HIE - Hypoxic - Ischemic EncephalopathySANENCT07136636
Speech of Kids After Neonatal Encephalopathy
An observational study of HIE - Hypoxic - Ischemic Encephalopathy and Language Delay, run by Semmelweis University at 1 site in Hungary.
Trial summary
The goal of this ambispective cohort study is to reveal the early indicators of delayed language development in children born with hypoxic-ischemic encephalopathy (HIE). We will examine the prognostic accuracy of different biomarkers, with a special focus on the ADC values of the corpus callosum. Read more about this study
- Who is it for?
- Ages 0 to 7 years
- Conditions the study is for
- HIE - Hypoxic - Ischemic Encephalopathy, Language Delay, Autism
- How many people
- 93 participants
- Where
- 1 siteHungary
- Study dates
- 1 Apr 2025to Dec 2026
- How long will I take part?
- 7 Years
- 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 0 to 7 years
- All sexes
- No healthy volunteers
- Child
Study population: Children with HIE
Who may be able to join
- Born at ≥ 35th week of gestation
- Attended follow-up examinations at two years of age
- Has parental informed consent
Who cannot join
- Hearing loss
- Multilingual language environment
- Congenital abnormalities
- Metabolic disease
- Sudden unexpected postnatal collapse
- Brain injury not caused by HIE
- Severe motor impairment defined as a score <70 on the psychomotor development index (PDI) at 2 years of age
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hungary1 site, 1 recruiting
- Recruiting
Semmelweis University
Budapest
Miklós Szabó, MD, PhD, 0613343186 ext. 52786, szabo.miklos@semmelweis.hu
Zsuzsanna Varga, PhD, 0613343186 ext. 52794, 52795, varga.zsuzsanna2@semmelweis.hu
About this study
Official title: Investigating the Prognostic Accuracy of Different Biomarkers for Detection of Developmental Language Disorder in Children With Neonatal Encephalopathy
The goal of this ambispective cohort study is to reveal the early indicators of delayed language development in children born with hypoxic-ischemic encephalopathy (HIE).
We will examine the prognostic accuracy of different biomarkers, with a special focus on the ADC values of the corpus callosum.
Read more
The main questions it aims to answer are:
- To what extent does hypoxic-ischemic encephalopathy (HIE) in infancy affect intellectual development (IQ), receptive and expressive language abilities at different levels of the language system, and memory capacities related to language development?
- What is the relationship between early biomarkers of brain injury-such as blood gas levels, lactate, aEEG, and MRI findings (Weeke scoring system, ADC values of the corpus callosum)-and long-term cognitive developmental outcomes?
- What is the incidence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in this high-risk population of infants with HIE?
- Is there an association between the Weeke Total Score and long-term language developmental outcomes?
- Can restricted diffusion (ADC values) of the splenium of the corpus callosum serve as an early neuroradiological marker of developmental language disorder (DLD)?
Our participants are children born between 2017 and 2023 with moderate to severe HIE, treated with therapeutic hypothermia at Semmelwies University Children's Hospital. During their first days of life, several neonatal measurements were taken (blood gas markers, aEEG etc.), and at day 4-5, they had an MRI scan of their brain. The MRI scans will be reanalyzed, using the Weeke MRI scoring system. These children underwent a neurodevelopmental follow-up at the age of 2 years and currently, they will have another follow-up at the age of 4-7 years.
Read the detailed description
This ambispective, single-center cohort study will investigate the cognitive and language development of children aged 4-7 years who were previously treated for hypoxic-ischemic encephalopathy (HIE) and underwent standardized neurodevelopmental assessment at two years of age. In addition to developmental outcomes, the study will incorporate clinical, laboratory, and imaging data collected during the neonatal period. All available neonatal MRI scans will be re-evaluated according to predefined criteria. Recruitment and data collection will take place from April 1, 2025, to December 31, 2026. The study population will include children whose parents provided consent for follow-up assessments at the two-year evaluation.
Phase 1.: Blood gas values like pH, base deficit, PCO2, PO2, HCO3, and lactate were registered. aEEG cerebral activity was recorded using continuous single channel (biparietal, P3-P4) aEEG monitoring. It started before 6 hours of age.
Phase 2. : MRI scans was perfomed between the 4-5th day of postnatal age. The MRI scans will be reanalyzed, using the Weeke MRI scoring system.
Phase 3. : At the age of 2 years participating children underwent neurodevelopemntal follow-up, where the Bayley Scales of Infant and Toddler Development, Second Edition (Bayley-II) was used. It is a standardized tool for assessing the developmental functioning of children from 1 to 42 months of age. The test provides both a Mental Development Index (MDI) and a Psychomotor Development Index (PDI) to summarize performance in key areas.
