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.

Clinical profiles and outcomes of neonates with neonatal hyperbilirubinemia and treated with double volume exchange transfusion: a retrospective study

Background: Double volume exchange transfusion (DVET) for severe unconjugated hyperbilirubinemia has become less common events now days in pediatric practices. But kernicterus is still common in low income country like India. The aim of the study was to determine the clinical profile and outcome in neonates who were treated with DVET.Methods: This was a retrospective study in neonate's ?34 weeks of gestation that were treated with DVET for severe neonatal hyperbilirubinemia over a period of four years.Results: In our study, 37 neonates underwent DVET. Male neonates (62.13%) and normal vaginal delivery (NVD) (70.2%) are common. ABO Isoimmunisation was commonest cause (56.75%) of exchange transfusion.' The mean TSBR at pre exchange and Post Exchange were 27.39 ' 5.99mg/dl and 15.16 ' 4.00mg/dl (p<0.05). Ten neonates (27%) among 37 neonates required twice DVET.Thrombocytopenia14 (37.83%); Seizure 5(13.5%) and Hypocalcaemia 3(8.1%) were common complication noted among total 17 (45.94%) neonates. BIND occurred in 15 neonates (40.5%) at the time of admission and seven (18.9%) neonates had persistent neurological abnormality at discharge. Neonate with BIND had early onset of jaundice (44.13'15.37 hours vs. 61.22'28.23hrs, p<0.05), with' higher' pre exchange TSBR value(28.96 '8.5mg/dl vs. 26.22'3.17mg/dl). Neonates admitted with BIND had higher percentage of persistent encephalopathy (40% vs. 4.5%,p<0.05), abnormal tone (33.3% vs. 4.5%,p<0.05), abnormal feeding (33.3% vs. 4.5%,p<0.05) and abnormal posture (26.6% vs. 0%,p<0.05)' at discharge as compared to those without BIND. No death occurred in this study population.Conclusions: Early detection and aggressive therapy with DVET can prevent neonates from brain injury.

Etiological study of jaundice in neonates

: Jaundice is the commonest abnormal finding with an incidence of about 60% in term babies and 80% in preterm babies. It is the commonest cause of admission to hospitals in the newborn period. In preterm babies, the percentage is exceedingly high due to their physiological handicaps and other hazards of prematurity like Asphyxia, septicemia, respiratory and circulatory Insufficiency. Non-physiological or pathological jaundice is also known to occur in (8-9)% of newborns. Its timely detection and optimal management are crucial to prevent brain damage and subsequent neuro-motor retardation. Aims of this study to find out the etiology of jaundice in neonates, admitted in neonates unit attached to SMS medical college Jaipur.Method: This Observational study was conducted in Neonatal Intensive Care Unit (NICU) and Post Natal Ward attached to SMS medical college Jaipur, after approval from the hospital ethical committee, over a period of 12 months(October 2011 to September 2012. Study was carried on 500 neonates presenting clinically with neonatal hyperbilirubinemia.Result: The onset of jaundice was seen maximum between live hour 24-72 hours (n=290, 58% cases), followed by live hour 72 hours-14 days (n=160, 32%). At more than 2 weeks there was only 3 case (0.6%). The etiological factors in the causation of jaundice in the decreasing order of frequency were exaggerated physiological jaundice accounts for (28%), ABO-incompatibility (24.4%), Rh-incompatibility (13.8%), Idiopathic (10.4%), cephalhematoma (10.2%), septicemia (6%), intrauterine infections (4%), BMJ (1.8%), Galactocemia (0.8%) and G6PD' Deficiency (0.6%) respectively.Conclusion: Hyperbilirubinemia is more severe in newborns, therefore precautionary measure should be adopted by both parents, and clinicians to diagnose and treat the diseases properly.

