Severe Indirect Hyperbilirubinemia Research Articles

A rare presentation of severe alloimmune hemolytic disease of newborn pertaining to minor blood group ‘c’ incompatibility: a case report and review of literature

Hyperbilirubinemia is one of the most widely seen causes of neonatal morbidity. Haemolytic disease of fetus and newborn is caused by maternal alloantibodies to the fetal RBCs. It is responsible for incompatibility between maternal and fetal blood groups, which results in destruction of fetal red blood cells causing hyperbilirubinemia. ABO and Rh incompatibility are the most common causes of severe indirect hyperbilirubinemia. Besides ABO and Rh isoimmunization, minor blood group incompatibilities such as anti-Kell, anti-C, anti-c, anti-E, anti MNS, Duffy, KIDD, P, Lutheran and Lewis have also been identified as causes of severe neonatal jaundice with an incidence of 385/1,00,000 live births in South-East Asia. We, hereby report a rare case of a full term 2.2 kg newborn presented with severe anemia with reticulocytosis and neonatal hyperbilirubinemia at second hour of life. In view of strongly positive DCT and no Rh negative or ABO setting, minor blood group incompatibility screening test was performed in the mother which revealed presence of multiple alloantibodies; however, the red cell phenotyping confirmed the presence of anti-c antibodies in maternal sera responsible for neonatal alloimmune haemolytic anemia. The baby was offered intensive phototherapy with intravenous immunoglobulin.

Adrenal hemorrhage presenting as severe indirect hyperbilirubinemia in a neonate

The Sri Lanka Journal of Perinatal Medicine (SLJPM) was launched in 2019 as the official journal of the Perinatal Society of Sri Lanka. This journal is unique in the fact that it brings together three core specialties of perinatal medicine - obstetrics, neonatology and community medicine. It is an open access peer reviewed journal containing original research articles, expert reviews, current practices and other articles of interest to all involved in perinatal medicine.

Single-surface Intensive Phototherapy or Double-Surface Intensive Phototherapy in Neonatal Non-Hemolytic Hyperbilirubinemia: A Comparison of Effectiveness and Complications.

Background: Severe indirect hyperbilirubinemia causes neurotoxicity, leading to potential permanent injuries to the neonatal nervous system. The present study intended to compare the effectiveness and complications of Single-Surface Intensive Phototherapy (SSIP) and Double-Surface Intensive Phototherapy (DSIP) in treating non-hemolytic hyperbilirubinemia in the neonatal ward of the Besat Hospital, Hamadan, Iran. Methods: In this prospective randomized clinical trial, 150 healthy full-term neonates born between 37-42 weeks gestation with ages <14 days old and birth weights ≥2500 gr who were affected by non-hemolytic hyperbilirubinemia with total serum bilirubin of 15-20 mg/dL were randomly allocated to two groups. Each group (n=75) underwent either SSIP or DSIP. Demographics, bilirubin level alterations, weight, platelet count, number of defecation per day, and body temperature of the patients were monitored and recorded in a specific questionnaire. Data analysis was performed using SPSS version 26.0 software, with the Chi-square and independent t-test. Results: The pre-intervention levels of indirect bilirubin were 17.07±1.46 mg/dL in the SSIP group and 17.10±1.54 mg/dL in the DSIP group (P-value = 0.853). After 24 and 48 hours of treatment, the mean indirect bilirubin level of the SSIP group reduced to 13.12±1.71 mg/dL and 9.69±1.68 mg/dL, respectively. In the DSIP group, the levels were 11.85±2.17 mg/dL and 8.43±1.56 mg/dL after 24 and 48 hours of treatment, respectively. The absolute reductions of indirect bilirubin were 7.76±3.28 mg/dL for the SSIP group and 8.96±4.49 mg/dL for the DSIP group (P-value = 0.458). Therefore, the indirect bilirubin levels were significantly different between the groups after 24 and 48 hours of treatment and at the time of discharge (P<0.05). There were no significant inter-group differences in weight, platelet count, and incidence of skin rash, while the number of defecation and body temperature were higher in the DSIP group (P <0.05). However, body temperature alterations had no clinical relevance. Conclusion: Compared to the SSIP, the DSIP showed faster effectiveness and led to a shorter hospital stay, while it did not entail higher levels of complications.

