Hypoxic Ischemic Encephalopathy of NewbornICONNCT05588960
Investigating Cerebral Oxygenation in the Newborn
An observational study of Hypoxic Ischemic Encephalopathy of Newborn and Neonatal Encephalopathy, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
The goal of this single centre observational study is to use near-infrared spectroscopy (NIRS) monitoring to investigate cerebral oxygenation in two groups of newborn infants who are at high risk of brain injury. The NIRS monitor used in this study will be the Masimo O3 regional oximeter with neonatal sensors. Read more about this study
- Who is it for?
- Ages 1 day to 14 weeks
- Conditions the study is for
- Hypoxic Ischemic Encephalopathy of Newborn, Neonatal Encephalopathy, Premature Infant Disease
- What is being tested?
- Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor)
- Type of treatment
- Medical device
- How many people
- 99 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Jul 2023to May 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 14 weeks
- All sexes
- No healthy volunteers
- Child
Study population: This study will recruit a cohort of term/near-term and preterm infants who admitted to the neonatal intensive care unit at the Simpson Centre for Reproductive Health (Edinburgh, NHS Lothian, UK) and are at risk of brain injury or brain dysmaturation. Potential participants will be identified through admission to the neonatal intensive care unit. Once eligibility is confirmed, a member of the research team will approach parents to discuss the study and invite the baby to enter the study. Participants will be recruited over a 2 year period. Preterm infants may be enrolled in more than one sub-study should their parents provide informed consent for this.
Who may be able to join
- Infants born at greater than or equal to 34 weeks gestational age undergoing therapeutic hypothermia as an intervention for moderate to severe neonatal encephalopathy. These infants will meet the following criteria for treatment:
- Evidence of intrapartum asphyxia as defined by ANY of the following features: Apgar score of 5 or less at 10 minutes after birth; ongoing need for endotracheal or mask ventilation at 10 minutes after birth; pH <7.00 in cord or baby sample within 60 minutes of birth; base deficit greater than or equal to 16mmol/L in cord or baby sample within 60 minutes of birth.
- Moderate or severe encephalopathy, including ALL of the following criteria OR altered consciousness plus seizures: altered consciousness (reduced or absent response to stimulation); abnormal primitive reflexes (weak or absent suck or Moro response); abnormal tone (hypotonia, flaccid).
- Signed parental consent form.
- Infants born at less than 28 weeks completed gestation.
- Signed informed parental consent form for each specific section/sub-study.
- For skin-to-skin sub-study: considered by responsible clinical team to be eligible for skin-to-skin care as per usual local practice.
- For BPD sub-study: infants born at less than 28 weeks gestational age surviving to 36 weeks corrected gestational age. Infants with and without a diagnosis of BPD will be recruited to allow for comparison of cerebral oxygenation between these groups.
Who cannot join
- Lack of signed parental consent form and/or parental decision not to participate.
- Infants with life threatening congenital malformations.
- Infants with encephalopathy caused by differing pathology to hypoxia-ischaemia.
- PRETERM GROUP
- Lack of signed parental consent form and/or parental decision not to participate.
- Decision not to provide active (survival focussed) neonatal management.
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- Infants with life threatening congenital malformation.
- Infants in whom there is a particularly high level of concerns regarding skin fragility or loss of skin integrity resulting in application of NIRS probe being contraindicated.
- Infants who are transferred back to local centres will be excluded from the BPD sub-study if transferred back to local centre prior to 36 weeks corrected gestational age and from follow-up data collection due to difficulties achieving acquisition of full data set for babies followed up in health boards outwith NHS Lothian.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Infirmary of Edinburgh
Edinburgh, Lothian, EH16 4SA
About this study
Official title: Investigating Cerebral Oxygenation in the Newborn: An Observational Study Investigating Cerebral Oxygenation in Newborn Infants at High Risk of Brain Injury
The goal of this single centre observational study is to use near-infrared spectroscopy (NIRS) monitoring to investigate cerebral oxygenation in two groups of newborn infants who are at high risk of brain injury. The NIRS monitor used in this study will be the Masimo O3 regional oximeter with neonatal sensors.
