Intensive phototherapy vs. exchange transfusion for the treatment of neonatal hyperbilirubinemia: a multicenter retrospective cohort study.

BACKGROUND: Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. METHODS: This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. RESULTS: A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. CONCLUSIONS: In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Trends in hospitalizations of newborns with hyperbilirubinemia and kernicterus in United States: an epidemiological study.

BACKGROUND: Hyperbilirubinemia is one of the most common diagnosis in newborn nurseries in United States. Universal pre-discharge bilirubin screening decreased the incidence of extreme hyperbilirubinemia and risk of kernicterus. OBJECTIVES: We sought to assess temporal population trends of hyperbilirubinemia, kernicterus and usage of phototherapy, intravenous immunoglobulin (IVIG), and exchange transfusion. DESIGN/METHODS: Data from Healthcare Cost and Utilization Project (HCUP)-the Kids' Inpatient Database (KID) obtained for years 1997-2012. All neonatal discharges with ICD-9 codes for neonatal jaundice (774.2, 774.6), kernicterus (773.4, 774.7) and procedure codes for phototherapy (99.83), IVIG infusion (99.14), exchange transfusion (99.01) were extracted. We compared the trends of diagnosis of hyperbilirubinemia, kernicterus, use of phototherapy, IVIG, and exchange transfusion. RESULTS: During the study period, the proportion of infants diagnosed with hyperbilirubinemia increased by 65% (9.4% vs. 15.5%; p<.001) in term infants and 34.5% (33.5% vs. 45%; p<.001) in preterm infants, respectively. Rate of kernicterus discharges significantly reduced from 7 to 1.9 per 100,000 newborns. Overall, the number of exchange transfusions has decreased by 67% during study period while phototherapy and IVIG use increased by 83% and 170%, respectively. CONCLUSIONS: In last two decades, there was a significant decrease in neonatal discharges with a history of exchange transfusion or with a diagnosis of kernicterus. However, there was a significant increase in number of neonates discharged home with a history of phototherapy during birth hospitalization and decreased number of exchange transfusions were observed during the study period. Incremental implementation of universal predischarge bilirubin screening and treatments based on 2004 AAP recommended risk-based strategies might have contributed to timely interventions in infants with significant hyperbilirubinemia.

Intensive phototherapy vs. exchange transfusion for the treatment of neonatal hyperbilirubinemia: a multicenter retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.@*METHODS@#This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years.@*RESULTS@#A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group.@*CONCLUSIONS@#In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Rates of Extreme Neonatal Hyperbilirubinemia and Kernicterus in Children and Adherence to National Guidelines for Screening, Diagnosis, and Treatment in Sweden.

Importance: Neonatal hyperbilirubinemia can cause lifelong neurodevelopmental impairment (kernicterus) even in high-resource settings. A better understanding of the incidence and processes leading to kernicterus may help in the design of preventive measures. Objectives: To determine incidence rates of hazardous hyperbilirubinemia and kernicterus among near-term to term newborns and to evaluate health care professional adherence to best practices. Design, Setting, and Participants: This population-based nationwide cohort study used prospectively collected data on the highest serum bilirubin level for all infants born alive at 35 weeks' gestation or longer and admitted to neonatal care at all 46 delivery and 37 neonatal units in Sweden from 2008 to 2016. Medical records for newborns with hazardous hyperbilirubinemia were evaluated for best neonatal practices and for a diagnosis of kernicterus up to 2 years of age. Data analyses were performed between September 2017 and February 2018. Exposures: Extreme (serum bilirubin levels, 25.0-29.9 mg/dL [425-509 µmol/L]) and hazardous (serum bilirubin levels, ≥30.0 mg/dL [≥510 µmol/L]) neonatal hyperbilirubinemia. Main Outcomes and Measures: The primary outcome was kernicterus, defined as hazardous neonatal hyperbilirubinemia followed by cerebral palsy, sensorineural hearing loss, gaze paralysis, or neurodevelopmental retardation. Secondary outcomes were health care professional adherence to national guidelines using a predefined protocol with 10 key performance indicators for diagnosis and treatment as well as assessment of whether bilirubin-associated brain damage might have been avoidable. Results: Among 992 378 live-born infants (958 051 term births and 34 327 near-term births), 494 (320 boys; mean [SD] birth weight, 3505 [527] g) developed extreme hyperbilirubinemia (50 per 100 000 infants), 6.8 per 100 000 infants developed hazardous hyperbilirubinemia, and 1.3 per 100 000 infants developed kernicterus. Among 13 children developing kernicterus, brain injury was assessed as potentially avoidable for 11 children based on the presence of 1 or several of the following possible causes: untimely or lack of predischarge bilirubin screening (n = 6), misinterpretation of bilirubin values (n = 2), untimely or delayed initiation of treatment with intensive phototherapy (n = 1), untimely or no treatment with exchange transfusion (n = 6), or lack of repeated exchange transfusions despite indication (n = 1). Conclusions and Relevance: Hazardous hyperbilirubinemia in near-term or term newborns still occurs in Sweden and was associated with disabling brain damage in 13 per million births. For most of these cases, health care professional noncompliance with best practices was identified, suggesting that a substantial proportion of these cases might have been avoided.