Phototherapy &amp; Exchange Transfusion in Neonatal Intensive Care Unit of Pediatric Hospital Kirkuk

Background: Jaudice is observed in first week of life in most neonates, it is usually benign but untreated severe indirect hyperbilirubinemia is potentially toxic to nervous system of neonates. Aim of study: Asses effect of some factors on modality of therapy in neonatal jaundice (phototherapy, exchange transfusion). Prematurity & Low birth weight is discussed in some detail. Methods: This cross sectional study was carried out at neonatal intensive care unit {NICU} of pediatric general hospital Kirkuk from first of March 2018 to first of September 2018 on 307 neonates admitted to hospital,154 of them had jaundice, these neonates were divided to those who had received phototherapy & those who had exchange transfusion, then divided to: term & preterm, normal weight & low birth weight, male & female, then the modality of therapy in each of these groups was analyzed & studied. Results: It was found that 307 neonates were admitted to NICU, 154 neonates (50.1%) of total admission to neonatal intensive care unit were due to jaundice, 115 neonate (74.6%) received phototherapy, 39 neonate (25.4%) had exchange transfusion. 100 neonates were male (64.9%) & 54(35.1%) were female. Phototherapy is used more frequently in preterm 28(77.7%) & 23(85.2%) LBW neonates than exchange transfusion, which was used in 8(22.3%) preterm & 4(14.8%) LBW. When the association between gestational age and type of therapy is statistically analyzed there was no significant association. No significant association between gender of baby and type of therapy was found. There was no significant association between weight of neonate & type of therapy. Conclusion: Fifty per cent of admissions to NICU were due to jaundice. Exchange transfusion is still used in relatively height percentage in NICU at Pediatric General Hospital Kirkuk because of late presentation of neonates with jaundice to medical team. Lack of awareness about the toxic effects of high bilirubin on the developing brain among families in our society. In addition old, over used phototherapy equipment in hospital, reduce the effectiveness of phototherapy.

Developmental outcome of severe neonatal indirect hyperbilirubinemia

Background: Indirect hyperbilirubinemia is one of the most common causes of hospitalization in the neonatal period and its potential association with brain damage is well established. This study was conducted to determine neurodevelopmental outcome of children who had severe indirect hyperbilirubinemia in neonatal period and received intensive phototherapy with or without double volume exchange transfusion for its management. Material &amp; methods: This descriptive analytical study was performed in healthy infants with the history of severe indirect hyperbilirubinemia and need intensive phototherapy with or without exchange transfusion. We invited the enrolled infants at their 2-3 years age. Neurodevelopmental assessment was performed by a trained nurse using Ages and Stages Questionnaire. Results: The mean total serum bilirubin (TSB) of studied children was 26.4±4.1 mg/dl at their neonatal period. The estimated rate of severe hyperbilirubinemia with the TSB of 25-30 mg/dl was 48.7/100,000 live born infants and 11.4 /100,000 for hyperbilirubinemia higher than 30 mg/dl. The most common cause of jaundice in patients with exchange transfusion was ABO incompatibility. At their follow up examination, the classic form of bilirubin induced encephalopathy (Kernicterus) was diagnosed in 3 neonates. Two of them had sensory neural hearing loss too. Eleven children had low score based on ASQ in at least one area. The score was less than 2SD in 3 patients. Conclusion: Severe hyperbilirubinemia and kernicterus is still occurring in term and late pre-term infants. Early detection and management of severe hyperbilirubinemia may improve the neurodevelopmental outcome in high risk infants.

Thrombocytopenia in a 7-day-old Male.