Near-infrared spectroscopy (NIRS) monitoring uses near-infrared light to measure oxygen levels in the brain tissue (cerebral oxygenation). It provides information about blood flow to the brain and the balance between oxygen supply and demand in the brain tissue. It is non-invasive, safe and used routinely to monitor term and premature babies in the neonatal intensive care unit (NICU).
Read more
This study will recruit two groups of infants admitted to the NICU who are at risk of brain injury in the newborn period, namely:
- Term and near-term babies who are undergoing cooling treatment (therapeutic hypothermia) for moderate to severe hypoxic ischaemic encephalopathy (HIE).
- Preterm babies who are born extremely prematurely (before 28 weeks of pregnancy).
In the term/near-term group, the primary aims of the study are:
- To investigate if cerebral oxygenation during and after cooling treatment relates to markers of brain injury detected on detailed brain scans (MRI and MRS scans).
- To describe any changes in cerebral oxygenation which occur during and after seizures (fits) in babies undergoing cooling treatment.
In the preterm group, the primary aims of the study are:
- To investigate if any changes in cerebral oxygenation occurring during skin-to-skin care are different in premature babies with brain injury (bleeding or cysts in the brain seen on ultrasound scan) compared to babies without these changes.
- To investigate if cerebral oxygenation at 36 weeks corrected gestational age differs in babies with bronchopulmonary dysplasia (BDP, a chronic lung disease of prematurity) compared to babies without BPD.
Read the detailed description
TERM/NEAR-TERM GROUP
Hypoxic-ischaemic encephalopathy (HIE) is the most common cause of newborn brain injury in term and near-term infants. It is caused by a lack of oxygen supply or blood flow to the brain around the time of delivery. It is classified as mild, moderate or severe based on the symptoms present. Babies with moderate or severe HIE are treated with 3 days of cooling treatment (therapeutic hypothermia). This treatment protects the brain and reduces the risk of death or disability. However, despite this treatment some babies do not survive or develop life-long disabilities. Therefore, research into potential new treatments for HIE is ongoing.
Currently, the best tests available to detect brain injury and predict later outcome are magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) scans of the brain. However, these are only performed after therapeutic hypothermia is complete, between 5 to 15 days after birth. It would be advantageous if there was a tool that could identify brain injury earlier in the course, as this could facilitate identification of babies who may benefit most from new treatments in the future. Brain injury due to HIE can cause altered blood flow and oxygen levels in the brain, which can be detected by NIRS monitoring. Therefore, it is possible that NIRS monitoring could facilitate earlier detection of brain injury in this group. To understand this further, it is essential to further investigate the relationship between cerebral oxygenation measurements derived by NIRS monitoring and current markers of brain injury. Therefore, the first research question in this group is:
▪ How does cerebral oxygenation during and after therapeutic hypothermia (TH) for moderate to severe HIE relate to markers of brain injury detected on MRI and MRS scans performed between 5 to 15 days after birth?
Seizures are common in babies with HIE. Frequent or prolonged seizures are associated with higher risk of adverse outcomes. It is possible that seizures contribute to on-going injury to the brain due to disrupting the balance of oxygen supply and demand in the brain. This study aims to understand more about this by answering the following research question:
▪ How does cerebral oxygenation change during seizures in infants undergoing therapeutic hypothermia for moderate to severe HIE?
In this group, NIRS monitoring is used routinely in the study centre for all infants undergoing therapeutic hypothermia. Therefore, data from routine NIRS monitoring alongside other data collected as part of routine clinical care (clinical assessments, aEEG and MRI/MRS) will be analysed in a novel way to answer the research questions.
Routinely acquired clinical data will also be analysed to meet the following secondary objectives:
- To assess the predictive value of mean cerebral oxygenation at each pre-defined time point as a marker for brain injury detected on MRI/MRS and to suggest optimal cut-offs for predicting brain injury at each time point if applicable.
- To compare any changes in cerebral oxygenation occurring in association with seizures occurring in infants with brain injury detected on MRI/MRS scans to those without brain injury on MRI/MRS scans.
