Detection of cerebral autoregulation by near-infrared spectroscopy in neonates: performance analysis of measurement methods

Cerebral Autoregulation, in clinical practice, is assessed by means of correlation or coherence analysis between mean arterial blood pressure (MABP) and cerebral blood flow (CBF). However, even though there is evidence linking cerebral autoregulation assessment with clinical outcome in preterm infants, available methods lack precision for clinical use. Classical methods, used for cerebral autoregulation, are influenced by the choice of parameters such as the length of the epoch under analysis and the choice of suitable frequency bands. The influence of these parameters, in the derived measurements for cerebral autoregulation, has not yet been evaluated. In this study, cerebral autoregulation was assessed using correlation, coherence, a modified version of coherence and transfer function gain, and phase. The influence of the extra-parameters on the final scores was evaluated by means of sensitivity analysis. The methods were applied to a database of 18 neonates with measurements of MABP and tissue oxygenation index (TOI). TOI reflects changes in CBF and was measured by means of near-infrared spectroscopy

Prenatal Use of Sildenafil in Fetal Growth Restriction and Its Effect on Neonatal Tissue Oxygenation-A Retrospective Analysis of Hemodynamic Data From Participants of the Dutch STRIDER Trial

Objective: Sildenafil is under investigation as a potential agent to improve uteroplacental perfusion in fetal growth restriction (FGR). However, the STRIDER RCT was halted after interim analysis due to futility and higher rates of persistent pulmonary hypertension and mortality in sildenafil-exposed neonates. This hypothesis-generating study within the Dutch STRIDER trial sought to understand what happened to these neonates by studying their regional tissue oxygen saturation (rSO2) within the first 72 h after birth. Methods: Pregnant women with FGR received 25 mg placebo or sildenafil thrice daily within the Dutch STRIDER trial. We retrospectively analyzed the cerebral and renal rSO2 monitored with near-infrared spectroscopy (NIRS) in a subset of neonates admitted to two participating neonatal intensive care units, in which NIRS is part of standard care. Secondarily, blood pressure and heart rate were analyzed to aid interpretation. Differences in oxygenation levels and interaction with time (slope) between placebo- and sildenafil-exposed groups were tested using mixed effects analyses with multiple comparisons tests. Results: Cerebral rSO2 levels were not different between treatment groups (79 vs. 77%; both n = 14) with comparable slopes. Sildenafil-exposed infants (n = 5) showed lower renal rSO2 than placebo-exposed infants (n = 6) during several time intervals on day one and two. At 69-72 h, however, the sildenafil group showed higher renal rSO2 than the placebo group. Initially, diastolic blood pressure was higher and heart rate lower in the sildenafil than the placebo group, which changed during day two. Conclusions: Although limited by sample size, our data suggest that prenatal sildenafil alters renal but not cerebral oxygenation in FGR neonates during the first 72 post-natal hours. The observed changes in renal oxygenation could reflect a vasoconstrictive rebound from sildenafil. Similar changes observed in accompanying vital parameters support this hypothesis

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

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 hy oxia 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). Conclusions: Cerebral NIRS monitoring was not associated with long‐term benefits or harm with regard to neurodevelopmental outcome at two years of corrected age

Технология извлечения структур знаний с использованием аппарата расширенных семантических сетей

