Audiological assessment of neonatal hyperbilirubinemia.

OBJECT: To evaluate the hearing of infants with history of neonatal hyperbilirubinemia using ABR. METHODS: A prospective randomized study carried on 100 infants whose hearing was assessed by ABR. Infants were allocated into two groups; case group which involve 60 infants with history of neonatal hyperbilirubinemia (bilirubin more than17 mg/dl and less than 30 mg/dl) and control group involve 40 healthy infants. Each group was divided into 3 groups based on their age i.e. ≤ 6 months, > 6-9 months &> 9-12 months. The evaluated variables were latency time & inter peak latency time. RESULTS: The mean latencies of wave III&V of ABR were significantly higher in the case group compared with the controls (P < 0.001) while the mean latencies of wave I did not show a significant difference between the two study groups (P > 0.05). The mean inter wave latencies I-III, I-V& III-V of ABR were significantly higher in the case group compared with the controls. There was a negative correlation between age and the studied variables. CONCLUSION: Hyperbilirubinemia have an adverse effect on neonatal hearing which was reflected by ABR parameters of this study.

Frequency-following response among neonates with progressive moderate hyperbilirubinemia.

OBJECTIVE: To evaluate the feasibility of auditory monitoring of neurophysiological status using frequency-following response (FFR) in neonates with progressive moderate hyperbilirubinemia, measured by transcutaneous (TcB) levels. STUDY DESIGN: ABR and FFR measures were compared and correlated with TcB levels across three groups. Group I was a healthy cohort (n = 13). Group II (n = 28) consisted of neonates with progressive, moderate hyperbilirubinemia and Group III consisted of the same neonates, post physician-ordered phototherapy. RESULT: FFR amplitudes in Group I controls (TcB = 83.1 ± 32.5µmol/L; 4.9 ± 1.9 mg/dL) were greater than Group II (TcB = 209.3 ± 48.0µmol/L; 12.1 ± 2.8 mg/dL). After TcB was lowered by phototherapy, FFR amplitudes in Group III were similar to controls. Lower TcB levels correlated with larger FFR amplitudes (r = -0.291, p = 0.015), but not with ABR wave amplitude or latencies. CONCLUSION: The FFR is a promising measure of the dynamic neurophysiological status in neonates, and may be useful in tracking neurotoxicity in infants with hyperbilirubinemia.

Effects of Massage Therapy on Indirect Hyperbilirubinemia in Newborns Who Receive Phototherapy.

OBJECTIVE: To evaluate the effects of massage therapy on total serum bilirubin (TSB) levels and frequency of defecation, urination, and feeding in newborns who receive phototherapy for indirect hyperbilirubinemia. DESIGN: A randomized controlled clinical trial. SETTING: Ankara University Cebeci Research and Training Hospital and 29 May State Hospital in Ankara, Turkey. PARTICIPANTS: Fifty full-term newborns with indirect hyperbilirubinemia who underwent phototherapy. METHODS: The newborns were randomly allocated to an intervention group (n = 25) or a control group (n = 25). Newborns in the intervention group received massage therapy throughout the duration of phototherapy for 15 minutes twice per day; newborns in the control group received routine care during phototherapy. Every 24 hours, TSB levels were measured, and the frequencies of defecation, urination, and feeding were also calculated for each newborn. RESULTS: We found no differences in the characteristics of the newborns or in TSB levels between groups at enrollment. After treatment, TSB levels were lower in the intervention group (p < .001). Frequencies of defecation, urination, and feeding were significantly greater in the intervention group than in the control group. CONCLUSION: Massage therapy had significant effects on TSB levels, feeding, breastfeeding, defecation, and urination in newborns who received phototherapy for indirect hyperbilirubinemia. Massage therapy can be added as routine care for full-term newborns with hyperbilirubinemia under phototherapy and may be an effective supplementary intervention.

A randomized control trial of phototherapy and 20% albumin versus phototherapy and saline in Kilifi, Kenya.