Frequency of Exchange Transfusion in Newborns with Neonatal Hyperbilirubinemia

Background: Almost all newborn infants develop some degree of hyperbilirubinemia as a normal transition in physiology. High levels of unbound unconjugated bilirubin can cross the blood-brain barrier and cause neurological symptoms. Objectives: To determine the frequency of exchange transfusion in neonates with hyperbilirubinemia and to describe the characteristics of neonates with hyperbilirubinemia including those who underwent exchange transfusion. Methods: A retrospective study was conducted to know the frequency of exchange transfusion in neonates admitted to hospital with hyperbilirubinemia and to study selected characteristics of these babies including; sex, gestational age, body weight, type of feeding, and mode of delivery, and to identify the causes of hyperbilirubinemia. Results: A total of 120 neonates were enrolled in the study, 70 males and 50 females. Most of them (67%) were fullterm, weighing more than 2.5 kg. The majority (77%) was delivered vaginally, and mixed feeding with breast and artificial milk formula was the main source of feeding. The mean value of serum bilirubin at time of admission was 14.7 mg/dl and for those underwent exchange transfusion was 22 mg/dl at the time of exchange. In 92 babies (77%), the cause of hyperbilirubinemia was unknown. Hemolytic anemia due to Rh and ABO incompatibility was identified in 16% of babies, and G6PD deficiency was identified in 7%. Exchange transfusion was performed in 16.6% of patients. Conclusion: Although neonatal jaundice is a benign condition in most cases, pathologic harmful hyperbilirubinemia can occur, and despite the benefits of phototherapy, exchange transfusion is still performed and kernicterus is still occurring. Recommendation: Newborn babies should be screened for hyperbilirubinemia and correctly managed to reduce the frequency of exchange transfusion which carries many risks for newborns, and to prevent kernicterus.

Acute bilirubin encephalopathy in term neonates: a hospital-based study

Background: Acute Bilirubin Encephalopathy and kernicterus is an important cause of cerebral palsy, developmental delay and hearing impairment in low-middle income countries. Interventions such as universal screening for neonatal jaundice, Rhesus immunoglobulins, intensive phototherapy and exchange transfusion have made kernicterus rare in high income countries, but in our set up such cases continue to be reported.  Methods: Retrospective observational study where case records of term neonates brought to the neonatal ICU with signs and symptoms of acute bilirubin encephalopathy during the years 2016 and 2017 were sought and analysed.Results: A total of ten term babies reported to the neonatal unit with severe hyperbilirubinemia along with signs and symptoms of bilirubin encephalopathy of which 60% were females. 90% had a birth weight of more than 2.5 kg and mean birth weight was 2.7±0.25 kgs. All the babies were out born. A 4 babies were born at home of which 3 pregnancies were completely unsupervised during the antenatal period. 90% of the babies were from the rural areas, 6 of the cases were from the districts Rajouri, Poonch and Reasi where the terrain is hilly, 2 from rural areas of Jammu and 1 from Kathua. Only 1 was from the Jammu city. The age at admission ranged from 3-9 days and serum bilirubin from 24 to 43.3 mg %. A 5 babies had ABO incompatibility, 1 Rh incompatibility, 1 sepsis, while no cause could be found in 3.Conclusions: Neonatal jaundice is often not easily appreciated by mothers and caregivers in the home setting until it becomes severe enough, at which point neurological damage may have already occurred. There is an urgent need to train the primary health care personnel in assessment and early identification of risk factors for severe neonatal hyperbilirubinemia. They can help the families to seek prompt treatment for this preventable cause of cerebral palsy and mental retardation.

Effect of exchange transfusion therapy on complications and prognosis in newborns with bilirubin encephalopathy / 中国基层医药