The Turkish Neonatal Jaundice Online Registry: A national root cause analysis.

BACKGROUND: Neonatal jaundice (NNJ) is common, but few root cause analyses based on national quality registries have been performed. An online registry was established to estimate the incidence of NNJ in Turkey and to facilitate a root cause analysis of NNJ and its complications. METHODS: A multicenter prospective study was conducted on otherwise healthy newborns born at ≥35 weeks of gestation and hospitalized for only NNJ in 50 collaborator neonatal intensive care units across Turkey over a 1-year period. Patients were analyzed for their demographic and clinical characteristics, treatment options, and complications. RESULTS: Of the 5,620 patients enrolled, 361 (6.4%) had a bilirubin level ≥25 mg/dL on admission and 13 (0.23%) developed acute bilirubin encephalopathy. The leading cause of hospital admission was hemolytic jaundice, followed by dehydration related to a lack of proper feeding. Although all infants received phototherapy, 302 infants (5.4%) received intravenous immunoglobulin in addition to phototherapy and 132 (2.3%) required exchange transfusion. The infants who received exchange transfusion were more likely to experience hemolytic causes (60.6% vs. 28.1%) and a longer duration of phototherapy (58.5 ± 31.7 vs. 29.4 ± 18.8 h) compared to infants who were not transfused (p < 0.001). The incidence of short-term complications among discharged patients during follow-up was 8.5%; rehospitalization was the most frequent (58%), followed by jaundice for more than 2 weeks (39%), neurological abnormality (0.35%), and hearing loss (0.2%). CONCLUSIONS: Severe NNJ and bilirubin encephalopathy are still problems in Turkey. Means of identifying at-risk newborns before discharge during routine postnatal care, such as bilirubin monitoring, blood group analysis, and lactation consultations, would reduce the frequency of short- and long-term complications of severe NNJ.

Effectiveness of universal hyperbilirubinemia screening on newborn health: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to assess the effectiveness of the universal hyperbilirubinemia screening program on common newborn health outcomes.Specifically, the review will assess: the incidence of severe hyperbilirubinemia/kernicterus/exchange transfusion, rate of readmission due to jaundice, length of hospital stay on birth admission, rate and utilization of phototherapy during birth hospitalization, and jaundice related emergency visits.

Neonatal management and outcome in alloimmune hemolytic disease.

