Hemolytic Disease of the Newborn Associated with Anti-Jr(a) Alloimmunization in a Twin Pregnancy: The First Case Report in Korea / 대한진단검사의학회지

Jr(a) is a high-frequency antigen found in all ethnic groups. However, the clinical significance of the anti-Jr(a) antibody has remained controversial. Most studies have reported mild hemolytic disease of the newborn and fetus (HDNF) in Jr(a)-positive patients. Recently, fatal cases of HDNF have also been reported. We report the first case of HDNF caused by anti-Jr(a) alloimmunization in twins in Korea. A 33-yr-old nulliparous woman with no history of transfusion or amniocentesis was admitted at the 32nd week of gestation because of vaginal bleeding caused by placenta previa. Anti-Jr(a) antibodies were detected in a routine laboratory examination. An emergency cesarean section was performed at the 34th week of gestation, and 2 premature infant twins were delivered. Laboratory examination showed positive direct antiglobulin test and Jr(a+) phenotype in the red blood cells and the presence of anti-Jr(a) antibodies in the serum in both neonates. The infants underwent phototherapy for neonatal jaundice; this was followed by conservative management. They showed no further complications and were discharged on the 19th postpartum day. Preparative management to ensure the availability of Jr(a-) blood, via autologous donation, and close fetal monitoring must be performed even in cases of first pregnancy in Jr(a-) women.

Neonatal jaundice and splenic hematoma.

In the newborn period, unconjugated hyperbilirubinemia (UHB) is common, multifactoral, and associated with a variety of physiologic and pathologic conditions. The most commonly identified pathologic cause leading to hyperbilirubinemia is hemolytic disease of the newborn. We report a five-days-old female infant with neonatal jaundice secondary to splenic hematoma.

Hiperbilirrubinemia neonatal prolongada devido à associação entre síndrome de Gilbert e doença hemolítica por incompatibilidade RhD / Persistent neonatal hyperbilirubinemia resulting from Gilbert's syndrome in association with RhD hemolytic disease

OBJETIVO: Relatar associação infreqüente de patologia que cause aumento considerável de produção de bilirrubina e outra diminuição importante na sua excreção. DESCRIÇÃO: Mãe tercigesta, Rh negativo. Na primeira gestação, gerou recém-nascido normal, de termo, não tendo recebido imunoglobulina humana anti-RhD. A segunda gestação complicou-se por isoimunização Rh, dando à luz neonato de termo, o qual necessitou três exsanguinotransfusões e faleceu com 8 dias de vida. Na gestação atual, conseguiu dar à luz a termo recém-nascido tipo ORh positivo, Coombs direto positivo, bilirrubina de cordão 6,5 mg/dl e hematócrito 44 por cento. Com 5 horas de vida, estava ictérico, tendo sido iniciados fenobarbital (por 3 dias) e fototerapia intensiva. A hiperbilirrubinemia foi logo controlada, porém ascendia rapidamente sempre que a fototerapia era suspensa. No 10° dia de vida, a criança foi transfundida por anemia importante. Em vista da persistência da icterícia, no 13° dia de vida pensou-se em associação com síndrome de Gilbert, e o seqüenciamento de DNA foi solicitado. O resultado mostrou genótipo mutante homozigoto UDPT1A1[TA]7TAA. Permaneceu em fototerapia até o 17° dia de vida. Recebeu alta no dia seguinte, após controle de bilirrubinemia. Voltou para acompanhamento ambulatorial e apresentou desenvolvimentos pondo-estatural e neurológico normais. COMENTARIOS: O caso ressalta a importância da associação do aumento de produção/diminuição de excreção de bilirrubina na gênese de hiperbilirrubinemias prolongadas, intensas e passíveis de causar kernicterus, se não tratadas vigorosamente. Demonstra, ainda, a eficácia da fototerapia intensiva, reduzindo os riscos de tratamentos mais agressivos. Ressalta, também, a importância do acompanhamento das icterícias neonatais até a completa remissão dos sintomas.

