Music therapy in tertiary neonatal intensive care: A matter of unlikely allies?

Over the past decades, music therapy in the neonatal intensive care unit (NICU) has been proven effective in physiological and psychological outcomes, including sucking, behaviour, stress reduction, neurodevelopment and promoting emotional bonding. However, not every NICU administers music therapy in their ward. Research on music therapy for neonates and their caregivers has lately accumulated, increasing the evidence of health benefits on brain development and across a variety of NICU-related pathologies, including neurological, cardiological, pulmonary and gastrointestinal problems. Conclusively, we will present the studied methods of music therapy for clinical benefits in neonatal intensive care.

Machine learning for the early prediction of infants with electrographic seizures in neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: To assess if early clinical and electroencephalography (EEG) features predict later seizure development in infants with hypoxic-ischemic encephalopathy (HIE). METHODS: Clinical and EEG parameters <12 h of birth from infants with HIE across eight European Neonatal Units were used to develop seizure-prediction models. Clinical parameters included intrapartum complications, fetal distress, gestational age, delivery mode, gender, birth weight, Apgar scores, assisted ventilation, cord pH, and blood gases. The earliest EEG hour provided a qualitative analysis (discontinuity, amplitude, asymmetry/asynchrony, sleep-wake cycle [SWC]) and a quantitative analysis (power, discontinuity, spectral distribution, inter-hemispheric connectivity) from full montage and two-channel amplitude-integrated EEG (aEEG). Subgroup analysis, only including infants without anti-seizure medication (ASM) prior to EEG was also performed. Machine-learning (ML) models (random forest and gradient boosting algorithms) were developed to predict infants who would later develop seizures and assessed using Matthews correlation coefficient (MCC) and area under the receiver-operating characteristic curve (AUC). RESULTS: The study included 162 infants with HIE (53 had seizures). Low Apgar, need for ventilation, high lactate, low base excess, absent SWC, low EEG power, and increased EEG discontinuity were associated with seizures. The following predictive models were developed: clinical (MCC 0.368, AUC 0.681), qualitative EEG (MCC 0.467, AUC 0.729), quantitative EEG (MCC 0.473, AUC 0.730), clinical and qualitative EEG (MCC 0.470, AUC 0.721), and clinical and quantitative EEG (MCC 0.513, AUC 0.746). The clinical and qualitative-EEG model significantly outperformed the clinical model alone (MCC 0.470 vs 0.368, p-value .037). The clinical and quantitative-EEG model significantly outperformed the clinical model (MCC 0.513 vs 0.368, p-value .012). The clinical and quantitative-EEG model for infants without ASM (n = 131) had MCC 0.588, AUC 0.832. Performance for quantitative aEEG (n = 159) was MCC 0.381, AUC 0.696 and clinical and quantitative aEEG was MCC 0.384, AUC 0.720. SIGNIFICANCE: Early EEG background analysis combined with readily available clinical data helped predict infants who were at highest risk of seizures, hours before they occur. Automated quantitative-EEG analysis was as good as expert analysis for predicting seizures, supporting the use of automated assessment tools for early evaluation of HIE.

Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy.

BACKGROUND: Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome. METHODS: Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count. RESULTS: CBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r2 = 0.46, p = 0.004, r2 = 0.45, p = 0.004, respectively), TUNEL cell count (r2 = 0.34, p = 0.02) and predicted both initial insult (r2 = 0.62, p = 0.002) and outcome group (r2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r2 = 0.34, p = 0.01 and r2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r2 = 0.43, p = 0.01). CONCLUSION: Optical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model. IMPACT: This study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome. Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.

The Extracellular Vesicle Citrullinome and Signature in a Piglet Model of Neonatal Seizures.