INTRODUCTION: Hemolytic disease of the fetus and newborn (HDFN) occurs when fetal and neonatal erythroid cells are destroyed by maternal erythrocyte alloantibodies, it leads to anemia and hydrops in the fetus, and hyperbilirubinemia and kernicterus in the newborn. Postnatal care consists of intensive phototherapy and exchange transfusions to treat severe hyperbilirubinemia and top-up transfusions to treat early and late anemia. Other postnatal complications have been reported such as thrombocytopenia, iron overload and cholestasis requiring specific management. Areas covered: This review focusses on the current neonatal management and outcome of hemolytic disease and discusses postnatal treatment options as well as literature on long-term neurodevelopmental outcome. Expert commentary: Despite major advances in neonatal management, multiple issues have to be addressed to optimize postnatal management and completely eradicate kernicterus. Except for strict adherence to guidelines, improvement could be achieved by clarifying the epidemiology and pathophysiology of HDFN. Several pharmacotherapeutic agents should be further researched as alternative treatment options in hyperbilirubinemia, including immunoglobulins, albumin, phenobarbital, metalloporphyrins, zinc, clofibrate and prebiotics. Larger trials are warranted to evaluate EPO, folate and vitamin E in neonates. Long-term follow-up studies are needed in HDFN, especially on thrombocytopenia, iron overload and cholestasis.

Glucose-6-Phosphate Dehydrogenase Deficiency and the Need for a Novel Treatment to Prevent Kernicterus.

Hyperbilirubinemia occurs frequently in newborns, and in severe cases can progress to kernicterus and permanent developmental disorders. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human enzymopathies, is a major risk factor for hyperbilirubinemia and greatly increases the risk of kernicterus even in the developed world. Therefore, a novel treatment for kernicterus is needed, especially for G6PD-deficient newborns. Oxidative stress is a hallmark of bilirubin toxicity in the brain. We propose that the activation of G6PD via a small molecule chaperone is a potential strategy to increase endogenous defense against bilirubin-induced oxidative stress and prevent kernicterus.

[Not Available]. / Ictère nucléaire dans un contexte de naissance à domicile.

This is the clinical history of a term baby born at home who presents a severe hyperbilirubinémia. The medical monitoring was assessed by a private midwife according to parental choice. On the third day of life, the newborn presented an icterus and was exposed to natural daylight in the familial greenhouse under the midwife recommandations. On that day, no laboratory test precised the bilirubin level. On the fifth day, a blood sampling revealed a very high blood bilirubinémia (31 mg/dl or 527 mmol/L), the baby is refered to our NICU and underwent an exchange transfusion. The radiological assessment report structural abnomalies in basal ganglia seen on both MRI and transfontannellar echography. These lesions are known to be responsible of cerebral palsy and hearing loos. The neurophysiologic investigations showed background abnormaly and depression. The extensive blood sampling excluded haemolysis. The clinical examination brought out neurologic impairement and weight loos in this exclusively breastfed baby. This clinical case point out the increasing risk of home Kernicterius as hospital stays diminish and homebirth enthousiasm rise up. The present clinical situation vouches for an adaptation of care giving to both mother and child at home in order to avoid this severe illness.

Heliotherapy for Neonatal Hyperbilirubinemia in Southwest, Nigeria: A Baseline Pre-Intervention Study.

BACKGROUND: A novel filtered-sunlight phototherapy (FSPT) device has been demonstrated to be safe and efficacious for treating infants with neonatal jaundice in resource-constrained tropical settings. We set out to provide baseline data for evaluating the clinical impact of this device in a referral pediatric hospital. METHODS: We reviewed the medical records of infants admitted for neonatal hyperbilirubinemia in an inner-city Children's Hospital in Lagos, between January 2012 and December 2014 to determine the pattern, treatment and outcomes during the pre-intervention period. Factors associated with adverse outcomes were identified through multivariable logistic regression. RESULTS: Of the 5,229 neonatal admissions over the period, a total of 1,153 (22.1%) were admitted for neonatal hyperbilirubinemia. Complete records for 1,118 infants were available for analysis. The incidence of acute bilirubin encephalopathy (ABE) and exchange transfusion (ET) were 17.0% (95% CI: 14.9%-19.3%) and 31.5% (95% CI: 28.8%-34.3%) respectively. A total of 61 (5.5%, 95% CI: 4.3%-6.9%) of the jaundiced infants died. Weight on admission, peak total serum bilirubin (TSB), sepsis and exposure to hemolytic products were predictive of ABE, while age on admission, peak TSB, ABO incompatibility and ABE were predictive of ET. Rhesus incompatibility, asphyxia, exposure to hemolytic substances and ABE were associated with elevated mortality risk, while ET was a protective factor. Lack of routine irradiance monitoring and steady energy supply were frequent challenges for conventional blue-light phototherapy. CONCLUSIONS: Severe hyperbilirubinemia is associated with high rates of ABE and ET in this setting, and remains a significant contributor to neonatal admissions and mortality. To be impactful, FSPT, complemented with improved diagnostic facilities, should effectively curtail jaundice-related adverse outcomes in this and comparable settings.

