Interpretation of the 2022 American Academy of Pediatrics guidelines for the management of hyperbilirubinemia in newborn infants / 中国当代儿科杂志

The American Academy of Pediatrics updated the guidelines for the management of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks in September 2022. Based on the evidence over the past 18 years, the guidelines are updated from the aspects of the prevention, risk assessment, intervention, and follow-up of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks. This article gives an interpretation of the key points in the guidelines, so as to safely reduce the risk of bilirubin encephalopathy and unnecessary intervention.

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.

Neonatal acute liver failure with pulmonary yellow hyaline membrane and kernicterus

Background Neonatal acute liver failure (NALF) is a rare and life-threatening condition. It causes bilirubin to accumulate to a dangerous level in the body, causing permanent damage to vital organs such as the brain and lungs. In many cases, the etiology of NALF remains unknown. Case presentation We described a case of an 8-day-old baby girl who presented with poor oral intake, lethargy, and jaundice. Her clinical condition rapidly deteriorated with progression to multi-organ failure, and despite intensive resuscitation efforts, she expired. At autopsy, the most significant findings were liver necrosis, yellow hyaline membrane deposition in the lungs, and bilirubin deposition in the brain (kernicterus). Conclusions NALF is a rare and potentially fatal condition necessitating prompt recognition and disease-specific treatment approaches. Toxic accumulation of bilirubin in the lungs can lead to hypoxia and precipitate further ischemic injury to the liver.

IIncreased serum expression of inflammatory cytokines may serve as potential diagnostic biomarker for bilirubin encephalopathy

OBJECTIVES: The present study was designed to explore the roles of inflammatory cytokines interleukin-1β (IL-1β) and Tumor growth factor-β (TGF-β) in the diagnosis and treatment of neonate bilirubin encephalopathy (BE). METHODS: A total of 128 BE neonates and 128 normal neonates were included. The serum samples of the BE children and controls were collected, and the levels of IL-1β and TGF-β were examined. Moreover, the correlation between the level of bilirubin and serum expression of IL-1β or TGF-β in BE patients was analyzed. Finally, receiver operating characteristic (ROC) curves were generated to determine the diagnostic value of the cytokines. RESULTS: IL-1β and TGF-β levels were higher in the serum of BE patients than those in non-BE patients, and the expression of either IL-1β or TGF-β showed a strong positive correlation with the serum expression of bilirubin in BE patients. Moreover, the results of ROC analysis showed that either IL-1β or TGF-β could distinguish BE patients from healthy controls. CONCLUSION: IL-1β and TGF-β levels were upregulated in BE and might function as potential biomarkers or therapeutic targets for BE patients.

Ictère néonatal. Etude des facteurs associés au Centre Hospitalier Départemental de l'Ouéme-Plateau (CHD-OP)

Introduction : l'ictère néonatal est très fréquent dans le monde et est dominé par les ictères à bilirubine libre. Son évolution est le plus souvent favorable mais il peut être grave et engendrer des complications comme une encéphalopathie hyperbilirubinique, une anémie, voire le décès en absence ou en cas de retard à la prise en charge. L'objectif de ce travail était d'étudier les facteurs associés à l'ictère néonatal dans l'unité de néonatologie du CHUD-OP.Méthodes : il s'agissait d'une étude transversale descriptive et analytique qui avait été conduite du 01 juillet 2015 au 30 juin 2016 et avait porté sur tous les nouveau-nés ayant présenté un ictère et admis dans l'unité de néonatologie du service de pédiatrie du CHUD-OP. La saisie et l'analyse des données avaient été faites à l'aide de Epi info 2000 version 3.5.3 et Microsoft Excel 2016. Le test de Pearson avait été utilisé pour les proportions et le test de Student pour la comparaison des moyennes. La différence était statistiquement significative lorsque p est inférieur à 0,05. Résultats : la fréquence hospitalière de l'ictère néonatal était de 11,0% (170, N=1542). Les principales causes retrouvées étaient : l'infection néonatale bactérienne (29,4% ; n=50), l'incompatibilité fœto-maternelle dans les systèmes ABO et rhésus (15,9% ; n=27). La majorité de ces nouveau-nés était guérie et 22,4% (n=38) avaient présenté : une anémie sévère 21,6% (n=25), une encéphalopathie hyperbilirubinémique 18,2% (n=31) et 26 étaient décédés (15,3%). Les nouveau-nés accouchés en dehors de l'hôpital, la prématurité et l'incompatibilité fœto-maternelle dans les systèmes ABO et rhésus étaient des facteurs associés aux complications de l'ictère néonatal. Conclusion : l'organisation de la référence et l'amélioration de la qualité des soins au couple mère-enfant permettra la réduction des facteurs associées à l'évolution défavorable de l'ictère

Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency / 소아과

PURPOSE: This study aimed to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among infants with neonatal indirect hyperbilirubinemia (NIH); compare G6PD-deficient and G6PD-normal patients regarding hyperbilirubinemia and need for exchange transfusions (ET); and assess risk factors for ET and kernicterus. METHODS: This is a case-control retrospective study. Medical records of NIH patients admitted to the Pediatric Department, Salmaniya Medical Complex, Bahrain, between January 2007 and June 2010 were reviewed. Data on sex, age at presentation, hospitalization duration, need for ET, hemoglobin (Hb) level, reticulocyte count, direct Coombs test, serum total and indirect bilirubin levels, thyroid function, blood and urine cultures, G6PD status, and blood groups were collected and compared between the G6PD-deficent and G6PD-normal patients. RESULTS: Of 1,159 NIH patients admitted, 1,129 were included, of whom 646 (57%) were male. Among 1,046 patients tested, 442 (42%) were G6PD deficient, 49 (4%) needed ET, and 11 (1%) had suspected Kernicterus. The G6PD-deficient patients were mainly male (P<0.0001), and had lower Hb levels (P<0.0001) and higher maximum bilirubin levels (P=0.001). More G6PD-deficient patients needed ET (P<0.0001). G6PD deficiency (P=0.006), lower Hb level (P=0.002), lower hematocrit count (P=0.02), higher bilirubin level (P<0.0001), higher maximal bilirubin level (P<0.0001), and positive blood culture result (P<0.0001) were significant risk factors for ET. Maximal bilirubin level was a significant risk factor for kernicterus (P=0.021) and independently related to ET (P=0.03). CONCLUSION: G6PD deficiency is an important risk factor for severe NIH. In G6PD-deficent neonates, management of NIH should be hastened to avoid irreversible neurological complications.

Importancia de la resonancia magnética en la encefalopatía bilirrubínica / Importance of magnetic resonance imaging in bilirubin encephalopathy

Con el objetivo de resaltar el valor diagnóstico de la resonancia magnética en la encefalopatía bilirrubínica se presenta el caso clínico de un recién nacido de 37 semanas de edad gestacional que reingresa al octavo día de vida por ictericia constatándose cifras de bilirrubina indirecta de 30,1 mg/dl. La disminución de las mismas se logró con exanguinotransfusión, fototerapia intensiva y adecuado aporte. Se solicita resonancia magnética de cráneo que informa, a nivel de ambos globos pálidos y subtalámico, un aumento de la señal en T1 y T2; contribuyendo al diagnóstico de encefalopatía bilirrubínica aguda.

In order to highlight the value of magnetic resonance imaging in the diagnosis of bilirubin encephalopathy, the clinical case of a 37 week of gestational age newborn is presented. The newborn was readmitted to hospital with jaundice on the eighth day of life, indirect bilirubin being 30.1 mg/dl. This level was decreased with exchange transfusion, intensive phototherapy and the appropriate oral supply. Magnetic resonance imaging of the skull was requested, revealing T1 and T2 hyperintensity within the globus pallidus, and the subthalamic nuclei; which contributed to the diagnose of acute bilirubin encephalopathy.

