Utilidad diagnóstica del método de Kramer para la detección clínica de la hiperbilirrubinemia neonatal / Usefullness of the Kramer’s index in the diagnosis of hyperbilirubinemia of the newborn

El objetivo de la presente investigación fue correlacionar los valores séricos de bilirrubina con el índice de Kramer en un grupo de pacientes con ictericia neonatal de tres diferentes etnias. Representa un estudio prospectivo, aleatorio, observacional descriptivo-analìtico, longitudinal, comparativo y controlado en 50 recién nacidos con ictericia neonatal sin complicaciones. Se dividieron en 3 grupos: A (Control), n = 25 de origen caucásico; B, n = 15 de origen indígena local Wayúu y C, n = 10 de origen Afro americano. Al ingreso, a cada neonato se le determinaron las zonas dérmicas de Kramer y se le tomó una muestra de sangre venosa braquial para medir la bilirrubina de ingreso. Los valores al ingreso fueron: bilirrubina sérica 12,02 ± 3,41 mg/dL y el 62,8% estaban en nivel 3 de Kramer. No hubo diferencias entre los grupos étnicos estudiados y la correlación bilirrubina sérica-índice de Kramer fue de r= 0,93 (p < 0,005). Al 3er día se empezó a notar el descenso de la bilirrubina y de los índices de Kramer. El método de Kramer ofrece múltiples ventajas en la evolución del RN ictérico. No se encontraron diferencias raciales. Se recomienda implementar la aplicación de este método de Kramer en todas las unidades de neonatos en los hospitales, preferentemente en aquellas que carezcan de bilirrubinómetros transcutáneos.

The objective of the present study was to correlate seric values of bilirubin with the Kramer’s index in a group of newborns with neonatal jaundice, from three different ethnic groups. This was a prospective, randomized, observational, descriptive-analytical, longitudinal, comparative and controlled study of 50 newborns with neonatal jaundice, without complications. They were divided into three groups: A (Control), n = 25, of Caucasian descent; B, n = 15, of local indigenous descent (Wayúu) and C, n = 10, of Afro-American descent. Each newborn was screened at the start of the study for their Kramer’s dermic areas and simultaneously, a venous blood sample from the arm was taken for bilirubin quantification. They were compared through a correlation-regression analysis. Values at the beginning of the study were: serum bilirubin 12.02 ± 3.41 mg/dL, and 62.8% of neonates were at Kramer’s level 3. There were no differences among the ethnic groups studied and the correlation bilirubin/Kramer’s index was r= 0.93 (p < 0.005). At the third day, both bilirubin and Kramer’s indexes started to decrease. There were no ethnic differences. In conclusion, the Kramer’s method offers multiple advantages to evaluate a jaundiced newborn; it is a safe, non-invasive method with no cost. Besides, it is of great help in the prevention of the kernicterus. It is recommended to implement the use of the Kramer method in all the newborns units in our Hospitals, preferably in those lacking transcutaneous bilirubinometers.

Study of the correlation between transcutaneous bilirubin levels [Jh20-1 bilirubinometer] and serum bilirubin levels [laboratory]

Hyperbilirubinemia is a common benign problem in neonates. Nonetheless, if untreated, severe hyperbilirubinemia is potentially neurotoxic. The standard method for diagnosis of hyperbilirubinemia is determination of serum bilirubin levels in the laboratory that requires a blood sample which is both painful and stressful for neonates and entails cost and time. The objective of this study was to study the correlation between transcutaneous bilirubin levels [JH 20-1 bilirobinometer] and serum bilirubin levels. This prospective study was done on 100 jaundiced newborn term infants from March to October, 2006. Initial clinical assessment of jaundice was carried out by a physician [researcher] and simultaneously, blood sample was collected and a JH20-1 bilirubinometer was applied at two sites; forehead and sternum. The study group consisted of 57 boys and 43 girls diagnosed as jaundiced neonates. The mean serum bilirubin and mean transcutaneous bilirubin levels at forehead and sternum were 13.35, 12.95 and 12.46 mg/dl, respectively. The correlation coefficient of bilirubin levels estimated by the bilirubinometer at the forehead and sternum and serum levels were 0.773 and 0.731, respectively. At bilirubin levels higher than 12 mg/dl [cut off point], the bilirubinometer had a decreased sensitivity, but an increased specificity. Transcutaneous bilirubin measurements using JH20-1 bilirubinimeter correlate well with total serum bilirubin levels, but when bilirubin levels are higher than 12mg/dl, sensitivity of the device is reduced and therefore not reliable

Transcutaneous bilirubin in the pre-term infants.

