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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Magnetic Resonance Spectroscopy and Auditory Brain- Stem Response Audiometry as Early Predictors of Bilirubin-Induced Neurologic Dysfunction in Full-term Jaundiced Neonates

Conditions
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Neonatal Hyperbilirubinemia

Intervention / Treatment
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* Device: MRS and ABR


Participation Criteria
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Eligibility Criteria
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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: 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. 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.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 28 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

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 |