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.

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.

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.

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.

Strategies for neonatal hyperbilirubinemia: a literature review.

"Common" neonatal jaundice can lead to dangerous levels of hyperbilirubinemia, causing neurological damage and even death. This article outlines evidence-based assessment techniques, management guidelines, and treatments for neonatal hyperbilirubinemia, addressing complexities that have arisen with new technologies and research results. We also explicate the role of the nurse in both prevention and care of patients and families who are affected by hyperbilirubinemia and jaundice.

Neonatal hyperbilirubinemia in infants with G6PD c.563C > T Variant.

BACKGROUND: There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4-14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T. METHODS: This was a case-control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing. RESULTS: G6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, p < 0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8 ± 5.4 mg/dl vs. 13.8 ± 4.6 mg/dl, p = 0.008) which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, p = 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups. CONCLUSIONS: We concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity.

An approach to the management of hyperbilirubinemia in the preterm infant less than 35 weeks of gestation.

We provide an approach to the use of phototherapy and exchange transfusion in the management of hyperbilirubinemia in preterm infants of <35 weeks of gestation. Because there are limited data for evidence-based recommendations, these recommendations are, of necessity, consensus-based. The recommended treatment levels are based on operational thresholds for bilirubin levels and represent those levels beyond which it is assumed that treatment will likely do more good than harm. Long-term follow-up of a large population will be needed to evaluate whether or not these recommendations should be modified.

Moderate unconjugated hyperbilirubinemia causes a transient but delayed suppression of amplitude-integrated electroencephalographic activity in preterm infants.

BACKGROUND: Unconjugated hyperbilirubinemia occurs frequently in preterm infants and may result in bilirubin encephalopathy. Amplitude-integrated electroencephalography (aEEG) is used to evaluate brain function in newborns. OBJECTIVES: To investigate the influence of total serum bilirubin (TSB) on the aEEG amplitude of preterm infants and to evaluate aEEG as a noninvasive method to identify acute bilirubin encephalopathy. METHODS: We performed a prospective observational study of 34 infants with a gestational age (GA) of 26-31 6/7 weeks. Infants had aEEG recordings on the 1st-5th, 8th and 15th day after birth. Infants with asphyxia, intraventricular hemorrhage >grade I or circulatory insufficiency were excluded. aEEG was evaluated by calculating the mean 5th, 50th and 95th centiles of the aEEG amplitudes. RESULTS: TSB peaked on the 4th day after birth. There was no synchronous relationship between TSB and aEEG amplitudes. The 5th, 50th, and 95th aEEG amplitude centiles on the 8th day correlated negatively with the TSB peak value (r = -0.37, p = 0.048; r = -0.60, p = 0.001; r = -0.44, p = 0.017, respectively), irrespective of GA. The 5th and 50th aEEG amplitude centiles increased with increasing GA (r = 0.45, p < 0.001, and r = 0.26, p < 0.001, respectively) and postnatal age (r = 0.25, p < 0.001, and r = 0.16, p = 0.023, respectively). CONCLUSIONS: TSB had no direct effect on aEEG amplitudes in preterm infants. There is, however, a delayed effect on electrocerebral activity in the 2nd week after birth.

Hyperbilirubinemia: current guidelines and emerging therapies.

It is estimated that about two thirds of newborns will appear clinically jaundiced during their first weeks of life. As newborns and their mothers spend fewer days in the hospital after birth, the number of infants readmitted yearly in the United States for neonatal jaundice over the last 10 years has increased by 160%. A portion of these infants present to the emergency department, requiring a careful history and physical examination assessing them for the risk factors associated with pathologic bilirubin levels. Although the spectrum of illness may be great, the overwhelming etiology of neonatal jaundice presenting to an emergency department is physiologic and not due to infection or isoimmunization. Therefore, a little more than a good history, physical examination, and indirect/direct bilirubin levels are needed to evaluate an otherwise well-appearing jaundiced newborn. The American Academy of Pediatrics' 2004 clinical practice guidelines for "Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation" are a helpful and easily accessible resource when evaluating jaundiced newborns (available at http://aappolicy.aappublications.org/cgi/content/full/pediatrics;114/1/297). There are several exciting developments on the horizon for the diagnosis and management of hyperbilirubinemia including increasing use of transcutaneous bilirubin measuring devices and medications such as tin mesoporphyrin and intravenous immunoglobulin that may decrease the need for exchange transfusions.