1. Lindy Zhang, MD*,† 2. Caroline DeBoer, MD†† 3. Alejandra Ellison-Barnes, MD‡ 4. Jessica Berger, MD‡‡ 5. Courtney E. Lawrence, MD*,¶ 6. Rosalyn W. Stewart, MD MS MBA‡,§ 7. Lydia H. Pecker, MD** 1. *Departments of Pediatric Hematology, 2. †Pediatric Oncology, 3. ‡Internal Medicine, and 4. §Pediatrics and 5. ¶Division of Transfusion Medicine, Department of Pathology, and 6. **Division of Hematology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD; 7. ††Advocate Aurora Healthcare, Milwaukee WI; 8. ‡‡Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 1. Address correspondence to Lindy Zhang, MD, Charlotte R. Bloomberg Children’s Center, Johns Hopkins Hospital, 1800 Orleans St, Baltimore, MD 21287. E-mail: lindyzhang{at}jhmi.edu A term boy was born via elective, repeat cesarean delivery to a mother whose prenatal laboratory tests were positive for group B Streptococcus genital infection and negative for human immunodeficiency virus, syphilis, gonorrhea, and chlamydia infections, and showed immunity for rubella. He was the third child born to this mother. The mother had no other diagnosed illnesses, including autoimmune diseases. The cesarean delivery was complicated by extensive adhesions from previous deliveries, but the delivery was atraumatic for the infant. The infant weighed 3.81 kg (82nd percentile for age), and had ABO mismatch with his mother (mother’s blood type was O+, infant’s blood type was A+). By 20 hours of age, the infant developed indirect hyperbilirubinemia (total bilirubin, 7.9 mg/dL). This elevation in bilirubin levels was attributed to ABO isoimmunization. He received 12 hours of phototherapy delivered by a fiberoptic mattress and fluorescent bulbs on an overhead lamp. On postnatal day 2, he had a circumcision, which was complicated by bleeding and required cauterization with silver nitrate. The remainder of his hospital course was uneventful. He was discharged without any ongoing evidence of easy bruising or bleeding and was scheduled for close follow-up with his pediatrician. On postnatal day 6, the infant was presented for his first newborn visit to his pediatrician with jaundice. His total bilirubin level was 19.3 mg/dL. The pediatrician sent the infant to the emergency department for additional evaluation and treatment. There, the infant was found to have severe thrombocytopenia (platelet count, 35 K/mm3) and indirect hyperbilirubinemia (total bilirubin, 20.2 mg/dL; direct bilirubin, 0.3 mg/dL). Mild anemia was present (hemoglobin, 13.8 …

Recognizing Hereditary TTP in Infants and Children

Recognition of hereditary disorders in newborn infants and early childhood is critical for anticipating and preventing adverse outcomes. Hereditary thrombotic thrombocytopenic purpura (HTTP) is caused by biallelicADAMTS13mutations. Absence of ADAMTS13 results in circulation of ultra-large von Willebrand factor multimers which increase risk for microvascular thrombosis, causing severe thrombocytopenia and microangiopathic hemolytic anemia. Extreme hemolysis with hyperbilirubinemia occurs in 42-45% of newborn infants (New Engl J Med2019;381:3653). Stroke occurs in 25-31% of patients with HTTP; the median age is 19 years; 22% of strokes occur before age 10 years (Blood Advances2019;3:3973). When HTTP is recognized, treatment with plasma infusion is simple and effective. Methods. To document the [1] relative frequency of initial symptoms, [2] age of initial symptoms and [3] age of diagnosis, we systematically searched for all case reports of patients with hereditary TTP whose diagnosis was confirmed by ADAMTS13 activity &amp;lt;10% and biallelicADAMTS13mutations, from 2001 (when ADAMTS13 was first described) to March 20, 2020 (original literature search described inBlood Advances2019;3:3973). We identified 80 articles describing 180 patients. Because the objective of most reports was to describe newADAMTS13mutations, we believe that the clinical data are not biased for exceptional cases. For this study we selected the the 98 patients &amp;lt;18 years old who had known age of initial symptoms and their description, and also their age at the time of diagnosis of HTTP. Results: The predominant initial symptoms were severe indirect hyperbilirubinemia (caused by hemolysis) at birth (40 [41%] patients) and thrombocytopenia (49 [50%] patients) [Table]. Even though thrombocytopenia was often associated with microangiopathic hemolytic anemia, HTTP was not diagnosed in these 49 patients. In 2 patients who had severe thrombocytopenia and microangiopathic hemolytic anemia as their initial symptoms at ages 3 and 4 years, TTP was diagnosed. Other initial symptoms were severe anemia (2 patients), gastrointestinal symptoms of vomiting and diarrhea (2 patients), and respiratory distress (1 patient). Although initial symptoms were present at birth in 57 (58%) patients, suspicion and recognition of HTTP did not occur until many months or years after the initial symptoms. The median age of initial symptoms was the first day after birth; the median age of diagnosis was 5.5 years. Future plans: Simpler access and more rapid reporting of results have increased familiarity with testing for ADAMTS13 activity. We are currently working with neonatology/perinatology to develop appropriate criteria (bilirubin level, platelet count) for ordering ADAMTS13 activity measurements in newborn infants, with neurology to recommend ADAMTS13 activity measurements in children and young adults with stroke, and with pediatric hematology to recommend ADAMTS13 measurements in children who are diagnosed with immune thrombocytopenia (ITP) associated with evidence for DAT negative hemolysis, including the presence of schistocytes on the peripheral blood smear. Conclusions: Simpler access to ADAMTS13 activity measurements increases familiarity with this test and provides the opportunity for much earlier diagnosis of HTTP in infants and children. With earlier recognition of HTTP, initiation of prophylactic plasma infusions can decrease children's morbidity and mortality. Future availability of recombinant ADAMTS13 will make prophylactic treatment more convenient and effective. Figure Disclosures No relevant conflicts of interest to declare.