OBJECTIVE: 1) To evaluate the accuracy of transcutaneous bilirubin (T(C)B) measurement compared to total serum bilirubin level (TSB) in the pre-term infants and 2) To establish cut-off values of T(C)B that indicated need for TSB. MATERIAL AND METHOD: Premature infants whose birth weight was more than 1,000 grams and gestational age less than 36 weeks had paired T(C)B-TSB assessment when jaundice was observed. T(C)B was done using JM 103 (Minolta AirShields Jaundice Meter) on the forehead. T(C)B, which corresponded to TSB level that required phototherapy, was chosen as the cut-off point that indicated blood sampling for TSB. RESULTS: Two hundred and forty-nine paired T(CB)-TSB measurements from 196 premature neonates were obtained. Birth weight was 1,887 +/- 344.4 grams. TSB ranged from 4.5-17.6 mg/dL (mean 9.4, SD 2.2 mg/dL), T(C)B 4.1-17.7 mg/dL (mean 9.7, SD 2.4 mg/dL). The correlation coefficient between T(C)B and TSB was significant (r 0.79, p < 0.0001). T(C)B had a tendency to overestimate TSB with the mean difference of TSB- T(C)B = -0.3 +/- 1.5 mg/dL and 95% confidence interval of the mean -0.1 to -0.5 mg/dL. Of all the variables of birth weight, gestational age, and postnatal age, only postnatal age significantly influenced the correlation of T(C)B-TSB. In the early postnatal age of 1-4 days, the number of T(C)B reading overestimated TSB more than underestimated. However, at > or = 5 days of age, the number of underestimation was more than those of overestimation. The cut-off points of T(C)B that indicated the need for blood sampling for TSB were chosen as the same level of TSB of 6, 8, 10, 11, and 12 mg/dL when phototherapy was recommended. Screening with T(C)B would eliminate painful procedure of blood taking by 40%. CONCLUSION: Noninvasive T(C)B assessment demonstrated significant accuracy when compared to TSB. T(C)B can be adopted as a screening test to identify the need for blood sampling of serum bilirubin in premature infants.

Evaluation of hyperbilirubinemia in acute inflammation of appendix: a prospective study of 45 cases.

BACKGROUND: Hyperbilirubinemia is the result of imbalance between production and excretion of bilirubin by the liver. It may be because of hepatocellular, cholestatic or haemolytic diseases. Liver receives blood mainly through portal venous system, which receives blood from abdominal organs. Portal blood carries nutrients and other substances absorbed from gut including bacteria and its product (toxins). In small percentage, even in normal healthy people, bacteria are found in portal blood. It is commonly cleared by detoxification and immunological action of reticuloendothelial (RES) system of liver that act as first line defence in clearing toxic substances, bacteria and it's products. But when bacterial load overwhelms the Kuffer cell function, may cause dysfunction or damage to the hepatocytes (liver parenchyma). It reflects, rise in serum bilirubin (SB) alone or in combination with liver enzymes depending upon the type, severity and site of lesion. Recently, another substance known as Cytokines e.g. IL-6, Tumour necrosis factor (TNF), have also been labelled to be responsible for depressed excretory function of liver and may lead to increase in SB level without rise in liver enzymes. AIM: To evaluate hyperbilirubinemia associated in acute inflammation of appendix (acute appendicitis and its complication). MATERIAL AND METHODS: This is a prospective study conducted at NGMC Teaching hospital Nepalgunj, Nepal during Oct.2004-Oct.2005. 45 Consecutive cases of acute appendicitis admitted in surgical unit III, were recruited for this study. Clinically suspected cases were subjected to investigations to confirm the diagnosis. Investigations included total leucocytes count, differential leucocytes count, urine analysis and ultrasound. These cases were also subjected to routine liver function tests. Subsequently these cases were operated and clinical diagnosis was confirmed per-operatively and post operatively by histopathological examination of the specimen. Their clinical and investigative data were compiled and analyzed and following observations were obtained. Routine liver function test results were compared with laboratory reference values given in Table- 1, 2 and 3. INCLUSION CRITERIA: Case with acute appendicitis and its complication with test negative for HBSAg and no past history of jaundice. EXCLUSION CRITERIA: Case with acute appendicitis and its complication with test positive for HBSAg and /or past history of jaundice. RESULTS: Total number cases were 45. Of 45, 25 were males and 20 were females. Their age ranged from 11 years to 60 years. The average was 27.2 years. Duration of symptoms ranged from 5 hours to maximum 9 days. Among 45 cases diagnosed as acute appendicitis clinically (preoperatively), per operatively, 36 cases had inflamed appendix, 3 cases had gangrene, 5 cases had perforation with peritonitis (4 localized and 1 generalized peritonitis) and only a single case was noted to be of normal appendix (Table 4). Liver function tests (LFT) analysis revealed following results, Among 45 cases, SB was raised in 39 cases where as 6 cases had normal SB level. The raised SB ranged from 1.2 mg/dL to 8.4 mg/dL. The average level of SB was 2.38 mg/dL. All the cases had indirect fraction of SB above 15%. (Table 4). The rise in SB was without concomitant much rise in liver enzymes. CONCLUSION: Following conclusion can be drawn from the present study. Firstly, There was Hyperbilirubinemia in 86.6% of the patients of acute inflammation of appendix (i.e. acute appendicitis and its complications). Secondly, Raised SB ranged from 1.2mg/dL - 8.4 mg/dL. Thirdly, The rise in SB was mixed in type (both indirect and direct). Finally, The hyperbilirubinemia was intra hepatic cholestatic in type due either to abnormality in permeability of hepatocyte or ductular membrane enzyme inhibition as the liver enzymes were not much elevated.

