Neonatal HyperbilirubinemiaNCT06018012
MRA and ABR as Early Predictors of Bilirubin-Induced Neurologic Dysfunction in Full-term Jaundiced Neonates
An observational study of Neonatal Hyperbilirubinemia, run by Tanta University at 1 site in Egypt.
Trial summary
The aim of the research was to define the role of MRS and ABR as early predictors of bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required intervention (phototherapy or exchange transfusion). Read more about this study
- Who is it for?
- Ages 1 day to 28 daysHealthy volunteers can take part
- Conditions the study is for
- Neonatal Hyperbilirubinemia
- What is being tested?
- MRS and ABR
- Type of treatment
- Medical device
- How many people
- 76 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Mar 2019to 1 Apr 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
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 1 day to 28 days
- All sexes
- Healthy volunteers accepted
- Child
Study population: This study included term, appropriate for gestational age (AGA) neonates with pathological unconjugated hyperbilirubinemia who were candidates for intervention (Intensive phototherapy versus Exchange transfusion) using the American Academy of Pediatrics guidelines; 2004. In addition, 20 healthy, age-matched neonates were included as controls.
Who may be able to join
- This study included term, appropriate for gestational age (AGA) neonates with pathological unconjugated hyperbilirubinemia who were candidates for intervention (Intensive phototherapy versus Exchange transfusion) using the American Academy of Pediatrics guidelines; 2004.
Who cannot join
- Preterm neonates (less than 37 weeks).
- Clinically moderate and severe acute bilirubin encephalopathy according to modified Bilirubin-induced neurologic dysfunction (BIND-M) score.
- Neonates born with birth asphyxia and/or poor Apgar score.
- Neonates with sepsis including CNS infection.
- Neonates with family history of childhood hearing loss.
- Congenital infection.
Show all 10Show fewer
- Chromosomal abnormalities.
- Congenital ear anomalies associated with hearing loss or brain abnormalities including craniofacial anomalies.
- Patients who were receiving ototoxic drugs as aminoglycosides.
- Conjugated hyperbilirubinemia.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Magnetic Resonance Spectroscopy and Auditory Brain- Stem Response Audiometry as Early Predictors of Bilirubin-Induced Neurologic Dysfunction in Full-term Jaundiced Neonates
The aim of the research was to define the role of MRS and ABR as early predictors of bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required intervention (phototherapy or exchange transfusion).
Read the detailed description
Neonatal jaundice is a prevalent condition. It's typically a harmless phase that occurs as the body adjusts to bilirubin levels after birth, representing a balance between its production and elimination. When there's an increase in bilirubin production and a decrease in elimination, infants become at risk for dangerous hyperbilirubinemia, potentially leading to bilirubin encephalopathy.
The range of neurological issues caused by excessive bilirubin is referred to as bilirubin-induced neurologic dysfunction. Detecting this condition early is crucial to prevent irreversible brain damage. Some of the neurological effects include gliosis, demyelination, and interference with glutamate uptake by astrocytes in the basal ganglia. Magnetic resonance spectroscopy (MRS) is an advanced imaging technique that holds promise for identifying these metabolic changes and aiding in the diagnosis and evaluation of neonates with hyperbilirubinemia.
Bilirubin neurotoxicity particularly affects the auditory system, starting with the brainstem cochlear nuclei, followed by the auditory nerve. This damage can occur even without the classic signs of bilirubin encephalopathy and is known as auditory neuropathy spectrum disorder (ANSD). ANSD is characterized by abnormal auditory neural function, while cochlear microphonics and otoacoustic emissions remain normal.
The impact on hearing can vary from subtle issues in sound processing to complete deafness. Abnormal results in auditory brainstem response (ABR) tests can indicate the presence of acute bilirubin encephalopathy (ABE), serving as the most common and earliest sign of ABE.