Neonatal seizures are commonly associated with acute perinatal brain injury, while understanding regarding the downstream molecular pathways related to seizures remains unclear. Furthermore, effective treatment and reliable biomarkers are still lacking. Post-translational modifications can contribute to changes in protein function, and post-translational citrullination, which is caused by modification of arginine to citrulline via the calcium-mediated activation of the peptidylarginine deiminase (PAD) enzyme family, is being increasingly linked to neurological injury. Extracellular vesicles (EVs) are lipid-bilayer structures released from cells; they can be isolated from most body fluids and act as potential liquid biomarkers for disease conditions and response to treatment. As EVs carry a range of genetic and protein cargo that can be characteristic of pathological processes, the current study assessed modified citrullinated protein cargo in EVs isolated from plasma and CSF in a piglet neonatal seizure model, also following phenobarbitone treatment. Our findings provide novel insights into roles for PAD-mediated changes on EV signatures in neonatal seizures and highlight the potential of plasma- and CSF-EVs to monitor responses to treatment.

Changes in Brain Tissue Oxygenation and Metabolism During Rewarming After Neonatal Encephalopathy are Related to Electrical Abnormality.

Hypoxic ischemic encephalopathy (HIE) leads to significant mortality and morbidity, and therapeutic hypothermia (TH) has become a standard of care following HIE. After TH, the body temperature is brought back to 37 °C. Early electroencephalography (EEG) is a reliable outcome biomarker following HIE. We hypothesized that changes in cerebral oxidative metabolism, measured as Δ[oxCCO], in relation to changes in brain tissue oxygenation (measured as Δ[HbD]) during rewarming will correlate with injury severity as evidenced on amplitude integrated EEG/EEG at initial presentation. Broadband near-infrared spectroscopy (NIRS) and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. All infants were monitored with video EEG telemetry using a standard neonatal montage. aEEG and EEG background was classified into mild, moderate and severely abnormal groups based on the background pattern. Two infants had mild, 6 infants had moderate and another 6 infants had severe abnormality at presentation. The relationship between [oxCCO] and [HbD] was evaluated between two groups of infants with abnormal electrical activity (mild vs moderate to severe). A significant difference was noted between the groups in the relationship between [oxCCO] and [HbD] (as r2) (p = 0.02). This result indicates that the mitochondrial injury and deranged oxidative metabolism persists in the moderate to severely abnormal group during rewarming.

Near-Infrared Spectroscopy Measured Cerebral Blood Flow from Spontaneous Oxygenation Changes in Neonatal Brain Injury.

Neonates with hypoxic-ischaemic (HI) brain injury were monitored using a broadband near-infrared spectroscopy (NIRS) system in the neonatal intensive care unit. The aim of this work is to use the NIRS cerebral oxygenation data (HbD = oxygenated-haemoglobin - deoxygenated-haemoglobin) combined with arterial saturation (SaO2) from pulse oximetry to calculate cerebral blood flow (CBF) based on the oxygen swing method, during spontaneous desaturation episodes. The method is based on Fick's principle and uses HbD as a tracer; when a sudden change in SaO2 occurs, the change in HbD represents a change in tracer concentration, and thus it is possible to estimate CBF. CBF was successfully calculated with broadband NIRS in 11 HIE infants (3 with severe injury) for 70 oxygenation events on the day of birth. The average CBF was 18.0 ± 12.7 ml 100 g-1 min-1 with a range of 4 ml 100 g-1 min-1 to 60 ml 100 g-1 min-1. For infants with severe HIE (as determined by magnetic resonance spectroscopy) CBF was significantly lower (p = 0.038, d = 1.35) than those with moderate HIE on the day of birth.

In Vivo Measurement of Cerebral Mitochondrial Metabolism Using Broadband Near Infrared Spectroscopy Following Neonatal Stroke.

Neonatal stroke presents with features of encephalopathy and can result in significant morbidity and mortality. We investigated the cerebral metabolic and haemodynamic changes following neonatal stroke in a term infant at 24 h of life. Changes in oxidation state of cytochrome-c-oxidase (oxCCO) concentration were monitored along with changes in oxy- and deoxy- haemoglobin using a new broadband near-infrared spectroscopy (NIRS) system. Repeated transient changes in cerebral haemodynamics and metabolism were noted over a 3-h study period with decrease in oxyhaemoglobin (HbO2), deoxy haemoglobin (HHb) and oxCCO in both cerebral hemispheres without significant changes in systemic observations. A clear asymmetry was noted in the degree of change between the two cerebral hemispheres. Changes in cerebral oxygenation (measured as HbDiff=HbO2-HHb) and cerebral metabolism (measured as oxCCO) were highly coupled on the injured side of the brain.