Neonatal screening for glucose-6-phosphate dehydrogenase deficiency.

OBJECTIVE: This study was carried out to detect the incidence of erythrocytic Glucose-6 -Phosphate dehydrogenase (G-6-PD) deficiency, to compare the incidence of hyperbilirubinemia in G-6-PD deficient neonates as compared to G-6-PD normal neonates and to asses the usefulness of neonatal screening for G-6-PD deficiency. METHOD: In a retrospective hospital based study 2,479 male and female neonates consecutively born at Indraprastha Apollo hospital between July 1998 to June 2003 who were screened for G-6-PD levels were evaluated for the incidence of G-6-PD deficiency. RESULTS: Incidence of G-6-PD deficiency was found to be 2.0%. Incidence in males was 283% and female was 1.05%. The incidence of hyperbilirubinemia was found to be 32% in G-6-PD deficient neonates which was significantly higher than the incidence of hyperbilirubinemia in neonates with normal G-6-PD, which was 12.3% (P< 0.001). CONCLUSION: Our data suggests that neonatal screening for G-6-PD deficiency is a useful test for preventing and early treatment of complications associated with it.

Unconjugated hyperbilirubinemia in nonalcoholic steatohepatitis--is it Gilbert's syndrome?

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have normal liver function tests except for raised transaminases until they have progressed to cirrhosis of liver. The objective of this study was to evaluate patients of NASH for the presence of hyperbilirubinemia at presentation. METHOD: Sixty-seven patients of NASH were studied for the presence of hyperbilirubinemia at presentation. All patients were worked up for the presence of cirrhosis and hemolytic work up and fasting test were done in those found with unconjugated hyperbilirubinemia. RESULTS: Five out of 67 patients (7.5%) of NASH were found to have unconjugated hyperbilirubinemia. Though the fasting test was not positive, they all had a negative hemolytic workup and none of them had underlying cirrhosis. Clinical characteristics of patients with unconjugated hyperbilirubinemia were similar to those with normal serum bilirubin levels. CONCLUSION: Unconjugated hyperbilirubinemia in patients with NASH may suggest an associated Gilbert's syndrome.

Transcutaneous bilirubinometer in assessment of neonatal jaundice in northern India.

This study was undertaken from April 2002 to March 2003 to find out the correlation of transcutaneous bilirubinometer index with serum bilirubin levels in term, pre-term, small for gestation age babies, with and without phototherapy in neonates with jaundice. Another aim was to evaluate the transcutaneous bilirubinometer as a screening device for neonatal hyperbilirubinemia by finding the action levels for TcBI at forehead and sternum at which sample for serum bilirubin estimation should be taken. A total of 104 neonates were evaluated. Mean (SD) age (hours), birth weight (grams) and gestational age (weeks) were 100.4 (37.90), 2264.9 (634.4) and 36.8 (2.9) respectively. Mean serum bilirubin was 16.6 (6) mg/dL. Overall a correlation coefficient of 0.878 at forehead and 0.859 at sternum was observed. On excluding infants receiving phototherapy coefficients of 0.900 at forehead and 0.908 at sternum were noted. Correlation coefficient over forehead and sternum was found to drop from 0.85 to as low as 0.33 with duration of phototherapy exceeding 48 hrs. Lastly the determined action levels had a sensitivity of 77.8 to 100 % in assessing the need for serum bilirubin estimation in various groups.

Laparoscopy in diagnosis of prolonged neonatal jaundice.

When managing neonatal jaundice, there is no single test or imaging modality that can reliably define biliary atresia and neonatal hepatitis. Early diagnosis is an important step for surgical success in extra hepatic biliary atresia. In many situations, exploratory laparotomy and operative cholangiography may be needed to settle the definitive diagnosis, with the risk of having negative exploration in those high risk patients with medical etiology. The use of laparoscopy may help in avoiding unnecessary exploration for such group of patients and arriving at a definite diagnosis. Six patients with conjugated hyperbilirubinemia were evaluated with a diagnostic laparoscopy, laparoscopic cholangiography and liver biopsy. Three of the six patients were diagnosed to have neonatal hepatitis and so an unnecessary laparotomy was avoided in these cases.