- Conditions
- Neonatal Hyperbilirubinemia
- Being tested
- MRS and ABR
- Medical subject headings
- Hyperbilirubinemia, Neonatal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRS and ABRDevice
Magnetic Resonance Spectroscopy and Auditory Brain- stem Response Audiometry
| Study group | Role | What they receive |
|---|---|---|
| 1 or acute bilirubin encephalopathy | Group (1): included 26 cases with BIND or acute bilirubin encephalopathy (ABE). Receives: Device: MRS and ABR | |
| 2 or neonatal hyperbilirubinemia | Group (2): included 30 cases with neonatal hyperbilirubinemia on Receives: Device: MRS and ABR | |
| Control | control group: 20 healthy, age-matched neonates Receives: Device: MRS and ABR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early detection of neurological abnormalities using MRS metabolic ratios in high-risk neonates without oblivious clinical signs
Early detection of neurological abnormalities in high-risk neonates, without oblivious clinical signs, chemically by using MRS metabolic ratio ( low NAA/Cr, NAA/Cho ratios, and high Lac/Cr ratio).
Measured: 2 years
Early detection of neurological abnormalities using ABR parameters in high-risk neonates without oblivious clinical signs
Early detection of neurological abnormalities in high-risk neonates, without oblivious clinical signs, functionally through ABR parameters ( prolonged wave III peak latency, wave V peak latency, I-III interpeak interval, and I-V interpeak interval )
Measured: 2 years
Bilirubin level and auditory abnormality
Finding out the lowest level of total serum bilirubin at which auditory pathway abnormality was found, in comparison to age.
Measured: 2 years
Bilirubin level and MRS abnormality
Finding out the lowest level of total serum bilirubin at which MRS abnormalities were found, in comparison to age.
Measured: 2 years
Secondary outcomes (2)
Discriminative capacity of MRS for acute bilirubin encephalopathy
Determining the discriminative capacity of MRS metabolic ratios (NAA/Cr and NAA/Cho) for neonates with acute bilirubin encephalopathy and those without it with identification of the cutoff value those ratios at which acute bilirubin encephalopathy is present.
Measured: 2 years
Discriminative capacity of ABR for acute bilirubin encephalopathy
Determining the discriminative capacity of ABR wave latencies and interpeak intervals abnormalities for neonates with acute bilirubin encephalopathy and those without it with identification of the cutoff value those latencies and intervals at which acute bilirubin encephalopathy is present.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2023
- Study start1 Mar 2019
- Primary completion1 Mar 2021
- Study completion1 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Neonatal HyperbilirubinemiaStudies of the same condition, open and under way.
- More trials run by Tanta UniversityThe sponsor's other registered studies.
- 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
- Retrospective
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lamiaa Khaled Zidan, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06018012
- Sponsor's protocol ID
- MRS& ABR in jaundiced neonates
- Status last verified
- Aug 2023
- First submitted
- 18 Aug 2023
- Last updated
- 1 Sep 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Watchko JF, Tiribelli C. Bilirubin-induced neurologic damage--mechanisms and management approaches. N Engl J Med. 2013 Nov 21;369(21):2021-30. doi: 10.1056/NEJMra1308124. No abstract available.
PubMed 24256380Usman, F., Diala, U., Shapiro, S., Le Pichon, J.-B., & Slusher, T. Acute bilirubin encephalopathy and its progression to kernicterus: current perspectives. Research and Reports in Neonatology, 8, 33-44 (2018).
Watchko JF. Bilirubin-Induced Neurotoxicity in the Preterm Neonate. Clin Perinatol. 2016 Jun;43(2):297-311. doi: 10.1016/j.clp.2016.01.007. Epub 2016 Mar 2.
PubMed 27235209Das S, van Landeghem FKH. Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus. Diagnostics (Basel). 2019 Feb 28;9(1):24. doi: 10.3390/diagnostics9010024.
PubMed 30823396Teixeira MH, Borges VMS, Riesgo RDS, Sleifer P. Hyperbilirubinemia impact on newborn hearing: a literature review. Rev Assoc Med Bras (1992). 2020 Jul;66(7):1002-1008. doi: 10.1590/1806-9282.66.7.1002. Epub 2020 Aug 24.