Triagem neonatal de deficiência de glicose-6-fosfato desidrogenase e prevalência das mutações G202A (G6PD A-) e C563T (G6PD Mediterrâneo) em Mato Grosso/Brasil / Neonatal Screening for glucose-6-phosphate dehydrogenase deficiency and prevalence of G202A (G6PD A-) and C563T (G6PD mediterranean) mutations in Mato Grosso / Brazil

Objetivos: A deficiência de glicose-6-fosfato desidrogenase (G6PD) está associada a um maior risco de encefalopatia bilirrubínica e de crise hemolítica aguda grave desencadeada por drogas como a primaquina e a dapsona. Conhecer a prevalência dessa deficiência enzimática em área onde a malária e a hanseníase ainda estão presentes e conhecer a prevalência das principais mutações traz subsídios para planejamento de estratégias com vistas à redução de riscos associados a esta deficiência enzimática. Métodos: Estudo descritivo transversal conduzido em uma região do centro-oeste do Brasil. Exame de triagem para deficiência de G6PD foi realizado em 3573 recémnascidos. Exame confirmatório foi necessário em 188 crianças triadas como possíveis portadores de deficiência. Nas crianças em que foi confirmada a deficiência de G6PD foi feita pesquisa das mutações G202A (G6PD A-) e C563T (G6PD Mediterrâneo) por PCR. Resultados: A deficiência de G6PD foi confirmada em 63 crianças, sendo 60 meninos (95,2%) e três meninas (4,8%). O percentual de exames falso-positivos na fase de triagem foi de 66,5%, estando o percentual de falso-positivos associado à temperatura e tempo de transporte das amostras. Entre as crianças que confirmaram deficiência de G6PD, foi mais frequente a história de anemia em familiares e de icterícia neonatal. Houve associação entre hematócrito baixo e deficiência enzimática, mas não com hemoglobina, contagem de reticulócitos ou neutrófilos. A prevalência da deficiência de G6PD (IC95%) foi de 1,76% (1,37; 2,24) entre os recém-nascidos triados e de 3,34% entre os meninos (2,58; 4,25). A mutação C563T não foi identificada em nenhuma criança, mas a mutação G202A estava presente em 58 crianças - 92,06% (IC95%: 83,29 - 97,03): 56/60 meninos e em 2/3 meninas homozigotas. Foi identificado um menino com Kernicterus portador da mutação G202A em hemizigose. Conclusão: O elevado percentual de falso-positivos na etapa de triagem, o tempo necessário entre coleta...

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with an increased risk of bilirubin encephalopathy in neonates and acute hemolytic crisis triggered by drugs such as primaquine and dapsone. In an area where malaria and Hansen's disease are still present, knowing the prevalence of this enzyme defect and determining the prevalence of major mutations is important for planning strategies for reducing the risks associated with this enzyme deficiency. Methods: Sectional study was conducted in a Midwestern region of Brazil. Screening for G6PD deficiency was performed in 3,573 neonates. Confirmatory tests were necessary for 188 positively screened children. After confirmation, PCR investigation was utilized to identify the mutations. Results: G6PD deficiency was confirmed in 63 children: 60 boys (95.2%) and 3 girls (4.8%). The percentage of false-positive cases in the screening phase, 66.5% and was associated with the temperature and transportation time of the samples. Family history of anemia and jaundice was more frequent among the children with confirmed G6PD deficiency. An association between a low hematocrit and enzyme deficiency was observed. However, there was no association with hemoglobin reticulocyte or neutrophils counts. The prevalence of G6PD deficiency (CI95%) was 1.76% (1.37; 2.24) among all screened neonates and 3.34% (2.58; 4.25) among male children. The C563T mutation was not identified in any child. The G202A mutation was present in 58 children - 92.06% (CI95%: 83.29 - 97.03), 56/60 boys and 2/3 homozygous girls. One boy with a hemizygous G202A mutation was identified as having Kernicterus. Conclusion: The high percentage of false-positive results when first screening for G6PD deficiency; the long delay time between the test and result; along with the high cost of the this screening test, are all factors that do not support adding this test to the already established Brazilian neonatal screening programs. The prevalence...

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.

