For Doctors in a Hurry
- Clinicians lack evidence on whether early cerebral oximetry monitoring improves long-term neurodevelopmental outcomes in extremely preterm infants.
- The study randomized 1601 infants across 70 international sites to receive either oximetry-guided care or usual care.
- Death or disability occurred in 47.1 percent of the intervention group versus 48.0 percent of controls (relative risk 0.96).
- The researchers concluded that oximetry monitoring did not reduce death or disability or improve cognitive scores at two years.
- These findings do not support the routine clinical use of cerebral oximetry to improve neurodevelopmental outcomes in preterm infants.
Cerebral Oxygenation and Neurodevelopmental Trajectories
Extremely preterm infants face a high risk of permanent neurologic impairment and mortality due to hemodynamic instability in the immediate postnatal period [1, 2]. To mitigate these risks, clinicians have increasingly utilized near-infrared spectroscopy, a noninvasive technology that provides real-time measurement of cerebral tissue oxygenation, to monitor brain perfusion [3]. Previous research established that using standardized treatment guidelines to respond to oximetry readings can successfully reduce the burden of cerebral hypoxia and hyperoxia [4, 3]. However, the clinical utility of targeting specific oxygenation ranges remains a subject of intense debate, as similar efforts to optimize systemic oxygen saturation have yielded conflicting results regarding long-term disability [5, 6]. A large-scale, multinational trial now provides definitive data on whether these early physiological interventions actually change neurodevelopmental trajectories at two years of age.
The SafeBoosC-III Trial Design and Methodology
The phase 3 Safeguarding the Brain of Our Smallest Children (SafeBoosC-III) randomized clinical trial was an international, multicenter study designed to evaluate the efficacy of cerebral oximetry-guided care. The trial involved 70 sites across 17 countries, where researchers randomized 1,601 infants within 6 hours of birth. The intervention group received treatment guided by cerebral oximetry monitoring, a noninvasive method of measuring oxygen saturation in the brain using near-infrared spectroscopy, during the first 72 hours of life, while the control group received usual care. The study population was comprised of extremely preterm infants with a mean gestational age of 26.0 weeks (SD 1.3), a group at high risk for neurological complications. For the longitudinal portion of the study, infants from 56 of the original sites participated in a 2-year follow-up. This follow-up cohort included 1,438 infants, of whom 758 were male (52.7%). Participants were followed from October 2021 to October 2024, with the final data analysis occurring between October and December 2024. To maintain objectivity, blinded assessors evaluated the primary outcomes using a predefined 3-tier data model, a hierarchical approach that combined formal clinical assessments, parental questionnaires, and informal assessments to provide a comprehensive view of each child's neurodevelopmental status at approximately 2 years of corrected age.
The longitudinal analysis of the 1,438 infants who participated in this follow-up study focused on two coprimary outcomes assessed at approximately 2 years of corrected age. The first coprimary outcome was a composite measure of death or moderate or severe neurodevelopmental disability. In the group receiving treatment guided by cerebral oximetry, this outcome occurred in 292 of 620 infants, representing a rate of 47.1 percent. This was nearly identical to the usual-care group, where 321 of 669 infants, or 48.0 percent, met the criteria for death or disability. Statistical analysis confirmed that the intervention did not provide a clinical benefit for this composite endpoint, yielding a relative risk of 0.96 (97.5% CI, 0.85-1.07; P = .45). The second coprimary outcome evaluated the Bayley cognitive composite score, a standardized tool used to measure developmental progress in domains such as memory, problem-solving, and early numeracy. At the 2-year assessment, the mean Bayley cognitive score was 92.8 (SD 17.0) in the cerebral oximetry group compared with 93.2 (SD 17.3) in the usual-care group. The mean difference between the two groups was -0.14 (97.5% CI, -3.24 to 2.96; P = .92), indicating no significant difference in cognitive performance. These data suggest that monitoring cerebral oxygenation during the first 72 hours of life does not alter long-term neurodevelopmental trajectories or survival in extremely preterm infants compared to standard clinical management.
Clinical Implications for Neonatal Intensive Care
The findings from this longitudinal follow-up align with earlier data from the same cohort, which demonstrated that cerebral oximetry monitoring in the first 72 hours after birth has not been shown to reduce death or severe brain injury at 36 weeks' postmenstrual age in extremely preterm infants. This lack of early clinical benefit appears to persist as the children age, suggesting that the physiological insights provided by near-infrared spectroscopy do not necessarily translate into improved clinical trajectories. Specifically, the researchers found that treatment guided by cerebral oximetry did not result in a lower incidence of death or disability nor higher Bayley cognitive scores at 2 years' corrected age compared to standard care. With a relative risk of 0.96 (97.5% CI, 0.85 to 1.07; P = .45) for the composite outcome of death or disability and a negligible mean difference in cognitive scores of -0.14 (97.5% CI, -3.24 to 2.96; P = .92), the intervention failed to demonstrate a measurable impact on the primary neurodevelopmental metrics. For clinicians managing the complex hemodynamic needs of extremely preterm infants, these results provide a definitive answer regarding the utility of early physiological monitoring. Because the intervention failed to improve either survival or functional outcomes, the trial does not support routine use of cerebral oximetry monitoring during the first 72 hours after birth in extremely preterm infants to reduce neurodevelopmental disability. While the technology provides real-time data on cerebral oxygen saturation, the clinical application of that data within the first three days of life does not alter long-term prognosis. Consequently, the researchers conclude that the current evidence is insufficient to justify the integration of this monitoring modality into standard neonatal intensive care protocols for the purpose of neuroprotection.
References
1. Hansen ML, Pellicer A, Hyttel-Sørensen S, et al. Cerebral Oximetry Monitoring in Extremely Preterm Infants. New England Journal of Medicine. 2023. doi:10.1056/nejmoa2207554
2. Hansen M, Pellicer A, Gluud C, et al. Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants. A protocol for the SafeBoosC phase III randomized clinical trial. 2019. doi:10.21203/rs.2.490/v1
3. Jani PR, Goyen T, Balegar KK, et al. Cerebral Oximetry-Guided Treatment and Cerebral Oxygenation in Extremely Preterm Infants: A Randomized Clinical Trial.. JAMA network open. 2026. doi:10.1001/jamanetworkopen.2025.57620
4. Pellicer A, Greisen G, Benders M, et al. The SafeBoosC Phase II Randomised Clinical Trial: A Treatment Guideline for Targeted Near-Infrared-Derived Cerebral Tissue Oxygenation versus Standard Treatment in Extremely Preterm Infants. Neonatology. 2013. doi:10.1159/000351346
5. Groups TBAAUKC. Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants. New England Journal of Medicine. 2016. doi:10.1056/nejmoa1514212
6. Askie L, Darlow BA, Finer N, et al. Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA. 2018. doi:10.1001/jama.2018.5725