Encefalopatía por Kernicterus. serie clínica / Kernicterus (bilirubin encephalopathy): case reports

Introducción: La ictericia es común en los recién nacidos (RN). Niveles de bilirrubina a partir de 20 mg/dL (en RN de término) pueden causar parálisis cerebral coreoatetósica, hipoacusia sensorioneural, trastornos de la mirada y displasia del esmalte dental, cuadro clínico conocido como kernicterus. Objetivo: Describir 5 casos de kernicterus controlados en una Unidad de Neurología, entre los años 2002-2012. Casos clínicos: Se presentan 5 niños con edades gestacionales entre 35 y 39 semanas, con peso de nacimiento rango 2.580 y 4.250 g y niveles de bilirrubina entre 24 y 47 mg/dL. Dos RN estaban en su domicilio cuando iniciaron la encefalopatía aguda. Todos se trataron con fototerapia y en 3 casos se realizó además exanguineotransfusión. La edad del diagnóstico de kernicterus fluctuó entre los 12 días y 10 años (3 pacientes se diagnosticaron en etapa neonatal) con una resonancia magnética que demostró impregnación de ganglios basales. Todos evolucionaron con trastornos del movimiento de severidad variable. En 3 pacientes se diagnosticó hipoacusia sensorioneural y en dos hubo trastornos de la mirada. Los test psicométricos evaluaron retraso cognitivo en 3 pacientes y desarrollo normal en los restantes. Conclusión: El kernicterus en una enfermedad devastadora que aún está presente en la realidad nacional. Es una causa de parálisis cerebral prevenible, por lo cual es necesario educar a los padres, población y equipo de salud para la detección precoz y tratamiento oportuno de la hiperbilirrubinemia neonatal.

Introduction: Jaundice is common in newborn babies (NB). Bilirubin levels of 20 mg/dL or higher may cause choreoathetoid cerebral palsy, sensorineural hearing loss, eye disorders and enamel dysplasia in term infants; clinical picture compatible with kernicterus. Objective: To describe five cases of kernicterus treated at a Neurology Unit between 2002 and 2012. Case reports: Five cases of babies with gestational ages between 35 and 39 weeks, birth-weight ranging from 2580 to 4250 grams and bilirubin levels between 24 and 47 mg/dL are presented. Two infants were at home when acute encephalopathy developed, all were treated with phototherapy and 3 of them underwent exchange transfusion. The age of diagnosis of kernicterus was between 12 days to 10 years; three patients were diagnosed in neonatal period through MRI that revealed basal ganglia impregnation. All patients evolved presenting movement disorders of varying severity. Three of them were diagnosed with sensorineural hearing impairments and two presented eye disorders. Psychometric tests showed cognitive delay in three patients and normal development in the remaining children. Conclusion: Kernicterus in a devastating disease present in the national reality. It is a preventable cause of cerebral palsy; therefore, it is necessary to educate parents, population and health care professionals about neonatal hyperbilirubinemia early detection and treatment.

The use of intensive phototherapy in severe neonatal hyperbilirubinemia.

Phototherapy has been the therapy of choice for the newborn with indirect hyperbilirubinemia. Intensive phototherapy requires a spectral irradiance of 30 microw/ cm2/nm, delivered over as much of the body surface as possible and is nowadays recommended for cases of neonatal hyperbilirubinemia with elevated total serum bilirubin (TSB) levels according to the guidelines. This study was conducted on neonates presenting to the out-born Neonatal Intensive Care Unit (NICU) of Cairo University Hospital with severe and extreme neonatal unconjugated hyperbilirubinemia during a 6 month period from August 2011 to January 2012. A total of 212 neonates presented with TSB > or = 20 mg/dl and were admitted for intensive phototherapy. The mean TSB on admission for all the cases was 26.8 +/- 6.2 mg/dl, ranging from 20 to 44 mg/dl. The mean duration of intensive phototherapy use was 14 hr. The mean rate of TSB declined during stay in the bilisphere was 1.019 mg/dl/hr. Exchange blood transfusion was indicated in 13 cases with extreme hyperbilirubinemia. 31 cases (14.62%) had rebound hyperbilirubinemia after phototherapy removal.