Objective To study the influence of exchange transfusion therapy on the complications and prognosis in newborns with bilirubin encephalopathy.Methods From June 2013 to June 2016,76 children with bilirubin encephalopathy in Feicheng People's Hospital were selected and divided into study group(n =41) and control group(n =35) according to whether or not accepted the exchange transfusion treatment.The levels of total bilirubin (TBIL),indirect bilirubin(IBIL),direct bilirubin(DBIL) and the ratio of total bilirubin to plasma albumin(B/A)were detected and compared between the two groups.The complications and prognosis of the two groups were recorded.Results After exchange transfusion,the TBIL,IBIL,DBIL and B/A values in the study group were (209.49 ± 48.82) μmol/L,(201.81 ± 39.62) μmoL/L,(21.92 ± 19.47) μmoL/L and (5.15 ± 1.89),respectively,which were significantly lower than those before exchange transfusion [(492.35 ± 42.41) μmol/L,(439.44 ± 52.56) μmol/L,(69.38 ± 21.56) μmol/L and (13.28 ± 0.40)] (t =28.007,23.117,10.461,26.947,all P ＜ 0.05).The incidence rates of anemia,sinus bradycardia and electrolyte disturbances in the study group were 48.78％,48.78,60.98％,respectively,which were significantly higher than those in the control group(17.14％,14.29％,14.29％) (x2 =8.397,10.178,17.228,all P ＜ 0.05).The incidence rates of death,hearing impairment and brain damage in the study group were 7.32％,70.73％ and 12.20％,respectively,which in the control group were 11.43％,71.43％ and 14.29％,respectively,there were no statistically significant differences between the two groups (x2 =0.382,0.004,0.072,all P ＞ 0.05).Conclusion Exchange transfusion can significantly reduce the levels of bilirubin and B/A in the treatment of newborns with bilirubin encephalopathy,but it can increase the incidence rate of anemia,sinus bradycardia and electrolyte disturbances,which has no significant influence on the prognosis of patients.

The predictive value of writhing stage general movement assessment for motor development outcomes in infants with severe neonatal jaundice / 中国新生儿科杂志

Objective To study the predictive values of the general movements (GMs) assessment in writhing stage for motor development outcomes in infants with severe neonatal jaundice.Method From December of 2012 to December of 2017,infants with severe neonatal jaundice (serum bilirubin reaching the corresponding level of exchange transfusion according to the reference nomogram) in our hospital were enrolled in the study.Inclusion criteria included corrected gestational age of 37 to 48 weeks,serum bilirubin level below phototherapy intervention value after treatment and general and detailed assessment were carried out in writhing stage when the infant was stable.The patients were regularly followed-up until one-year-old to evaluate the predictive values.Result A total of 241 patients with severe neonatal jaundice were enrolled in the study,including 153 males (63.5％) and 88 females (36.5％),with gestational age between 35 and 42 weeks.The mean gestational age was (37.9± 1.8) weeks,the average birth weight was (3 057±480) g,and the mean serum bilirubin value was (458.9± 119.1) μmol/L.The general evaluation of the GMs was normal in 15 cases (6.2％),and abnormal in 226 cases (93.8％) with 217 cases (90.0％) were poor repertoire (PR) and 9 cases (3.7％) were cramped-synchronized (CS).The predictive values of abnormal GMs for abnormal motor development outcomes were as following:sensitivity 100％,specificity 7.6％,negative predictive value(NPV) 100％.The predictive values of CS for cerebral palsy were as following:sensitivity 22.2％,specificity 97.8％,NPV 94.0％.Detailed evaluation of 241 subjects showed that 13 items had statistically significant differences in the prediction of cerebral palsy (P＜0.05),and 18 items in the prediction of abnormal motor development (P＜0.05).Conclusion The CS pattern and detailed assessment of GMs in the writhing stage may be correlated with the outcomes of motor development in infants with severe neonatal jaundice until one-year-old.

Síndrome del bebe bronceado, una complicación impredecible de la fototerapia / Bronze baby syndrome, an unpredictable complication of phototherapy: A case report

Resumen El síndrome del bebe bronceado es una rara discromía que se presenta como una complicación de la fototerapia en recién nacidos con ictericia neonatal. Aunque el fenotipo común se ha descrito en pacientes con hiperbilirrubinemia directa secundaria a colestasis, también se conocen casos con hiperbilirrubinemia indirecta en quienes se invierte el patrón de hiperbilirrubinemia e, incluso, otros con hiperbilirrubinemia indirecta aislada. La fisiopatología de la enfermedad sigue siendo motivo de controversia, por lo que no se ha establecido claramente cuál es la mejor aproximación diagnóstica y terapéutica. En general, el síndrome se considera leve y se resuelve con la suspensión de la fototerapia; no suele prolongarse más allá del periodo neonatal y no tiene secuelas a largo plazo. Sin embargo, su aparición constituye una contraindicación absoluta para continuar la fototerapia. En caso de persistir, se recomienda disminuir los niveles de bilirrubina y recurrir a la exanguinotransfusión, pero dado que esta implica riesgos para el neonato, una conducta adecuada sería suspender la fototerapia y reiniciarla si la bilirrubina directa disminuye y se ha descartado el compromiso colestásico, aunque siempre evaluando en forma seriada posibles manifestaciones de encefalopatía aguda por bilirrubina. El objetivo de este estudio fue presentar el caso de un recién nacido con incompatibilidad de grupo sanguíneo ABO que presentó el síndrome del bebé bronceado. El bebé respondió satisfactoriamente a la suspensión de la fototerapia y a su posterior reanudación, sin necesidad de recurrir a la exanguinotransfusión.