Síndrome de Dubin-Johnson y embarazo: primer caso clínico en Venezuela / Dubin-Johnson syndrome: first Venezuela case clinic

Se describe el primer caso nacional de una embarazada con síndrome de Dubin-Johnson. El síndrome se caracteriza por una hiperbilirrubinemia crónica a predominio de la directa de origen familiar, no hemolítica, debido a un trastorno del transporte de la bilirrubina del hepatocito hasta el canalículo biliar y depósito en el hepatocito de un pigmento oscuro, similar a la melamina. La ictericia, usualmente ausente en el primer trimestre, aumenta en el segundo y sobre todo en el tercer trimestre del embarazo. En nuestro caso, la paciente es II gesta, II para, en ambos embarazos se observó el patrón clínico y bioquímico, con exacerbación durante el tercer trimestre y valores más acentuados en el segundo embarazo. Las dos gestaciones cursaron normalmente y en ambos se obtuvieron recién nacidos normales sin posteriores complicaciones

Hepatitis crónica activa asociada con enfermedades reumáticas / Active chronic hepatitis associated with rheumatic diseases

Diversas alteraciones hepáticas se han encontrado en las enfermedades reumáticas. La hepatitis crónica activa (HCA) es una de ellas, aunque sus reportes según la revisión de la literatura que hemos efectuado, son escasos. El objetivo de este trabajo es presentar 7 casos de HCA asociados a enfermedades reumáticas autoinmunes, manejados en nuestro servicio. Todos los pacientes son del sexo femenino, con edad entre la cuarta y sexta décadas de la vida. Bioquímicamente muestran elevación de enzimas hepáticas, ligeramente de la bilirrubinas, y positividad para antígenos de VHC y VHB. No existe patrón obstructivo de conductos biliares por ultrasonido o gamagrafía. De las 7, tres cumplen criterios para AR y 4 para LEG. La supervivencia y clase funcional son satisfactorias. Consideramos que un fondo común de predisposición a la autoinmunidad puede intervenir en el desarrollo de ambas entidades

The benefit of the direct antiglobulin test using gel technique in ABO hemolytic disease of the newborn.

The direct antiglobulin test (DAT) using the gel technique was included in the investigation of infants with hyperbilirubinemia in the first week of life. Twelve cases were preterm and 48 cases were full term infants. The patients were divided into 2 groups: the study group comprised 22 cases of blood group A or B infants born to blood group O mothers; the control group comprised 38 cases of ABO blood groups compatible with those of their mothers. The mean +/- SD (39 +/- 26 hours) of the age at the onset of hyperbilirubinemia induced by ABO hemolytic disease of the newborn (HDN) was significantly earlier than that due to other causes. The positive rate of DAT in the ABO incompatible group was similar by both the conventional technique and the gel technique, 54.5% and 50% respectively. However, the scores by the gel technique were higher than those of the conventional technique. The gel technique is simple, reliable, involves less technical error and requires a small amount of blood sample. The grading system is clear-cut, especially grade 1 + or weak positive as compared to the conventional technique which requires examination under a microscope. Therefore, the DAT using the gel technique is beneficial to the diagnosis of ABO HDN. It should be included in the investigation of infants with hyperbilirubinemia especially in case of suspected ABO HDN.

Hepatobiliary scintigraphy in persistent direct hyperbilirubinemia in the neonate

To present the value and usefulness of hepatobiliary scintigraphy in the investigation of infants with persistent hyperbilirubinemia through our experience in King Khaled University Hospital at King Saud University, Riyadh. King Khalid University Hospital, Departments of Nuclear Medicine, Pediatrics and Pediatric Surgery. Patients and methods: Seventy-seven patients aged between 5 days and 6 months [average 62 days], 43 females and 34 males, 65 Saudi and 12 non-Saudi were investigated. Laboratory tests, abdominal ultrasound, hepatobiliary scintigraphy. liver biopsy, explorative laparatomy and intraoperative cholangiography were performed whenever indicated. The findings on hepatobiliary scintigraphy of non-visualization of the gallbladder and no activity in the bowel up to 24 hours post injection [p.i] were considered consistent with the diagnosis of biliary atresia. Thirty four infants were diagnosed by hepatobiliary scintigraphy as having biliary atresia. Only 3 of the 34 were false positives as compared to liver biopsy results. Twenty-nine of the other 43 patients showed bowel activity sometime between 6 and 8 hours p.i. whereas the other 14 showed it at 24 hours p.i. Fourteen cases of the 19 with hepatitis showed decreased and delayed liver uptake in an irregular pattern. The other 5 cases of hepatitis showed good liver uptake similar to that seen in cases with biliary atresia. Hepatobiliary scintigraphy has become an essential part of the investigational work-up plan of infants with persistent hyperbilirubinemia before and after surgery because it is a simple and noninvasive technique