Hyperbilirubinemia, NeonatalNCT06603753
Role of Serum (B/A) Ratio Compared to (TSB) for Early Prediction of Bilirubin-induced Neurological Dysfunction (BIND).
An observational study of Hyperbilirubinemia, Neonatal, run by alaa aboelhassan mohamed aboelhassan.
Trial summary
The aim of this study is to evaluate serum bilirubin/albumin (B/A) ratio compared to total serum bilirubin (TSB) for early prediction of bilirubin-induced neurological dysfunction (BIND). Read more about this study
- Who is it for?
- Ages 1 day to 28 daysHealthy volunteers can take part
- Conditions the study is for
- Hyperbilirubinemia, Neonatal
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2025to 1 Jul 2026
- 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: Assiut university children hospital Prospective descriptive study
Who may be able to join
None listed.
Who cannot join
- Conjugated hyperbilirubinemia.
- Perinatal asphyxia.
- Patients with encephalopathy due to causes other than hyperbilirubinemia.
- Severe birth defects or congenital anomalies.
- Hemodynamic instability.
- Septic patients.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Use of Serum Bilirubin/Albumin Ratio for Early Prediction of Bilirubin Induced Neurological Dysfunction
The aim of this study is to evaluate serum bilirubin/albumin (B/A) ratio compared to total serum bilirubin (TSB) for early prediction of bilirubin-induced neurological dysfunction (BIND).
Read the detailed description
Introduction Neonatal hyperbilirubinemia is a common problem in neonates. Approximately 60% of term and 80% of preterm babies develop jaundice in the first week of life and about 10% of breastfed babies are still jaundiced at 1 month.
Jaundice due to either indirect (unconjugated) or direct (conjugated) bilirubin within the first 24 h of life should be taken seriously. Early identification and proper management are needed to prevent the serious neurological complications .
When the total serum bilirubin (TSB) rises above the 95th percentile for age (high-risk zone), entry of unconjugated bilirubin into the brain can cause both short-term and long-term neurological dysfunctions (bilirubin encephalopathy) . The increased level of bilirubin is detrimental for nervous system, especially damage the basal ganglia, cerebellum, and brainstem, thus, resulting in bilirubin-induced neurological dysfunction (BIND) .
Bilirubin-induced neurologic dysfunction (BIND) is the term applied to the spectrum of neurologic abnormalities associated with hyperbilirubinemia. It can be further divided into characteristic signs and symptoms that appear in the early stages (acute) and those that evolve over a prolonged period (chronic) . Signs and symptoms of BIND include tone abnormalities such as hypotonia, hypertonia, retrocollis and opisthotonos, in association with varying degrees of drowsiness, lethargy, decreased feeding and irritability .
BIND was also associated with Kernicterus leading to devastating disability including athetoid cerebral palsy, speech and hearing impairment. BIND in neonates is a significant cause of death or lifelong disability, including cerebral palsy (CP) and auditory disorders .
The earliest signs and symptoms of BIND are nonspecific therefore may be easily missed thus an early diagnostic tool is required. BIND score is a scoring system, in which characteristics of mental state, muscle tone, and cry are grouped into three levels of increasing abnormality: stage IA, minimal signs; stage IB, progressive but reversible with treatment; stage II, advanced and largely irreversible, but may be significantly decreased by treatment .
The pathogenesis of BIND is multifactorial and includes interaction between the level of unconjugated bilirubin, free bilirubin, bilirubin bound to albumin, bilirubin passed through brain blood barrier and nerves damage. Although 99.9% of unconjugated bilirubin in the circulation is bound to albumin, a relatively small fraction (only less than 0.1%) remains unbound (free bilirubin) and it can go into the brain across an intact blood brain barrier (BBB) .
There is currently no method available for measuring free bilirubin concentrations accurately in plasma or serum; therefore, adjunct measurements of albumin concentration and bilirubin albumin ratio (B/A) may provide more insight into the likelihood of bilirubin-induced encephalopathy. The B/A ratio is considered a surrogate parameter for free bilirubin and an interesting additional parameter in the management of hyperbilirubinemia. Few studies suggested the utilization of B/A ratios as a predictor for bilirubin-induced neurotoxicity .
- Conditions
- Hyperbilirubinemia, Neonatal
- Medical subject headings
- Hyperbilirubinemia, Neonatal
What is being measured
The primary outcome is the main question the study is designed to answer.