For the Commemoration of the 20th Anniversary of the Korean Society of Neonatology

The Special Edition of Neonatal Medicine was published to commemorate the 20th anniversary of the Korean Society of Neonatology. This volume covers the footprint of academic achievement in neonatology in Korea over the past 20 years. It contains articles regarding the changing trends in epidemiology of neonatal diseases including strategies to overcome survival limits of extreme premies and improvements in neonatal intensive care practices. We tried to cover various therapeutic areas such as bilirubin metabolism, bilirubin encephalopathy, metabolic bone diseases of prematurity, neonatal lung diseases, pathophysiology and identification of risk factors of bronchopulmonary dysplasia, and clinical application of plasma B-type natriuretic peptide test in preterm babies with patent ductus arteriosus. In addition, articles concerning clinical application of neural stem cells as well as pharmacotherapy of neonatal hypoxic ischemic encephalopathy are featured. Other topics that are not covered in this volume will be published as review articles in the following issues of Neonatal Medicine. This compilation of valuable articles by contributing authors is the culmination of hard work and sleepless nights of Korean neonatologists. I would like to express sincere gratitude for the interest and participation of all the members of the Korean Society of Neonatology for the advancement of neonatal care and the society.

Bilirubin Metabolism and Bilirubin Encephalopathy

During the last 30 years, there has been much advances in the understanding of pathogenisis of neonatal hyperbilirubinemia, but the risk of bilirubin encephalopathy are still remained for the high risk neonates. The mechanisms of bilirubin encephalopathy are not thouroughly understood. Various theories may explain bilirubin transport acoss the blood-brain barrier. Free bilirubin, not bound to albumin, can enter the brain. The permeability of the blood brain barrier to bilirubin or albuimin and bilirubin binding may play an important role in the bilirubin encephalopathy. Bilirubin binding ability of Korean infants, similar to American infants, is shown to be less than that of adults. Factors influencing bilirubin-albumin binding, such as acidosis, hypoxia, sepsis, hypothermia, hypoglycemia and immaturity should be considered for neonates at high risk of bilirubin encephalopathy. Free bilirubin is found to be significantly increased in preterm infants with low albumin level. Sulfisoxazole inhibits the bilirubin-albumin binding that resulted in increased free bilirubin concentrations even at low total bilirubin levels. Phenobarbital has no effects on bilirubin binding capacity of albumin. Phototherapy for 48 hours has no influence on bilirubin-albumin binding capacitiy and affinity. Auditory evoked repsonse (ABR) changes in the form of I, III, and IV wave reduction are associated with brainstem and cerebellum bilirubin deposition. Since early detection of bilirubin neurotoxicity is promising for improving outcome for high risk neonates, ABR and other electrophysiological measure will be useful.

Diagnostic value of amplitude-integrated electroencephalography in predicting outcome of newborn patients in neonatal intensive care unit / 中华儿科杂志

<p><b>OBJECTIVE</b>To assess the diagnostic value of amplitude-integrated electroencephalography (aEEG) in predicting outcome of newborns who were at high risk for central nervous system without severe hypoxic-ischemic encephalopathy.</p><p><b>METHODS</b>Forty-two consecutive patients at risks for neurological disorders referred to our level-III NICU were prospectively enrolled in the study over a period of 3 years. They were classified on the basis of their primary diagnoses including hypoglycemic brain damage, meningoencephalitis, bilirubin encephalopathy, and metabolic disease. Clinical data were collected. Amplitude-integrated and raw EEG tracings were assessed for background pattern, sleep-wake cycling, and epileptiform activity. The neuromotor development of survivors was assessed by using the Infant Neurological International Battery (INFANIB).</p><p><b>RESULT</b>The characteristic of aEEG tracings in 42 infants showed continuous normal voltage (CNV)(n = 15), discontinuous voltage (DC)(n = 9), burst-suppression (BS) BS(+) (n = 6), BS(-)(n = 7), flat (FT, n = 5); mature sleep-wake cycling (SWC, n = 4), immature SWC (n = 14), no SWC (n = 24); 30 infants (71.4%) had electrical seizures: single seizure (n = 6); repetitive seizures (n = 7), and status epilepticus (SE) (n = 17).aEEG of 20 infants who had poor outcome showed FT (n = 5), BS(-)/SE (n = 6), BS(-)/ repetitive seizures (n = 1) , BS(+)/SE (n = 1), BS(+)/repetitive seizures (n = 1), DC/SE(n = 6). Chi-square analysis and Spearman rank correlation analysis showed the classification of aEEG background pattern, SWC and comprehensive score (score system was developed by evaluation of the above 3 variables) were correlated with the outcome of these infants at high neurological risks.</p><p><b>CONCLUSION</b>Amplitude-integrated electroencephalography can provide important information of the status of cerebral function in neonates at high neurological risk and help to predict their outcome.</p>

