Early hyperoxemia and 2-year outcomes in infants with hypoxic-ischemic encephalopathy: a secondary analysis of the infant cooling evaluation;trial
Open accessAbstract
Objective To determine the causal relationship between exposure to early hyperoxemia and death or major 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 hours 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 or major disability. Among hyperoxemic infants (pO 2 100–500 mmHg) the proportion with death or major disability was 40/58 (0.69), while the proportion in normoxemic infants (pO 2 40 – 99mmHg) was 20/48 (0.42). In the adjusted model, hyperoxemia increased the risk of death or major disability (adjusted risk ratio 1.61, 95% CI 1.07 – 2.00, p=0.03) in relation to normoxemia. Conclusion Early hyperoxemia increased the risk of death or major 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.
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Emerging evidence highlights that factors such as hypocapnia, hyperoxia, extreme fluctuations in blood pressure and glucose are associated with worse outcomes in neonates with HIE.
“Emerging evidence highlights that factors such as hypocapnia, hyperoxia, extreme fluctuations in blood pressure and glucose are associated with worse outcomes in this population (1, 4–8).”
From Lab values in neonates with hypoxic ischemic encephalopathy over time during and after therapeutic hypothermia (2026) · cites this paper as [5]
The Results report that early hyperoxemia was associated with a higher risk of death or major disability in infants with HIE. The Discussion also reports an earlier study linking severe hypocarbia to death or disability. Our copy does not support the sentence’s additional claim about extreme fluctuations in blood pressure or glucose. (LLM, conf=0.88)
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Elias, M., Bliznyuk, N., Yasova Barbeau, D., Sukumar, S., Carlos Roig, J., Rajderkar, D., Sura, L., Wynn, J. L., & Weiss, M. D. (2026) · Frontiers in pediatrics · doi:10.3389/fped.2026.1743749
- Authors
- Badurdeen, S., Cheong, J. L. Y., Donath, S., Graham, H., Hooper, S. B., Polglase, G. R., Jacobs, S., & Davis, P. G.
- Affiliations
- Royal Women's Hospital (AU)
- Murdoch Children's Research Institute (AU)
- The University of Melbourne (AU)
- Hudson Institute of Medical Research (AU)
- Corresponding author
- Badurdeen, Shiraz
- ORCID
- Venue
- The Journal of Pediatrics
- Publisher
- Elsevier BV
- Published
- 2024-04
- Volume
- 267
- Pages
- 113902
- ISSN
- 0022-3476 (ISSN-L)
- OpenAlex
- W4390619732
- Cited by
- 6
- References
- 26
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Pediatrics (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council (606789)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Keywords
- hyperoxemia, hypoxic-ischemic encephalopathy, arterial oxygen partial pressure, therapeutic hypothermia, neonatal hypoxia-ischemia, infant mortality, arterial carbon dioxide, causal inference
- MeSH terms
- Hypoxia, Cold Temperature, Female, Gestational Age, Humans, Hypothermia, Induced, Infant, Infant, Newborn, Pregnancy, Hypoxia-Ischemia, Brain
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