Abstract The bronze baby syndrome is an infrequent dyschromia resulting from phototherapy in newborn babies with neonatal jaundice. Even though the common phenotype has been described in patients with direct neonatal hyperbilirubinemia secondary to cholestasis, several cases of patients with indirect neonatal hyperbilirubinemia who have managed to reverse it have been reported, as well as patients with isolated hyperbilirubinemia. Currently, the physiopathology of this condition is still a subject of controversy and, therefore, there is a lack of clear conducts for its correct diagnosis and treatment. Generally, this syndrome has been considered as a mild condition that is resolved with the suspension of phototherapy. Its duration is usually not greater than the neonatal period, and it has no long-term sequelae. However, its occurrence is considered an absolute contraindication for the continuation of phototherapy. In case of persistence, the recommendation is to decrease bilirrubin levels and proceed with exchange transfusion; this procedure, however, represents risks for the newborn, so our recommendation is to suspend phototherapy and reinitiate it if the direct bilirrubin value decreases, and cholestasis compromise has been discarded. Serial evaluations of acute encephalopathy caused by bilirrubin are absolutely recommended. The objective of this paper was to describe the case of a newborn with ABO incompatibility who developed the bronze baby syndrome. This patient responded satisfactorily to the suspension and resumption of phototherapy without exchange transfusion.

Early Prediction Of Significant Hyperbilirubinemia In Preterm Neonates Using 24 Hours Serum Bilirubin- A Prospective Study.

Background: Bilirubin induced neurological dysfunction is one of the major causes of morbidity in preterm neonates secondary to uncontrolled hyperbilirubinemia.While jaundice per se is not preventable none the less early detection of threatening bilirubin levels permit initiation of phototherapy and prevents kernicterus. Objectives: To determine the first day total bilirubin value, at 24 hours of life; which will predict with reasonable accuracy, preterm neonates likely to develop subsequent significant hyperbilirubinemia requiring treatment.To establish the cut-off values and comparison of the obtained value for prediction of significant neonatal hyperbilirubinemia in preterm neonates.Material and methods: The study was conducted on a group of 90 preterm neonates, with no comorbidities,over a period of one year. The main outcome measured was hyperbilirubinemia requiring intervention.Serum bilirubin level was sent at 24 hours of age. These babies were followed up clinically for the development of jaundice, and subsequent TSB values were obtained and assessed the need of phototherapy.Results: Mean age at bilirubin estimation was 24 ± 2 hours with mean TSB of 6.03 ± 1.48 mg/dl. Significant hyperbilirubinemia was present in 60/90 babies (66.6%).Neonates belonging to < 32 weeks of gestation age irrespective of their initial TSB values, nearly 100% ended up developing significant hyperbilirubinemia. Whereas in infants belonging to > 32 weeks of gestation age, a TSB level at 24 hours of life, was < <4.0 mg/dl in 4 newborns and none of them developed hyperbilirubinemia subsequently. In the remaining 86 newborns with TSB ≥4.0 mg/dl, subsequent hyperbilirubinemia, requiring phototherapy developed in 60 babies (69.8 %) {Sensitivity: 100 %, specificity: 13.3 %, positive predictive value 69.8%, negative predictive value 100% }Conclusion:Late Preterm babies with TSB levels higher than 4mg/dl at 24 hours of life have a significant risk of developing hyperbilirubinemia.

