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Cerebral Oxygenation Stability In Extremely Preterm Infants: A Randomized Clinical Trial

Jani, P. R.; Goyen, T.-A.; Balegar, K. K.; Maheshwari, R.; Saito-Benz, M.; Schindler, T.; Moore, J.; Merhi, M.; Cruz, M.; Song, Y.; McDonagh, H.; Luig, M.; Tracy, M.; DCruz, D.; Perdomo, A.; Morakeas, S.; Dasireddy, V.; Culcer, M.; Shingde, V.; Bennington, K.; Michalowski, J.; Fucek, A.; Querim, J.; Stevens, S.; Santanelli, J.; Elhindi, J.; Gloss, B.; Halliday, R.; Shah, D.; Popat, H.

2025-10-23 pediatrics
10.1101/2025.10.21.25338440 medRxiv
Show abstract

ImportancePreterm infants are at high-risk of developing brain injury. Near-infrared spectroscopy (NIRS) offers the ability to measure cerebral oxygenation, potentially reducing brain injury. What remains unknown is the impact of using a standardized treatment guideline combined with a single NIRS device manufacturer and neonatal sensor on cerebral oxygenation, which has not been previously examined. ObjectiveTo determine whether cerebral NIRS monitoring with a dedicated treatment guideline improves cerebral oxygenation stability. DesignThis was a single-blinded, two-arm randomized controlled trial conducted from October 2021 to July 2024. SettingFive tertiary neonatal intensive care units across Australia, New Zealand and the United States. ParticipantsInfants born <29 weeks gestation and <6 hours of age underwent 1:1 random allocation, stratified by gestational age (<26 weeks and [&ge;]26 weeks) and study site. InterventionThe intervention group received cerebral NIRS monitoring and dedicated guideline-based treatment when the cerebral oxygenation was outside the range of 65%-90%. The control group had blinded cerebral NIRS monitoring and treatment guided by standard clinical monitoring. Main Outcome(s) and Measure(s)The burden of cerebral hypoxia and hyperoxia during the first 5 days after birth expressed as percent hours was the primary outcome. Key secondary outcomes were mortality, morbidities before discharge, and NIRS-related skin injury. ResultsOf the 149 screened infants, 100 were included in the final analysis. The median gestational age was 27 weeks (inter quartile range [IQR 25-28]) and the median birth weight was 883 grams (IQR 709-1079). The intervention group (n=50) had a significantly lower median burden of hypoxia and hyperoxia of 5.7% hours (IQR 2.8-15) compared to 39.6% hours (IQR 6.5-82.3) in the standard care group (n=50), with an adjusted reduction of 42.8% hours (95% confidence interval 35.6-53.3, p=0.0002). Mortality, morbidities before discharge and safety outcomes were comparable between groups. Conclusions and RelevanceTreatment guided by cerebral NIRS monitoring with a single device manufacturer and neonatal sensor, is a safe and low-risk intervention that significantly improves 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 RegistrationThe trial is registered at The Australian New Zealand Clinical Trials Registry, registration number: ACTRN12621000778886, and https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621000778886 Key pointsO_ST_ABSQuestionC_ST_ABSDoes cerebral near infrared spectroscopy (NIRS) with a dedicated treatment guideline using NIRS device from a single manufacturer and neonatal sensor improve cerebral oxygenation stability in extremely preterm infants? FindingsIn this randomized clinical trial of 100 infants, the burden of cerebral hypoxia and hyperoxia was significantly lower in the intervention group (5.7% hours) compared to standard care group 39.6% hours. MeaningTreatment guided by cerebral NIRS monitoring is a safe and low-risk intervention that improves stability of cerebral oxygenation in extremely preterm infants.

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