В статье рассматривается задача извлечения из текстов естественного языка структур знаний: информационных объектов («именованных сущностей»), их свойств, связей и фактов участия в действиях. Для этих целей разработан инструментарий: язык представления знаний (расширенные семантические сети – РСС) и их обработки (язык преобразования структур – ДЕКЛ). На этой основе созданы технологии, которые обладают следующими особенностями. Из текстов извлекаются не отдельные объекты (именованные сущности), а структуры знаний, представляющие связи объектов и их участие в действиях и событиях. Для извлечения структур знаний разработан уникальный семантико-ориентированный лингвистический процессор (ЛП), осуществляющий глубинный анализ текстов ЕЯ и выявляющий десятки типов объектов вместе с их структурами. Процессор ЛП управляется лингвистическими знаниями, представляющими собой декларативные структуры и обеспечивающие быструю настройку ЛП на предметную область и язык. Основой лингвистических знаний являются правила, обладающие высокой степенью избирательности при выявлении объектов («сущностей»), средствами устранения коллизий при их применении. Это позволяет минимизировать шумы и потери.У статті розглядається задача знайдення у текстах природної мови структур знань: інформаційних об’єктів («іменованих сутностей»), їх якостей зв’язків і фактів участі у діях. Для цих цілей розроблений інструментарій: мова представлення знань (розширені семантичні мережі – РСМ) та їх обробки (мова перетворення структур – ДЕКЛ). На цій основі створені технології, що мають наступні особливості. З тестів виділяються не окремі об’єкти (іменовані сутності), а структури знань, що представляють зв’язки об’єктів та їх участь у діях та подіях. З метою виділення структур знань розроблений винятковий семантико-орієнтований лінгвістичний процесор (ЛП), що здійснює глибинний аналіз текстів ЕЯ та виявляє десятки типів об’єктів разом з їх структурами. Процесор ЛП керується лінгвістичними знаннями, які представляють собою декларативні структури та забезпечують швидке настроювання ЛП на предметну сферу та мову. Основою лінгвістичних знань є правила, що мають високий ступінь вибірковості при виявленні об’єктів («сутностей»), засобами усунення колізій при їхньому використанні. Це дозволяє мінімізувати шуми та втрати.The paper is devoted to the extracting of knowledge structures from the natural language texts, i.e. information objects (“Named Entities”), their features, relationships, and participation in the actions and events. For this purpose, the language used for knowledge representation (extended semantic networks/ESN) and tools for processing (language for structure conversion LSC) are considered. On this base, the new technologies are proposed. These technologies have the following features: extraction from the texts of knowledge structures that represent the links of named entities and their participation in actions and events. For the knowledge extraction the unique semantic-oriented language processor (LP) are designed. Processor LP provides the deep analysis of NL-texts and revealing set of objects together with their structures. Processor LP is controlled by the linguistic knowledge, which are declarative structures (on ESN) and which provides the quick tuning of LP on subject area and language, both Russian and English

Clinical use of cerebral oximetry in extremely preterm infants is feasible

Introduction: The research programme Safeguarding the Brains of our smallest Children (SafeBoosC) aims to test the benefits and harms of cerebral near-infrared spectroscopy (NIRS) oximetry in infants born before 28 weeks of gestation. In a phase II trial, infants will be randomised to visible cerebral NIRS oximetry with pre-specified treatment guidelines compared to standard care with blinded NIRS-monitoring. The primary outcome is duration multiplied with the extent outside the normal range of regional tissue oxygen saturation of haemoglobin (rStO2) of 55 to 85% in percentage hours (burden). This study was a pilot of the Visible ­Oximetry Group. Material and methods: This was an observational study including ten infants. Results: The median gestational age was 26 weeks + three days, and the median start-up time was 133 minutes after delivery. The median recording time was 69.7 hours, mean rStO2 was 64.2 ± 4.5%, median burden of hyper- and hy­poxia was 30.3% hours (range 2.8-112.3). Clinical staff responded to an out of range value 29 times – only once to values above 85%. In comparison, there were 83 periods of more than ten minutes with an rStO2 below 55% and four episodes with an rStO2 above 85%. These periods accounted for 72% of the total hypoxia burden. A total of 18 of the 29 interventions were adjustments of FiO2 which in 13 of the 18 times resulted in an out-of-range SpO2. Two infants suffered second-degree burns from the sensor. Five infants died. In all cases, this was unrelated to NIRS monitoring and treatment. Conclusion: The intervention of early cerebral NIRS monitoring proved feasible, but prolonged periods of hypoxia went untreated. Thus, a revision of the treatment guideline and an alarm system is required

Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial

Objective To determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry. Design Phase II randomised, single blinded, parallel clinical trial. Setting Eight tertiary neonatal intensive care units in eight European countries. Participants 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. Interventions 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).Main outcome measures 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. Randomisation 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).Blinding Cerebral oxygenation measurements were blinded in the control group. All outcome assessors were blinded to group allocation. Results 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. Conclusions Cerebral oxygenation was stabilised in extremely preterm infants using a dedicated treatment guideline in combination with cerebral NIRS monitoring.Trial registration ClinicalTrial.gov NCT0159031

A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial

Background: 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. Methods/Design: 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. Discussion: 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. Trial registration: ClinicalTrial.gov, NCT0159031

A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial.

BACKGROUND: 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. METHODS/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01590316.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants:A protocol for the SafeBoosC randomised clinical phase III trial

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

Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants: a protocol for the SafeBoosC randomised clinical phase III trial.

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