- To compare mean cerebral oxygenation at pre-specified time points during and after therapeutic hypothermia to outcomes of neurodevelopmental assessments in infancy and at the age of 2 years.
PRETERM GROUP
Although survival of infants born extremely prematurely (before 28 weeks of pregnancy) has improved over recent decades, these babies remain at high risk of neurodevelopmental disabilities due to brain injury or dysmaturation. The immature brain is vulnerable to fluctuations in cerebral blood flow and oxygenation, which may be detected by NIRS monitoring. In this group of infants, recognisable patterns of brain injury include intraventricular haemorrhage (bleeding into the fluid filled spaces in the brain) and periventricular leukomalacia (cysts in the brain tissue). These conditions can be detected by ultrasound scans of the brain which are performed routinely for all premature babies.
Skin-to-skin care, when an infant is nursed in direct skin-to-skin contact with a parent or carer, is commonly undertaken in the neonatal intensive care unit. There are many documented benefits for babies and their parents. Previous studies have investigated cerebral oxygenation during skin-to-skin care, however, these studies have not included infants with severe brain injury. This study seeks to understand whether more severe patterns of brain injury detected on cranial ultrasound affects cerebral oxygenation during skin-to-skin care by answering the following research question:
▪ Do changes in cerebral oxygenation during periods of skin-to-skin care versus flanking periods of incubator care differ in preterm infants with severe brain injury compared to infants without severe brain injury?
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that occurs in premature babies. It is diagnosed if a baby still requires extra oxygen or other breathing support at 36 weeks corrected gestational age (4 weeks before their due date). It is associated with brain dysmaturation and a higher chance of neurodevelopmental disabilities. It is possible that lower cerebral oxygenation levels contribute to brain dysmaturation in this group. Therefore, this study aims to answer the following research question:
▪ Does cerebral oxygenation and cerebral hypoxic burden (a measure of low oxygen levels in the brain accounting for severity and duration) differ in extremely preterm infants with bronchopulmonary dysplasia (BPD) compared to infants without BPD at 36 weeks corrected gestational age?
In the study centre, NIRS monitoring is routine for all infants born at less than 28 weeks for the first 72 hours after birth. Therefore, to answer the above research questions, NIRS monitoring will also be applied for additional periods out with routine clinical care for infants recruited to the study. No other changes to routine clinical care will be made for infants recruited to the study.
Data from routine NIRS monitoring for the first 72 hours after birth and from routine scans and neurodevelopmental follow up assessments will also be collected to fulfil the following secondary objectives:
▪ To compare cerebral oxygenation and cerebral hypoxic burden over the first 72 hours after birth to: worst grade of injury detected on routine screening cranial ultrasound scans and outcomes of neurodevelopmental assessments in infancy and at the age of 2 years.
- Conditions
- Hypoxic Ischemic Encephalopathy of Newborn, Neonatal Encephalopathy, Premature Infant Disease
- Being tested
- Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor)
- Keywords
- Spectroscopy, near infrared, Cerebral oxygenation, Cerebral haemodynamics, Newborn brain injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor)Device
Masimo O3 neonatal sensor will be applied:
- At least 30 minutes before a period of skin-to-skin care with a caregiver commences (baseline condition).
- Throughout the period of skin-to-skin care, which should continue for a minimum of 1 hour.
- For at least 1 hour after the participant is returned to their incubator (post-intervention condition).
The protocol accounts for a 30 minute washout period between each study epoch. Therefore, at least 30 minutes of study data will be collected for each epoch.
Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor)Device
Masimo O3 neonatal sensor will be applied:
▪ For 24 hours once the participant reaches 36 weeks corrected gestational age.