Amplitude-integrated electroencephalographic changes in neonates with acute bilirubin encephalopathy / 中华儿科杂志

<p><b>OBJECTIVE</b>To characterize amplitude-integrated electroencephalo graphic (aEEG) traces in neonates with acute bilirubin encephalopathy (ABE), explore the value of aEEG in early diagnosis and prediction of neurological outcome of ABE.</p><p><b>METHOD</b>aEEG records of 10 cases with ABE (Oct 2009-Nov 2011) were reviewed to identify neonates with a diagnosis of ABE. Clinical data were collected. The aEEG traces were classified according to background activity (normal, moderate, or severely abnormal), presence of seizures and sleep-wake cycling (SWC). Brainstem auditory evoked potential (BAEP) and magnetic resonance imaging (MRI) were studied. The neuromotor development of survivors with ABE was assessed by using the Infant Neurological International Battery (INFANIB).</p><p><b>RESULT</b>The characteristics of aEEG tracings in these infants with ABE were shown continuous normal voltage (CNV, n = 5), discontinuous voltage (DNV, n = 4), discontinuous voltage with burst-suppression (BS)BS+ (n = 1); mature SWC (n = 2), immature SWC (n = 5), no SWC (n = 3); 8 infants (80%) had electrical seizures: single seizure (n = 2); repetitive seizures (n = 2), and status epilepticus (SE) (n = 4). Among the 10 infants with ABE, no infants had normal aEEG, 3 had mildly abnormal aEEG, and 7 had severely abnormal aEEG. Eight infants accepted BAEP test, 2 were mildly abnormal and 6 were severely abnormal. Six infants accepted MRI, 1 was normal and 5 were abnormal. By chi-square analysis and Spearman rank correlation analysis, the results of aEEG classification were correlated with the phase of ABE and the severity of BAEP. These infants were followed up for more than 6 months (range 6 months to 1 year). In 3 infants with mildly abnormal aEEG, 2 were normal and 1 was transit in infanib score at 6 months of age. Of 7 infants with severely abnormal aEEG, 1 died, 3 were abnormal (2 Spastic dyskinesia and 1 hypotonia), 2 were transit in infanib score at 6 months old. 1 lost to follow-up.</p><p><b>CONCLUSION</b>Amplitude-integrated electroencephalography can provide important information of the status of cerebral function in neonates with ABE and help to predict its neurological outcome.</p>

Icterícia neonatal / Neonatal jaundice

Icterícia ocorre na maioria dos recém-nascidos e representa clinicamente a elevação dos níveis séricos de bilirrubina. Com o objetivo de prevenir os danos neurológicos da hiperbilirrubinemia grave, todo recém-nascido com icterícia deve ser monitorado e tratado adequadamente.

Jaundice occurs in most newborn infants and visually represents the elevation of the serum levels of bilirubin. Every jaundiced newborn must be monitored and treated, when necessary, to prevent the neurological damage that may result from severe hyperbilirubinemia.

Estimación visual de la ictericia neonatal y detección del riesgo de hiperbilirrubinemia significativa / Visual estimate of clinical jaundice and detection of the risk of significant hyperbilirubinemia

La predicción del riesgo de hiperbilirrubinemia significativa a través de la medición de una bilirrubina previa al alta ha sido validada en neonatos. La estimación visual de la extensión de la ictericia es comúnmente usada para la decisión de la obtención de la prueba de bilirrubina. Determinar la confiabilidad de la evaluación visual de la ictericia en la detección del riesgo de hiperbilirrubinemia significativa. 123 neonatos fueron examinados antes del alta por un pediatra quien asignó la extensión de la ictericia según su progresión céfalo-caudal. Una medida simultánea de bilirrubina transcutánea fue hecha por otro observador. Luego se comparó la calificación del riesgo de hiperbilirrubinemia significativa por ambos métodos, a través de un nomograma clasificado por zonas de riesgo. Resultados: El porcentaje de coincidencia global en relación a la designación de riesgo por ambos métodos fue 73%, pero esta proporción decreció a 56,3% cuando se analizó sólo para las zonas de alto riesgo. De hecho, 18 (43,7%) de los 32 neonatos calificados de alto riesgo por la prueba transcutánea fueron erróneamente identificados por la evaluación visual como niños de bajo riesgo. A pesar de que la concordancia general entre la estimación visual de la ictericia y la bilirrubina real es aceptable, la confiabilidad de la valoración visual como el procedimiento primario para identificar el riesgo de una hiperbilirrubinemia significativa es limitada. La detección de la severidad de la ictericia debe basarse en otros métodos, como la medición de la bilirrubina sérica o transcutánea