OBJECTIVE: The study evaluated the efficacy of phototherapy and 20% albumin infusion to reduce total serum bilirubin (TSB) in neonates with severe hyperbilirubinemia. The primary outcome was a reduction of TSB at the end of treatment. The secondary outcomes were the need for exchange transfusion, inpatient mortality, neurological outcomes at discharge, and development outcomes at 12-months follow-up. RESULTS: One hundred and eighteen neonates were randomly assigned to phototherapy and 20% albumin (n = 59) and phototherapy and saline (n = 69). The median age at admission was 5 (interquartile range (IQR) 3-6) days, and the median gestation was 36 (IQR 36-38) weeks. No significant differences were found in the change in TSB (Mann-Whitney U =609, p = 0.98) and rate of change in TSB per hour after treatment (Mann-Whitney U = 540, p = 0.39) between the two groups. There were no significant differences between the two groups in the proportion of participants who required exchange transfusion (χ2 (2) = 0.36, p = 0.546); repeat phototherapy (χ2 (2) = 2.37, p = 0.123); and those who died (χ2 (2) = 0.92, p = 0.337). Trial registration The trial was registered in the International Standardized Randomized Controlled Trial Number (ISRCTN); trial registration number ISRCTN89732754.

Unusual cause of severe neonatal hyperbilirubinaemia: a twin case.

We present twins born to the 31-year-old, multigravida mother, who were referred to our centre at 90 hours of life for severe hyperbilirubinaemia. Twin 1 had already received two double volume exchange transfusions at 55 and 83 hours of life, in view of the persistent rise in bilirubin despite receiving phototherapy. Twin 2 had received phototherapy and 1 packed red blood cell transfusion in view of the fall in haematocrit. Mother's blood group was B positive and that of both twins was O positive. Both the twins were started on intensive phototherapy and their serum bilirubin and haematocrit were evaluated. On investigation, a minor blood incompatibility was found. Double volume exchange transfusion was done for twin 2 at 100 hours of life in view of the rapid rise in serum bilirubin. Both the babies were monitored for their serum bilirubin and treated for sepsis and discharged after 15 days.

High unbound bilirubin for age: a neurotoxin with major effects on the developing brain.

Neonatal hyperbilirubinemia is one of the most frequent diagnoses made in neonates. A high level of unconjugated bilirubin that is unbound to albumin is neurotoxic when the level exceeds age-specific thresholds or at lower levels in neonates with neurotoxic risk factors. Lower range of unbound bilirubin results in apoptosis, while moderate-to-high levels result in neuronal necrosis. Basal ganglia and various brain stem nuclei are more susceptible to bilirubin toxicity. Proposed mechanisms of bilirubin-induced neurotoxicity include excessive release of glutamate, mitochondrial energy failure, release of proinflammatory cytokines, and increased intracellular calcium concentration. These mechanisms are similar to the events that occur following hypoxic-ischemic insult in neonates. Severe hyperbilirubinemia in term neonates has been shown to be associated with increased risk for autism spectrum disorders. The neuropathological finding of bilirubin-induced neurotoxicity also includes cerebellar injury with a decreased number of Purkinje cells, and disruption of multisensory feedback loop between cerebellum and cortical neurons which may explain the clinical characteristics of autism spectrum disorders. Severe hyperbilirubinemia occurs more frequently in infants from low- and middle-income countries (LMIC). Simple devices to measure bilirubin, and timely treatment are essential to reduce neurotoxicity, and improve outcomes for thousands of neonates around the world.

Iron-mediated oxidative cell death is a potential contributor to neuronal dysfunction induced by neonatal hemolytic hyperbilirubinemia.

The review article discusses current knowledge of iron-mediated oxidative cell death (ferroptosis) and its potential role in the pathogenesis of neuronal dysfunction induced by neonatal hemolytic hyperbilirubinemia. The connection between metabolic conditions related to hemolysis (iron and bilirubin overload) and iron-induced lipid peroxidation is highlighted. Neurotoxicity of iron and bilirubin is associated with their release from destructed erythrocytes in response to hemolytic disease. Iron overload initiates lipid peroxidation through the reactive oxygen species production resulting to oxidative damage to cells. Excessive loading of immature brain cells by iron-induced formation of reactive oxygen species contributes to the development of various neurodevelopmental disorders. The causal relationship between iron overload and susceptibility of brain cells to oxidative damage by ferroptosis appears to be associated not only with the amount of redox-active iron involved in oxidative cell damage but also with the degree of maturity of the neonatal brain. Neuronal dysfunction induced by neonatal hemolytic disease can represent a specific model of ferroptosis. The mechanism by which iron overload triggers ferroptosis is not completely explained. However, hemolysis of neonatal red blood cells appears to be a determining factor. Potential therapeutic strategy with iron-chelating agents to inhibit ferroptosis has a promising future in postnatal care.