Hearing status in neonatal hyperbilirubinemia by auditory brain stem evoked response and transient evoked otoacoustic emission.

Hyperbilirubinemia at neonatal period is one of the major deteriorating factors of the auditory system. If left untreated, it may cause certain cerebral damage. This study aims to evaluate the impact of hyperbilirubinemia on the hearing of neonate. This study was conducted on 35 newborn babies with jaundice (bilirubin more than 20 mg/dL). Auditory brainstem response (ABR) and transient evoked otoacoustic emission (TEOAE) tests were performed, after treatment and one year after. ABR test results indicated that 26 children (74.3%) had normal hearing but 9 (25.7%) suffered from an impairment. As for TEOAE test, 30 children (85.7%) passed whereas the remaining (14.3%) seemed to be failures. The comparative results of the two tests pointed to autonomic neuropathy /autonomic dysreflexia symptoms in 5 babies. Due to the high incidence of autonomic neuropathy/autonomic dysreflexia among hyperbilirubinemic babies, screening in this regard seems reasonable. Our result emphasizes the necessity of more experiments on the afflicted areas.

Implementation and analysis of a pilot in-hospital newborn screening program for glucose-6-phosphate dehydrogenase deficiency in the United States.

OBJECTIVE: The purpose of this study was to analyze a targeted screening program for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDdef) and clinical outcomes of G6PD-deficient vs G6PD normal newborns. STUDY DESIGN: Retrospective chart review for 1578 male newborns was performed. The study group was those screened for G6PDdef. Comparisons between G6PD-deficient and normal infants were made with χ (2)-test and unpaired t-test. RESULT: A total of 1095 male newborns were screened, 11.1% had G6PDdef. 97.8% of screen results were reported by 48 h. Total bilirubin (TB) levels in deficient infants were significantly higher than in normal infants throughout birth hospitalization and they were more likely to receive phototherapy. Nineteen screened newborns were rehospitalized for hyperbilirubinemia, 47% had G6PDdef. CONCLUSION: In-hospital newborn screening for G6PDdef with rapid turnaround time is possible. G6PDdef is a risk factor for hyperbilirubinemia in American newborns. US centers with large at-risk populations can identify newborns at risk for severe hyperbilirubinemia with similar screening.

Confirmed association between neonatal phototherapy or neonatal icterus and risk of childhood asthma.

We have previously demonstrated an association between neonatal phototherapy and/or neonatal icterus and risk of hospitalization for childhood asthma. This study included children who were prescribed anti-asthmatic medication on a population basis to study exposures during the foetal and neonatal period and risk of childhood asthma. The Swedish Medical Birth Register was linked to the Swedish Prescribed Drug Register. Perinatal data for singleton children who were prescribed anti-asthmatic medication (n = 61,256) were compared with corresponding data for all singleton children born in Sweden from 1 January 1990 to 30 June 2003 and surviving to 1 July 2005 (n = 1,338,319). Mantel-Haenszel's odds ratios were calculated after adjustment for various known confounders. Being the first-born child, maternal age above 44 yr, involuntary childlessness for more than 1 yr, maternal smoking during pregnancy, maternal diabetes mellitus of any kind, pre-eclampsia, caesarean section, and instrumental vaginal delivery were all associated with an increased prescription of anti-asthmatic medication during childhood. Preterm birth, low birth weight, being small for gestational age, respiratory problems, mechanical ventilation, and sepsis and/or pneumonia were also associated with increased drug prescriptions. Neonatal phototherapy and/or icterus were risk determinants for children who developed asthma before the age of 12. After controlling for confounders, the odds ratio for phototherapy and/or icterus remained at 1.30 (95% confidence interval 1.16-1.47). In conclusion, this large population-based study confirms an association between some maternal and perinatal factors and childhood asthma, including neonatal phototherapy and/or icterus.

