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No neurodevelopmental benefit of cerebral oximetry in the first randomised trial (SafeBoosC II) in preterm infants during the first days of life.

ABSTRACT: AIM:Cerebral hypoxia has been associated with neurodevelopmental impairment. We studied whether reducing cerebral hypoxia in extremely preterm infants during the first 72 hours of life affected neurological outcomes at two years of corrected age. METHODS:In 2012-2013, the phase II randomised Safeguarding the Brains of our smallest Children trial compared visible cerebral near-infrared spectroscopy (NIRS) monitoring in an intervention group and blinded NIRS monitoring in a control group. Cerebral hypoxia was significantly reduced in the intervention group. We followed up 115 survivors from eight European centres at two years of corrected age, by conducting a medical examination and assessing their neurodevelopment with the Bayley Scales of Infant and Toddler Development, Second or Third Edition, and the parental Ages and Stages Questionnaire (ASQ). RESULTS:There were no differences between the intervention (n = 65) and control (n = 50) groups with regard to the mean mental developmental index (89.6 ± 19.5 versus 88.4 ± 14.7, p = 0.77), ASQ score (215 ± 58 versus 213 ± 58, p = 0.88) and the number of children with moderate-to-severe neurodevelopmental impairment (10 versus six, p = 0.58). CONCLUSION:Cerebral NIRS monitoring was not associated with long-term benefits or harm with regard to neurodevelopmental outcome at two years of corrected age.

SUBMITTER: Plomgaard AM

PROVIDER: S-EPMC6585779 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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No neurodevelopmental benefit of cerebral oximetry in the first randomised trial (SafeBoosC II) in preterm infants during the first days of life.

Plomgaard Anne M AM Alderliesten Thomas T van Bel Frank F Benders Manon M Claris Olivier O Cordeiro Malaika M Dempsey Eugene E Fumagalli Monica M Gluud Christian C Hyttel-Sorensen Simon S Lemmers Petra P Pellicer Adelina A Pichler Gerhard G Greisen Gorm G

Acta paediatrica (Oslo, Norway : 1992) 20180705 2

<h4>Aim</h4>Cerebral hypoxia has been associated with neurodevelopmental impairment. We studied whether reducing cerebral hypoxia in extremely preterm infants during the first 72 hours of life affected neurological outcomes at two years of corrected age.<h4>Methods</h4>In 2012-2013, the phase II randomised Safeguarding the Brains of our smallest Children trial compared visible cerebral near-infrared spectroscopy (NIRS) monitoring in an intervention group and blinded NIRS monitoring in a control ...[more]

PMID: 29908039

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Project description:To determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry.Phase II randomised, single blinded, parallel clinical trial.Eight tertiary neonatal intensive care units in eight European countries.166 extremely preterm infants born before 28 weeks of gestation: 86 were randomised to cerebral NIRS monitoring and 80 to blinded NIRS monitoring. The only exclusion criterion was a decision not to provide life support.Monitoring of cerebral oxygenation using NIRS in combination with a dedicated treatment guideline during the first 72 hours of life (experimental) compared with blinded NIRS oxygenation monitoring with standard care (control).The primary outcome measure was the time spent outside the target range of 55-85% for cerebral oxygenation multiplied by the mean absolute deviation, expressed in %hours (burden of hypoxia and hyperoxia). One hour with an oxygenation of 50% gives 5%hours of hypoxia. Secondary outcomes were all cause mortality at term equivalent age and a brain injury score assessed by cerebral ultrasonography.Allocation sequence 1:1 with block sizes 4 and 6 in random order concealed for the investigators. The allocation was stratified for gestational age (<26 weeks or ? 26 weeks).Cerebral oxygenation measurements were blinded in the control group. All outcome assessors were blinded to group allocation.The 86 infants randomised to the NIRS group had a median burden of hypoxia and hyperoxia of 36.1%hours (interquartile range 9.2-79.5%hours) compared with 81.3 (38.5-181.3) %hours in the control group, a reduction of 58% (95% confidence interval 35% to 73%, P<0.001). In the experimental group the median burden of hypoxia was 16.6 (interquartile range 5.4-68.1) %hours, compared with 53.6 (17.4-171.3) %hours in the control group (P=0.0012). The median burden of hyperoxia was similar between the groups: 1.2 (interquartile range 0.3-9.6) %hours in the experimental group compared with 1.1 (0.1-23.4) %hours in the control group (P=0.98). We found no statistically significant differences between the two groups at term corrected age. No severe adverse reactions were associated with the device.Cerebral oxygenation was stabilised in extremely preterm infants using a dedicated treatment guideline in combination with cerebral NIRS monitoring.Trial registration ClinicalTrial.gov NCT01590316.

