Oxygen resuscitation and oxidative-stress biomarkers in premature infants

Abstract

Background: Resuscitation of premature infants with 100% O 2 may initiate significant oxidant stress during development, predisposing them to bronchopulmonary dysplasia. In the study reported here, we examined the effects of three different oxygen concentrations at resuscitation on oxygen saturations (SpO 2) and oxidant stress in premature infants. Study design: Infants ,32 weeks gestational age were randomized to 21%, 40%, or 100% O 2 and resuscitated as per 2005 neonatal resuscitation guidelines. Oxygen groups and SpO 2 were unmasked at 10 minutes of age and FiO 2 adjusted to maintain an SpO 2 of 85%-95% for the next 20 minutes. Blood was collected at 24 hours, 1 week, and 4 weeks for measurement of the oxidative-stress markers, such as a reduced glutathione (GSH) to oxidized glutathione (GSSG) ratio (GSH/GSSG), nitrotyrosine levels, and 8-hydroxydeoxyguanosine (8-OHdG) levels. The study was stopped at 30% enrollment following publication of the 2010 neonatal resuscitation guidelines. Results: We enrolled 18 patients during the study period. SpO 2 increased over time (P,0.0001); however, this increase was not different among the three oxygen groups in the first 10 minutes after birth. FiO 2 was significantly higher in the 100% O 2 group, despite weaning (P,0.02) to maintain target saturations at 30 minutes of age. The GSH/GSSG ratio was significantly lower in the 100% O 2 group at 24 hours than in the other groups (P,0.01). Plasma nitrotyrosine was significantly higher in the 40% and 100% O 2 groups over time (P,0.01). Levels of 8-OHdG were significantly higher at 4 weeks compared with at 24 hours, independent of the oxygen group (P,0.0001). Conclusion: In this study, we defined the natural evolution of SpO 2 in the first 10 minutes of life with exposure to three different concentrations of oxygen. Randomization to higher FiO 2 led to higher total oxygen exposure at resuscitation, and this was significantly correlated with markers of systemic oxidant stress.

Oxygen and Resuscitation: Saturations, Oxidative Stress and Outcomes in Premature Infants

“…This may be related to production of reactive oxygen species from higher oxygen load at birth in the face of inadequate antioxidant defense mechanisms. Both, GSH/GSSG ratio 25 and oxidative balance ratio, 16 were lower within 24 hours of birth following resuscitation with high oxygen concentration. Both these markers are useful measures of oxidative stress in tissues.…”

“…In a small pilot study infants <32 weeks GA were randomized to 21%, 40% or 100% O 2 and resuscitated as per 2005 NRP guidelines. 25 Oxygen groups and SpO 2 were unmasked at 10 minutes of age and FiO 2 was adjusted to maintain SpO 2 of 85%-95% for the next 20 minutes. The study was stopped at 30% enrollment following publication of the 2010 NRP guidelines, which is a limitation.…”

“…The mean SpO 2 values were 50%, 53% and 69% at 1 min; 77%, 83% and 95% at 5 min and 92%, 92% and 98% at 10 min in 21% O 2 , 40% O 2 & 100% O 2 groups respectively (Figure 1). 25 Resuscitation The novelty of this study was in administering a fixed concentration of oxygen and blinding the study gas for the first 10 minutes irrespective of the SpO 2 . Larger studies are needed to address SpO 2 targets in premature infants to help define the oxygen concentration at resuscitation, however starting at 21% O 2 to 30% O 2 as recommended by NRP is a good starting point.…”

“…The studies have used common markers of oxidative stress such as GSH/GSSH ratio, total hydroperoxide and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Most of the studies measured oxidative stress markers within the first week of birth 16,18,19,25,26 and occasionally up to 4 weeks of age. 25 The studies validated that resuscitation with higher oxygen concentration leads to oxidative stress, particularly in the first week after birth.…”

“…Most of the studies measured oxidative stress markers within the first week of birth 16,18,19,25,26 and occasionally up to 4 weeks of age. 25 The studies validated that resuscitation with higher oxygen concentration leads to oxidative stress, particularly in the first week after birth. This may be related to production of reactive oxygen species from higher oxygen load at birth in the face of inadequate antioxidant defense mechanisms.…”