Hypoxic-Ischemic EncephalopathySOPHIENCT07770035
School-aged Outcomes Post Hypoxic Ischaemic Encephalopathy
An observational study of Hypoxic-Ischemic Encephalopathy, run by University College Cork at 1 site in Ireland.
Trial summary
Neonatal HIE increases the risk for cognitive impairments in childhood. Neonatal MRI brain scans are a strong predictor for outcome, however a normal scan has only a 35% sensitivity and 85% specificity for a normal outcome. Read more about this study
- Who is it for?
- Ages 5 to 12 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy
- How many people
- 196 participants
- Where
- 1 siteIreland
- Study dates
- 9 Mar 2024to 31 Dec 2028
- 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 5 to 12 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Cases: Potential participants will be identified from seven previous studies conducted in Cork University Maternity Hospital (CUMH), between January 2013-December 2019. Over this period, term infants ≥36 weeks considered at significant risk of HIE were recruited prospectively to these studies as soon as possible after delivery. Clinical data, blood biomarkers, MRI and EEG recordings were collected and stored in the INFANT databank using unique study numbers. Controls: Children aged between 4-12 years of age, who are attending general paediatric outpatients' clinics at Cork University Hospital (CUH) will be selected as potential participants for the control group. Controls will be healthy children born at ≥ 36 weeks gestation now attending mainstream school who did not have a diagnosis of HIE at birth. To be eligible, they must not have been admitted to the neonatal unit in the first 12 hours after birth and have had a 5-minute Apgar score of ≥7.
Who may be able to join
- Known diagnosis of HIE of any grade and enrolled in one of seven studies carried out in CUMH and born between 01 JAN 2013 and 31 DEC 2020
- Documented parental informed consent for their study data to be used in the future for related research and for them to be contacted again.
- Born at ≥ 36 weeks gestation
- Attending mainstream primary school without a specific developmental diagnosis
Who cannot join
- Lack of parental consent for the original study and no permission to be contacted for future research.
- Death prior to study initiation
- Congenital malformation or genetic syndrome
- Controls:
- Diagnosis of perinatal asphyxia or HIE at birth
- Admission to the neonatal unit within 12 hours of birth
- Attending a paediatric clinic for a developmental concern
- Congenital malformation or genetic syndrome
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Neonatal HIE increases the risk for cognitive impairments in childhood. Neonatal MRI brain scans are a strong predictor for outcome, however a normal scan has only a 35% sensitivity and 85% specificity for a normal outcome. This may be explained by variability in the brain's development over time in response to the initial insult.
This project will aim to develop a neonatal MRI machine learning algorithm that incorporates both initial injury and radiomic features associated with future brain development (based on school-age MRI) to predict school-age outcome. This will be achieved by conducting a case-control cohort study looking at School-age MRI and outcomes of children with a history of neonatal HIE.
Read the detailed description
The study will recruit children with a history of HIE in the newborn period (cases) and healthy children with an unremarkable newborn period (controls) born between January 2013-December 2020. During this period several prospective cohort studies of term infants ≥36 weeks at risk of HIE were conducted in Cork University Maternity Hospital (CUMH) neonatal intensive care unit (NICU).
Infants enrolled in these previous studies had neonatal data collected, in addition to detailed neurological assessments, neurophysiological monitoring, neonatal MRIs, and standardised neuro-developmental follow-up at two years of age using the Bayley Scale of Infant Development (BSID). These children were not followed after the BSID was performed. Approval for these studies was given by the Clinical Research Ethics Committee of the Cork Teaching Hospitals (CREC), and informed consent obtained. Cases for the proposed study will be identified from those who agreed on the original consent form to be contacted for future related research.
For control recruitment, the study will be advertised on social media, the INFANT website and in the Paediatric outpatient area in the adjacent Paediatric department. Healthy children aged between 5 and 12 years of age will be invited to contact the research team to be part of the control group. To be eligible, they must have been born at ≥ 36 weeks gestation, now attending mainstream school, did not have a diagnosis of HIE or have been admitted to the neonatal unit in the first 12 hours of birth. A new ethics submission for the current study was approved by the local CREC.
