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

SafeBoosC-III Follow-Up Writing Group for the SafeBoosC-III Follow-Up Collaborator Group

doi:10.1001/jamapediatrics.2026.1066

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

SafeBoosC-III Follow-Up Writing Group for the SafeBoosC-III Follow-Up Collaborator Group

School of Medicine

Copenhagen University Hospital - Rigshospitalet
La Paz University Hospital-IdiPAZ
Gazi University Hospital
University of Medical Sciences Poznan
Children's University Hospital of Zurich
Department of Development and Regeneration
Mountainside Medical Center
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Patras Medical School
University Hospital Motol
Oslo University Hospital
Royal Hospital for Sick Children
Medical University of Graz
Medical Center - University of Freiburg
St John's Medical College
Department of Neonatology
The Institute for the Care of Mother and Child
BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine
Children's Hospital Lucerne
Bursa Uludag University
Aristotle University of Thessaloniki
Loma Linda University Children's Hospital
University of Health Sciences
Hospital Clinico San Carlos-IdISSC
Marmara University Research and Education Hospital
Hospital De Sant Joan De Deu
University of Utah Hospital
Service de Néonatologie
University Hospital Center Nene Tereza
Donostia University Hospital-IIS Biogipuzkoa
Gødstrup Hospital
Puerta del Mar University Hospital
Aalborg University Hospital
Jagiellonian University Medical College
Royal College of Surgeons in Ireland
National Maternity Hospital
The Coombe Maternity Hospital
Alexandra University and State Maternity Hospital
Washington University School of Medicine in St Louis
Unità Operativa Complessa di Neonatologia

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Journal	JAMA Pediatrics
DOIs	https://doi.org/10.1001/jamapediatrics.2026.1066
Publication status	E-pub ahead of print - 20 Apr 2026

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10.1001/jamapediatrics.2026.1066

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@article{470f440f69c9427b84268ba876255375,

title = "Cerebral Oximetry in Extremely Preterm Infants: 2-Year Follow-Up of the SafeBoosC-III Randomized Clinical Trial",

abstract = "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.",

author = "\{SafeBoosC-III Follow-Up Writing Group for the SafeBoosC-III Follow-Up Collaborator Group\} and Rasmussen, \{Marie Isabel Skov\} and Hansen, \{Mathias L\} and Adelina Pellicer and Simon Hyttel-S{\o}rensen and Ebru Ergenekon and Tomasz Szczapa and Cornelia Hagmann and Gunnar Naulaers and Jonathan Mintzer and Monica Fumagalli and Gabriel Dimitriou and Eugene Dempsey and Jakub Tkaczyk and Siv Fredly and Heuchan, \{Anne M\} and Gerhard Pichler and Hans Fuchs and Saudamini Nesargi and Hahn, \{Gitte H\} and Salvador Piris-Borregas and Jan {\v S}irc and Miguel Alsina-Casanova and Martin Stocker and Hilal Ozkan and Kosmas Sarafidis and Kraus, \{Nicole J\} and Tanja Karen and Beata Rzepecka-Weglarz and Oguz, \{Serife S\} and Liesbeth Thewissen and Luis Arruza and Memisoglu, \{Asli C\} and \{Del Rio Florentino\}, Ruth and Mariana Baserga and Pierre Maton and Juliane Schneider and \{de Las Cuevas\}, \{M Isabel\} and Hedegaard, \{Sofie Sommer\} and Pamela Zafra and Lars Bender and Sarah Farquharson and Agnieszka Ochoda-Mazur and Chantal Lecart and Afif El-Khuffash and Chathasaigh, \{Caitr{\'i}ona N{\'i}\} and Jan Miletin and Evangelia Papathoma and Zachary Vesoulis and Francesca Serrao and Luc Cornette",

year = "2026",

month = apr,

day = "20",

doi = "10.1001/jamapediatrics.2026.1066",

language = "English",

journal = "JAMA Pediatrics",

issn = "2168-6203",

publisher = "American Medical Association",

}

TY - JOUR

T1 - Cerebral Oximetry in Extremely Preterm Infants

T2 - 2-Year Follow-Up of the SafeBoosC-III Randomized Clinical Trial

AU - SafeBoosC-III Follow-Up Writing Group for the SafeBoosC-III Follow-Up Collaborator Group

AU - Rasmussen, Marie Isabel Skov

AU - Hansen, Mathias L

AU - Pellicer, Adelina

AU - Hyttel-Sørensen, Simon

AU - Ergenekon, Ebru

AU - Szczapa, Tomasz

AU - Hagmann, Cornelia

AU - Naulaers, Gunnar

AU - Mintzer, Jonathan

AU - Fumagalli, Monica

AU - Dimitriou, Gabriel

AU - Dempsey, Eugene

AU - Tkaczyk, Jakub

AU - Fredly, Siv

AU - Heuchan, Anne M

AU - Pichler, Gerhard

AU - Fuchs, Hans

AU - Nesargi, Saudamini

AU - Hahn, Gitte H

AU - Piris-Borregas, Salvador

AU - Širc, Jan

AU - Alsina-Casanova, Miguel

AU - Stocker, Martin

AU - Ozkan, Hilal

AU - Sarafidis, Kosmas

AU - Kraus, Nicole J

AU - Karen, Tanja

AU - Rzepecka-Weglarz, Beata

AU - Oguz, Serife S

AU - Thewissen, Liesbeth

AU - Arruza, Luis

AU - Memisoglu, Asli C

AU - Del Rio Florentino, Ruth

AU - Baserga, Mariana

AU - Maton, Pierre

AU - Schneider, Juliane

AU - de Las Cuevas, M Isabel

AU - Hedegaard, Sofie Sommer

AU - Zafra, Pamela

AU - Bender, Lars

AU - Farquharson, Sarah

AU - Ochoda-Mazur, Agnieszka

AU - Lecart, Chantal

AU - El-Khuffash, Afif

AU - Chathasaigh, Caitríona Ní

AU - Miletin, Jan

AU - Papathoma, Evangelia

AU - Vesoulis, Zachary

AU - Serrao, Francesca

AU - Cornette, Luc

PY - 2026/4/20

Y1 - 2026/4/20

N2 - 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.

AB - 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.

U2 - 10.1001/jamapediatrics.2026.1066

DO - 10.1001/jamapediatrics.2026.1066

M3 - Article

C2 - 42008246

SN - 2168-6203

JO - JAMA Pediatrics

JF - JAMA Pediatrics

ER -

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

Abstract

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