Investigating Cerebral Oxygenation in the Newborn

NCT05588960 | Active Not Recruiting

• 1 other identifier: AC22120
• Study Type: observational
• Target: 99
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoxic Ischemic Encephalopathy of Newborn; Neonatal Encephalopathy; Premature Infant Disease

Keywords

Spectroscopy, near infrared; Cerebral oxygenation; Cerebral haemodynamics; Newborn brain injury

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  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

  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.

  24 hours

Secondary Outcomes (5)

• 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 1

  Birth-max 14 weeks

• Preterm Group: Secondary Outcome 2

  Birth-12 to 15 weeks

• Preterm Group: Secondary Outcome 3

  2 years

Study Arms (4)

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.

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.

Device: Near-infrared spectroscopy monitoring (Masimo O3 Regional Oximeter with Neonatal Sensor)

Interventions

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.

Preterm Group (Sub-study 2, Skin-to-skin care)

Eligibility Criteria

• Age: 1 Day - 14 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.
• 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.

Sponsors & Collaborators

• Prism Training and Consultancy: collaborator
• Simpsons Special Care Babies: collaborator
• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, Lothian, EH16 4SA, United Kingdom

Location

Study Officials

• Helen L Turner, MBChB (Hons)

  University of Edinburgh/NHS Lothian

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: October 20, 2022
• Study Start: July 21, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be shared after primary publications by the study team, which are likely to take 6-12 months after the end of the project.
• Access Criteria: When data is deposited in DataShare, a DOI will be acquired. This DOI will be used in all communications regarding the data, for example, publications and presentations. A data access statement will be included in all publications. Data on DataShare will be licensed under a CC BY license. A metadata will be created in Pure (the University's Current Research Information System) which will be linked to the dataset in DataShare. Pure metadata records are published to Edinburgh Research Explorer, which provides a searchable public view of the University's research activities.

Locations

GB (1)