MRA and ABR as Early Predictors of Bilirubin-Induced Neurologic Dysfunction in Full-term Jaundiced Neonates

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).

Study Overview

• Status: Completed
• Conditions: Neonatal Hyperbilirubinemia
• Intervention / Treatment: Device: MRS and ABR

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 Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• Egypt
  • Q2x2+cp Tanta 2
    • Tanta, Q2x2+cp Tanta 2, Egypt, 31527
      • faculty of medicine,Tanta University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1 or acute bilirubin encephalopathy; Group (1): included 26 cases with BIND or acute bilirubin encephalopathy (ABE).	Device: MRS and ABR; Magnetic Resonance Spectroscopy and Auditory Brain- stem Response Audiometry
2 or neonatal hyperbilirubinemia; Group (2): included 30 cases with neonatal hyperbilirubinemia on	Device: MRS and ABR; Magnetic Resonance Spectroscopy and Auditory Brain- stem Response Audiometry
Control; control group: 20 healthy, age-matched neonates	Device: MRS and ABR; Magnetic Resonance Spectroscopy and Auditory Brain- stem Response Audiometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	2 years
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).	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 )	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	2 years

Collaborators and Investigators

• Sponsor: Tanta University

Publications and helpful links

General 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.
• 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).
• 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.
• Das S, van Landeghem FKH. Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus. Diagnostics (Basel). 2019 Feb 28;9(1):24. doi: 10.3390/diagnostics9010024.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 30, 2023

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Infant, Newborn, Diseases; Neurologic Manifestations; Hyperbilirubinemia; Hyperbilirubinemia, Neonatal
• Other Study ID Numbers: MRS& ABR in jaundiced neonates

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No