| Study group | Role | What they receive |
|---|---|---|
| Term/Near-Term Group | Cohort of term/near-term infants undergoing therapeutic hypothermia for moderate to severe HIE. Data collected from NIRS monitoring and other assessments/investigations that are part of routine clinical care. There are no additional study specific interventions or exposures for this group. | |
| Preterm Group (Sub-study 1, First 72 hours after birth) | Cohort of infants born at less than 28 weeks gestational age. Data collected from NIRS monitoring, other physiological monitoring, cranial ultrasound scans and neurodevelopmental follow up assessments that are part of routine clinical care. This data will be analysed to fulfil secondary study objectives. There are no additional study specific interventions or exposures for this group. | |
| Preterm Group (Sub-study 2, Skin-to-skin care) | Cohort of infants born at less than 28 weeks gestational age who are considered by clinical team to be suitable to undergo period of skin-to-skin care. Participants will undergo additional research-specific period(s) of NIRS monitoring before, during and after period(s) of skin-to-skin care. Participants with and without severe brain injury on cranial ultrasound will be recruited to allow comparison. Receives: Device: Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor) | |
| Preterm Group (Sub-study 3, Bronchopulmonary dysplasia) | Cohort of infants born at less than 28 weeks gestational age who will undergo an additional research-specific period of NIRS monitoring at 36 weeks corrected gestational age. Participants with and without bronchopulmonary dysplasia (BPD) will be recruited to allow comparison. Receives: Device: Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Term/Near-Term Group: Primary Outcome 1
Mean cerebral oxygenation calculated over 1 hour periods at pre-defined time points during therapeutic hypothermia and after completion of rewarming compared to presence/absence of brain injury on magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) performed between 5-15 days after birth.
Brain injury will be defined as:
- NICHD NRN MRI score of ≥2A
- Lactate to n-acetylaspartate peak ratio of >0.39 on MRS
Measured: Birth-15 days
Term/Near-Term Group: Primary Outcome 2
Maximum change in cerebral oxygenation from baseline occurring during electrical seizures detected on aEEG and cerebral hypoxic burden (expressed in % hours) for any periods of cerebral hypoxia associated with seizures.
Measured: Birth-5 days
Preterm Group - Skin-to-skin sub-study: Primary Outcomes
Change in mean cerebral oxygenation (calculated every 5 minutes) and in variability of cerebral oxygenation during a period of skin-to-skin care compared to periods of incubator care before (pre-intervention) and after (post-intervention) skin-to-skin care.
These measures will be compared in infants with and without severe brain injury detected on routine cranial ultrasound scans. Severe brain injury will be defined as:
- Grade III or IV intraventricular haemorrhage
- Cystic periventricular leucomalacia
Measured: 2.5 hours
Preterm Group - BPD sub-study: Primary Outcomes
Mean cerebral oxygenation measured over a 24-hour period at 36 weeks corrected gestational age and cerebral hypoxic burden (expressed in % hours) of any periods of cerebral hypoxia over this 24-hour epoch.
These measures will be compared in infants with and without a diagnosis of bronchopulmonary dysplasia. Bronchopulmonary dysplasia will be defined as the need for any additional respiratory support (including supplementary oxygen) at 36 weeks corrected gestational age.
Measured: 24 hours
Secondary outcomes (5)
Term/Near-Term Group: Secondary Outcome 1
Outcome of General Movements Assessment at term and between 12 to 15 weeks post-term age. High-risk patterns will be defined as cramped synchronised pattern (term equivalent age) and absent fidgety movements (12-15 weeks post-term).
Measured: Birth-12 to 15 weeks
Term/Near-Term Group: Secondary Outcome 2
Outcome at 2 years of age. Adverse outcome will be defined as death or moderate-severe neurodevelopmental disability as follows:
- Moderate: Cerebral palsy with GMFCS level 2; Bayley III composite motor/congitive/language score of <85; hearing impairment without need for amplification; persistent seizure disorder.
- Severe: Cerebral palsy with GMFCS level ≥3; Bayley III composite motor/cognitive/language score of <70; hearing impairment requiring hearing aids; blindness.
Measured: 2 years
Preterm Group: Secondary Outcome 1
Comparison of mean cerebral oxygenation and cerebral hypoxic burden (expressed in % hours) for the first 72 hours after birth to findings of routine cranial ultrasound scans at:
- 1 day after birth
- 2 days after birth
- 3 days after birth
- 7 days after birth
- Term equivalent age
Measured: Birth-max 14 weeks
Preterm Group: Secondary Outcome 2
Comparison of mean cerebral oxygenation and cerebral hypoxic burden (expressed in % hours) for the first 72 hours after birth to outcomes of General Movements Assessment at term equivalent age and between 12 to 15 weeks post-term age. High-risk patterns will be defined as cramped synchronised pattern (term equivalent age) and absent fidgety movements (12-15 weeks post-term).