Hyperthyroxinemia at birth: a cause of idiopathic neonatal hyperbilirubinemia?

BACKGROUND: Some neonates develop idiopathic hyperbilirubinemia (INHB) requiring phototherapy, yet with no identifiable causes. We searched for an association between abnormal thyroid levels after birth and INHB. METHODS: Of 5188 neonates, 1681 (32.4%) were excluded due to one or more risk factors for hyperbilirubinemia. Total thyroxine (TT4) and thyroid stimulating hormone values were sampled routinely at 40-48 hours of age and measured in the National Newborn Screening Program. RESULTS: Of the 3507 neonates without known causes for hyperbilirubinemia, 61 (1.7%) developed INHB and received phototherapy. Univariate analyses found no significant association between mode of delivery and INHB (vacuum-delivered neonates were a priori excluded). Nonetheless, in cesarean-delivered (CD) neonates, two variables had significant association with INHB: TT4 ≥ 13 µg/dL and birth at 38-38.6 weeks. In vaginally delivered (VD) born neonates, INHB was associated with weight loss > 7.5% up to 48 hours of age. Multivariate logistic regression analysis showed a strong effect of mode of delivery on possible significant association with INHB. In CD neonates, such variables included: TT4 ≥ 13 µg/dL [P = 0.025, odds ratio (OR) 5.49, 95% confidence interval (CI) 1.23-24.4] and birth at 38-38.6 weeks (P = 0.023, OR 3.44, 95% CI 1.19-9.97). In VD neonates, weight loss > 7.5% (P = 0.019, OR 2.1, 95% CI 1.13-3.83) and 1-min Apgar score < 9 (P < 0.001, OR 3.8, 95% CI 1.83-7.9), but not TT4, showed such an association. CONCLUSIONS: INHB was significantly associated with birth on 38-38.6 week and TT4 (≥ 13 µg/dL) in CD neonates, and with a weight loss > 7.5% in VD neonates. We herein highlight some acknowledged risk factors for neonatal hyperbilirubinemia, and thus minimize the rate of INHB.

Severe neonatal hyperbilirubinemia induces temporal and occipital lobe seizures.

To examine the origin of seizures induced by severe neonatal hyperbilirubinemia, The EEG characteristics of seizures were analyzed in newborns with and without severe neonatal hyperbilirubinemia. Fisher's exact test was used to determine the specificity. In total, 931 patients had a total serum bilirubin (TSB) level of 340-425 µmol/L, only 2 of whom had seizures. Compared to patients with hyperbilirubinemia and a TSB level of 340-425 µmol/L, those with a TSB level >425 µmol/L had a significant risk of seizure (OR = 213.2, 95% CI = 113.0-405.8, P<0.001). Of all 28 patients with severe hyperbilirubinemia and seizure, 26 had seizures that originated in the temporal and/or occipital lobe. In seizure patients without severe hyperbilirubinemia, origination in the temporal/occipital and other lobes occurred in 19 and 117 cases, respectively. Compared to the risk of seizure origination in the temporal and/or occipital lobe in other diseases, the risk in patients with severe hyperbilirubinemia was increased by approximately 80 times (OR = 80.1, 95% CI = 28.3-226.4, P<0.001). Severe neonatal hyperbilirubinemia can selectively induce temporal and occipital lobe seizures. This is the first report of a new syndrome with the same etiology and electrophysiological features as epilepsy.

Attenuation of neuro-inflammation improves survival and neurodegeneration in a mouse model of severe neonatal hyperbilirubinemia.

All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combination of unfavorable complications may lead to acute hyperbilirubinemia. Excessive hyperbilirubinemia may be toxic for the developing nervous system leading to severe neurological damage and death by kernicterus. Survivors show irreversible neurological deficits such as motor, sensitive and cognitive abnormalities. Current therapies rely on the use of phototherapy and, in unresponsive cases, exchange transfusion, which is performed only in specialized centers. During bilirubin-induced neurotoxicity different molecular pathways are activated, ranging from oxidative stress to endoplasmic reticulum (ER) stress response and inflammation, but the contribution of each pathway in the development of the disease still requires further investigation. Thus, to increase our understanding of the pathophysiology of bilirubin neurotoxicity, encephalopathy and kernicterus, we pharmacologically modulated neurodegeneration and neuroinflammation in a lethal mouse model of neonatal hyperbilirubinemia. Treatment of mutant mice with minocycline, a second-generation tetracycline with anti-inflammatory and neuroprotective properties, resulted in a dose-dependent rescue of lethality, due to reduction of neurodegeneration and neuroinflammation, without affecting plasma bilirubin levels. In particular, rescued mice showed normal motor-coordination capabilities and behavior, as determined by the accelerating rotarod and open field tests, respectively. From the molecular point of view, rescued mice showed a dose-dependent reduction in apoptosis of cerebellar neurons and improvement of dendritic arborization of Purkinje cells. Moreover, we observed a decrease of bilirubin-induced M1 microglia activation at the sites of damage with a reduction in oxidative and ER stress markers in these cells. Collectively, these data indicate that neurodegeneration and neuro-inflammation are key factors of bilirubin-induced neonatal lethality and neuro-behavioral abnormalities. We propose that the application of pharmacological treatments having anti-inflammatory and neuroprotective effects, to be used in combination with the current treatments, may significantly improve the management of acute neonatal hyperbilirubinemia, protecting from bilirubin-induced neurological damage and death.