PubMed 32844928Olds C, Oghalai JS. Audiologic impairment associated with bilirubin-induced neurologic damage. Semin Fetal Neonatal Med. 2015 Feb;20(1):42-46. doi: 10.1016/j.siny.2014.12.006. Epub 2015 Jan 7.
PubMed 25575899Zidan LK, Rowisha MA, Nassar MAE, Elshafey RA, El Mahallawi TH, Elmahdy HS. Magnetic resonance spectroscopy and auditory brain-stem response audiometry as predictors of bilirubin-induced neurologic dysfunction in full-term jaundiced neonates. Eur J Pediatr. 2024 Feb;183(2):727-738. doi: 10.1007/s00431-023-05246-z. Epub 2023 Nov 18.
PubMed 37979048
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnetic Resonance Spectroscopy and Auditory Brain- Stem Response Audiometry as Early Predictors of Bilirubin-Induced Neurologic Dysfunction in Full-term Jaundiced Neonates
- ClinicalTrials.gov ID
- NCT06018012
- Acronym / sponsor ID
- MRS& ABR in jaundiced neonates
- Conditions
- Neonatal Hyperbilirubinemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 1 Mar 2021 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 30 Aug 2023 (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 aim of the research was to define the role of MRS and ABR as early predictors of bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required intervention (phototherapy or exchange transfusion).
Detailed description
Neonatal jaundice is a prevalent condition. It's typically a harmless phase that occurs as the body adjusts to bilirubin levels after birth, representing a balance between its production and elimination. When there's an increase in bilirubin production and a decrease in elimination, infants become at risk for dangerous hyperbilirubinemia, potentially leading to bilirubin encephalopathy.
The range of neurological issues caused by excessive bilirubin is referred to as bilirubin-induced neurologic dysfunction. Detecting this condition early is crucial to prevent irreversible brain damage. Some of the neurological effects include gliosis, demyelination, and interference with glutamate uptake by astrocytes in the basal ganglia. Magnetic resonance spectroscopy (MRS) is an advanced imaging technique that holds promise for identifying these metabolic changes and aiding in the diagnosis and evaluation of neonates with hyperbilirubinemia.
Bilirubin neurotoxicity particularly affects the auditory system, starting with the brainstem cochlear nuclei, followed by the auditory nerve. This damage can occur even without the classic signs of bilirubin encephalopathy and is known as auditory neuropathy spectrum disorder (ANSD). ANSD is characterized by abnormal auditory neural function, while cochlear microphonics and otoacoustic emissions remain normal.
The impact on hearing can vary from subtle issues in sound processing to complete deafness. Abnormal results in auditory brainstem response (ABR) tests can indicate the presence of acute bilirubin encephalopathy (ABE), serving as the most common and earliest sign of ABE.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 or acute bilirubin encephalopathy | – | Device: MRS and ABRGroup (1): included 26 cases with BIND or acute bilirubin encephalopathy (ABE). |
| 2 or neonatal hyperbilirubinemia | – | Device: MRS and ABRGroup (2): included 30 cases with neonatal hyperbilirubinemia on |
| Control | – | Device: MRS and ABRcontrol group: 20 healthy, age-matched neonates |
Who may qualify
- Ages
- 1 day to 28 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- This study included term, appropriate for gestational age (AGA) neonates with pathological unconjugated hyperbilirubinemia who were candidates for intervention (Intensive phototherapy versus Exchange transfusion) using the American Academy of Pediatrics guidelines; 2004. In addition, 20 healthy, age-matched neonates were included as controls.
Key inclusion criteria (1 listed)
- This study included term, appropriate for gestational age (AGA) neonates with pathological unconjugated hyperbilirubinemia who were candidates for intervention (Intensive phototherapy versus Exchange transfusion) using the American Academy of Pediatrics guidelines; 2004.
Key exclusion criteria (10 listed)
- Preterm neonates (less than 37 weeks).
- Clinically moderate and severe acute bilirubin encephalopathy according to modified Bilirubin-induced neurologic dysfunction (BIND-M) score.
- Neonates born with birth asphyxia and/or poor Apgar score.
- Neonates with sepsis including CNS infection.