Measured: Birth-12 to 15 weeks
Preterm Group: Secondary Outcome 3
Comparison of mean cerebral oxygenation and cerebral hypoxic burden (expressed in % hours) for the first 72 hours after birth to outcome at 2 years corrected gestational age. Adverse outcome will be defined as death or moderate-severe neurodevelopmental disability as follows:
- Moderate: Cerebral palsy with GMFCS level 2; Bayley III composite motor/congitive/language score of <85; hearing impairment without need for amplification; persistent seizure disorder.
- Severe: Cerebral palsy with GMFCS level ≥3; Bayley III composite motor/cognitive/language score of <70; hearing impairment requiring hearing aids; blindness.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2022
- Study start21 Jul 2023
- Primary completionJan 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypoxic Ischemic Encephalopathy of NewbornStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 99 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian, Prism Training and Consultancy, Simpsons Special Care Babies
- Responsible party
- Sponsor
- Investigators
- Helen L Turner, MBChB (Hons), Principal investigator, University of Edinburgh/NHS Lothian
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05588960
- Sponsor's protocol ID
- AC22120
- Acronym
- ICON
- Status last verified
- Mar 2026
- First submitted
- 17 Oct 2022
- Last updated
- 17 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Following completion of the study and after primary publications by the study team, all collected anonymous IPD will be shared in line with the FAIR principles (findable, accessible, interoperable and resuable). Parents will have the option to opt out of their child's anonymous data being shared for the purposes of further research at the time of consent. Data will be made available through DataShare, a data respository run by The University of Edinburgh. This will be maintained indefinitely by the University of Edinburgh Data Library staff. Associated metadata will be created in Pure (the University's Current Research Information System) which will be linked to the dataset in DataShare.
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Cerebral Oxygenation in the Newborn: An Observational Study Investigating Cerebral Oxygenation in Newborn Infants at High Risk of Brain Injury
- ClinicalTrials.gov ID
- NCT05588960
- Acronym / sponsor ID
- ICON / AC22120
- Conditions
- Hypoxic Ischemic Encephalopathy of Newborn, Neonatal Encephalopathy, Premature Infant Disease
- Keywords
- Spectroscopy, near infrared, Cerebral oxygenation, Cerebral haemodynamics, Newborn brain injury
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 99 participants (estimated)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian, Prism Training and Consultancy, Simpsons Special Care Babies
- Study start
- 21 Jul 2023 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 20 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this single centre observational study is to use near-infrared spectroscopy (NIRS) monitoring to investigate cerebral oxygenation in two groups of newborn infants who are at high risk of brain injury. The NIRS monitor used in this study will be the Masimo O3 regional oximeter with neonatal sensors.
Near-infrared spectroscopy (NIRS) monitoring uses near-infrared light to measure oxygen levels in the brain tissue (cerebral oxygenation). It provides information about blood flow to the brain and the balance between oxygen supply and demand in the brain tissue. It is non-invasive, safe and used routinely to monitor term and premature babies in the neonatal intensive care unit (NICU).
This study will recruit two groups of infants admitted to the NICU who are at risk of brain injury in the newborn period, namely:
- Term and near-term babies who are undergoing cooling treatment (therapeutic hypothermia) for moderate to severe hypoxic ischaemic encephalopathy (HIE).
- Preterm babies who are born extremely prematurely (before 28 weeks of pregnancy).
In the term/near-term group, the primary aims of the study are:
- To investigate if cerebral oxygenation during and after cooling treatment relates to markers of brain injury detected on detailed brain scans (MRI and MRS scans).
- To describe any changes in cerebral oxygenation which occur during and after seizures (fits) in babies undergoing cooling treatment.