Pre-discharge bilirrubin percentiles have proved to be useful in predicting which infants will develop significant neonatal hyperbilirubinemia. The extent of clinical jaundice is commonly used to decide when to take a sample test for serum bilirubin. To determine the reliability of visual assessment of jaundice in the identification of the risk of significant hyperbilirubinemia. Clinical estimate of cephalocaudal progression of jaundice was carried out by a pediatrician in 123 neonates. Transcutaneous bilirubin (TCB) was simultaneously measured by an independent observer. Measurements by both methods were plotted into a nomogram stratified by risk zones to determine their level of agreement as to the classification of the risk. General agreement between the two measurements was 73%. However, this proportion decreased to 56.3% when only high-risk zones were analyzed. In fact, 18 (43.7%) of the 32 infants with transcutaneous bilirubin levels in high-risk zones were missclasified as low-risk cases by visual estimate. Although there was good general agreement between clinical evaluation of jaundice and TCB, visual assessment was not fully reliable as a primary screening method to identify significant hyperbilirubinemia. Further means should be used to support decisions regarding this risk, such as serum bilirubin sampling or transcutaneous bilirubin

Hiperbilirrubinemia indirecta de origen genético: informe de un caso de síndrome de Crigler-Najjar de tipo II / Indirect hyperbilirubinemia of genetic origin: case report of Crigler-Najjar syndrome type II

El síndrome de Crigler Najjar II aparece por un déficit en la conjugación de la bilirrubina debido a la deficiencia parcial de la enzima uridindifosfato-glucuronil transferasa. Por lo general, tiene un curso benigno, a diferencia del Crigler Najjar de tipo I, donde el déficit enzimático es total y los afectados mueren a edades tempranas. Se presenta el caso de una adolescente de16 años con hiperbilirrubinemia indirecta, síndrome convulsivante y parálisis cerebral. Una correcta historia clínica con estudio genealógico y pruebas funcionales apropiadas, permitieron determinar el diagnóstico definitivo. Esta enfermedad genética se transmite de forma autosómica recesiva, tiene una prevalencia muy baja a nivel mundial y constituye, en general, un reto diagnóstico para los médico.

Crigler Najjar syndrome type II is related to a defect of bilirubin conjugation due to partial deficiency of the enzyme uridine diphosphate-glucuronyl transferase. Usually has a benign course, unlike Crigler Najjar type I, where the enzyme deficiencyis total and the affected patients usually die at early ages. We present the case of a teenager with indirect hyperbilirubinemia, seizures and cerebral palsy. A good clinical historywith pedigree and appropriate functional tests allowed us to determine the definitive diagnosis. This is an autosomal recessive disorder, has a very low prevalence worldwide, and is adiagnostic challenge for physicians in general.

The Clinical Characteristics According to the Risk Factors of Idiopathic Nonhemolytic Hyperbilirubinemia