Hyperbilirubinemia-induced pro-angiogenic activity of infantile endothelial progenitor cells.

OBJECTIVES: Bilirubin, a by-product of heme degradation, is suggested to have a role for vascular protection. There is increasing evidence that bilirubin may directly affect the function and secretory activity of endothelial cells. In this study, potential effect of hyperbilirubinemia on biological features of circulation endothelial progenitor cells (cEPCs) isolated from infants was investigated. METHODS: Circulation concentration, differentiation and migratory activity of cEPCs isolated from infants with (n = 111) or without (n = 73) hyperbilirubinemia were analyzed. Then, the potential beneficial effect of conditioned medium of cEPCs from infants with or without hyperbilirubinemia was examined on experimental mouse wounds. RESULTS: Our results revealed significantly higher percentages of cEPCs in infants with hyperbilirubinemia. Cell proliferation, and migratory properties of cEPCs isolated and expanded from infants with hyperbilirubinemia were significantly improved. Also, the conditioned medium of cEPCs from hyperbilirubinemic infants possessed a superior beneficial effect on wound healing, which was associated with increased protein levels of VEGF, IL-10, and Pho-ERK/ERK, and decreased TNF-α in the wound tissues. CONCLUSIONS: Our results showed that hyperbilirubinemia can activate migration, proliferating and angiogenic properties of cEPCs. Hyperbilirubinemia can promote the proangiogenic secretory activity of cEPCs, thereby resulting in enhancement of their regenerative wound healing properties.

Clinical study on amplitude integrated electroencephalogram in cerebral injury caused by severe neonatal hyperbilirubinemia.

BACKGROUND: This study was designed in order to assess the validity of the use of amplitude-integrated electroencephalogram (aEEG) in cerebral injury caused by severe neonatal hyperbilirubinemia. METHODS: A total of 56 full-term neonates diagnosed with severe neonatal hyperbilirubinemia and admitted to the NICU of our hospital from July 2013 to December 2014 were continuously selected for the study. The total serum bilirubin (TSB) was higher than 342 µmol/L and was dominated by a higher amount of unconjugated bilirubin. Each patient underwent aEEG monitoring upon admission. And according to the results of the test, they were assigned into an aEEG normal group (N.=38) or an aEEG abnormal group (N.=18). Dynamic monitoring of bilirubin and blood biochemistry was also conducted for all the children after admission. Patients were treated with blue light, anti-infection agents, acidosis correction measures, transfusion exchanges, intravenous drips of albumin or globulin and other specific treatments as needed in each particular case. Brainstem auditory evoked potential (BAEP), MRI examination and a behavioral neurological assessment (NBNA) with 20-item examinations were provided within 4-17 days after admission. Follow-up observations were conducted on growth level (physical development and Gesell scores) at 3, 6, 12 and 18 months. RESULTS: The results of all the diagnostic tests performed in the patients of both groups all yielded a significantly higher abnormality rate in the aEEG abnormal group compared to the results in the aEEG normal group. Furthermore, the results of follow-up tests showing growth and child development also showed higher abnormality rates in the aEEG abnormal group than in the aEEG normal group. CONCLUSIONS: Since the results of our aEEG monitoring were consistent with the findings of other diagnostic tests, we proved the convenience and effectivity of aEEG for guiding the treatment and prognosis of severe hyperbilirubinemia in neonates.

Heating of Newborn Infants due to Blue Light-Emitting Diode Fibreoptic Phototherapy Pads.