In the preterm group, the primary aims of the study are:
- To investigate if any changes in cerebral oxygenation occurring during skin-to-skin care are different in premature babies with brain injury (bleeding or cysts in the brain seen on ultrasound scan) compared to babies without these changes.
- To investigate if cerebral oxygenation at 36 weeks corrected gestational age differs in babies with bronchopulmonary dysplasia (BDP, a chronic lung disease of prematurity) compared to babies without BPD.
Detailed description
TERM/NEAR-TERM GROUP
Hypoxic-ischaemic encephalopathy (HIE) is the most common cause of newborn brain injury in term and near-term infants. It is caused by a lack of oxygen supply or blood flow to the brain around the time of delivery. It is classified as mild, moderate or severe based on the symptoms present. Babies with moderate or severe HIE are treated with 3 days of cooling treatment (therapeutic hypothermia). This treatment protects the brain and reduces the risk of death or disability. However, despite this treatment some babies do not survive or develop life-long disabilities. Therefore, research into potential new treatments for HIE is ongoing.
Currently, the best tests available to detect brain injury and predict later outcome are magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) scans of the brain. However, these are only performed after therapeutic hypothermia is complete, between 5 to 15 days after birth. It would be advantageous if there was a tool that could identify brain injury earlier in the course, as this could facilitate identification of babies who may benefit most from new treatments in the future. Brain injury due to HIE can cause altered blood flow and oxygen levels in the brain, which can be detected by NIRS monitoring. Therefore, it is possible that NIRS monitoring could facilitate earlier detection of brain injury in this group. To understand this further, it is essential to further investigate the relationship between cerebral oxygenation measurements derived by NIRS monitoring and current markers of brain injury. Therefore, the first research question in this group is:
▪ How does cerebral oxygenation during and after therapeutic hypothermia (TH) for moderate to severe HIE relate to markers of brain injury detected on MRI and MRS scans performed between 5 to 15 days after birth?
Seizures are common in babies with HIE. Frequent or prolonged seizures are associated with higher risk of adverse outcomes. It is possible that seizures contribute to on-going injury to the brain due to disrupting the balance of oxygen supply and demand in the brain. This study aims to understand more about this by answering the following research question:
▪ How does cerebral oxygenation change during seizures in infants undergoing therapeutic hypothermia for moderate to severe HIE?
In this group, NIRS monitoring is used routinely in the study centre for all infants undergoing therapeutic hypothermia. Therefore, data from routine NIRS monitoring alongside other data collected as part of routine clinical care (clinical assessments, aEEG and MRI/MRS) will be analysed in a novel way to answer the research questions.
Routinely acquired clinical data will also be analysed to meet the following secondary objectives:
- To assess the predictive value of mean cerebral oxygenation at each pre-defined time point as a marker for brain injury detected on MRI/MRS and to suggest optimal cut-offs for predicting brain injury at each time point if applicable.
- To compare any changes in cerebral oxygenation occurring in association with seizures occurring in infants with brain injury detected on MRI/MRS scans to those without brain injury on MRI/MRS scans.
- To compare mean cerebral oxygenation at pre-specified time points during and after therapeutic hypothermia to outcomes of neurodevelopmental assessments in infancy and at the age of 2 years.
PRETERM GROUP
Although survival of infants born extremely prematurely (before 28 weeks of pregnancy) has improved over recent decades, these babies remain at high risk of neurodevelopmental disabilities due to brain injury or dysmaturation. The immature brain is vulnerable to fluctuations in cerebral blood flow and oxygenation, which may be detected by NIRS monitoring. In this group of infants, recognisable patterns of brain injury include intraventricular haemorrhage (bleeding into the fluid filled spaces in the brain) and periventricular leukomalacia (cysts in the brain tissue). These conditions can be detected by ultrasound scans of the brain which are performed routinely for all premature babies.
Skin-to-skin care, when an infant is nursed in direct skin-to-skin contact with a parent or carer, is commonly undertaken in the neonatal intensive care unit. There are many documented benefits for babies and their parents. Previous studies have investigated cerebral oxygenation during skin-to-skin care, however, these studies have not included infants with severe brain injury. This study seeks to understand whether more severe patterns of brain injury detected on cranial ultrasound affects cerebral oxygenation during skin-to-skin care by answering the following research question:
▪ Do changes in cerebral oxygenation during periods of skin-to-skin care versus flanking periods of incubator care differ in preterm infants with severe brain injury compared to infants without severe brain injury?