Early detection of cases of severe neonatal jaundice for exchange transfusion to avoid complications of kernicterus
- The Bind score will be used. The BIND score includes 3 categories: mental status, muscle tone, and cry patterns. Each category will be given a score ranging from 0 to 3.
- A BIND score of 7-9 will represent advanced signs of encephalopathy, Score of 4-6 will represent moderate signs of encephalopathy and Score of 1-3 encephalopathy subtle signs.
Laboratory methods:
- Blood sampling: venous blood will be obtained from each patient under aseptic conditions and collected into 3.2% sodium citrate tubes, except for CBC samples which will be drawn into EDTA tubes.
- Complete blood count and reticulocyte count: The CBC and reticulocyte counts for both mothers and their babies will be analyzed using an automated hematology analyzer. The CBC parameters analyzed will include hemoglobin level, RBCs, WBCs, and platelet count.
- Blood Grouping: Blood groups will be detected for both mother and her baby.
- Liver function tests: The tests will include serum levels of AST, ALT, total bilirubin,
Measured: baseline
Secondary outcomes (1)
Avoidance of complications of severe neonatal jaundice
- Personal data including age and sex, demographics including residence and socioeconomic status.
- Clinical data including vital signs, body mass index (BMI) and the BIND score.
- Laboratory data including Complete blood count and reticulocyte count, blood grouping for mother and baby, liver and bilirubin to albumin ration
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start1 Jan 2025 (estimated)
- Primary completion1 Jan 2026 (estimated)
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Hyperbilirubinemia, NeonatalStudies 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
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- alaa aboelhassan mohamed aboelhassan
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, alaa aboelhassan mohamed aboelhassan, Assiut University
- Investigators
- Mahmoud A Ahmed, Dr, Study director, Assiut UniversityJaafar I Mohamad, Prof, Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06603753
- Sponsor's protocol ID
- B/A ratio to predict of bind
- Status last verified
- Sep 2024
- First submitted
- 7 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Karimzadeh P, Fallahi M, Kazemian M, Taslimi Taleghani N, Nouripour S, Radfar M. Bilirubin Induced Encephalopathy. Iran J Child Neurol. 2020 Winter;14(1):7-19.
PubMed 32021624Hameed NN, Hussein MA. BIND score: A system to triage infants readmitted for extreme hyperbilirubinemia. Semin Perinatol. 2021 Feb;45(1):151354. doi: 10.1016/j.semperi.2020.151354. Epub 2020 Dec 1.
PubMed 33309176Paar M, Fengler VH, Reibnegger G, Schnurr K, Waterstradt K, Schwaminger SP, Stauber RE, Oettl K. Determination of binding characteristics as a measure for effective albumin using different methods. Biochim Biophys Acta Gen Subj. 2023 Sep;1867(9):130427. doi: 10.1016/j.bbagen.2023.130427. Epub 2023 Jul 15.
PubMed 37454915Wang Y, Sheng G, Shi L, Cheng X. Increased serum total bilirubin-albumin ratio was associated with bilirubin encephalopathy in neonates. Biosci Rep. 2020 Jan 31;40(1):BSR20192152. doi: 10.1042/BSR20192152.
PubMed 31950971Kasirer Y, Kaplan M, Hammerman C. Kernicterus on the Spectrum. Neoreviews. 2023 Jun 1;24(6):e329-e342. doi: 10.1542/neo.24-6-e329.
PubMed 37258501El Houchi SZ, Iskander I, Gamaleldin R, El Shenawy A, Seoud I, Abou-Youssef H, Wennberg RP. Prediction of 3- to 5-Month Outcomes from Signs of Acute Bilirubin Toxicity in Newborn Infants. J Pediatr. 2017 Apr;183:51-55.e1. doi: 10.1016/j.jpeds.2016.12.079. Epub 2017 Jan 25.
PubMed 28131490Ding Y, Wang S, Guo R, Zhang A, Zhu Y. High levels of unbound bilirubin are associated with acute bilirubin encephalopathy in post-exchange transfusion neonates. Ital J Pediatr. 2021 Sep 15;47(1):187. doi: 10.1186/s13052-021-01143-z.