BACKGROUND: Surface temperatures of fibreoptic phototherapy pads using a high intensity blue light-emitting diode (LED) light source have not been studied. OBJECTIVES: The aim of this study was to measure the temperature of LED fibreoptic phototherapy pads during phototherapy in a bench-top study, and to determine temperature effects on babies during phototherapy. METHODS: A commercially available LED fibreoptic phototherapy system was tested. In a bench-top setting, pad surface temperatures were measured before, during and after a 12-h period of phototherapy (10 different LED light box-pad combinations). A prospective, cohort study of well babies at >34 weeks' gestation receiving phototherapy was then conducted to determine changes in pad and body temperatures during a 90-min phototherapy period. RESULTS: In the bench-top study, the mean (95% CI) pad temperature was 21.8°C (21.5-22.1) before lights, 27.0°C (26.5-27.5) after 12 h of lights, and 22.1°C (21.9-22.4) 8 h after turning off the lights (F = 366.1, p < 0.0005). The magnitude of change in pad temperature with phototherapy was linearly correlated with irradiance (r = 0.89, p < 0.0005). The pad plastic covering absorbed 13% of blue light from fibres. In the clinical study, the warmest pad temperature during phototherapy was 38.9°C. Axillary temperature increased by a mean (95% CI) of 0.3°C (0.1-0.5), p < 0.019, and exceeded 37.5°C in 4 babies. CONCLUSIONS: LED fibreoptic phototherapy pads are heated by high-intensity blue light. The thermal environment and temperature of babies should be monitored closely during LED fibreoptic phototherapy. A temperature probe placed between the skin and the pad will not accurately reflect the core temperature during fibreoptic phototherapy.

Influence of hyperbilirubinemia on neonatal sucking.

BACKGROUND: Mothers of hyperbilirubinemic newborns frequently report to us that their infant is feeding poorly. As poor feeding in an extremely hyperbilirubinemic newborn may be an early sign of bilirubin encephalopathy, we hypothesized that neonatal hyperbilirubinemia would suppress the volume of feed ingested and diminish sucking parameters in comparison with minimally jaundiced neonates. OBJECTIVE: To determine whether hyperbilirubinemia does diminish feeding and sucking in neonates. STUDY DESIGN: Neonates in a well-baby nursery with serum total bilirubin (STB) ≥15.0mg/dL were compared with those with transcutaneous bilirubin ≤10mg/dL. Neonur, a modification of Krohn's Nutritive Sucking Apparatus, was used to quantify sucking parameters. Measurements during a 5min feeding period included volume ingested (measured manually), number of sucks, average maximum sucking pressure, number of bursts, average burst duration, pause between bursts duration, number of sucks per burst, and average intersuck interval. Outcome measures were volume ingested and, presuming decreased volume, sucking parameter analysis would determine the component affected by hyperbilirubinemia. RESULTS: 17 hyperbilirubinemic newborns (STB 17.8±1.6mg/dL) were compared with 24 controls, all with transcutaneous bilirubin <10.0mg/dL. The volume of feed ingested was similar between the hyperbilirubinemic newborns and controls (30.00 [20.00-42.50] ml vs. 25.00 [15.00-30.00] ml, p=0.2) (median [95% confidence interval]). No significant differences were noted in any of the other sucking parameters measured. CONCLUSIONS: At concentrations of STB in the range of 15-20mg/dL, hyperbilirubinemia did not diminish feed volume or sucking parameters in term newborns. Poor feeding in moderately hyperbilirubinemic newborns cannot be attributed to the level of bilirubin per se.

Bilirubin-Induced Audiologic Injury in Preterm Infants.

Although hyperbilirubinemia is extremely common among neonates and is usually mild and transient, it sometimes leads to bilirubin-induced neurologic damage (BIND). The auditory pathway is highly sensitive to the effects of elevated total serum/plasma bilirubin (TB) levels, with damage manifesting clinically as auditory neuropathy spectrum disorder. Compared to full-term neonates, preterm neonates are more susceptible to BIND and suffer adverse effects at lower TB levels with worse long-term outcomes. Furthermore, although standardized guidelines for management of hyperbilirubinemia exist for term and late preterm neonates, similar guidelines for neonates less than 35 weeks gestational age are limited.