Interrelationship Between Broadband NIRS Measurements of Cerebral Cytochrome C Oxidase and Systemic Changes Indicates Injury Severity in Neonatal Encephalopathy.

Perinatal hypoxic ischaemic encephalopathy (HIE) is associated with severe neurodevelopmental problems and mortality. There is a clinical need for techniques to provide cotside assessment of the injury extent. This study aims to use non-invasive cerebral broadband near-infrared spectroscopy (NIRS) in combination with systemic physiology to assess the severity of HIE injury. Broadband NIRS is used to measure the changes in haemodynamics, oxygenation and the oxidation state of cytochrome c oxidase (oxCCO). We used canonical correlation analysis (CCA), a multivariate statistical technique, to measure the relationship between cerebral broadband NIRS measurements and systemic physiology. A strong relationship between the metabolic marker, oxCCO, and systemic changes indicated severe brain injury; if more than 60 % of the oxCCO signal could be explained by the systemic variations, then the neurodevelopmental outcome was poor. This boundary has high sensitivity and specificity (100 and 83 %, respectively). Broadband NIRS measured concentration changes of the oxidation state of cytochrome c oxidase has the potential to become a useful cotside tool for assessment of injury severity following hypoxic ischaemic brain injury.

Relationship Between Cerebral Oxygenation and Metabolism During Rewarming in Newborn Infants After Therapeutic Hypothermia Following Hypoxic-Ischemic Brain Injury.

Therapeutic hypothermia (TH) has become a standard of care following hypoxic ischemic encephalopathy (HIE). After TH, body temperature is brought back to 37 °C over 14 h. Lactate/N-acetylasperatate (Lac/NAA) peak area ratio on proton magnetic resonance spectroscopy ((1)H MRS) is the best available outcome biomarker following HIE. We hypothesized that broadband near infrared spectroscopy (NIRS) measured changes in the oxidation state of cytochrome-c-oxidase concentration (Δ[oxCCO]) and cerebral hemodynamics during rewarming would relate to Lac/NAA. Broadband NIRS and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. (1)H MRS was performed on day 5-9. Heart rate increased by 20/min during rewarming while blood pressure and peripheral oxygen saturation (SpO2) remained stable. The relationship between mitochondrial metabolism and oxygenation (measured as Δ[oxCCO] and Δ[HbD], respectively) was calculated by linear regression analysis. This was reviewed in three groups: Lac/NAA values <0.5, 0.5-1, >1. Mean regression coefficient (r (2)) values in these groups were 0.41 (±0.27), 0.22 (±0.21) and 0.01, respectively. The relationship between mitochondrial metabolism and oxygenation became impaired with rising Lac/NAA. Cardiovascular parameters remained stable during rewarming.

Monitoring of Cerebrovascular Reactivity for Determination of Optimal Blood Pressure in Preterm Infants.

OBJECTIVE: To define levels of mean arterial blood pressure (MABP) where cerebrovascular reactivity is strongest in preterm infants (ie, optimal MABP, or MABPOPT) and correlate deviations from MABPOPT with mortality and intraventricular hemorrhage (IVH). STUDY DESIGN: A total of 60 preterm infants born at median gestational age 26 ± 2 weeks (23 ± 2 to 32 ± 1) with indwelling arterial catheter were studied at a median 34 hours (range 5-228) of age. Tissue oxygenation heart rate (HR) reactivity index, which estimates cerebrovascular reactivity, was calculated as the moving correlation coefficient between slow waves of tissue oxygenation index, measured with near-infrared spectroscopy, and HR. MABPOPT was defined by dividing MABP into 2-mm Hg bins and averaging the tissue oxygenation HR reactivity index within those bins. A measurement of divergence from MABPOPT was calculated as the absolute difference between mean MABP and mean MABPOPT. RESULTS: Individual MABPOPT was defined in 81% of the patients. A measurement of divergence from MABPOPT was greater in those patients who died (mean 4.2 mm Hg; 95% CI 3.33-4.96) compared with those who survived (mean 2.1 mm Hg; 95% CI 1.64-2.56), P = .013. Patients who had MABP lower than MABPOPT by 4 mm Hg or more had a greater rate of mortality (40%) than those with MABP close to or above MABPOPT (13%), P = .049. Patients with MABP greater than MABPOPT by 4 mm Hg had greater IVH scores, P = .042. CONCLUSIONS: Continuous monitoring of cerebrovascular reactivity allows the determination of MABPOPT in preterm neonates. Significant deviation below MABPOPT was observed in infants who died. Deviation of MABP above optimal level was observed in infants who developed more severe IVH.

