Subhabrata Mitra

• MBBS DCH FHEA FRCPCH PhD
• Associate Professor and Honorary Consultant Neonatologist at University College London

Seizures are common following hypoxic–ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain; however, the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broa...

Hypoxic ischemic encephalopathy (HIE) leads to significant morbidity and mortality. Impaired autoregulation after hypoxia-ischaemia has been suggested to contribute further to injury. Thalamic lactate/N-Acetylasperate (Lac/NAA) peak area ratio of > 0.3 on proton (¹H) magnetic resonance spectroscopy (MRS) is associated with poor neurodevelopment out...

Objective Brain proton ( ¹ H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) ¹ H MRS Lac/NAA for the prediction of Bayley...

Background Despite the availability of continuous conventional electroencephalography (cEEG), accurate diagnosis of neonatal seizures is challenging in clinical practice. Algorithms for decision support in the recognition of neonatal seizures could improve detection. We aimed to assess the diagnostic accuracy of an automated seizure detection algor...

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...

MAESTROS is a state-of-the-art in-house developed multi-wavelength time-domain NIRS system. Using NIRS to measure in-vivo placenta oxygenation non-invasively at the bedside could potentially provide valuable insights into the health status of the pregnancy. However, the variable depth of the placenta in the abdomen results in reliability issues for...

Broadband NIRS (bNIRS) is an extension of fNIRS that provides the same assessment of oxygenation biomarkers along with a valuable marker for oxygen metabolism at a cellular level, the oxidation state of cytochrome-c-oxidase (oxCCO). bNIRS implements many (100s) NIR wavelengths in the full NIR spectrum to address this and provide insight to tissue e...

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 neonat...

Neonatal outcomes have improved over the last decade following significant thrust in this area, but stillbirth, preterm birth and neonatal brain injury remain acute global problems with long-lasting parental and family psychological trauma. In 2020, 1 in every 225 pregnancies in UK ended in stillbirth, with 2 million stillbirths reported worldwide....

Background Despite extensive research on neonatal hypoxic-ischaemic encephalopathy, detailed information about electrographic seizures during active cooling and rewarming of therapeutic hypothermia is sparse. We aimed to describe temporal evolution of seizures and determine whether there is a correlation of seizure evolution with 2-year outcome. M...

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-transla...

Figure S1: Histogram showing comparison of seizure duration and EEG scoring between the vehicle control group (CTR), the seizure group (BIC) and the seizure group receiving phenobarbitone (BIC + PHB). The duration of abnormal EEG activity was assessed by counting the number of minutes of abnormal brain activity on EEG for both dosing periods combin...

Figure S1: Histogram showing comparison of seizure duration and EEG scoring between the vehicle control group (CTR), the seizure group (BIC) and the seizure group receiving phenobarbitone (BIC + PHB). The duration of abnormal EEG activity was assessed by counting the number of minutes of abnormal brain activity on EEG for both dosing periods combin...

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 bl...

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 rec...

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 in...

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, a...

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 n...

The Babies in Glasses (BiG ) Study: Feasibility and acceptability of early spectacle intervention to babies and parents to improve visual outcomes in infants at risk of perinatal brain insult.

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...

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 t...

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 meta...

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 recover...

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45–55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology...

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 S...

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45-55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology...

Neonatal monitoring in neonatal intensive care is pushing the technological boundaries of newborn brain monitoring in order to improve patient outcome. There is an urgent need of a cot side, real-time monitoring for assessment of brain injury severity and neurodevelopmental outcome, in particular for term newborn infants with hypoxic-ischemic brain...

Hemodynamic impairment occurs in up to 80% of infants with neonatal encephalopathy (NE). Not all infants benefit from therapeutic hypothermia (HT); there are some indications that the trajectory of brain injury might be modified by neurologic monitoring and early management over the first 72-hour period. It is also possible that optimizing hemodyna...

Background: Neonatal hypoxic ischemic encephalopathy (HIE) remains a significant cause of mortality and morbidity worldwide. Cerebral near infrared spectroscopy (NIRS) can provide cot side continuous information about changes in brain hemodynamics, oxygenation and metabolism in real time. Objective: To perform a systematic review of cerebral NIRS m...

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 oxidativ...

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 c...

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 c...

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 oxidativ...

We describe the development of a miniaturized broadband near-infrared spectroscopy system (bNIRS), which measures changes in cerebral tissue oxyhemoglobin ( [ HbO 2 ] ) and deoxyhemoglobin ([HHb]) plus tissue metabolism via changes in the oxidation state of cytochrome-c-oxidase ([oxCCO]). The system is based on a small light source and a cust...

Perinatal brain injury causes significant mortality and morbidity. Hypoxic ischemic (HI) brain injury is the commonest cause for early neonatal encephalopathy (NE) with other common causes being neonatal stroke and neonatal seizures. There is an urgent need for an early real-time cot side biomarker of perinatal brain injury. Near infrared spectrosc...

