Investigating Cerebral Oxygenation in the Newborn — ICON  

Neonatal Encephalopathy Clinical Trial

Official title: Investigating Cerebral Oxygenation in the Newborn: An Observational Study Investigating Cerebral Oxygenation in Newborn Infants at High Risk of Brain Injury

Status Recruiting

Clinical 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.

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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypoxia-Ischemia, Brain
• Infant, Premature, Diseases
• Neonatal Encephalopathy
• Premature Infant Disease

• NCT number: NCT05588960
• Study type: Observational
• Source: University of Edinburgh
• Contact: Helen L Turner, MBChB (Hons)
• Phone: +44131 242 2601
• Email: helen.turner@ed.ac.uk
• Status: Recruiting
• Start date: July 21, 2023
• Completion date: January 2027