UGT1A1 gene polymorphisms in North Indian neonates presenting with unconjugated hyperbilirubinemia.

Genetic factors are implicated in pathogenesis of neonatal hyperbilirubinemia. In this nested case-control study, we determined 1) frequency of thymine-adenine (TA)n promoter polymorphism and Gly71Arg mutation in uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene in neonates > or =35-wk gestation presenting with bilirubin levels > or =18 mg/dL and controls, 2) interaction among (TA)n promoter polymorphism, glucose-6-phosphate dehydrogenase (G6PD) gene mutations, and peak bilirubin. The number of TA repeats was assessed by PCR-single-strand conformation polymorphism (SSCP) analysis and Gly71Arg mutation by PCR-RFLP. Fifty samples of both mutations were verified with DNA sequencing. One hundred twenty-seven neonates were enrolled (77 hyperbilirubinemics, 50 controls). The incidence of (TA)n polymorphism was higher in babies with hyperbilirubinemia [89.6% vs. 50%, OR 8.63 (95% CI, 3.2-24.1)]. Gly71Arg mutation was not found either in hyperbilirubinemics or controls. A novel polymorphism (Ala72Pro) at codon position 72 of exon 1 was detected in all 50 samples (21 hyperbilirubinemics, 29 controls), which were sequenced. Presence of variant (TA)n promoter (adjusted OR, 10.6; 95% CI, 3.3-34.2), G6PD deficiency (adjusted OR, 20.6; 95% CI, 3.6-117.3), and history of jaundice in sibling requiring phototherapy (adjusted OR, 12.6; 95% CI, 1.1-141.6) were independent risk factors for bilirubin levels > or =18 mg/dL.

Late preterm infants: severe hyperbilirubinemia and postnatal glucose homeostasis.

The identification of late preterm infants as a high-risk group of infants has been an important public health breakthrough. These infants have suffered a relative 'silent morbidity and mortality' before the recognition that they have unique physiology and risks. These infants represent almost three-fourths of all premature births in the United States. Many of these infants, because of their birthweight and appearance, have been treated in Well Baby Nurseries and even discharged by 48 h of birth despite specific unidentified or unappreciated risks that have led to their readmission and possible severe morbidities or even death. Two common problems for these infants include neonatal hypoglycemia and severe hyperbilirubinemia. The definition of hypoglycemia remains controversial but is nonetheless a problem of increasing frequency in these infants.

Unbound bilirubin predicts abnormal automated auditory brainstem response in a diverse newborn population.

OBJECTIVE: The objective of this study was to determine if plasma unbound or 'free' bilirubin concentration (B(f)) measured during the first 30 days of life is associated with subsequent abnormal hearing screening testing by automated auditory brainstem response (AABR) in a diverse population of newborns. STUDY DESIGN: An observational study of newborns receiving AABR, plasma total bilirubin concentration (TBC) and B(f) measurements and without underlying conditions known to affect hearing was conducted. Logistic regression was used to determine associations between abnormal AABR and B(f) or TBC. The impacts of a variety of clinical factors on the regression model were also assessed. RESULT: A total of 191 patients with birth weights and gestations ranging from 406 to 4727 g and 24 to 42 weeks, respectively, were studied. Among them, 175 (92%) had normal (bilateral PASS) AABR and 16 had abnormal AABR (6 had unilateral REFER AABR, and 10 had bilateral REFER AABR). Mean TBC was not significantly different in babies with normal or abnormal AABR, but mean B(f) was greater in the latter group (1.76 versus 0.93 microg per 100 ml, respectively, P=0.012). B(f), but not TBC, was associated with an abnormal AABR (B(f) adjusted odds ratio 3.3, 95% CI 1.8 to 6.1). Comparing receiver-operating characteristics curves, the B(f)/TBC ratio was a better predictor of an abnormal AABR than B(f) alone. Intraventricular hemorrhage was the only confounding clinical variable. CONCLUSION: An abnormal AABR is associated with an elevated B(f) or B(f)/TBC ratio, but not the TBC alone. The prevalence of bilirubin neurotoxicity as a cause of audiological dysfunction may be underestimated if the TBC alone is used to assess the severity of newborn jaundice.