- Neonates with family history of childhood hearing loss.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRS and ABRMagnetic Resonance Spectroscopy and Auditory Brain- stem Response Audiometry | Device | 1 or acute bilirubin encephalopathy, 2 or neonatal hyperbilirubinemia, Control |
Primary outcome
Early detection of neurological abnormalities using MRS metabolic ratios in high-risk neonates without oblivious clinical signs
Time frame: 2 years
Early detection of neurological abnormalities in high-risk neonates, without oblivious clinical signs, chemically by using MRS metabolic ratio ( low NAA/Cr, NAA/Cho ratios, and high Lac/Cr ratio).
Early detection of neurological abnormalities using ABR parameters in high-risk neonates without oblivious clinical signs
Time frame: 2 years
Early detection of neurological abnormalities in high-risk neonates, without oblivious clinical signs, functionally through ABR parameters ( prolonged wave III peak latency, wave V peak latency, I-III interpeak interval, and I-V interpeak interval )
Bilirubin level and auditory abnormality
Time frame: 2 years
Finding out the lowest level of total serum bilirubin at which auditory pathway abnormality was found, in comparison to age.
Bilirubin level and MRS abnormality
Time frame: 2 years
Finding out the lowest level of total serum bilirubin at which MRS abnormalities were found, in comparison to age.
2 secondary outcomes
Discriminative capacity of MRS for acute bilirubin encephalopathy
Time frame: 2 years
Discriminative capacity of ABR for acute bilirubin encephalopathy
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
- Background: PubMed 24256380Watchko JF, Tiribelli C. Bilirubin-induced neurologic damage--mechanisms and management approaches. N Engl J Med. 2013 Nov 21;369(21):2021-30. doi: 10.1056/NEJMra1308124. No abstract available.
- BackgroundUsman, F., Diala, U., Shapiro, S., Le Pichon, J.-B., & Slusher, T. Acute bilirubin encephalopathy and its progression to kernicterus: current perspectives. Research and Reports in Neonatology, 8, 33-44 (2018).
- Background: PubMed 27235209Watchko JF. Bilirubin-Induced Neurotoxicity in the Preterm Neonate. Clin Perinatol. 2016 Jun;43(2):297-311. doi: 10.1016/j.clp.2016.01.007. Epub 2016 Mar 2.
- Background: PubMed 30823396Das S, van Landeghem FKH. Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus. Diagnostics (Basel). 2019 Feb 28;9(1):24. doi: 10.3390/diagnostics9010024.
- Background: PubMed 32844928Teixeira MH, Borges VMS, Riesgo RDS, Sleifer P. Hyperbilirubinemia impact on newborn hearing: a literature review. Rev Assoc Med Bras (1992). 2020 Jul;66(7):1002-1008. doi: 10.1590/1806-9282.66.7.1002. Epub 2020 Aug 24.
- Background: PubMed 25575899Olds C, Oghalai JS. Audiologic impairment associated with bilirubin-induced neurologic damage. Semin Fetal Neonatal Med. 2015 Feb;20(1):42-46. doi: 10.1016/j.siny.2014.12.006. Epub 2015 Jan 7.
- Derived from this study: PubMed 37979048Zidan LK, Rowisha MA, Nassar MAE, Elshafey RA, El Mahallawi TH, Elmahdy HS. Magnetic resonance spectroscopy and auditory brain-stem response audiometry as predictors of bilirubin-induced neurologic dysfunction in full-term jaundiced neonates. Eur J Pediatr. 2024 Feb;183(2):727-738. doi: 10.1007/s00431-023-05246-z. Epub 2023 Nov 18.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 Neonatal Hyperbilirubinemia, run by Tanta University at 1 site in Egypt.
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 1 inclusion and 10 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: finished, as of the sponsor's last update on 1 Sep 2023. 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 Egypt. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Early detection of neurological abnormalities using MRS metabolic ratios in high-risk neonates without oblivious clinical signs (time frame: 2 years). The study lists 4 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 NCT06018012, which also lists 7 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 1 Sep 2023.