Project description:BACKGROUND:Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC III trial is to investigate the benefits and harms of treatment based on near-infrared spectroscopy (NIRS) monitoring compared with treatment as usual for extremely preterm infants. METHODS/DESIGN:SafeBoosC III is an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. Inclusion criteria will be infants born below 28?weeks postmenstrual age and parental informed consent (unless the site is using 'opt-out' or deferred consent). Exclusion criteria will be no parental informed consent (or if 'opt-out' is used, lack of a record that clinical staff have explained the trial and the 'opt-out' consent process to parents and/or a record of the parents' decision to opt-out in the infant's clinical file); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6?h after birth. Participants will be randomised 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72?h of life with a cerebral NIRS oximeter. Cerebral hypoxia will be treated according to an evidence-based treatment guideline. Participants in the control group will not undergo cerebral oxygenation monitoring and will receive treatment as usual. Each participant will be followed up at 36?weeks postmenstrual age. The primary outcome will be a composite of either death or severe brain injury detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to 36?weeks postmenstrual age. Severe brain injury will be assessed by a person blinded to group allocation. To detect a 22% relative risk difference between the experimental and control group, we intend to randomise a cohort of 1600 infants. DISCUSSION:Treatment guided by cerebral NIRS oximetry has the potential to decrease the risk of death or survival with severe brain injury in preterm infants. There is an urgent need to assess the clinical effects of NIRS monitoring among preterm neonates. TRIAL REGISTRATION:ClinicalTrial.gov, NCT03770741. Registered 10 December 2018.

Project description:Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2.SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the 'burden of hypoxia and hyperoxia' expressed in '%hours'. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events.Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia.ClinicalTrial.gov, NCT01590316.

Project description:BackgroundInfants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses.Methods/designThe SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis.DiscussionIn line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis.Trial registrationClinicalTrials.org, NCT03770741. Registered on 10 December 2018.

Project description:BackgroundInflammation may be an important predictor of long-term neurodevelopment in preterm infants. The identification of specific inflammatory biomarkers that predict outcomes is an important research goal.ObjectivesThe purpose of this analysis was to identify associations between an early measure of inflammation and neurodevelopment in very preterm infants and to identify differences in the relationship between inflammation and neurodevelopment based on infant gender and race.MethodsWe conducted a secondary analysis of data from a randomized controlled trial of a caregiving intervention for preterm infants born less than 33 weeks postmenstrual age. Plasma was collected with a clinically indicated laboratory draw by neonatal intensive care unit nurses and analyzed by multiplex assay for cytokines, chemokines, and growth factors. Neurobehavior was assessed by research nurses at the time of discharge from the neonatal intensive care unit using the motor development and vigor and alertness/orientation clusters from the Neurobehavioral Assessment of the Preterm Infant. Neurodevelopment was assessed at 6 months corrected age by the developmental specialist in the hospital's neonatal follow-up clinic using the Bayley Scales of Infant Development, Third Edition. We used linear regressions to estimate the effect of cytokine levels on neurodevelopment and allowed the effects to differ by infant gender and race.ResultsIn a sample of 62 preterm infants with discharge neurobehavioral assessments and a sample of 40 preterm infants with 6-month neurodevelopmental assessments, we found inconsistent associations between single-time point inflammatory measures and neurobehavior or neurodevelopment in analyses of the total sample. However, regressions with interactions revealed effects for multiple inflammatory measures on early neurobehavior and neurodevelopment that differed by infant gender and race.DiscussionAlthough early single-time point measures of inflammation may be insufficient to predict neurodevelopment for all preterm infants, the effect of inflammation appears to differ by infant gender and race. These demographic factors may be important considerations for future studies of inflammation and neurodevelopment as well was the development of future interventions to optimize outcomes.

Dataset Information

No neurodevelopmental benefit of cerebral oximetry in the first randomised trial (SafeBoosC II) in preterm infants during the first days of life.

Publications

No neurodevelopmental benefit of cerebral oximetry in the first randomised trial (SafeBoosC II) in preterm infants during the first days of life.

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