Hiperbilirrubinemia neonatal, encefalopatía bilirrubínica aguda y Kernicterus: La secuencia sigue vigente en el siglo XXI

Aunque la ictericia afecta a más de la mitad de los neonatos en la primera semana de vida, sólo un grupo de ellos pueden desarrollar hiperbilirrubinemia severa y estar en riesgo de desarrollar encefalopatía bilirrubínica. La afectación neurológica puede presentarse con un cuadro agudo (la encefalopatía bilirrubínica aguda), la cual puede o no progresar a una forma crónica (Kernicterus), o con una constelación de síntomas sensoriales, motores y cognitivos, subagudos o crónicos, dependiendo de la presencia de factores de riesgo que aumentan la susceptibilidad al daño neurológico. La bilirrubina libre interactúa con citoquinas inflamatorias y es la responsable del daño neuronal y de las células de la glía en el sistema nervioso central. A pesar de las diferentes medidas de prevención de hiperbilirrubinemia severa, se siguen reportando casos de Kernicterus sobre todo en países en vías de desarrollo, en algunos de los cuales constituyen un problema de salud pública.

Although jaundice affects more than half of infants in the first week of life, only a few of them develop severe hyperbilirubinemia and are at risk of developing bilirubin encephalopathy. Neurological involvement may occur acutely (acute bilirubin encephalopathy,) which may or may not progress to a chronic form (Kernicterus), or with a constellation of sensory, motor and cognitive, subacute or chronic symptoms, depending on the presence of risk factors that increase susceptibility to neurological damage. Free bilirubin interacts with inflammatory cytokines and is responsible for neuronal and glial cell damage in the central nervous system. Despite different methods to prevent severe hyperbilirubinemia, Kernicterus cases continue to be reported, especially in developing countries, including some where this condition constitutes a public health problem.

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.

Brain Cell Injuries and Behavioral Changes in Rats with Kernicterus / 中国康复理论与实践

@#Objective To study the brain cell injuries and behavioral changes of newborn rats with kernicterus. Methods Twenty-five 5-day-old Sprague-Dawley rats were divided into control group (n=11) and model group (n=14) radomly. The model group was injected with bilirubin solution 10 μg/g in the cisterna magna, while the control group was injected with equal volume of normal saline. The neurobehavioral changes were observed and the body mass were recorded. TUNEL staining was used to check the apoptosis of striatal nerve cells of basal ganglia in the model group (n=3) on the first day after modeling. The remaining rats were assessed by gait analysis and beam-walking test 19 days after birth, and Morris water maze test was performed 30 days after birth. Results The model group showed apparently abnormal neurobehavioral changes, such as clenched fists, opisthotonos and the body mass were significantly lower in the model group than in the control group (F>27.707, P<0.001). TUNEL staining showed striatal nerve cells apoptosis in the model group. For the gait analysis, the step lengths of both hind legs were shorter (t>4.129, P<0.01), and the difference of step length was longer (t=-4.415, P<0.001) in the model group than in the control group, however, there was no significantly difference in the step width between two groups (t=0.462, P=0.649). For the beam-walking test, the score was lower in the model group than in the control group (t=-3.644, P=0.004). For the Morris water maze test, the escape latency was longer (F>6.206, P<0.05), and the number of crossing platform was less (t=3.297, P=0.004) in the model group than in the control group. Conclusion The newborn rats' model of kernicterus showed deficits in multiple motor functions and learning and memory ability, which could be assessed by gait analysis, beam-walk test and Morris water maze test, respectively.

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.

Umbilical Cord Blood Bilirubin Level Measurement in Predicting the Development of Significant Hyperbilirubinemia