PubMed 34526082Kang W, Yuan X, Zhang Y, Song J, Xu F, Liu D, Li R, Xu B, Li W, Cheng Y, Zhu C. Early prediction of adverse outcomes in infants with acute bilirubin encephalopathy. Ann Clin Transl Neurol. 2020 Jul;7(7):1141-1147. doi: 10.1002/acn3.51077. Epub 2020 Jun 4.
PubMed 32495505
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Serum Bilirubin/Albumin Ratio for Early Prediction of Bilirubin Induced Neurological Dysfunction
- ClinicalTrials.gov ID
- NCT06603753
- Acronym / sponsor ID
- B/A ratio to predict of bind
- Conditions
- Hyperbilirubinemia, Neonatal
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- alaa aboelhassan mohamed aboelhassanUniversity, hospital or other
- Study start
- 1 Jan 2025 (estimated)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 1 Jul 2026 (estimated)
- First posted
- 19 Sep 2024 (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 this study is to evaluate serum bilirubin/albumin (B/A) ratio compared to total serum bilirubin (TSB) for early prediction of bilirubin-induced neurological dysfunction (BIND).
Detailed description
Introduction Neonatal hyperbilirubinemia is a common problem in neonates. Approximately 60% of term and 80% of preterm babies develop jaundice in the first week of life and about 10% of breastfed babies are still jaundiced at 1 month.
Jaundice due to either indirect (unconjugated) or direct (conjugated) bilirubin within the first 24 h of life should be taken seriously. Early identification and proper management are needed to prevent the serious neurological complications .
When the total serum bilirubin (TSB) rises above the 95th percentile for age (high-risk zone), entry of unconjugated bilirubin into the brain can cause both short-term and long-term neurological dysfunctions (bilirubin encephalopathy) . The increased level of bilirubin is detrimental for nervous system, especially damage the basal ganglia, cerebellum, and brainstem, thus, resulting in bilirubin-induced neurological dysfunction (BIND) .
Bilirubin-induced neurologic dysfunction (BIND) is the term applied to the spectrum of neurologic abnormalities associated with hyperbilirubinemia. It can be further divided into characteristic signs and symptoms that appear in the early stages (acute) and those that evolve over a prolonged period (chronic) . Signs and symptoms of BIND include tone abnormalities such as hypotonia, hypertonia, retrocollis and opisthotonos, in association with varying degrees of drowsiness, lethargy, decreased feeding and irritability .
BIND was also associated with Kernicterus leading to devastating disability including athetoid cerebral palsy, speech and hearing impairment. BIND in neonates is a significant cause of death or lifelong disability, including cerebral palsy (CP) and auditory disorders .
The earliest signs and symptoms of BIND are nonspecific therefore may be easily missed thus an early diagnostic tool is required. BIND score is a scoring system, in which characteristics of mental state, muscle tone, and cry are grouped into three levels of increasing abnormality: stage IA, minimal signs; stage IB, progressive but reversible with treatment; stage II, advanced and largely irreversible, but may be significantly decreased by treatment .
The pathogenesis of BIND is multifactorial and includes interaction between the level of unconjugated bilirubin, free bilirubin, bilirubin bound to albumin, bilirubin passed through brain blood barrier and nerves damage. Although 99.9% of unconjugated bilirubin in the circulation is bound to albumin, a relatively small fraction (only less than 0.1%) remains unbound (free bilirubin) and it can go into the brain across an intact blood brain barrier (BBB) .
There is currently no method available for measuring free bilirubin concentrations accurately in plasma or serum; therefore, adjunct measurements of albumin concentration and bilirubin albumin ratio (B/A) may provide more insight into the likelihood of bilirubin-induced encephalopathy. The B/A ratio is considered a surrogate parameter for free bilirubin and an interesting additional parameter in the management of hyperbilirubinemia. Few studies suggested the utilization of B/A ratios as a predictor for bilirubin-induced neurotoxicity .
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 1 day to 28 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Assiut university children hospital Prospective descriptive study
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- Conjugated hyperbilirubinemia.
- Perinatal asphyxia.
- Patients with encephalopathy due to causes other than hyperbilirubinemia.
- Severe birth defects or congenital anomalies.
- Hemodynamic instability.