Neonatal Management During the Coronavirus Disease (COVID-19) Outbreak: The Chinese Experience.

Novel coronavirus infection is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was named COVID-19 by the World Health Organization on January 7, 2020. In early December 2019, a number of pneumonia cases of unknown origin emerged in Wuhan, Hubei province, China. (1)(2) The disease then spread rapidly throughout China and has now become a global pandemic. As of March 23, 2020, more than 340,000 cases have been reported in more than 150 countries. Because the disease is primarily an airborne respiratory infection and is documented to have a strong human-to-human transmission, the pediatric and neonatal populations are vulnerable to this disease. However, the incidence and clinical presentations of pediatric COVID-19 infections are varied and differ from those found in adult patients. The atypical clinical presentations and 2 potential modes of transmission in neonates (ie, maternal-fetal or maternal-neonatal) have led to diagnostic and management challenges. In this perspective, we would like to share some published information from Chinese pediatric and neonatal societies about their approach to handling the 2019-2020 COVID-19 outbreak in China. Since the COVID-19 outbreak in December 2019, more than 81,000 confirmed cases have been reported in China (as of March 23, 2020). Most of these cases occurred between late January and early February 2020. The diagnosis of COVID-19 is based on the epidemiologic history of contact with an infected person, typical clinical features such as fever and respiratory distress, and a positive real-time polymerase chain reaction to the SARS-CoV-2 RNA test. The nucleic test is considered the gold standard for confirmation. As of February 8, 2020, 731 confirmed pediatric cases were reported in China, mainly from Wuhan city. (3) Relative to the total number of cases (n=34,664) reported in China, on February 8, 2020, the pediatric COVID-19 population accounted for 2.1% …

G6PD Deficiency Prevalence as a Cause of Neonatal Jaundice in a Neonatal Ward in Dohuk, Iraq.

The current study initiated to address the effect of glucose-6-phosphate dehydrogenase (G6PD) deficiency on the pathogenesis and the severity of neonatal hyperbilirubinemia (NHB). A total of 100 newborns with moderate to severe indirect hyperbilirubinemia and 50 normal neonates without hyperbilirubinemia had been enrolled in the current case-control study. All enrolled neonates had been tested for ABO and Rh(D) blood grouping, Total serum bilirubin measurement, complete blood count, morphology, reticulocyte counts, direct Coombs' test, and G6PD enzyme assay. From all enrolled hyperbilirubinemic neonates, 16% were G6PD deficient and this displays a statistically significant difference in comparison to controls (only 6% were G6PD deficient). Also, significant difference was found in the level of serum indirect bilirubin among G6PD-deficient neonate in comparison to G6PD nondeficient neonates which had contributed significantly to the difference in the duration of phototherapy and hospitalization among deficient neonate. Despite this, no significant difference found in the onset of presentation, reticulocytes count, and age of neonates between the two groups (G6PD-deficient and G6PD nondeficient neonates). The current study augments the etiological role of G6PD in the causation and severity of NHB in the region; however, in the absence of significant difference in the reticulocytes and the hemoglobin level, the underlying mechanism cannot be backed to the excess hemolysis alone.

Intravenous Immunoglobulins as Adjunct Treatment to Phototherapy in Isoimmune Hemolytic Disease of the Newborn: A Retrospective Case-Control Study.

BackgroundIsoimmune hemolytic disease is a major cause of neonatal severe indirect hyperbilirubinemia that requires phototherapy or exchange transfusion which is an invasive procedure to avoid brain injury. Administration of intravenous immunoglobulin (IVIG) is used as an adjunct treatment to phototherapy in order to decrease the rate of exchange transfusion.MethodsThis retrospective case-control study aimed to describe the safety and efficacy of IVIG therapy in newborns with isoimmune hemolytic disease and to compare their clinical outcomes to those of a control group who were treated only with phototherapy. Criteria for IVIG treatment were variable; when phototherapy threshold was reached or when exchange transfusion level was approached, using either indication is based on the attending discretion.ResultsNinety-four infants were included in the IVIG group, compared to 108 infants in the control group. Most of the included infants were term infants and most common cause was ABO incompatibility. There were no side effects documented in all the included infants. The IVIG group had more severe hemolysis with average highest bilirubin of 14.6 ± 3.7 mg/dL in the IVIG group versus 12.6 ± 3 in the control group (P = 0.0001). Complication of hemolysis was seen more in the IVIG group with higher rate of rebound hyperbilirubinemia, blood transfusion and exchange transfusion.ConclusionsIVIG use as an adjunct treatment to phototherapy in isoimmune hemolytic disease of the newborns is safe. The favorable results of the phototherapy only group were supportive of using selective criteria for administration of IVIG in neonates with isoimmune hemolytic disease.