Phase 4.: At the age of 4-7 years the children will undergo their second neurodevelopmental assessment. Within this assessment we will administer the following:
Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV), which assesses Full-Scale IQ, Verbal IQ, and Performance IQ in children aged 4 years to 7 years.
Complex Test of Spoken Language Skills (KOBAK), the first comprehensive, standardized language assessment developed for Hungarian-speaking children. The KOBAK comprises 16 subtests evaluating expressive and receptive language functions across multiple domains (phonology, lexical semantics, morphology, syntax, and pragmatics), as well as speech motor functions and verbal working memory. The test enables evidence-based differentiation of average, above-average, and below-average language abilities; provides a detailed language profile; supports the assessment of school readiness; and facilitates screening, diagnosis, differential diagnosis, and longitudinal monitoring of language development.
As part of the neurodevelopmental assessment, parents will complete several questionnaires:
Socioeconomic Questionnaire (assessing parental education, income, and related variables) Jaworsky Questionnaire Social Communication Questionnaire (SCQ) ScreenQ ADHD Rating Scale Strengths and Difficulties Questionnaire (SDQ)
- Conditions
- HIE - Hypoxic - Ischemic Encephalopathy, Language Delay, Autism, ADHD - Attention Deficit Disorder With Hyperactivity, Specific Language Impairment, Intellectual Developmental Disorder
- Keywords
- HIE - Hypoxic - Ischemic Encephalopathy, delayed language development, neurodevelopment, MRI, biomarker, corpus callosum diffusion restriction, IQ, newborn prediction tool
- Medical subject headings
- Language Development Disorders, Autistic Disorder, Attention Deficit Disorder with Hyperactivity, Specific Language Disorder, Intellectual Disability
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 |
|---|---|---|
| Children born with Hypoxic-Ischemic Encephalopathy (HIE) | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive abilities - WPPSI-IV
Measured: At the age of 4-7 years
Language abilities - KOBAK
Measured: At the age of 4-7 years
Secondary outcomes (6)
Socioeconomic status - Socioeconomic questionnaire
Measured: At the age of 4-7 years
Parental concerns - Jaworsky Questionnaire
Measured: At the age of 4-7 years
Social and Communication skills - Social Communication Questionnaire
Measured: At the age of 4-7 years
Digital screen use - ScreenQ
Measured: At the age of 4-7 years
ADHD traits - ADHD Rating Scale
Measured: At the age of 4-7 years
Behavior - Strengths and Difficulties Questionnaire
Measured: At the age of 4-7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2025
- Study start1 Apr 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIE - 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
- Cohort
- Time perspective
- Other
- Enrolment
- 93 participants (estimated)
- Target duration
- 7 Years
Sponsor and investigators
- Lead sponsor
- Semmelweis University
- Sponsor type
- University, hospital or other
- Collaborators
- UiT The Arctic University of Norway, Budapest University of Technology and Economics, Eotvos Lorand University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07136636
- Sponsor's protocol ID
- NNGYK/24844-9/2025
- Acronym
- SANE
- Status last verified
- Aug 2025
- First submitted
- 14 Aug 2025
- Last updated
- 22 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bartha-Doering L, Kollndorfer K, Schwartz E, Fischmeister FPS, Alexopoulos J, Langs G, Prayer D, Kasprian G, Seidl R. The role of the corpus callosum in language network connectivity in children. Dev Sci. 2021 Mar;24(2):e13031. doi: 10.1111/desc.13031. Epub 2020 Sep 1.
PubMed 32790079Weeke LC, Groenendaal F, Mudigonda K, Blennow M, Lequin MH, Meiners LC, van Haastert IC, Benders MJ, Hallberg B, de Vries LS. A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia. J Pediatr. 2018 Jan;192:33-40.e2. doi: 10.1016/j.jpeds.2017.09.043.
PubMed 29246356Ni Bhroin M, Kelly L, Sweetman D, Aslam S, O'Dea MI, Hurley T, Slevin M, Murphy J, Byrne AT, Colleran G, Molloy EJ, Bokde ALW. Relationship Between MRI Scoring Systems and Neurodevelopmental Outcome at Two Years in Infants With Neonatal Encephalopathy. Pediatr Neurol. 2022 Jan;126:35-42. doi: 10.1016/j.pediatrneurol.2021.10.005. Epub 2021 Oct 13.
PubMed 34736061Chin EM, Jayakumar S, Ramos E, Gerner G, Soares BP, Cristofalo E, Leppert M, Allen M, Parkinson C, Johnston M, Northington F, Burton VJ. Preschool Language Outcomes following Perinatal Hypoxic-Ischemic Encephalopathy in the Age of Therapeutic Hypothermia. Dev Neurosci. 2019 Jun 5:1-11. doi: 10.1159/000499562. Online ahead of print.
