 2009.


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eLetters:

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