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that occurs in premature babies. It is diagnosed if a baby still requires extra oxygen or other breathing support at 36 weeks corrected gestational age (4 weeks before their due date). It is associated with brain dysmaturation and a higher chance of neurodevelopmental disabilities. It is possible that lower cerebral oxygenation levels contribute to brain dysmaturation in this group. Therefore, this study aims to answer the following research question:
▪ Does cerebral oxygenation and cerebral hypoxic burden (a measure of low oxygen levels in the brain accounting for severity and duration) differ in extremely preterm infants with bronchopulmonary dysplasia (BPD) compared to infants without BPD at 36 weeks corrected gestational age?
In the study centre, NIRS monitoring is routine for all infants born at less than 28 weeks for the first 72 hours after birth. Therefore, to answer the above research questions, NIRS monitoring will also be applied for additional periods out with routine clinical care for infants recruited to the study. No other changes to routine clinical care will be made for infants recruited to the study.
Data from routine NIRS monitoring for the first 72 hours after birth and from routine scans and neurodevelopmental follow up assessments will also be collected to fulfil the following secondary objectives:
▪ To compare cerebral oxygenation and cerebral hypoxic burden over the first 72 hours after birth to: worst grade of injury detected on routine screening cranial ultrasound scans and outcomes of neurodevelopmental assessments in infancy and at the age of 2 years.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Term/Near-Term Group | – | –Cohort of term/near-term infants undergoing therapeutic hypothermia for moderate to severe HIE. Data collected from NIRS monitoring and other assessments/investigations that are part of routine clinical care. There are no additional study specific interventions or exposures for this group. |
| Preterm Group (Sub-study 1, First 72 hours after birth) | – | –Cohort of infants born at less than 28 weeks gestational age. Data collected from NIRS monitoring, other physiological monitoring, cranial ultrasound scans and neurodevelopmental follow up assessments that are part of routine clinical care. This data will be analysed to fulfil secondary study objectives. There are no additional study specific interventions or exposures for this group. |
| Preterm Group (Sub-study 2, Skin-to-skin care) | – | Device: Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor)Cohort of infants born at less than 28 weeks gestational age who are considered by clinical team to be suitable to undergo period of skin-to-skin care. Participants will undergo additional research-specific period(s) of NIRS monitoring before, during and after period(s) of skin-to-skin care. Participants with and without severe brain injury on cranial ultrasound will be recruited to allow comparison. |
| Preterm Group (Sub-study 3, Bronchopulmonary dysplasia) | – | Device: Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor)Cohort of infants born at less than 28 weeks gestational age who will undergo an additional research-specific period of NIRS monitoring at 36 weeks corrected gestational age. Participants with and without bronchopulmonary dysplasia (BPD) will be recruited to allow comparison. |
Who may qualify
- Ages
- 1 day to 14 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- This study will recruit a cohort of term/near-term and preterm infants who admitted to the neonatal intensive care unit at the Simpson Centre for Reproductive Health (Edinburgh, NHS Lothian, UK) and are at risk of brain injury or brain dysmaturation. Potential participants will be identified through admission to the neonatal intensive care unit. Once eligibility is confirmed, a member of the research team will approach parents to discuss the study and invite the baby to enter the study. Participants will be recruited over a 2 year period. Preterm infants may be enrolled in more than one sub-study should their parents provide informed consent for this.
Key inclusion criteria (8 listed)
- Infants born at greater than or equal to 34 weeks gestational age undergoing therapeutic hypothermia as an intervention for moderate to severe neonatal encephalopathy. These infants will meet the following criteria for treatment:
- Signed parental consent form.
- Infants born at less than 28 weeks completed gestation.
- Signed informed parental consent form for each specific section/sub-study.
- For skin-to-skin sub-study: considered by responsible clinical team to be eligible for skin-to-skin care as per usual local practice.