Sample Size: Taking the mean population IQ as 100 with a standard deviation of 15, we calculated that 98 cases will be needed to detect a 6-point difference in composite IQ with an alpha of 0.05 and a power of 80%. The same number of controls will be recruited, giving a total number of 196 participants. This sample is powered to show a meaningful difference in IQ between populations from which the predictive models are built. Regarding the radiomic analysis proposed there is very limited data in neonatal populations, but the sample size proposed would represent the largest neonatal radiomic study to-date, and would also be comparable to recent adult studies with similar proposed methodology.
Study Procedures:
If the parents/guardians agree to participate, written informed consent and age-appropriate assent will be obtained.
There will be two study visits. The first will involve performing the cognitive assessment, administration of questionnaires, and a short play therapy session to introduce the child to the MRI using a mock MRI scanner and video of the MRI department and scanner. The assessment will take a standardised format, taking approximately 1.5 hours in total and breaks will be provided as necessary.
The MRI will be performed at the second visit. The scanning protocol will be approximately 19 minutes in duration, with four key MRI sequences being performed. No sedation or anesthesia will be provided for the MRI. Qualitative and quantitative analysis of the MRI will be performed.
The goal of this project is to develop a predictive neonatal MRI biomarker algorithm that combines radiomic features associated with evolution of brain injury on School-age MRI scans, and qualitative neonatal MRI assessment, to predict School-age cognitive outcome following Neonatal HIE.
The specific objectives are
- To develop a Neonatal MRI machine learning model of radiomic features predictive of significant future evolutional changes evident on school-age MRI following HIE
- Perform School-age MRI in both a large cohort of infants with HIE (with available neonatal MRI) and an age-matched control population (did not have neonatal MRI).
- School-age MRI to be assessed for qualitative injury, and perform regional volumetric analysis.
- Psychological assessment of cognitive function, executive function, and full-scale IQ in all grades of HIE (mild, moderate, and severe) and compare to an age-matched control population.
- Correlation of School-age MRIs (Case and Control) with School age psychological outcome to identify key features associated with outcome.
- In HIE cohort, following identification of key features predictive of cognitive outcome on School-age MRI (regions of interest[ROI]), to project these ROIs onto the Neonatal MRI to identify radiomic features predictive of evolution of brain imaging findings.
- Develop machine learning algorithm of radiomic features on neonatal MRI predictive of significant school-age MRI changes
- To develop MRI Only predictive model for School-age Outcome: To develop predictive algorithm combining Neonatal MRI radiomic model developed (objective 1) and qualitative neonatal MRI findings, to predict School-age Psychological outcome.
- To develop MRI and Clinical model for School-age Outcome: To develop a predictive machine learning algorithm combining Clinical and sociodemographic factors, with our Neonatal MRI radiomic model, and qualitative neonatal MRI findings to predict School-age Psychological outcome.
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Keywords
- HIE, neonatal encephalopathy, neurodevelopment, cognitive outcome, MRI
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Hypoxic Ischaemic Encephalopathy (Case) | Children aged 5-12 years old with HIE meeting study inclusion criteria | |
| Age-Matched Control | Healthy controls aged 5-12 years old, now attending mainstream school, who did not have HIE or were not admitted to the neonatal unit within 12 hours of birth. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intelligence Quotient
Kaufman Brief Intelligence Test Second Edition (KBIT-2) is a brief measure of verbal and nonverbal intelligence used with individuals aged from 4 to 90 years.