PURPOSE: Hospital readmissions have recently increased due to early hospital discharge and increased trends in breast-feeding. Neonatal hyperbilirubinemia can lead to fatal permanent neurological sequelae without appropriate management. Early detection and intervention are critical. We evaluated the clinical features, risk factors, and brain MRI findings of Korean newborns with idiopathic nonhemolytic hyperbilirubinemia to determine the optimal management policy. METHODS: A retrospective review of the medical records of 79 newborns with idiopathic nonhemolytic hyperbilirubinemia was performed at the NICU of the Kyungpook National University Hospital from January 2006 to September 2009. All patients were 35 or more weeks of gestation, and their peak level of serum total bilirubin was more than 20 mg/dL. RESULTS: The mean gestational age was 38(+3)+/-1(+4) weeks, and the mean age on admission was 8.8+/-4.0 days. The mean body weight (3,105+/-479 g) was decreased by 2.8+/-6.4 percent compared to the mean birth weight (3,174+/-406 g). There were no statistically significant differences for the peak serum bilirubin level or the duration and effects of phototherapy between the patients with and without risk factors, which included: breastfeeding, cephalohematoma, subdural hemorrhage, and/or ABO incompatibility. Patients were grouped according to change of body weight. Group I consisted of patients that gained weight compared to birth weight, and group II of patients that lost weight compared to birth weight. There were significant differences in the peak serum total bilirubin level between the two groups. Thirty nine patients had brain MRI evaluation; 21 patients had bilateral symmetric signal intensity increases in the globus pallidus compared to adjacent corticospinal tract and putamen on T1-weighted images. CONCLUSION: Bilirubin encephalopathy is preventable with early screening and proper management. Parents require instruction on feeding practices and follow-up to prevent complications from idiopathic nonhemolytic hyperbilirubinemia.

The Clinical Characteristics According to the Risk Factors of Idiopathic Nonhemolytic Hyperbilirubinemia

PURPOSE: Hospital readmissions have recently increased due to early hospital discharge and increased trends in breast-feeding. Neonatal hyperbilirubinemia can lead to fatal permanent neurological sequelae without appropriate management. Early detection and intervention are critical. We evaluated the clinical features, risk factors, and brain MRI findings of Korean newborns with idiopathic nonhemolytic hyperbilirubinemia to determine the optimal management policy. METHODS: A retrospective review of the medical records of 79 newborns with idiopathic nonhemolytic hyperbilirubinemia was performed at the NICU of the Kyungpook National University Hospital from January 2006 to September 2009. All patients were 35 or more weeks of gestation, and their peak level of serum total bilirubin was more than 20 mg/dL. RESULTS: The mean gestational age was 38(+3)+/-1(+4) weeks, and the mean age on admission was 8.8+/-4.0 days. The mean body weight (3,105+/-479 g) was decreased by 2.8+/-6.4 percent compared to the mean birth weight (3,174+/-406 g). There were no statistically significant differences for the peak serum bilirubin level or the duration and effects of phototherapy between the patients with and without risk factors, which included: breastfeeding, cephalohematoma, subdural hemorrhage, and/or ABO incompatibility. Patients were grouped according to change of body weight. Group I consisted of patients that gained weight compared to birth weight, and group II of patients that lost weight compared to birth weight. There were significant differences in the peak serum total bilirubin level between the two groups. Thirty nine patients had brain MRI evaluation; 21 patients had bilateral symmetric signal intensity increases in the globus pallidus compared to adjacent corticospinal tract and putamen on T1-weighted images. CONCLUSION: Bilirubin encephalopathy is preventable with early screening and proper management. Parents require instruction on feeding practices and follow-up to prevent complications from idiopathic nonhemolytic hyperbilirubinemia.

Breast Feeding and Jaundice / 한양의대학술지

Even though there is a strong link between breast feeding and jaundice, it is natural and it may have a partially beneficial role in the neonate. There are two types of jaundice associated with breast feeding. First, insufficient caloric intake during the first week of life may increase serum unconjugated bilirubin concentration, which is known as "breast feeding jaundice (BFJ)". This increased severity of physiologic jaundice results from the increased enterohepatic circulation (EHC) of bilirubin, but not because of a factor in breast milk. Second, prolongation of unconjugated hyperbilirubinemia into the third and later weeks of life in the healthy newborn is a regularly occurring extension of physiologic jaundice, which is known as "breast milk jaundice (BMJ)". This is caused by a factor in breast milk inhibits the glucuronyl transferase in the liver and/or increases the EHC of bilirubin. The acceptable bilirubin level in the full-term healthy breast-fed infant needs to be discussed not only to prevent unnecessary interruption of breast feeding, but also to prevent kernicterus. Optimal breast feeding practices are crucial to prevent the BFJ and to minimize the intensity of BMJ. Further research is needed to clarify the benefit of bilirubin in relation to adaptation of extrauterine life.