Neonatal cholestasis

Neonatal cholestasis is caused by impaired excretion of biliary substances resulting in their accumulation in blood. Neonatal cholestasis should be ruled out in infants presenting with jaundice that persists after 2 weeks of life. It is important to check fractionated serum bilirubin levels in these patients and immediately refer the patients with conjugated hyperbilirubinemia to a pediatric gastroenterologist for further evaluation. Conjugated hyperbilirubinemia, pale stools and dark urine are the cardinal features of neonatal cholestasis. Early recognition and a stepwise diagnostic evaluation of the infant with cholestasis are essential in successfully treating or managing the complications of the metabolic and infectious liver diseases of the infant as well as surgically relieving obstruction in patients who have biliary atresia. Biliary atresia is the most common cause of neonatal cholestasis and the prognosis is directly related to the age at the time of surgery, with better prognosis if surgery is done before 60 days of age. Cholestasis in premature infants is multifactorial and should have a modified approach to the evaluation of cholestasis. Medical management of cholestasis is mostly supportive, consisting of management of complications of chronic cholestasis like pruritus and nutritional support for malabsorption and vitamin deficiency

Perda auditiva neonatal associada a hiperbilirrubinemia por deficiência de glicose-6-fosfato desidrogenase: relato de caso / Neonatal hearing loss associated hyperbilirubinemia in a newborn with glucose-6-phosphate dehidrogenase deficêncy: case report

Objetivo: relatar um caso de grave perda auditiva neonatal assiaciada a hiperbilirrubinemia por deficiência de glicose-6 fosfato desidrogenase. Descrição: um recé-nascido a termo, adequado para a idade gestacional, realizou triagem auditiva neonatal por método de emissões otoacústicas / Objective: to report a case of serious neonatal loss associated to hypeerbilirubinemia in a newbornwith glucose-6-phosphate dehydrogenase deficiency...

Glucose-6-phosphate dehydrogenase deficiency in neonates.

OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited deficiency that may be the cause of neonatal hyperbilirubinemia, as has been found in several countries and among widely different ethnic groups, especially in Mediterranean region. Our aim was to study the prevalence of G6PD deficiency in relation to neonatal jaundice. METHODS: From March 1998 to April 2001 we studied 705 clinically icteric neonates who were admitted to Al-Zahra and Beheshti hospitals, two teaching hospitals in Isfahan, Iran. Laboratory investigations included determination of direct and indirect serum bilirubin concentrations, blood group typing, direct coomb's test, hemoglobin, blood smear, reticulocyte count and G6PD level. RESULTS: In only 53 (7.5%) of cases G6PD deficiency was diagnosed. In all G6PD deficient neonates no evidence of other factors known to cause hyperbilirubinemia were detected. The sex distribution was 13 (24.5%) females and 40 (75.5%) males in the G6PD deficient group. The mean bilirubin level in G6PD deficient and G6PD normal groups were 22.26 +/- 8.36 and 18.14 +/- 3.85 mg/dl, respectively (p=0.001). Phototherapy was required in G6PD deficient and other icteric neonates with duration of 3.76 +/- 1.93 and 3.13 +/- 2.14 days, respectively (p=0.045). Twenty-seven of the 53 (50.9%) G6PD deficient infants required exchange transfusion. None of them developed kernicterus. CONCLUSIONS: Since the prevalence of severe hyperbilirubinemia among our neonates was relatively high and about half of them required exchange transfusion, early detection of this enzymopathy regardless of sex and close surveillance of the affected newborns may be important in reducing the risk of severe hyperbilirubinemia and exchange transfusion.

Newborn jaundice and kernicterus--health and societal perspectives.

Kernicterus, a preventable injury to the brain from severe neonatal jaundice, has re-emerged in the United States as a public and societal health concern. Kernicterus, in its usually recognized form, causes devastating disabilities, including athetoid cerebral palsy and speech and hearing impairment. This condition not only ranks amongst the highest cost per new case (per CDCs Financial Burden of Disability study, 1992), but also results in profound and uncompromising grief for the family and loss to siblings of healthy, talkative playmates. And for the child with kernicterus (usually remarkably intelligent, but trapped in an uncontrollable body), grief and frustration are enormous. In 2001 national healthcare organizations, including Centers for Disease Control (CDC), the Joint Commission for the Accreditation of Healthcare Organizations (JACHO) and the American Academy of Pediatrics (AAP) issued alerts to all accredited hospitals and public health professionals in the United States that all healthy infants are at potential risk of kernicterus if their newborn jaundice is unmonitored and inadequately treated. The re-emergence of kernicterus in the United States is the result of interacting phenomena including (a) Early hospital discharge (before extent of jaundice is known and signs of impending brain damage have appeared); (b) Lack of adequate concern for the risks of severe jaundice in healthy term and near newborns; (c) An increase in breast feeding; (d) Medical care cost constraints; (e) Paucity of educational materials to enable parents to participate in safeguarding their newborns; and (f) Limitations within in healthcare systems to monitor the outpatient progression of jaundice. A multidisciplinary approach that encompasses both healthcare and societal needs should be evaluated at a national level for practical and easy to implement strategies. An approach that is based on principles of evidence-based medicine, patient-safety and family centeredness is presented in this article. These strategies should also be based on public awareness campaign such that the healthcare providers can attempt to achieve a "Zero Tolerance of Kernicterus" and thereby decrease both childhood disabilities and infant mortality within the community.