Measured: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Assessment of Exectuive Function
Cambridge Neuropsychological Test Automated Battery (CANTAB) will be used to assess the following domains:
Visual Memory- Delayed Match to Sample (DMS) Working memory- Spatial Working Memory Task (SWM), Spatial Span Task (SSP), Digit Span Task (DGS) Attention/processing speed- Reaction Time Task (RTI), Rapid Visual Processing Task (RVP), Motor Screening Task (MOT) Inhibitory control- Stop Signal Task (SST)
Measured: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Volumetric analysis of MRI brain
Total and regional brain volumetric analysis
Measured: Visit 2 - 20 minute MRI scan, approximately 2-4 months after Visit 1
Connectivity analysis of MRI brain
Analysis of brain connectivity using diffusion tensor data and fransctional anisotopy imaging.
Measured: Visit 2 - 20 minute MRI scan, approximately 2-4 months after Visit 1
MRI Machine Learning Model
Using MRIs completed at school-age and neonatal data, extract radiomic features and ragions of interest (ROIs) to develop machine learning models to predict school-aged cognitive outcome.
Measured: Visit 2 - 20 minute MRI scan, approximately 2-4 months after Visit 1
Secondary outcomes (4)
Behavioural Profile
Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire about 2-17 year olds, examining attributes across 4 scales: emotional symptoms (0-10), condict problems (0-10), hyperactivity/inattention (0-10) and peer relationship problems (0-10). These 4 scales contribute to the total difficulties score (0-40), with a higher socre indicting a higher level of difficulty. There is also a prosocial behaviour scale, which runs from 10-0; a higher socre on this scale indicates a more typical social profile, and is not included in the total difficulties score.
Measured: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Incidence of additional school supports
Parents will complete a sociodemographic questionnaire which asks about school support, need for special needs assistant, and additonal diagnosis, e.g., attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), dyslexia, dyspraxia
Measured: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Socioeconomic Background
Parental education and occupation
Measured: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Cognitively Stimulating Home Environment
Adapted survey from Chew et al, 2024, examining measure of the home environment which can influence cognitive abilities
Measured: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2026
- Study start9 Mar 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypoxic-Ischemic EncephalopathyStudies of the same condition, open and under way.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 196 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College Cork
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Walsh, University College Cork
- Investigators
- Brian H Walsh, PhD, Principal investigator, University College Cork
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07770035
- Sponsor's protocol ID
- Inf_Sophie_23110
- Other IDs
- 24/FFP-P/12824(N) CHF
- Acronym
- SOPHIE
- Status last verified
- Aug 2026
- First submitted
- 9 Jul 2026
- Last updated
- 18 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The datasets analysed during the current study will be available from the corresponding author on reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- School-aged Outcomes Post Hypoxic Ischaemic Encephalopathy
- ClinicalTrials.gov ID
- NCT07770035
- Acronym / sponsor ID
- SOPHIE / Inf_Sophie_23110
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Keywords
- HIE, neonatal encephalopathy, neurodevelopment, cognitive outcome, MRI
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 196 participants (estimated)
- Lead sponsor
- University College CorkUniversity, hospital or other
- Study start
- 9 Mar 2024 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 18 Aug 2026 (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.
Neonatal HIE increases the risk for cognitive impairments in childhood. Neonatal MRI brain scans are a strong predictor for outcome, however a normal scan has only a 35% sensitivity and 85% specificity for a normal outcome. This may be explained by variability in the brain's development over time in response to the initial insult.
This project will aim to develop a neonatal MRI machine learning algorithm that incorporates both initial injury and radiomic features associated with future brain development (based on school-age MRI) to predict school-age outcome. This will be achieved by conducting a case-control cohort study looking at School-age MRI and outcomes of children with a history of neonatal HIE.
Detailed description
The study will recruit children with a history of HIE in the newborn period (cases) and healthy children with an unremarkable newborn period (controls) born between January 2013-December 2020. During this period several prospective cohort studies of term infants ≥36 weeks at risk of HIE were conducted in Cork University Maternity Hospital (CUMH) neonatal intensive care unit (NICU).