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
Early detection of cases of severe neonatal jaundice for exchange transfusion to avoid complications of kernicterus
Time frame: baseline
* The Bind score will be used. The BIND score includes 3 categories: mental status, muscle tone, and cry patterns. Each category will be given a score ranging from 0 to 3. * A BIND score of 7-9 will represent advanced signs of encephalopathy, Score of 4-6 will represent moderate signs of encephalopathy and Score of 1-3 encephalopathy subtle signs. Laboratory methods: * Blood sampling: venous blood will be obtained from each patient under aseptic conditions and collected into 3.2% sodium citrate tubes, except for CBC samples which will be drawn into EDTA tubes. * Complete blood count and reticulocyte count: The CBC and reticulocyte counts for both mothers and their babies will be analyzed using an automated hematology analyzer. The CBC parameters analyzed will include hemoglobin level, RBCs, WBCs, and platelet count. * Blood Grouping: Blood groups will be detected for both mother and her baby. * Liver function tests: The tests will include serum levels of AST, ALT, total bilirubin,
1 secondary outcome
Avoidance of complications of severe neonatal jaundice
Time frame: baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Background: PubMed 32021624Karimzadeh P, Fallahi M, Kazemian M, Taslimi Taleghani N, Nouripour S, Radfar M. Bilirubin Induced Encephalopathy. Iran J Child Neurol. 2020 Winter;14(1):7-19.
- Background: PubMed 33309176Hameed NN, Hussein MA. BIND score: A system to triage infants readmitted for extreme hyperbilirubinemia. Semin Perinatol. 2021 Feb;45(1):151354. doi: 10.1016/j.semperi.2020.151354. Epub 2020 Dec 1.
- Background: PubMed 37454915Paar M, Fengler VH, Reibnegger G, Schnurr K, Waterstradt K, Schwaminger SP, Stauber RE, Oettl K. Determination of binding characteristics as a measure for effective albumin using different methods. Biochim Biophys Acta Gen Subj. 2023 Sep;1867(9):130427. doi: 10.1016/j.bbagen.2023.130427. Epub 2023 Jul 15.
- Background: PubMed 31950971Wang Y, Sheng G, Shi L, Cheng X. Increased serum total bilirubin-albumin ratio was associated with bilirubin encephalopathy in neonates. Biosci Rep. 2020 Jan 31;40(1):BSR20192152. doi: 10.1042/BSR20192152.
- Background: PubMed 37258501Kasirer Y, Kaplan M, Hammerman C. Kernicterus on the Spectrum. Neoreviews. 2023 Jun 1;24(6):e329-e342. doi: 10.1542/neo.24-6-e329.
- Results publication: PubMed 28131490El Houchi SZ, Iskander I, Gamaleldin R, El Shenawy A, Seoud I, Abou-Youssef H, Wennberg RP. Prediction of 3- to 5-Month Outcomes from Signs of Acute Bilirubin Toxicity in Newborn Infants. J Pediatr. 2017 Apr;183:51-55.e1. doi: 10.1016/j.jpeds.2016.12.079. Epub 2017 Jan 25.
- Results publication: PubMed 34526082Ding Y, Wang S, Guo R, Zhang A, Zhu Y. High levels of unbound bilirubin are associated with acute bilirubin encephalopathy in post-exchange transfusion neonates. Ital J Pediatr. 2021 Sep 15;47(1):187. doi: 10.1186/s13052-021-01143-z.
- Results publication: PubMed 32495505Kang W, Yuan X, Zhang Y, Song J, Xu F, Liu D, Li R, Xu B, Li W, Cheng Y, Zhu C. Early prediction of adverse outcomes in infants with acute bilirubin encephalopathy. Ann Clin Transl Neurol. 2020 Jul;7(7):1141-1147. doi: 10.1002/acn3.51077. Epub 2020 Jun 4.
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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.
Mahmoud A Ahmed, Dr study director
Assiut University
Jaafar I Mohamad, Prof study director
Assiut University
Questions about this trial
What is this clinical trial studying?
An observational study of Hyperbilirubinemia, Neonatal, run by alaa aboelhassan mohamed aboelhassan.
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 0 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact alaa A mohamed (800 555 5555, aboelhassanalaa209@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early detection of cases of severe neonatal jaundice for exchange transfusion to avoid complications of kernicterus (time frame: baseline). 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 NCT06603753, which also lists 8 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 19 Sep 2024.