PubMed 31167188Ouwehand S, Smidt LCA, Dudink J, Benders MJNL, de Vries LS, Groenendaal F, van der Aa NE. Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis. Neonatology. 2020;117(4):411-427. doi: 10.1159/000505519. Epub 2020 Apr 1.
PubMed 32235122Bodocs DL, Rago A, Farkas N, Lakatos A, Kas B, Lukacs A, Jermendy A, Hernadfoi M, Lokkos E, Kiss N, Major J, Hegyi P, Szabo M, Varga Z, Banvolgyi A. Study protocol of the Speech of children After Neonatal Encephalopathy (SANE): a single-centre prospective cohort study. BMJ Open. 2026 Aug 10;16(8):e120474. doi: 10.1136/bmjopen-2026-120474.
PubMed 42575547
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Prognostic Accuracy of Different Biomarkers for Detection of Developmental Language Disorder in Children With Neonatal Encephalopathy
- ClinicalTrials.gov ID
- NCT07136636
- Acronym / sponsor ID
- SANE / NNGYK/24844-9/2025
- Conditions
- HIE - Hypoxic - Ischemic Encephalopathy, Language Delay, Autism, ADHD - Attention Deficit Disorder With Hyperactivity, Specific Language Impairment, Intellectual Developmental Disorder
- Keywords
- HIE - Hypoxic - Ischemic Encephalopathy, delayed language development, neurodevelopment, MRI, biomarker, corpus callosum diffusion restriction, IQ, newborn prediction tool
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 93 participants (estimated)
- Lead sponsor
- Semmelweis UniversityUniversity, hospital or other
- Collaborators
- UiT The Arctic University of Norway, Budapest University of Technology and Economics, Eotvos Lorand University
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 22 Aug 2025 (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 ambispective cohort study is to reveal the early indicators of delayed language development in children born with hypoxic-ischemic encephalopathy (HIE).
We will examine the prognostic accuracy of different biomarkers, with a special focus on the ADC values of the corpus callosum.
The main questions it aims to answer are:
- To what extent does hypoxic-ischemic encephalopathy (HIE) in infancy affect intellectual development (IQ), receptive and expressive language abilities at different levels of the language system, and memory capacities related to language development?
- What is the relationship between early biomarkers of brain injury-such as blood gas levels, lactate, aEEG, and MRI findings (Weeke scoring system, ADC values of the corpus callosum)-and long-term cognitive developmental outcomes?
- What is the incidence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in this high-risk population of infants with HIE?
- Is there an association between the Weeke Total Score and long-term language developmental outcomes?
- Can restricted diffusion (ADC values) of the splenium of the corpus callosum serve as an early neuroradiological marker of developmental language disorder (DLD)?
Our participants are children born between 2017 and 2023 with moderate to severe HIE, treated with therapeutic hypothermia at Semmelwies University Children's Hospital. During their first days of life, several neonatal measurements were taken (blood gas markers, aEEG etc.), and at day 4-5, they had an MRI scan of their brain. The MRI scans will be reanalyzed, using the Weeke MRI scoring system. These children underwent a neurodevelopmental follow-up at the age of 2 years and currently, they will have another follow-up at the age of 4-7 years.
Detailed description
This ambispective, single-center cohort study will investigate the cognitive and language development of children aged 4-7 years who were previously treated for hypoxic-ischemic encephalopathy (HIE) and underwent standardized neurodevelopmental assessment at two years of age. In addition to developmental outcomes, the study will incorporate clinical, laboratory, and imaging data collected during the neonatal period. All available neonatal MRI scans will be re-evaluated according to predefined criteria. Recruitment and data collection will take place from April 1, 2025, to December 31, 2026. The study population will include children whose parents provided consent for follow-up assessments at the two-year evaluation.
Phase 1.: Blood gas values like pH, base deficit, PCO2, PO2, HCO3, and lactate were registered. aEEG cerebral activity was recorded using continuous single channel (biparietal, P3-P4) aEEG monitoring. It started before 6 hours of age.
Phase 2. : MRI scans was perfomed between the 4-5th day of postnatal age. The MRI scans will be reanalyzed, using the Weeke MRI scoring system.
Phase 3. : At the age of 2 years participating children underwent neurodevelopemntal follow-up, where the Bayley Scales of Infant and Toddler Development, Second Edition (Bayley-II) was used. It is a standardized tool for assessing the developmental functioning of children from 1 to 42 months of age. The test provides both a Mental Development Index (MDI) and a Psychomotor Development Index (PDI) to summarize performance in key areas.
Phase 4.: At the age of 4-7 years the children will undergo their second neurodevelopmental assessment. Within this assessment we will administer the following:
Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV), which assesses Full-Scale IQ, Verbal IQ, and Performance IQ in children aged 4 years to 7 years.