[Neurological dysfunction induced by bilirrubin]. / Disfunción neurológica inducida por bilirrubina.

INTRODUCTION: "Kernicterus" is a term currently used to describe bilirrubin induced brain injury in the neuro-pathological studies. This is a confusing term and nowadays we prefer bilirrubin encephalopathy or bilirrubin induced neurological dysfunction. The clinical signs vary and it is clearly decreasing in prevalence in developed countries. MATERIAL AND METHODS: We review a series of 7 patients with bilirrubin encephalopathy and variable neurological manifestations, who were seen in the Neuropaediatric Department in the last 10 years. Only one patient died in the neonatal period with hyperbilirubinaemia, sepsis and multi-organ failure. RESULTS: Diverse aetiological factors were related to hyperbilirubinaemia. All patients had clinical symptoms due to hyperbilirubinaemia. Neuroimaging during the neonatal period showed involvement of the nucleus pallidus, with hyperintensity in T1 in the brain MR scan as the most consistent finding. All the patients who survived developed neurological signs and we try to correlate them with biochemical, clinical, neuroimaging and neurophysiological parameters. CONCLUSIONS: An increase in the number of patients with bilirrubin encephalopathy has been observed over the last few years, and we attempt to find out the causes. The increased survival of the low birth weight newborns, the increase in the immigration population and the use of diagnostic neuroimaging contribute to this increase. It is a great challenge for the neonatologist and for neuropaediatricians to prevent its occurrence and to minimise the effects of bilirrubin encephalopathy.

Phototherapy for neonatal jaundice--therapeutic effects on more than one level?

Phototherapy for jaundice is a common treatment in neonatal medicine and is used to prevent the neurotoxic effects of bilirubin. Studies have assessed the optimal wavelength of phototherapy light, the importance of irradiance and spectral power, and the types of light source, including the use of single versus multiple light sources. Outcome measures have been duration of need for phototherapy or rate of reduction of serum bilirubin over a given time. An apparent resurgence of kernicterus in recent years has forced us to focus on the emergency management of severely jaundiced infants. Several studies have shown that very rapid reductions of total serum bilirubin levels are possible. The speed with which photoisomers are formed appears to be important both from this perspective and theoretically may also be neuroprotective because of the more polar nature of the photoisomers. This work reviews the evidence concerning the speed of photoisomer formation, as well as the evidence regarding the relative neurotoxicity of bilirubin isomers.

Neonatal hyperbilirubinemia and kernicterus - not gone but sometimes forgotten.

The introduction of exchange transfusion made it possible to prevent severe hyperbilirubinemia and kernicterus, but kernicterus has never completely disappeared and it is still occurring in North America and, more frequently in Western Europe and the developing world. I discuss the epidemiology and major causes of severe hyperbilirubinemia and the potential root causes and system failures associated with the development of extreme hyperbilirubinemia and, subsequently, kernicterus. In the Western world, kernicterus remains a rare cause of cerebral palsy but, in contrast to the other causes of cerebral palsy, kernicterus should almost always be preventable. The key elements in preventing kernicterus are risk assessment and appropriate follow-up for the newborn infant and these are presented in a recently developed algorithm. Implementation of this approach might contribute to the prevention of severe hyperbilirubinemia and bilirubin encephalopathy.

Severe hyperbilirubinaemia and kernicterus: more caution is needed in newborn jaundice surveillance.

Since the 1990s, there has been a re-emergence of cases of severe hyperbilirubinaemia and kernicterus. The current UK incidence of bilirubin encephalopathy is 0.9/100,000 with a higher reported incidence in some countries. Three otherwise healthy newborn infants, who presented with severe hyperbilirubinaemia, including one who developed kernicterus, are reported here. Some of the current challenges in newborn jaundice surveillance are highlighted.