Infants enrolled in these previous studies had neonatal data collected, in addition to detailed neurological assessments, neurophysiological monitoring, neonatal MRIs, and standardised neuro-developmental follow-up at two years of age using the Bayley Scale of Infant Development (BSID). These children were not followed after the BSID was performed. Approval for these studies was given by the Clinical Research Ethics Committee of the Cork Teaching Hospitals (CREC), and informed consent obtained. Cases for the proposed study will be identified from those who agreed on the original consent form to be contacted for future related research.
For control recruitment, the study will be advertised on social media, the INFANT website and in the Paediatric outpatient area in the adjacent Paediatric department. Healthy children aged between 5 and 12 years of age will be invited to contact the research team to be part of the control group. To be eligible, they must have been born at ≥ 36 weeks gestation, now attending mainstream school, did not have a diagnosis of HIE or have been admitted to the neonatal unit in the first 12 hours of birth. A new ethics submission for the current study was approved by the local CREC.
Sample Size: Taking the mean population IQ as 100 with a standard deviation of 15, we calculated that 98 cases will be needed to detect a 6-point difference in composite IQ with an alpha of 0.05 and a power of 80%. The same number of controls will be recruited, giving a total number of 196 participants. This sample is powered to show a meaningful difference in IQ between populations from which the predictive models are built. Regarding the radiomic analysis proposed there is very limited data in neonatal populations, but the sample size proposed would represent the largest neonatal radiomic study to-date, and would also be comparable to recent adult studies with similar proposed methodology.
Study Procedures:
If the parents/guardians agree to participate, written informed consent and age-appropriate assent will be obtained.
There will be two study visits. The first will involve performing the cognitive assessment, administration of questionnaires, and a short play therapy session to introduce the child to the MRI using a mock MRI scanner and video of the MRI department and scanner. The assessment will take a standardised format, taking approximately 1.5 hours in total and breaks will be provided as necessary.
The MRI will be performed at the second visit. The scanning protocol will be approximately 19 minutes in duration, with four key MRI sequences being performed. No sedation or anesthesia will be provided for the MRI. Qualitative and quantitative analysis of the MRI will be performed.
The goal of this project is to develop a predictive neonatal MRI biomarker algorithm that combines radiomic features associated with evolution of brain injury on School-age MRI scans, and qualitative neonatal MRI assessment, to predict School-age cognitive outcome following Neonatal HIE.
The specific objectives are
- To develop a Neonatal MRI machine learning model of radiomic features predictive of significant future evolutional changes evident on school-age MRI following HIE
- Perform School-age MRI in both a large cohort of infants with HIE (with available neonatal MRI) and an age-matched control population (did not have neonatal MRI).
- School-age MRI to be assessed for qualitative injury, and perform regional volumetric analysis.
- Psychological assessment of cognitive function, executive function, and full-scale IQ in all grades of HIE (mild, moderate, and severe) and compare to an age-matched control population.
- Correlation of School-age MRIs (Case and Control) with School age psychological outcome to identify key features associated with outcome.
- In HIE cohort, following identification of key features predictive of cognitive outcome on School-age MRI (regions of interest[ROI]), to project these ROIs onto the Neonatal MRI to identify radiomic features predictive of evolution of brain imaging findings.
- Develop machine learning algorithm of radiomic features on neonatal MRI predictive of significant school-age MRI changes
- To develop MRI Only predictive model for School-age Outcome: To develop predictive algorithm combining Neonatal MRI radiomic model developed (objective 1) and qualitative neonatal MRI findings, to predict School-age Psychological outcome.