Complex Test of Spoken Language Skills (KOBAK), the first comprehensive, standardized language assessment developed for Hungarian-speaking children. The KOBAK comprises 16 subtests evaluating expressive and receptive language functions across multiple domains (phonology, lexical semantics, morphology, syntax, and pragmatics), as well as speech motor functions and verbal working memory. The test enables evidence-based differentiation of average, above-average, and below-average language abilities; provides a detailed language profile; supports the assessment of school readiness; and facilitates screening, diagnosis, differential diagnosis, and longitudinal monitoring of language development.
As part of the neurodevelopmental assessment, parents will complete several questionnaires:
Socioeconomic Questionnaire (assessing parental education, income, and related variables) Jaworsky Questionnaire Social Communication Questionnaire (SCQ) ScreenQ ADHD Rating Scale Strengths and Difficulties Questionnaire (SDQ)
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 7 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children born with Hypoxic-Ischemic Encephalopathy (HIE) | – | – |
Who may qualify
- Ages
- 0 to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Children with HIE
Key inclusion criteria (3 listed)
- Born at ≥ 35th week of gestation
- Attended follow-up examinations at two years of age
- Has parental informed consent
Key exclusion criteria (7 listed)
- Hearing loss
- Multilingual language environment
- Congenital abnormalities
- Metabolic disease
- Sudden unexpected postnatal collapse
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
Cognitive abilities - WPPSI-IV
Time frame: At the age of 4-7 years
Language abilities - KOBAK
Time frame: At the age of 4-7 years
6 secondary outcomes
Socioeconomic status - Socioeconomic questionnaire
Time frame: At the age of 4-7 years
Parental concerns - Jaworsky Questionnaire
Time frame: At the age of 4-7 years
Social and Communication skills - Social Communication Questionnaire
Time frame: At the age of 4-7 years
Digital screen use - ScreenQ
Time frame: At the age of 4-7 years
ADHD traits - ADHD Rating Scale
Time frame: At the age of 4-7 years
Behavior - Strengths and Difficulties Questionnaire
Time frame: At the age of 4-7 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 22 Aug 2025.
- Background: PubMed 32790079Bartha-Doering L, Kollndorfer K, Schwartz E, Fischmeister FPS, Alexopoulos J, Langs G, Prayer D, Kasprian G, Seidl R. The role of the corpus callosum in language network connectivity in children. Dev Sci. 2021 Mar;24(2):e13031. doi: 10.1111/desc.13031. Epub 2020 Sep 1.
- Background: PubMed 29246356Weeke LC, Groenendaal F, Mudigonda K, Blennow M, Lequin MH, Meiners LC, van Haastert IC, Benders MJ, Hallberg B, de Vries LS. A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia. J Pediatr. 2018 Jan;192:33-40.e2. doi: 10.1016/j.jpeds.2017.09.043.
- Background: PubMed 34736061Ni Bhroin M, Kelly L, Sweetman D, Aslam S, O'Dea MI, Hurley T, Slevin M, Murphy J, Byrne AT, Colleran G, Molloy EJ, Bokde ALW. Relationship Between MRI Scoring Systems and Neurodevelopmental Outcome at Two Years in Infants With Neonatal Encephalopathy. Pediatr Neurol. 2022 Jan;126:35-42. doi: 10.1016/j.pediatrneurol.2021.10.005. Epub 2021 Oct 13.
- Background: PubMed 31167188Chin EM, Jayakumar S, Ramos E, Gerner G, Soares BP, Cristofalo E, Leppert M, Allen M, Parkinson C, Johnston M, Northington F, Burton VJ. Preschool Language Outcomes following Perinatal Hypoxic-Ischemic Encephalopathy in the Age of Therapeutic Hypothermia. Dev Neurosci. 2019 Jun 5:1-11. doi: 10.1159/000499562. Online ahead of print.
- Background: PubMed 32235122Ouwehand S, Smidt LCA, Dudink J, Benders MJNL, de Vries LS, Groenendaal F, van der Aa NE. Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis. Neonatology. 2020;117(4):411-427. doi: 10.1159/000505519. Epub 2020 Apr 1.
- Derived from this study: PubMed 42575547Bodocs DL, Rago A, Farkas N, Lakatos A, Kas B, Lukacs A, Jermendy A, Hernadfoi M, Lokkos E, Kiss N, Major J, Hegyi P, Szabo M, Varga Z, Banvolgyi A. Study protocol of the Speech of children After Neonatal Encephalopathy (SANE): a single-centre prospective cohort study. BMJ Open. 2026 Aug 10;16(8):e120474. doi: 10.1136/bmjopen-2026-120474.
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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.
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 HIE - Hypoxic - Ischemic Encephalopathy and Language Delay, run by Semmelweis University at 1 site in Hungary.
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 3 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 22 Aug 2025. 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 Hungary. 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive abilities - WPPSI-IV (time frame: At the age of 4-7 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07136636, which also lists 6 linked publications.
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 22 Aug 2025.