Impact of resuscitation with 100% oxygen during physiological-based cord clamping or immediate cord clamping on lung inflammation and injury.

Abstract

We examined whether physiological based cord clamping (PBCC) reduces oxygen-induced lung inflammation compared to immediate cord clamping (ICC) in preterm lambs ventilated with 100% oxygen for 10 min after birth. Instrumented, steroid exposed preterm lambs (125 ± 1 days' gestation) were randomized to receive 10 min of resuscitation with 100% oxygen before umbilical cord clamping or 30 s after ICC. After 10 min, oxygen was titrated to target SpO₂ of 90-95%. At 1 h, the lungs were collected for analysis of oxidative stress and inflammation, including RNASeq, and compared to an unventilated control group (UVC). PBCC prevented the transient fall in SpO₂ caused by ICC and reduced PaO₂, pulmonary blood flow, mean and diastolic blood pressure during 100% oxygen ventilation. Lung markers of oxidative stress and inflammation were increased in PBCC and ICC lambs compared to UVC (all p < 0.01). IL1ß and IL6 gene expression was higher in PBCC than ICC lambs. Transcriptome analysis revealed novel pathways related to inflammation, immune response, and cytokine signalling. PBCC prevents initial hypoxia and subsequent hyperoxia from 100% oxygen ventilation, but it does not reduce lung oxidative stress, inflammation, or injury, nor the risk or severity of lung damage during high-oxygen resuscitation. The appropriate oxygen level to use during the initial resuscitation of preterm infants during delayed cord clamping/physiological based cord clamping is not known. We found that providing prolonged high oxygen during physiological based cord clamping to preterm lambs does not protect the preterm lung from inflammation, injury or oxidative stress compared to immediate cord clamping. The use of prolonged high oxygen during the initial resuscitation of preterm newborns should be avoided irrespective of what cord clamping strategy is being used.