- To develop MRI and Clinical model for School-age Outcome: To develop a predictive machine learning algorithm combining Clinical and sociodemographic factors, with our Neonatal MRI radiomic model, and qualitative neonatal MRI findings to predict School-age Psychological outcome.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypoxic Ischaemic Encephalopathy (Case) | – | –Children aged 5-12 years old with HIE meeting study inclusion criteria |
| Age-Matched Control | – | –Healthy controls aged 5-12 years old, now attending mainstream school, who did not have HIE or were not admitted to the neonatal unit within 12 hours of birth. |
Who may qualify
- Ages
- 5 to 12 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Cases: Potential participants will be identified from seven previous studies conducted in Cork University Maternity Hospital (CUMH), between January 2013-December 2019. Over this period, term infants ≥36 weeks considered at significant risk of HIE were recruited prospectively to these studies as soon as possible after delivery. Clinical data, blood biomarkers, MRI and EEG recordings were collected and stored in the INFANT databank using unique study numbers. Controls: Children aged between 4-12 years of age, who are attending general paediatric outpatients' clinics at Cork University Hospital (CUH) will be selected as potential participants for the control group. Controls will be healthy children born at ≥ 36 weeks gestation now attending mainstream school who did not have a diagnosis of HIE at birth. To be eligible, they must not have been admitted to the neonatal unit in the first 12 hours after birth and have had a 5-minute Apgar score of ≥7.
Key inclusion criteria (4 listed)
- Known diagnosis of HIE of any grade and enrolled in one of seven studies carried out in CUMH and born between 01 JAN 2013 and 31 DEC 2020
- Documented parental informed consent for their study data to be used in the future for related research and for them to be contacted again.
- Born at ≥ 36 weeks gestation
- Attending mainstream primary school without a specific developmental diagnosis
Key exclusion criteria (8 listed)
- Lack of parental consent for the original study and no permission to be contacted for future research.
- Death prior to study initiation
- Congenital malformation or genetic syndrome
- Diagnosis of perinatal asphyxia or HIE at birth
- Admission to the neonatal unit within 12 hours of birth
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Intelligence Quotient
Time frame: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Kaufman Brief Intelligence Test Second Edition (KBIT-2) is a brief measure of verbal and nonverbal intelligence used with individuals aged from 4 to 90 years.
Assessment of Exectuive Function
Time frame: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Cambridge Neuropsychological Test Automated Battery (CANTAB) will be used to assess the following domains: Visual Memory- Delayed Match to Sample (DMS) Working memory- Spatial Working Memory Task (SWM), Spatial Span Task (SSP), Digit Span Task (DGS) Attention/processing speed- Reaction Time Task (RTI), Rapid Visual Processing Task (RVP), Motor Screening Task (MOT) Inhibitory control- Stop Signal Task (SST)
Volumetric analysis of MRI brain
Time frame: Visit 2 - 20 minute MRI scan, approximately 2-4 months after Visit 1
Total and regional brain volumetric analysis
Connectivity analysis of MRI brain
Time frame: Visit 2 - 20 minute MRI scan, approximately 2-4 months after Visit 1
Analysis of brain connectivity using diffusion tensor data and fransctional anisotopy imaging.
MRI Machine Learning Model
Time frame: Visit 2 - 20 minute MRI scan, approximately 2-4 months after Visit 1
Using MRIs completed at school-age and neonatal data, extract radiomic features and ragions of interest (ROIs) to develop machine learning models to predict school-aged cognitive outcome.
4 secondary outcomes
Behavioural Profile
Time frame: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Incidence of additional school supports
Time frame: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Socioeconomic Background
Time frame: Visit 1 - Approx 1.5 hours, aged 5-12 years old
Cognitively Stimulating Home Environment
Time frame: Visit 1 - Approx 1.5 hours, aged 5-12 years old
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 18 Aug 2026.
- Individual participant dataSharing planned: Undecided. The datasets analysed during the current study will be available from the corresponding author on reasonable request.
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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.
Brian H Walsh, PhD principal investigator
University College Cork
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, run by University College Cork at 1 site in Ireland.
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 4 inclusion and 8 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: enrolling by invitation, as of the sponsor's last update on 18 Aug 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 Ireland. 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?
Intelligence Quotient (time frame: Visit 1 - Approx 1.5 hours, aged 5-12 years old). The study lists 5 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 18 Aug 2026.