The Role of Music Therapy with Infants with Perinatal Brain Injury.

Perinatal brain injury occurs in 5.14/1000 live births in England. A significant proportion of these injuries result from hypoxic ischaemic encephalopathy (HIE) in term infants and intracranial haemorrhage (IVH) or periventricular leukomalacia (PVL) in preterm infants. Standardised care necessitates minimal handling from parents and professionals to reduce the progression of injury. This can potentially increase parental stress through the physical inability to bond with their baby. Recent research highlights the ability of music therapy (MT) to empower parental bonding without handling, through sharing culturally informed personal music with their infant. This review therefore aimed to systematically evaluate the use of MT with infants diagnosed with perinatal brain injury in a neonatal intensive care unit (NICU). Search terms were combined into three categories (audio stimulation (MT), population (neonates) and condition (brain injury), and eight electronic databases were used to identify relevant studies following PRISMA guidelines. Eleven studies using music or vocal stimulation with infants diagnosed with perinatal brain injury were identified and quality assessed using Cochrane ROB2, the ROBINSI Tool and the Newcastle Ottawa Scale. Studies used either voice as live (n = 6) or pre-recorded (n = 3) interventions or pre-recorded instrumental music (n = 2). Studies had two primary areas of focus: developmental outcomes and physiological effects. Results suggested the use of music interventions led to a reduction of infants' pain scores during procedures and cardiorespiratory events, improved feeding ability (increase oral feeding rate, volume intake and feeds per day) and resulted in larger amygdala volumes than control groups. Additionally, MT intervention on the unit supported long-term hospitalised infants in the acquisition of developmental milestones. Vocal soothing was perceived to be an accessible intervention for parents. However, infants with PVL showed signs of stress in complex interventions, which also potentially resulted in an increase in maternal anxiety in one study. MT with infants diagnosed with perinatal brain injury can have positive effects on infants' behavioural and neurological parameters and support parental involvement in their infants' developmental care. Further feasibility studies are required using MT to determine appropriate outcome measures for infants and the support required for parents to allow future comparison in large-scale randomised control trials.

Brain temperature monitoring in newborn infants: Current methodologies and prospects.

Brain tissue temperature is a dynamic balance between heat generation from metabolism, passive loss of energy to the environment, and thermoregulatory processes such as perfusion. Perinatal brain injuries, particularly neonatal encephalopathy, and seizures, have a significant impact on the metabolic and haemodynamic state of the developing brain, and thereby likely induce changes in brain temperature. In healthy newborn brains, brain temperature is higher than the core temperature. Magnetic resonance spectroscopy (MRS) has been used as a viable, non-invasive tool to measure temperature in the newborn brain with a reported accuracy of up to 0.2 degrees Celcius and a precision of 0.3 degrees Celcius. This measurement is based on the separation of chemical shifts between the temperature-sensitive water peaks and temperature-insensitive singlet metabolite peaks. MRS thermometry requires transport to an MRI scanner and a lengthy single-point measurement. Optical monitoring, using near infrared spectroscopy (NIRS), offers an alternative which overcomes this limitation in its ability to monitor newborn brain tissue temperature continuously at the cot side in real-time. Near infrared spectroscopy uses linear temperature-dependent changes in water absorption spectra in the near infrared range to estimate the tissue temperature. This review focuses on the currently available methodologies and their viability for accurate measurement, the potential benefits of monitoring newborn brain temperature in the neonatal intensive care unit, and the important challenges that still need to be addressed.