Key exclusion criteria (9 listed)
- Lack of signed parental consent form and/or parental decision not to participate.
- Infants with life threatening congenital malformations.
- Infants with encephalopathy caused by differing pathology to hypoxia-ischaemia.
- PRETERM GROUP
- Lack of signed parental consent form and/or parental decision not to participate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor)Masimo O3 neonatal sensor will be applied: * At least 30 minutes before a period of skin-to-skin care with a caregiver commences (baseline condition). * Throughout the period of skin-to-skin care, which should continue for a minimum of 1 hour. * For at least 1 hour after the participant is returned to their incubator (post-intervention condition). The protocol accounts for a 30 minute washout period between each study epoch. Therefore, at least 30 minutes of study data will be collected for each epoch. | Device | Preterm Group (Sub-study 2, Skin-to-skin care) |
| Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor)Masimo O3 neonatal sensor will be applied: ▪ For 24 hours once the participant reaches 36 weeks corrected gestational age. | Device | Preterm Group (Sub-study 3, Bronchopulmonary dysplasia) |
Primary outcome
Term/Near-Term Group: Primary Outcome 1
Time frame: Birth-15 days
Mean cerebral oxygenation calculated over 1 hour periods at pre-defined time points during therapeutic hypothermia and after completion of rewarming compared to presence/absence of brain injury on magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) performed between 5-15 days after birth. Brain injury will be defined as: * NICHD NRN MRI score of ≥2A * Lactate to n-acetylaspartate peak ratio of >0.39 on MRS
Term/Near-Term Group: Primary Outcome 2
Time frame: Birth-5 days
Maximum change in cerebral oxygenation from baseline occurring during electrical seizures detected on aEEG and cerebral hypoxic burden (expressed in % hours) for any periods of cerebral hypoxia associated with seizures.
Preterm Group - Skin-to-skin sub-study: Primary Outcomes
Time frame: 2.5 hours
Change in mean cerebral oxygenation (calculated every 5 minutes) and in variability of cerebral oxygenation during a period of skin-to-skin care compared to periods of incubator care before (pre-intervention) and after (post-intervention) skin-to-skin care. These measures will be compared in infants with and without severe brain injury detected on routine cranial ultrasound scans. Severe brain injury will be defined as: * Grade III or IV intraventricular haemorrhage * Cystic periventricular leucomalacia
Preterm Group - BPD sub-study: Primary Outcomes
Time frame: 24 hours
Mean cerebral oxygenation measured over a 24-hour period at 36 weeks corrected gestational age and cerebral hypoxic burden (expressed in % hours) of any periods of cerebral hypoxia over this 24-hour epoch. These measures will be compared in infants with and without a diagnosis of bronchopulmonary dysplasia. Bronchopulmonary dysplasia will be defined as the need for any additional respiratory support (including supplementary oxygen) at 36 weeks corrected gestational age.
5 secondary outcomes
Term/Near-Term Group: Secondary Outcome 1
Time frame: Birth-12 to 15 weeks
Term/Near-Term Group: Secondary Outcome 2
Time frame: 2 years
Preterm Group: Secondary Outcome 1
Time frame: Birth-max 14 weeks
Preterm Group: Secondary Outcome 2
Time frame: Birth-12 to 15 weeks
Preterm Group: Secondary Outcome 3
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
- Individual participant dataSharing planned: Yes. Following completion of the study and after primary publications by the study team, all collected anonymous IPD will be shared in line with the FAIR principles (findable, accessible, interoperable and resuable). Parents will have the option to opt out of their child's anonymous data being shared for the purposes of further research at the time of consent. Data will be made available through DataShare, a data respository run by The University of Edinburgh. This will be maintained indefinitely by the University of Edinburgh Data Library staff. Associated metadata will be created in Pure (the University's Current Research Information System) which will be linked to the dataset in DataShare.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen L Turner, MBChB (Hons) principal investigator
University of Edinburgh/NHS Lothian
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypoxic Ischemic Encephalopathy of Newborn and Neonatal Encephalopathy, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Term/Near-Term Group: Primary Outcome 1 (time frame: Birth-15 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2026.