Objectives This prospective study was undertaken to identify the newborns at risk for developing significant hyperbilirubinemia using cord blood serum bilirubin levels. Methodology This was prospective study with total of 282 healthy term newborns delivered at MNR Hospital, were included in study with birth weight more than 2,500 grams during one year period from March 2013 to March 2014. Soon after delivery cord blood was sent for serum bilirubin analysis. The data was analyzed using t-test, ROC curve and chi test and was considered statically significant, if value is P<0.05. Results In total 282 children, 51 developed significant hyperbilirubinemia (18.09%). There were no significant differences between the cases who did and who did not develop significant hyperbilirubinemia with respect to various factors that may be associated with the risk of hyperbilirubinemia such as birth weight, type of delivery, gestational age, maternal age, gender, and APGAR value P > 0.05, while in cord bilirubin level there is highly significant difference P <0.05. In our study on the amount of umbilical cord bilirubin cut off pointof 2 mg/dl had good sensitivity(94.12), specificity(90.9%), positivepredictivevalue (69.57%) and negative predictive value (98.59%). Conclusion The present study led to the conclusion that the bilirubin levels that were equal to or greater than 2 mg/100 ml umbilical cord blood can predict significant hyperbilirubinemia with high negative and positive predictive values and high levels of sensitivity and specificity.

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...

Establishment and evaluation of a hyperbilirubinemia and kernicterus model in neonatal rats / 中国病理生理杂志

[ABSTRACT]AIM:ToestablishandevaluateahyperbilirubinemiaandkernicterusmodelinneonatalSDrats. METHODS:Three-day-old SD rats were randomly divided to 7 experimental groups by litter and body weight , and were in-traperitoneally injected with physiological saline (control group), and 6.25μg/g (T1), 12.5μg/g (T2), 25μg/g (T3), 50μg/g (T4), 100μg/g (T5) and 200μg/g (T6) bilirubin, respectively, twice every day for 3 d.All rats were photo-graphed , weighed and killed 12 h after the last injection .The contents of the stomach were drawn and weighed , and the index was calculated .The liver/body weight ratio was determined , the total and unconjugated bilirubin in the serum and total bili-rubin in the brain were calculated , and the contents of ATP and water in the brain were measured .HE and Nissl staining were used to observe the pathological changes .RESULTS:Along with the increase in bilirubin , gradual exacerbation of the general performance of the rats , and yellowish discoloration of the skin and mucous membranes were observed .The degree of the activity gradually reduced , and the weight gain was suppressed .The weight of T6 group showed negative growth , and the 72 h mortality rate was close to 100%.The mortality rate in T4 and T5 groups continued to rise 1 week after injection .Com-pared with control group , the weight of stomach contents and stomach content index in T 3~T5 groups significantly decreased (P<0.01).The liver/body weight ratio in T5 group was significantly higher (P<0.05).The concentrations of serum total and unconjugated bilirubin and brain bilirubin levels in T 1~T5 groups were gradually increased , while the brain water con-tent had no difference among groups .The brain ATP content in T1~T5 groups increased at the beginning and reached its peak in T3 group, but compared with control group , that in T4 group and T5 group significantly reduced (P<0.05).HE re-sults showed that , with the increase in bilirubin concentration , the number of the neurons in the cerebral cortex of the rats de-creased.In T4 group and T5 group, the neuronal structural disorder , cell swelling, nuclear pyknosis, fragmentation and dis-solution, increase in non-homogeneous structure of the material dyed red , and disappearance of nuclear staining were ob-served.Nissl staining showed that , compared with control group , in T1 group and T2 group, the cortical neurons became smaller, Nissl bodies decreased , and cytoplasmic staining changed little .The cortical neuronal tigroid body color became light gradually, neuron cells become small , and Nissl bodies decreased obviously in T 3, T4 and T5 groups.The T4 and T5 rat ce-rebral cortical neurons dissolved or even disappeared .CONCLUSION:Newborn 3-day-old SD rats receiving intraperitoneal injection of bilirubin at doses of 12.5, 25, 50 and 100μg/g, 2 times a day, can induce hyperbilirubinemia , and 50 and 100μg/g can cause bilirubin encephalopathy .

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.

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.

Crigler-Najjar syndrome type 2: Novel UGT1A1 mutation.

Crigler-Najjar syndrome type 2 is a rare cause for persistent unconjugated hyperbilirubinemia, inherited in an autosomal recessive manner. Even though it is compatible with normal life span, in the absence of prompt suspicion and intensive management it can prove fatal not only in the neonatal period but also during adult life. Here, we describe a case with a novel homozygous UGT1A1 p.Pro176Leu mutation.