Sigue siendo un problema la hiperbilirrubinemia en el recien nacido de término sano alimentado a pecho con las cifras actuales de tratamiento? / Is it still the hyperbilirubinemia a problem in the healthy term breast fed newborns with current rates of treatment?

Objetivo: evaluar en la población de recién nacidos de término sanos alimentados a pecho: 1) Porcentaje de niños que alcanzan nivel de bilirrubina sérica de 15, 17 y 20 mg/dl. 2) Número de determinaciones de bilirrubina sérica hasta alcanzar nivel de bilirrubina ó 13 mg/dl. 3) Tiempo requerido hasta alcanzar bilirrubina sérica ó 13 mg/dl. Diseño: prospectivo, observacional, descriptivo. Sujetos: incluimos en forma consecutiva todos los recien nacidos de término sanos alimentados a pecho nacidos en el Hospital Materno Infantil R. Sardá. Material y métodos: controlamos a los recién nacidos para valorar la presencia de ictericia en internación y mediante seguimiento por consultorio externo. De presentarla se realizó determinación de bilirrubina sérica. Al alta se los citó según estuviesen anictéricos o ictéricos. Anictéricos: a los 7-10 días. Ictéricos: según cifras de bilirrubina(BI) y días de vida: BIò15 mg/dl y ó5 días: cada 24 horas, >5 días: cada 48 horas; BI<15 mg/dl y ó5 días: cada 48 horas, >5 días: cada 4 días. Se los controló hasta BI ó13 mg/dl, con dos valores en descenso. Se indicó fototerapia con niveles de BI sérica total ò20 mg/dl. Resultados: entre el 23/1 y el 18/2/95 nacieron 195 recién nacidos de término sanos alimentados a pecho. Desertaron 31 (15.9 por ciento). El promedio de horas de estadía en internación conjunta fue de 55 ñ14.2 (mín: 34-máx: 107) mediana: 52. Del total de la población del estudio alcanzaron cifras de BI sérica ò17 mg/dl el 12 por ciento (20/164), y BIò20 mg/dl 3 por ciento (5/164). De los que presentaron ictericia el promedio de determinaciones de BI fue 3.48ñ2.05 (mín:1-máx:10) mediana:3. La cantidad de días hasta recuperar BIó13 mg/dl (2 valores en descenso) fue de: X 12ñ6.2 (3-33) mediana:11. Conclusiones: la ictericia neonatal, aún en el recién nacido de término sano, continúa siendo un problema para los médicos y para las madres: 1) por el alto porcentaje de la población que presenta hiperbilirrubinemias severas, 12 por ciento alcanza niveles de 17mg/dl y un 3 por ciento de 20 mg/dl, 2) por el tiempo requerido y número de determinaciones hasta alcanzar bilirrubina ó13 mg/dl. Es fundamental establecer esquemas de seguimientos adecuados a la institución y a la población que se asiste, que aseguren el control de todos los recién nacidos hasta resolución del problema. Además creemos que es necesario profundizar la investigación de nuevas líneas terapéuticas con características preventivas.