Broadband-NIRS System Identifies Epileptic Focus in a Child with Focal Cortical Dysplasia-A Case Study.

Epileptic seizures are transiently occurring symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Previous functional near-infrared spectroscopy (fNIRS) studies during seizures have focused in only monitoring the brain oxygenation and haemodynamic changes. However, few tools are available to measure actual cellular metabolism during seizures, especially at the bedside. Here we use an in-house developed multichannel broadband NIRS (or bNIRS) system, that, alongside the changes in oxy-, deoxy- haemoglobin concentration (HbO2, HHb), also quantifies the changes in oxidised cytochrome-c-oxidase Δ(oxCCO), a marker of cellular oxygen metabolism, simultaneously over 16 different brain locations. We used bNIRS to measure metabolic activity alongside brain tissue haemodynamics/oxygenation during 17 epileptic seizures at the bedside of a 3-year-old girl with seizures due to an extensive malformation of cortical development in the left posterior quadrant. Simultaneously Video-EEG data was recorded from 12 channels. Whilst we did observe the expected increase in brain tissue oxygenation (HbD) during seizures, it was almost diminished in the area of the focal cortical dysplasia. Furthermore, in the area of seizure origination (epileptic focus) ΔoxCCO decreased significantly at the time of seizure generalization when compared to the mean change in all other channels. We hypothesize that this indicates an incapacity to sustain and increase brain tissue metabolism during seizures in the region of the epileptic focus.

Optical Monitoring in Neonatal Seizures.

BACKGROUND: Neonatal seizures remain a significant cause of morbidity and mortality worldwide. The past decade has resulted in substantial progress in seizure detection and understanding the impact seizures have on the developing brain. Optical monitoring such as cerebral near-infrared spectroscopy (NIRS) and broadband NIRS can provide non-invasive continuous real-time monitoring of the changes in brain metabolism and haemodynamics. AIM: To perform a systematic review of optical biomarkers to identify changes in cerebral haemodynamics and metabolism during the pre-ictal, ictal, and post-ictal phases of neonatal seizures. METHOD: A systematic search was performed in eight databases. The search combined the three broad categories: (neonates) AND (NIRS) AND (seizures) using the stepwise approach following PRISMA guidance. RESULTS: Fifteen papers described the haemodynamic and/or metabolic changes observed with NIRS during neonatal seizures. No randomised controlled trials were identified during the search. Studies reported various changes occurring in the pre-ictal, ictal, and post-ictal phases of seizures. CONCLUSION: Clear changes in cerebral haemodynamics and metabolism were noted during the pre-ictal, ictal, and post-ictal phases of seizures in neonates. Further studies are necessary to determine whether NIRS-based methods can be used at the cot-side to provide clear pathophysiological data in real-time during neonatal seizures.

Effectiveness of early spectacle intervention on visual outcomes in babies at risk of cerebral visual impairment: a parallel group, open-label, randomised clinical feasibility trial protocol.

INTRODUCTION: Hypoaccommodation is common in children born prematurely and those with hypoxic ischaemic encephalopathy (HIE), with the potential to affect wider learning. These children are also at risk of longer-term cerebral visual impairment. It is also well recognised that early intervention for childhood visual pathology is essential, because neuroplasticity progressively diminishes during early life. This study aims to establish the feasibility and acceptability of conducting a randomised controlled trial to test the effectiveness of early near vision correction with spectacles in infancy, for babies, at risk of visual dysfunction. METHODS AND ANALYSIS: This is a parallel group, open-label, randomised controlled (feasibility) study to assess visual outcomes in children with perinatal brain injury when prescribed near vision spectacles compared with the current standard care-waiting until a problem is detected. The study hypothesis is that accommodation, and possibly other aspects of vision, may be improved by intervening earlier with near vision glasses. Eligible infants (n=75, with either HIE or <29 weeks preterm) will be recruited and randomised to one of three arms, group A (no spectacles) and two intervention groups: B1 or B2. Infants in both intervention groups will be offered glasses with +3.00 DS added to the full cycloplegic refraction and prescribed for full time wear. Group B1 will get their first visit assessment and intervention at 8 weeks corrected gestational age (B1) and B2 at 16 weeks corrected gestational age. All infants will receive a complete visual and neurodevelopmental assessment at baseline and a follow-up visit at 3 and 6 months after the first visit. ETHICS AND DISSEMINATION: The South-Central Oxford C Research Ethics Committee has approved the study. Members of the PPI committee will give advice on dissemination of results through peer-reviewed publications, conferences and societies. TRIAL REGISTRATION NUMBER: ISRCTN14646770, NCT05048550, NIHR ref: PB-PG-0418-20006.

