Investigating Cerebral Oxygenation in the Newborn: An Observational Study Investigating Cerebral Oxygenation in Newborn Infants at High Risk of Brain Injury
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- University of Edinburgh
- Enrollment
- 99
- Locations
- 1
- Primary Endpoint
- Term/Near-Term Group: Primary Outcome 1
Study Overview
Brief 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.
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:
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 1 Day to 14 Weeks (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •TERM/NEAR-TERM GROUP
- •INCLUSION CRITERIA:
- •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.
Exclusion Criteria
- •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
- •INCLUSION CRITERIA:
- •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.
- •EXCLUSION CRITERIA:
- •Lack of signed parental consent form and/or parental decision not to participate.
- •Decision not to provide active (survival focussed) neonatal management.
- •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.
Arms & Interventions
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.
Intervention: Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor) (Device)
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.
Intervention: Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor) (Device)
Outcomes
Primary Outcomes
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 - 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.
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
Secondary Outcomes
- Term/Near-Term Group: Secondary Outcome 1(Birth-12 to 15 weeks)
- Term/Near-Term Group: Secondary Outcome 2(2 years)
- Preterm Group: Secondary Outcome 2(Birth-12 to 15 weeks)
- Preterm Group: Secondary Outcome 1(Birth-max 14 weeks)
- Preterm Group: Secondary Outcome 3(2 years)