Real-time assessment of brain metabolism is possible with broadband NIRS-measured changes in cytochrome-c-oxidase oxidase along with changes in oxy- and de-oxyhaemoglobin. Cerebral metabolic reactivity is related to outcome of injury in neonatal hypoxic-ischaemic encephalopathy.

It has been 20 years since functional near-infrared spectroscopy (fNIRS) was first used to investigate the evoked hemodynamic response to a stimulus in newborns. The hemodynamic response to functional activation is well-established in adults, with an observed increase in concentration change of oxygenated hemoglobin (Δ[HbO2]) and decrease in deoxyg...

Performing absolute measurements of tissue saturation of the brain with near-infrared spectroscopy (NIRS) is a clinically desirable brain monitoring tool. Tissue oxygenation index (TOI) is an indicator of absolute tissue mixed arterial and venous oxygen saturation, and can be calculated using a NIRS technique called spatially resolved spectroscopy...

There is a need for a method of real-time assessment of brain metabolism during neonatal hypoxic-ischaemic encephalopathy (HIE). We have used broadband near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation and metabolic changes in 50 neonates with HIE undergoing therapeutic hypothermia treatment. In 24 neonates, 54 episodes of spontaneo...

A significant proportion of term and preterm infants develop neonatal jaundice. Jaundice in an otherwise healthy term infant is the most common reason for readmission to hospital. Jaundice is caused by an increase in serum bilirubin levels, largely as a result of breakdown of red blood cells. Bilirubin is conveyed in the blood as 'unconjugated' bil...

Hypoxic ischaemic brain injury remains as a significant cause of neonatal mortality and morbidity, even after therapeutic hypothermia (TH). A better understanding of pathophysiological changes in cerebral metabolism and haemodynamics is critical for early assessment. We hypothesised that a novel multivariate network analysis of near infrared spectr...

Broadband near-infrared spectroscopy (NIRS) can provide an endogenous indicator of tissue temperature based on the temperature dependence of the water absorption spectrum. We describe a first evaluation of the calibration and prediction of brain tissue temperature obtained during hypothermia in newborn piglets (animal dataset) and rewarming in newb...

This review discusses an approach to determining the cause of neonatal encephalopathy, as well as current evidence on resuscitation and subsequent management of hypoxic-ischaemic encephalopathy (HIE). Encephalopathy in neonates can be due to varied aetiologies in addition to hypoxic-ischaemia. A combination of careful history, examination and the j...

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 t...

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 t...

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 (1H MRS) is the best available outcome biomarker following HIE. We hypothesized that...

SUMMARY: The development of cognitive function in children has been related to a regional metabolic increase and an increase in regional brain perfusion. Moreover, brain perfusion plays an important role in the pathogenesis of brain damage in high-risk neonates, both preterm and full-term asphyxiated infants. In this article, we will review and dis...

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-...

Broadband NIRS was used to monitor neonates with hypoxic-ischaemic encephalopathy in the first days of life. A high correlation between cerebral metabolism and oxygenation during spontaneous hypoxias was significantly associated with severe 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 th...

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...

We present a novel lens-based broadband near-infrared spectroscopy system to simultaneously measure cerebral changes in tissue oxygenation and haemodynamics via estimation of the changes in haemoglobin concentration; in addition to oxygen utilization via the measurement of the oxidation state of cytochrome-c-oxidase (CCO). We demonstrate the use of...

Aim: Near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) allow non-invasive assessment of cerebral haemodynamics. We assessed cerebrovascular reactivity in preterm infants by investigating the relationship between NIRS- and TCD-derived indices and correlating them with severity of clinical illness. Methods: We recorded the NIRS-deri...

We report a novel broadband near-infrared spectroscopy system to measure cerebral changes in haemodynamics and cytochrome c oxidase in neonates. Neonates with hypoxic-ischaemic encephalopathy were studied in the first days of life.

Background and Aims Continuous physiological parameter monitoring is routine in NICU. However, high false alarm rates exist that can lead to inappropriate responses from clinical staff. At present, parameters are assessed independently to generate alarms. The positive predictive value can be increased in adult patients by combining the physiologica...

Background and Aims Neonatal care has developed dramatically over the last few decades. In spite of this, the neonatal mortality remains high. As clinicians we strive to deliver high quality care and by reviewing the care in all neonatal deaths we hope to identify the avoidable risk factors, areas of good practice and areas for improving care and o...

Background: The characteristics of cerebral autoregulation and the ideal range of systemic blood pressure in preterm infants remain unclear. Transcranial Ccerebral Doppler (TCD)1 and near infra-red spectroscopy (NIRS)2 are established techniques for the assessment of cerebral blood flow velocity (Fv) and cerebral oxygenation respectively.Aim: To st...

We describe a series of novel simultaneous EEG and diffuse optical imaging studies of newborn infants. These experiments provide evidence of large, transient haemodynamic events which occur repeatedly and consistently within and across several infants with neurological damage, all of whom were diagnosed with seizures. A simple but independent proce...

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 af...