Heart rate variability analysis for the prediction of EEG grade in infants with hypoxic ischaemic encephalopathy within the first 12†h of birth.

Background and aims: Heart rate variability (HRV) has previously been assessed as a biomarker for brain injury and prognosis in neonates. The aim of this cohort study was to use HRV to predict the electroencephalography (EEG) grade in neonatal hypoxic-ischaemic encephalopathy (HIE) within the first 12 h. Methods: We included 120 infants with HIE recruited as part of two European multi-centre studies, with electrocardiography (ECG) and EEG monitoring performed before 12 h of age. HRV features and EEG background were assessed using the earliest 1 h epoch of ECG-EEG monitoring. HRV was expressed in time, frequency and complexity features. EEG background was graded from 0-normal, 1-mild, 2-moderate, 3-major abnormalities to 4-inactive. Clinical parameters known within 6 h of birth were collected (intrapartum complications, foetal distress, gestational age, mode of delivery, gender, birth weight, Apgar at 1 and 5, assisted ventilation at 10 min). Using logistic regression analysis, prediction models for EEG severity were developed for HRV features and clinical parameters, separately and combined. Multivariable model analysis included 101 infants without missing data. Results: Of 120 infants included, 54 (45%) had normal-mild and 66 (55%) had moderate-severe EEG grade. The performance of HRV model was AUROC 0.837 (95% CI: 0.759-0.914) and clinical model was AUROC 0.836 (95% CI: 0.759-0.914). The HRV and clinical model combined had an AUROC of 0.895 (95% CI: 0.832-0.958). Therapeutic hypothermia and anti-seizure medication did not affect the model performance. Conclusions: Early HRV and clinical information accurately predicted EEG grade in HIE within the first 12 h of birth. This might be beneficial when EEG monitoring is not available in the early postnatal period and for referral centres who may want some objective information on HIE severity.

Subcutaneous fat necrosis in newborn-an unusual case and review of literature.

UNLABELLED: Subcutaneous fat necrosis (SCFN) of the newborn is an uncommon, self-limiting panniculitis mostly occurring within the first few weeks after birth. SCFN has been described mostly in term or post-term newborn infants in literature. We report a preterm infant developing extensive subcutaneous fat necrosis within the first week of life after significant perinatal hypoxic injury. The infant was conservatively managed for subcutaneous fat necrosis but developed hypercalcaemia and required prolonged medical treatment. Hypercalcaemia is a rare but serious complication of subcutaneous fat necrosis and needs prolonged follow-up. The etiopathogenesis of both subcutaneous fat necrosis in newborn and the resultant hypercalcaemia are poorly understood. CONCLUSION: Significant subcutaneous fat necrosis can develop in both preterm and term infants, and preterm infants also develop significant complications including hypercalcaemia.

Absolute quantification of cerebral tissue oxygen saturation with multidistance broadband NIRS in newborn brain.