Reversibility of acute intermediate phase bilirubin encephalopathy.

AIM: To show the potential for reversing acute intermediate to advanced phase bilirubin encephalopathy. METHODS: Case studies. RESULTS: Six extremely jaundiced infants had symptoms of intermediate to advanced phase acute bilirubin encephalopathy. The infants were treated aggressively. Two patients had brain magnetic resonance imaging showing increased signals in the globus pallidus. On follow-up, all infants are neurologically normal. CONCLUSIONS: Intermediate-to-advanced stage acute bilirubin encephalopathy may occasionally be reversible. These cases provide a strong argument in favour of rapid and aggressive intervention in infants presenting with extreme jaundice and neurological symptoms.

The significance of measurement of serum unbound bilirubin concentrations in high-risk infants.

BACKGROUND: In the management of neonatal hyperbilirubinemia, total bilirubin (TB) concentration is not specific enough to predict the brain damage caused by bilirubin toxicity. Unbound bilirubin (UB) easily passes the blood-brain barrier and causes neurotoxicity. We aimed to evaluate whether serum UB concentration would be a useful predictor of bilirubin encephalopathy in high-risk infants. METHODS: We measured the serum TB and UB concentrations of 388 newborn infants treated with phototherapy or exchange transfusion for their hyperbilirubinemia at Takatsuki General Hospital between January 2002 and October 2003. Peak serum TB and UB levels and UB/TB ratios were studied on each birthweight group: below 1500 g (very low birthweight), 1500 g-2499 g (low birthweight), above 2500 g (normal birthweight); and several clinical factors influencing hyperbilirubinemia were also studied. RESULTS: Peak serum TB and UB levels increased with increasing birthweight, while UB/TB ratios decreased. The very low birthweight group showed higher UB levels and UB/TB ratios despite lower TB levels in intraventricular hemorrhage or severe infection compared to those in the others. The low birthweight and normal birthweight groups showed higher TB and UB levels in cases of hemolytic disease of the newborn compared to non-hemolytic disease of the newborn cases. Eight of 44 cases showed high UB levels accompanied by abnormal auditory brainstem responses, one of whom subsequently developed ataxic cerebral palsy with hearing loss, whereas the other seven showed transient abnormalities of auditory brainstem responses by the treatment of exchange transfusion or phototherapy. CONCLUSION: The UB measurement was considered to be significant for the assessment of the risk of bilirubin neurotoxicity and the appropriate intervention for hyperbilirubinemia in high-risk infants.

Kernicterus in preterm infants.

OBJECTIVE: We sought to clarify the features of kernicterus in preterm infants. METHODS: The subjects of this study were 8 preterm infants with athetoid cerebral palsy whose gestational ages were < or =34 weeks. We retrospectively investigated clinical, laboratory, MRI, and brainstem auditory evoked potential (BAEP) findings. RESULTS: Gestational age was < or =26 weeks in 6 of the 8 infants, and birth weight was <1000 g in 5 infants. Serious postnatal complications with systemic deterioration were observed in 3 infants. Total bilirubin levels were measured frequently in the majority of infants; peak values of >15 mg/dL were observed in 3 infants. No infant showed neurologic symptoms characteristic of classical acute bilirubin encephalopathy during the neonatal period. Dystonic posture and abnormal muscle tone were first recognized within 6 months' corrected age in all patients. During infancy, MRI was performed in 7 infants. Abnormal high-intensity areas were observed in the bilateral globi pallidi in all 7 infants. However, MRI during the neonatal period or after 1 year's corrected age showed no abnormal findings. BAEP measurements were abnormal in 7 of the 8 infants. CONCLUSIONS: Preterm infants with athetotic cerebral palsy showed rather homogeneous features, similar to term infants with kernicterus, with marked hyperbilirubinemia. This combination of clinical, laboratory, neuroimaging, and neurophysiological data will contribute to the increased recognition of preterm infants with kernicterus.