Clinical trial NCT06018012: MRA and ABR as Early Predictors of Bilirubin-Induced Neurologic Dysfunction in Full-term Jaundiced Neonates
Official title: Magnetic Resonance Spectroscopy and Auditory Brain- Stem Response Audiometry as Early Predictors of Bilirubin-Induced Neurologic Dysfunction in Full-term Jaundiced Neonates
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neonatal Hyperbilirubinemia
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2023-08-30
Enrollment: 76
Sex: ALL
Minimum age (years): 1
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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).

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

1. Preterm neonates (less than 37 weeks).
2. Clinically moderate and severe acute bilirubin encephalopathy according to modified Bilirubin-induced neurologic dysfunction (BIND-M) score.
3. Neonates born with birth asphyxia and/or poor Apgar score.
4. Neonates with sepsis including CNS infection.
5. Neonates with family history of childhood hearing loss.
6. Congenital infection.
7. Chromosomal abnormalities.
8. Congenital ear anomalies associated with hearing loss or brain abnormalities including craniofacial anomalies.
9. Patients who were receiving ototoxic drugs as aminoglycosides.
10. Conjugated hyperbilirubinemia.

Primary outcomes:
measure: Early detection of neurological abnormalities using MRS metabolic ratios in high-risk neonates without oblivious clinical signs
timeFrame: 2 years
measure: Early detection of neurological abnormalities using ABR parameters in high-risk neonates without oblivious clinical signs
timeFrame: 2 years
measure: Bilirubin level and auditory abnormality
timeFrame: 2 years
measure: Bilirubin level and MRS abnormality
timeFrame: 2 years
Secondary outcomes:
measure: Discriminative capacity of MRS for acute bilirubin encephalopathy
timeFrame: 2 years
measure: Discriminative capacity of ABR for acute bilirubin encephalopathy
timeFrame: 2 years
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: faculty of medicine,Tanta University
state: Q2x2+cp Tanta 2
Study officials:
References:
citation: 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.
citation: Usman, 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).
citation: 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.
citation: Das S, van Landeghem FKH. Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus. Diagnostics (Basel). 2019 Feb 28;9(1):24. doi: 10.3390/diagnostics9010024.
citation: Teixeira 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.
citation: Olds 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.