Tissue oximetry with near-infrared spectroscopy (NIRS) is a technique for the measurement of absolute tissue oxygen saturation (StO2). Offering a real-time and non-invasive assessment of brain oxygenation and haemodynamics, StO2 has potential to be used for the assessment of newborn brain injury. Multiple algorithms have been developed to measure StO2, however, issues with low measurement accuracy or extracranial tissue signal contamination remain. In this work, we present a novel algorithm to recover StO2 in the neonate, broadband multidistance oximetry (BRUNO), based on a measurement of the gradient of attenuation against distance measured with broadband NIRS. The performance of the algorithm was compared to two other published algorithms, broadband fitting (BF) and spatially resolved spectroscopy (SRS). The median error when recovering StO2 in light transport simulations on a neonatal head mesh was 0.4% with BRUNO, 4.2% with BF and 9.5% with SRS. BRUNO was more sensitive to brain tissue oxygenation changes, shown in layered head model simulations. Comparison of algorithm performance during full oxygenation-deoxygenation cycles in a homogeneous dynamic blood phantom showed significant differences in the dynamic range of the algorithms; BRUNO recovered StO2 over 0-100%, BF over 0-90% and SRS over 39-80%. Recovering StO2 from data collected in a neonate treated at the neonatal intensive care showed different baseline values; mean StO2 was 64.9% with BRUNO, 67.2% with BF and 73.2% with SRS. These findings highlight the effect of StO2 algorithm selection on oxygenation recovery; applying BRUNO in the clinical care setting could reveal further insight into complex haemodynamic processes occurring during neonatal brain injury.

Role of Optical Neuromonitoring in Neonatal Encephalopathy-Current State and Recent Advances.

Neonatal encephalopathy (NE) in term and near-term infants is a significant global health problem; the worldwide burden of disease remains high despite the introduction of therapeutic hypothermia. Assessment of injury severity and effective management in the neonatal intensive care unit (NICU) relies on multiple monitoring modalities from systemic to brain-specific. Current neuromonitoring tools provide information utilized for seizure management, injury stratification, and prognostication, whilst systemic monitoring ensures multi-organ dysfunction is recognized early and supported wherever needed. The neuromonitoring technologies currently used in NE however, have limitations in either their availability during the active treatment window or their reliability to prognosticate and stratify injury confidently in the early period following insult. There is therefore a real need for a neuromonitoring tool that provides cot side, early and continuous monitoring of brain health which can reliably stratify injury severity, monitor response to current and emerging treatments, and prognosticate outcome. The clinical use of near-infrared spectroscopy (NIRS) technology has increased in recent years. Research studies within this population have also increased, alongside the development of both instrumentation and signal processing techniques. Increasing use of commercially available cerebral oximeters in the NICU, and the introduction of advanced optical measurements using broadband NIRS (BNIRS), frequency domain NIRS (FDNIRS), and diffuse correlation spectroscopy (DCS) have widened the scope by allowing the direct monitoring of oxygen metabolism and cerebral blood flow, both key to understanding pathophysiological changes and predicting outcome in NE. This review discusses the role of optical neuromonitoring in NE and why this modality may provide the next significant piece of the puzzle toward understanding the real time state of the injured newborn brain.

Prognostic value of neonatal EEG following therapeutic hypothermia in survivors of hypoxic-ischemic encephalopathy.

OBJECTIVE: Early prediction of neurological deficits following neonatal hypoxic-ischemic encephalopathy (HIE) may help to target support. Neonatal animal models suggest that recovery following hypoxia-ischemia depends upon cortical bursting. To test whether this holds in human neonates, we correlated the magnitude of cortical bursting during recovery (≥postnatal day 3) with neurodevelopmental outcomes. METHODS: We identified 41 surviving infants who received therapeutic hypothermia for HIE (classification at hospital discharge: 19 mild, 18 moderate, 4 severe) and had 9-channel electroencephalography (EEG) recordings as part of their routine care. We correlated burst power with Bayley-III cognitive, motor and language scores at median 24 months. To examine whether EEG offered additional prognostic information, we controlled for structural MRI findings. RESULTS: Higher power of central and occipital cortical bursts predicted worse cognitive and language outcomes, and higher power of central cortical bursts predicted worse motor outcome, all independently of structural MRI findings. CONCLUSIONS: Clinical EEG after postnatal day 3 may provide additional prognostic information by indexing persistent active mechanisms that either support recovery or exacerbate brain damage, especially in infants with less severe encephalopathy. SIGNIFICANCE: These findings could allow for the effect of clinical interventions in the neonatal period to be studied instantaneously in the future.