Auditory evoked potentials in a newborn Wistar rat model of hyperbilirubinemia / Potenciais evocados auditivos em um modelo de rato Wistar neonato com hiperbilirrubinemia

ABSTRACT INTRODUCTION: Hyperbilirubinemia is a common health problem in newborns. Its effects can be different according to the level and duration of the hyperbilirubinemia. The toxic effect of bilirubin on the auditory system can be seen as a sensory neural hearing loss or auditory neuropathy spectrum disorder (ANSD). OBJECTIVE: The purpose of our study was to determine the effects of toxic bilirubin level on the auditory system by using Auditory Brainstem Response audiometry. METHODS: Rats are used as animal models due to their low cost and easy attainability. Auditory Brainstem Response was used for auditory assessment. In this study, three groups were established: experimental, control and placebo groups. RESULTS: In the experimental group, which consists of rats with hyperbilirubinemia, sensory neural hearing loss was found bilaterally in 4 rats (66.67%) and unilaterally in 2 rats (16.67%) and auditory neuropathy spectrum disorder was found unilaterally in 1 rat (8.33%). Auditory Brainstem Response thresholds were significantly elevated compared to control and placebo groups (p < 0.05). CONCLUSION: Hyperbilirubinemia of newborn rats may result both in sensory neural hearing loss and auditory neuropathy spectrum disorder.

RESUMO INTRODUÇÃO: A hiperbilirrubinemia é um problema de saúde comum em neonatos. Seus efeitos podem variar, dependendo do nível e da duração da hiperbilirrubinemia. O efeito tóxico da bilirrubina no sistema auditivo pode ser observado na forma de deficiência auditiva sensorioneural ou de distúrbio do espectro da neuropatia auditiva. OBJETIVO: A finalidade de nosso estudo foi determinar os efeitos de nível tóxico de bilirrubina no sistema auditivo, com o uso da audiometria da resposta auditiva evocada de tronco cerebral. MÉTODO: Os ratos são empregados como modelos animais graças a seu baixo custo e fácil obtenção. Utilizamos a resposta auditiva evocada de tronco cerebral para avaliação da audição. No estudo, foram estabelecidos três grupos: experimental, controle e placebo. RESULTADOS: No grupo experimental, constituído de ratos com hiperbilirrubinemia, disacusia auditiva neurosensorial foi diagnosticada bilateralmente em quatro ratos (66,67%), e unilateralmente em dois (16,67%); e distúrbio do espectro da neuropatia auditiva foi observado unilateralmente em um rato (8,33%). Os limiares da resposta evocada de tronco cerebral estavam significantemente elevados, em comparação com os grupos controle e placebo (p < 0,05). CONCLUSÃO: A hiperbilirrubinemia de ratos neonatos pode resultar tanto em disacusia auditiva neurosensorial como em distúrbio do espectro da neuropatia auditiva.

Auditory evoked potentials in a newborn Wistar rat model of hyperbilirubinemia.

INTRODUCTION: Hyperbilirubinemia is a common health problem in newborns. Its effects can be different according to the level and duration of the hyperbilirubinemia. The toxic effect of bilirubin on the auditory system can be seen as a sensory neural hearing loss or auditory neuropathy spectrum disorder (ANSD). OBJECTIVE: The purpose of our study was to determine the effects of toxic bilirubin level on the auditory system by using Auditory Brainstem Response audiometry. METHODS: Rats are used as animal models due to their low cost and easy attainability. Auditory Brainstem Response was used for auditory assessment. In this study, three groups were established: experimental, control and placebo groups. RESULTS: In the experimental group, which consists of rats with hyperbilirubinemia, sensory neural hearing loss was found bilaterally in 4 rats (66.67%) and unilaterally in 2 rats (16.67%) and auditory neuropathy spectrum disorder was found unilaterally in 1 rat (8.33%). Auditory Brainstem Response thresholds were significantly elevated compared to control and placebo groups (p<0.05). CONCLUSION: Hyperbilirubinemia of newborn rats may result both in sensory neural hearing loss and auditory neuropathy spectrum disorder.

Audiologic impairment associated with bilirubin-induced neurologic damage.

Hyperbilirubinemia occurs commonly in neonates and is usually mild and transient, with no long-lasting sequelae. However, bilirubin-induced neurologic damage may occur in some infants. The auditory pathway is the most sensitive part of the central nervous system to bilirubin-induced toxicity, and permanent sequelae may result from only moderately elevated total serum/plasma bilirubin levels. The damage to the auditory system occurs primarily within the brainstem and cranial nerve VIII, and manifests clinically as auditory neuropathy spectrum disorder.