Hiperbilirrubinemia abo en recién nacidos, diagnóstico precoz y manejo, Hospital Regional Honorio Delgado de Arequipa 1993

El estudio fue realizado en el servicio de Neonatología de una muestra de 500 recién nacidos se obtuvo los siguientes resultados: 12 por ciento de niños tuvieron grupo sanguineo diferente al O, presentaron riesgo de incompatibilidad ABO 7 por ciento ictericia clínica 4.6 por ciento y enfermedad hemolítica por incompatibilidad ABO el 2.4 por ciento, predominando la incompatibilidad AO. La ictericia en los niños afectados apareció en las primeras 24 horas de vida, todos los niños con hemólisis presentaron valores elevados de reticulocitos y esferocitos y la hemoglobina fue baja en el 33.33 por ciento de estos niños. El 87.05 por ciento de estos niños con cuadro hemolítico tuvo el antecedente materno de infección y administración de vacuna antitetánica, hubo mayor frecuencia de hemólisis en hijos de madres multíparas; todos los niños recibieron fototerapia y tres de ellos fueron tratados con exanguinotransfusión total. No hubo ningún fallecido y ninguno presento manifestaciones de alteración neurológica durante la hospitalización y en el seguimiento al mes de edad

Hemocromatosis perinatal / Perinatal hemochromatosis

Se describe un recién nacido afectado por varias malformaciones cardiovasculares (estenosis valvular pulmonar severa, defecto septal interventricular, aorta bicúspide), riñón en herradura, polidactilia y sindactilia de los ortejos, quien presentó muy precozmente hiperbilirrubinemia de predominio directo, edema, hipoprotrombinemia refractaria a la vitamina K e hipoproteinemia. Después de suministrarle prostaglandina E en las primeras horas de vida y realizar un procedimiento cardiovascular paliativo (anastomosis de arteria sistémica a arteria pulmonar de Blalock-Taussig), con el que cedieron las crisis de apnea y bradicardia que le afectaban, el paciente evolucionó con insuficiencia renal y falleció a la edad de 28 días. En la necropsia se encontró fibrosis hepática, proliferación ductal y con tinción histoquímica de azul de Prusia, múltiples depósitos de fierro en hígado, páncreas, pulmón, tiroides, tracto intestinal y glándulas salivales. Estos hallazgos son característicos de la hemocromatosis perinatal, afección colestásica poco frecuente y de alta letalidad que debe tenerse presente en recién nacidos con insuficiencia hepática precoz y mantenida. La hemocromatosis neonatal no había sido descrita en asociación con malformaciones congénitas significativas, excepto por un caso con atresia esofágica

Experiência do berçário anexo à Maternidade do Hospital das Clínicas da FMUSP (BAM-HC) com exsanguíneotransfusäo em hiperbilirrubinemia neonatal nos anos de 90-91 / Experience in the BAM of Chinic Hospital FMUSP with exchange transfusion during 90-91 in neonatal hyperbilirrubenemia

Os autores descrevem a populaçäo de recém-nascidos - RNs - submetidos à exsanguineotransfusäo -EXT- entre 1990 e 1991, dividindo-a em dois grupos (A-EXT nas primeiras 24 horas de vida e, B-EXT após 24 horas de vida). A etiologia mais frequente da síndrome ictérica foi a doença hemolítica pelo sistema Rh. Foram colhidas hemoculturas das bolsas sanguíneas, obtendo-se três positivas. As complicaçöes mais frequentes foram a bradicardia reversível e a síndrome hemorrágica. Os autores concluem que a morbimortalidade do método é bastante baixa, desde que sejam prevenidas as compicaçöes hemorrágicas e infecciosas

Ictericia no hemolítica hereditaria familiar: análisis clínico / Family hereditary non hemolytic jundice: clinical analysis

Se analiza a propósito de una experiencia clínica el caso de una lactante femenina con tinte ictérico persistente desde los 3 días de vida; antecedentes de hospitalizaciones previas, incluyendo exanguinotransfusiones seriadas. El cuadro clínico además de la ictericia prolongada, se caracterizó inicialmente por un buen estado general, sin hepato o esplenomegalia, ni síntomas de anemia. La evolución o ingreso al hospital fue motivado por episodios de hipertemia, sin aparente explicación infecciosa y cuadros convulsivos generalizados tónico-clónicos. La historia familiar destaca antecedentes de 3 hermanos fallecidos a corta edad, todos con una ictericia como rasgo clínico dominante.Al primer hermano fallecido se le llegó a practicar una autopsia que reportó kefrnicterus. Los nivelesde bilirrubina en sangre oscilaron entre 18 y 36 mgr por ciento, casi toda la bilirrubina era indirecta, pues la directa nunca fue mayor de 3 mgr por ciento. Se descartó incompatibilidad de grupo u otras anormalidades que propiciaran una hemólisis. Se descartó además por ECO la eventualidad de obstrucción de las vías biliares extrahepáticas, tratándose así de un problema de tipo parenquimatoso hepático. La administración de fenobarbital no modificó los niveles de bilirribina en sangre, no así la fototerapia contínua que si llegó a disminuir la hiperbilirrubinemia no conjugada. Los familiares de la menor se opusieron a la biopsia hepática. Luego de varios reingresos, la paciente falleció a la edad seis meses

