Early Hyperoxaemia and 2-year Outcomes in Infants with Hypoxic-ischemic Encephalopathy- a Secondary Analysis of the Infant Cooling Evaluation (ICE) trial
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Objective(s)
To determine the causal relationship between exposure to early hyperoxaemia and death/disability in infants with hypoxic-ischemic encephalopathy (HIE).
Study design
We analyzed data from the Infant Cooling Evaluation (ICE) trial that enrolled newborns ≥35 weeks’ gestation with moderate-severe HIE, randomly allocated to hypothermia or normothermia. The primary outcome was death or major sensorineural disability at 2 years. We included infants with arterial pO 2 measured within 2 h of birth. Using a directed acyclic graph, we established that markers of severity of perinatal hypoxia-ischemia and pCO 2 were a minimally sufficient set of variables for adjustment in a regression model to estimate the causal relationship between arterial pO 2 and death/disability.
Results
Among 221 infants, 116 (56%) had arterial pO 2 and primary outcome data. The unadjusted analysis revealed a U-shaped relationship between arterial pO 2 and death/disability. Among hyperoxaemic infants (pO 2 100–500 mmHg) the risk of death/disability was 40/58 (0.69), while the risk in normoxaemic infants (pO 2 40 – 99mmHg) was 20/48 (0.42). In the adjusted model, hyperoxaemia increased the risk of death/disability (adjusted risk ratio 1.61, 95% CI 1.07 – 2.00, p= 0.03) in relation to normoxaemia.
Conclusions
Early hyperoxaemia increased the risk of death/disability among infants who had an early arterial pO 2 in the ICE trial. Limitations include the possibility of residual confounding and other causal biases. Further work is warranted to confirm this relationship in the era of routine therapeutic hypothermia.
