Randomized Controlled Trial

. 2026 Feb 2;9(2):e2557620.

doi: 10.1001/jamanetworkopen.2025.57620.

Cerebral Oximetry-Guided Treatment and Cerebral Oxygenation in Extremely Preterm Infants: A Randomized Clinical Trial

Pranav R Jani^{1

2}, Traci-Anne Goyen^{1

2}, Kiran Kumar Balegar^{3

4}, Rajesh Maheshwari^{1

2}, Maria Saito-Benz^{5

6}, Tim Schindler^{7

8}, James Moore^{9

10}, Manelle Merhi¹¹, Melinda Cruz^{12

13

14}, Yang Song¹⁵, Hayley McDonagh¹, Melissa Luig¹, Mark Tracy^{1

2}, Daphne D'Cruz¹, Aldo Perdomo¹, Stephanie Morakeas^{1

16}, Vishnu Dasireddy³, Mihaela Culcer³, Vijay Shingde³, Karen Bennington⁵, Joanna Michalowski⁷, Andreja Fucek⁷, Jennifer Querim⁹, Sean Stevens⁹, James Santanelli⁹, James Elhindi^{2

15}, Brian Gloss¹⁷, Robert Halliday^{2

18}, Dharmesh Shah^{1

2}, Himanshu Popat^{2

12

18}

Affiliations

¹ Department of Neonatology, Westmead Hospital, Westmead, New South Wales, Australia.
² Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
³ Department of Neonatology, Nepean Hospital, Nepean Blue Mountains Local Health District, Kingswood, Australia.
⁴ Sydney Medical School Nepean, The University of Sydney, Sydney, New South Wales, Australia.
⁵ Neonatal Intensive Care Unit, Wellington Regional Hospital, Wellington, New Zealand.
⁶ Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.
⁷ Department of Newborn Care, The Royal Hospital for Women, Sydney, New South Wales, Australia.
⁸ School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁹ Connecticut Children's, Division of Neonatal-Perinatal Medicine, Connecticut Children's Medical Center, Hartford.
¹⁰ UConn School of Medicine Farmington, Farmington, Connecticut.
¹¹ Kennards Hire Group, Sydney, Australia.
¹² National Health and Medical Research Council Clinical Trial Centre, University of Sydney, Camperdown, New South Wales, Australia.
¹³ NICU Lived Network, Sydney, Australia.
¹⁴ Lived Experience Advisory Network, Perinatal Society of Australia and New Zealand, Mornington, Australia.
¹⁵ Research and Education Network, Westmead Hospital, Westmead, New South Wales, Australia.
¹⁶ Faculty of Engineering and Information Technologies, Biomedical Engineering Institute, The University of Sydney, Sydney, New South Wales, Australia.
¹⁷ Westmead Research Hub, Westmead Institute for Medical Research, Sydney, New South Wales, Australia.
¹⁸ Grace Centre for Newborn Intensive Care, The Children's Hospital for Westmead, Westmead, New South Wales, Australia.

PMID: 41642624
PMCID: PMC12878427
DOI: 10.1001/jamanetworkopen.2025.57620

Randomized Controlled Trial

Cerebral Oximetry-Guided Treatment and Cerebral Oxygenation in Extremely Preterm Infants: A Randomized Clinical Trial

Pranav R Jani et al. JAMA Netw Open. 2026.

. 2026 Feb 2;9(2):e2557620.

doi: 10.1001/jamanetworkopen.2025.57620.

Authors

Affiliations

¹ Department of Neonatology, Westmead Hospital, Westmead, New South Wales, Australia.
² Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
³ Department of Neonatology, Nepean Hospital, Nepean Blue Mountains Local Health District, Kingswood, Australia.
⁴ Sydney Medical School Nepean, The University of Sydney, Sydney, New South Wales, Australia.
⁵ Neonatal Intensive Care Unit, Wellington Regional Hospital, Wellington, New Zealand.
⁶ Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.
⁷ Department of Newborn Care, The Royal Hospital for Women, Sydney, New South Wales, Australia.
⁸ School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁹ Connecticut Children's, Division of Neonatal-Perinatal Medicine, Connecticut Children's Medical Center, Hartford.
¹⁰ UConn School of Medicine Farmington, Farmington, Connecticut.
¹¹ Kennards Hire Group, Sydney, Australia.
¹² National Health and Medical Research Council Clinical Trial Centre, University of Sydney, Camperdown, New South Wales, Australia.
¹³ NICU Lived Network, Sydney, Australia.
¹⁴ Lived Experience Advisory Network, Perinatal Society of Australia and New Zealand, Mornington, Australia.
¹⁵ Research and Education Network, Westmead Hospital, Westmead, New South Wales, Australia.
¹⁶ Faculty of Engineering and Information Technologies, Biomedical Engineering Institute, The University of Sydney, Sydney, New South Wales, Australia.
¹⁷ Westmead Research Hub, Westmead Institute for Medical Research, Sydney, New South Wales, Australia.
¹⁸ Grace Centre for Newborn Intensive Care, The Children's Hospital for Westmead, Westmead, New South Wales, Australia.

