Cerebral Oximetry in Extremely Preterm Infants. 2-Year Follow-Up of the SafeBoosC-III Randomized Clinical Trial

Importance: 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. The long-term effects remain uncertain. Objective: To determine whether treatment guided by cerebral oximetry monitoring during the first 72 hours after birth reduces the risk of death or longer-term neurodevelopmental outcomes at 2 years’ corrected age, compared with usual care. Design, Setting, and Participants: In the phase 3 Safeguarding the Brain of Our Smallest Children (SafeBoosC-III) randomized clinical trial, we compared treatment guided by cerebral oximetry monitoring with usual care for the first 72 hours after birth. Seventy sites across 17 countries randomized 1601 infants within 6 hours of birth. Infants from 56 sites participated in this follow-up. Blinded assessors evaluated outcomes using a predefined 3-tier data model combining formal clinical assessments, parental questionnaires, and informal assessments. Data were analyzed from October to December 2024. Interventions: Treatment guided by cerebral oximetry monitoring for the first 72 hours after birth vs usual care. Main Outcomes and Measures: The coprimary outcomes were as follows: (1) death or moderate or severe neurodevelopmental disability and (2) Bayley cognitive composite score, both assessed at approximately 2 years’ corrected age. Results: A total of 1438 infants (mean [SD] age, 26.0 [1.3] weeks; 758 male [52.7%]) participated in this follow-up study. Participants were followed up from October 2021 to October 2024. Death or moderate or severe neurodevelopmental disability occurred in 292 of 620 infants (47.1%) in the cerebral oximetry group compared with 321 of 669 infants (48.0%) in the usual-care group (relative risk with cerebral oximetry, 0.96; 97.5% CI, 0.85-1.07; P = .45). The mean (SD) Bayley cognitive score was 92.8 (17.0) in the cerebral oximetry group compared with 93.2 (17.3) in the usual-care group (mean difference with cerebral oximetry, −0.14; 97.5% CI, −3.24 to 2.96; P = .92). Conclusions and Relevance: In extremely preterm infants, treatment guided by cerebral oximetry monitoring compared with usual care for the first 72 hours after birth did not result in a lower incidence of death or moderate or severe neurodevelopmental disability nor higher Bayley cognitive scores at 2 years’ corrected age. The routine use of cerebral oximetry monitoring during the first 72 hours after birth in extremely preterm infants to reduce neurodevelopmental disability was not supported by this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT05134116