Brain stem electric response audiometry in neonates with hyperbilirubinemia.

Auditory evoked responses using BERA were studied in 30 newborn babies with plasma bilirubin > or = 15 mgm/dl and repeated after treatment of neonatal jaundice with bilirubin levels of < or = 10 mgm/dl. A few jaundiced babies (16.5%) showed absent BERA response at the initial/subsequent examination. After treatment, 3/30 babies showed absent wave form responses and 2 of these were clinically kernicteric. Jaundiced babies had prolonged wave peak latencies and inter peak latencies. Treated babies showed a tendency towards recovery in their BERA responses which were however not complete. Total plasma bilirubin value at the time of BERA examination and mean maximal bilirubin values had no correlation with the incidence and degree of BERA abnormalities.

Evaluación de un programa de pesquisa de hipoacusia en recien nacidos / Evaluation of the program of research on hypoacusia in newborn infants

Un equipo multidisciplinario desarrolló el Programa de Pesquisa de Niños Sordos (PROPENSO) en dos maternidades de la ciudad de Buenos Aires, una pública, R. Sardá (RS) y la otra privada del Sanatorio Otamendi y Miroli (SOM). El tamizado sistemático de 5489 recién nacidos desde mayo a diciembre de 1984 reveló 267 (4,8 por ciento) que reunían factores de "alto riesgo" para hipoacusia. La evaluación diagnóstica posterior, realizada en su mayoría en el centro del CEIDHI se completó en 155 (58 por ciento) niños de la cohorte de riesgo: 112 (52,6 por ciento) de los 213 pesquisados en RS y 43 (79,6 por ciento) de los 54 del SOM. En esta etapa se analizó la validez de una prueba subjetiva (audiometría conductual) en relación a un barrido de alta intensidad con potenciales evocados audiométricos de tronco (PEAT) observando una sensibilidad de 46 por ciento y una especificidad de 94 por ciento. Se detectaron finalmente 4 lactantes con hipoacusia severa bilateral persistente y 5 con sordera unilateral y se inició en ellos tempranamente la orientación y tratamiento. Debe contemplarse, para mejorar la eficiencia de futuras estrategias de pesquisa de hipoacusia infantil, que: a) el uso de un listado para identificar factores de riesgo en recién nacidos es un procedimiento efectivo, b) es difícil lograr el seguimiento ambulatorio, especialmente para familias de bajos ingresos, y c) la audiometría conductal parece ser un método suficientemente confiable para el reconocimiento inicial de hipoacusia severa (pero no en los primeros meses de vida).

Neonatal hemochromatosis: report of an autopsy case

A case of neonatal hemochromatosis in a 3-hour-old male is described. He presented with hypotonia, mild jaundice, and respiratory difficulty immediately after birth. He had no evidence of congenital infection, immune-related hemolysis or exogenous iron uptake. Postmortem examination revealed abnormal facial features. The organs were of normal weight for his age except a small liver and lungs, and a large spleen. The most prominent changes were in the liver and pancreas. The liver was coarsely nodular and fibrotic. The lobular architecture was totally distorted by innumerable multinucleated giant cells, loss or collapse of the hepatocytes, and diffuse fibrosis. A large amount of hemosiderin was seen in the liver, pancreatic acini and thyroid follicular cells. Scanty amount of hemosiderin was also found in the myocardial fibers and renal tubular cells. The pancreas showed hyperplasia and hypertrophy of the islets. The spleen showed severe congestion and a moderate extramedullary hemopoiesis but no deposits of hemosiderin. This patient had three siblings died in neonatal period, one of which had clinical features of neonatal hemochromatosis.