PMID: 41642624
PMCID: PMC12878427
DOI: 10.1001/jamanetworkopen.2025.57620

Abstract

Importance: Preterm infants are at high risk of developing brain injury, and near-infrared spectroscopy (NIRS) offers the ability to measure cerebral oxygenation. The impact of using a standardized treatment guideline combined with a single NIRS device manufacturer (Nonin Medical Inc) and neonatal sensor on cerebral oxygenation has not been previously examined.

Objective: To investigate whether cerebral oximetry with a dedicated treatment guideline improves cerebral oxygenation stability.

Design, setting, and participants: This was a single-blinded, 2-arm randomized clinical trial conducted from October 2021 to July 2024 at 5 tertiary neonatal intensive care units across Australia, New Zealand, and the US. Infants born at less than 29 weeks' gestation and aged younger than 6 hours underwent 1:1 random allocation stratified by gestational age (<26 weeks and ≥26 weeks) and study site.

Intervention: The intervention group received cerebral oximetry and dedicated guideline-based treatment when cerebral oxygenation was outside the range of 65% to 90%. The control group had blinded cerebral oximetry and treatment guided by standard clinical monitoring.

Main outcomes and measures: The burden of cerebral hypoxia and hyperoxia during the first 5 days after birth expressed as percentage hours was the primary outcome. Key secondary outcomes were mortality, morbidities before discharge, and NIRS-related skin injury.

Results: Of 149 screened infants (53 randomized to the intervention and 51 randomized to standard care), 100 infants were included in the final analysis (median [IQR] gestational age, 27 [25-28] weeks; 48 male [48.0%]). The median (IQR) birth weight was 883 (709-1079) g. The intervention group (50 infants) had a significantly lower median (IQR) burden of hypoxia and hyperoxia of 5.7% hours (2.8% hours to 15.0% hours) compared with 39.6% hours (6.5% hours to 82.3% hours) in the standard care group (50 infants), with an adjusted reduction of 42.8% hours (95% CI, 35.6% hours to 53.3% hours; P < .001). Mortality, morbidities before discharge, and safety outcomes were comparable between groups.

Conclusions and relevance: In this study, treatment guided by cerebral oximetry with a single device manufacturer and a neonatal sensor significantly improved the stability of cerebral oxygenation in extremely preterm infants. Larger multicenter trials are warranted to determine if this finding leads to improved survival without brain injury.

Trial registration: Australian New Zealand Clinical Trials Registry registration number ACTRN12621000778886.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Cruz reported receiving personal fees from the Australian National Health and Medical Research Council Clinical Trials Centre outside the submitted work. No other disclosures were reported.

Figures

**Figure 1.. Study Flowchart**
Flow of study infants is presented as per the updated Consolidated Standards of Reporting Trials (CONSORT) reporting guideline. Other reasons were missed eligible participants and no research staff after hours for consenting. Recruitment by sites was as follows: 3 participants at site A, 32 participants at site B, 20 participants each at sites C and D, and 25 participants at site E.

**Figure 2.. Primary Outcome by Treatment**
The burden of cerebral hypoxia and hyperoxia outside 65% to 90% is expressed as % hours based on the allocated group. Bold horizontal lines within boxes indicate medians; boxes, IQRs; lower whiskers, hinge to smallest value at most 1.5 × IQR of hinge; dots, individual values; upper whiskers, largest value no further than 1.5 × IQR from the hinge (edge of central box).

See this image and copyright information in PMC

References

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Cerebral Oximetry-Guided Treatment and Cerebral Oxygenation in Extremely Preterm Infants: A Randomized Clinical Trial

Affiliations

Cerebral Oximetry-Guided Treatment and Cerebral Oxygenation in Extremely Preterm Infants: A Randomized Clinical Trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

Full Text Sources