Blood eosinophil levels in newborns with severe indirect hyperbilirubinemia treated with phototherapy

Objective The aim of this study was to investigate the effect of phototherapy on peripheral eosinophil counts in newborns with severe indirect hyperbilirubinemia needing phototherapy. Methods We conducted a search of Medline databases (PubMed, Medscape, ScienceDirect) and all materials available on the Internet. The initial search presented one articles that met the inclusion criteria. The articles studied the relation between peripheral eosinophil count and exposure to phototherapy. If the studies did not fulfill the inclusion criteria, they were excluded. Studies were assessed for whether ethical approval had been obtained, eligibility criteria has been specified, appropriate controls had been considered, adequate information had been provided, and assessment measures had been defined. Comparisons were made by means of structured review with the results tabulated. Results The study was conducted on 30 neonates suffering from severe indirect hyperbilirubinemia who served as the patient group and another 30 neonates who were normal and served as the control group. It was found that there was an increase in peripheral eosinophil count in neonates who were treated with phototherapy for 48–72 h. Conclusion Peripheral eosinophil count may be affected by phototherapy. The exact mechanism of neonatal jaundice/phototherapy and later risk of developing asthma is not clear yet, and further prospective studies in larger groups are needed. Neonatologists should concentrate on underlying problems, as eosinophilia is sometimes clinically insignificant with regard to morbidity and requires no specific treatment. In fact, it may be indirect evidence of clinical recovery. Unless eosinophilia is associated with clinical symptomatology, medical evaluation should be limited to routine follow-up examinations and repeat monitoring of absolute eosinophil counts.

Can Exchange Transfusion Normalize Serum Levels of Copper, Zinc, and Magnesium in Severe Neonatal Hyperbilirubinemia?

Neonatal hyperbilirubinemia is a frequently encountered problem. Erythrocytes, especially reticulocytes are rich in copper (Cu) and magnesium (Mg) so its serum levels increase after hemolysis. Zinc (Zn) plays an important role in synthesis of some enzymes included in the bilirubin metabolism and may cause hemolysis. Exchange transfusion is the main treatment for severe neonatal hyperbilirubinemia but can exchange transfusion affect the previous trace elements. We measured Cu, Zn, and Mg serum levels in full-term neonates admitted to neonatal intensive care unit of Minia University hospital with severe indirect hyperbilirubinemia before and after exchange transfusion. There were significant higher serum Cu and Mg and lower Zn serum levels in neonates with hyperbilirubinemia than controls and their levels were significantly normalized after exchange transfusion. Significant positive correlations between the total bilirubin levels and hemoglobin, Cu and Mg serum levels and significant negative correlations with Zn levels were present. There were no significant correlations between maternal and neonatal serum levels of any of them. Exchange transfusion can normalize the significant higher Cu and Mg and lower Zn serum levels in neonates with severe indirect hyperbilirubinemia which were not related to their maternal serum levels.

Association between UGT-1A1 gene GLY71Arg polymorphism and severe unexplained indirect hyperbilirubinemia among neonates

Background Neonatal jaundice is considered the most prevailing clinical health problem among neonates. Numerous etiological factors are responsible for the development of pathological neonatal jaundice. Almost half of the cases have no well-identified risk factor suggesting an underlying genetic risk. Aim We aimed at investigating the relation between uridyl-diphosphate-glucuronosyltransferase 1A1 (UGT-1A1) gene Gly71Arg (G71R) polymorphism and the occurrence of unexplained severe indirect hyperbilirubinemia among Egyptian neonates. Patients and methods A case–control study was conducted on 81 term neonates presented with serum total bilirubin greater than or equal to 17 mg/dl with no identified underlying cause. Eighty-one age-matched and sex-matched term neonates without clinical jaundice were taken as controls. All neonates (cases and controls) were genotyped for the presence of UGT-1A1 gene G71R polymorphism using PCR restriction fragment length polymorphism. Neonatal cases were classified according to serum total bilirubin into four classes of severity: significant, severe, extreme, and hazardous hyperbilirubinemia. Results Genotype distribution frequency for G71R polymorphism was in accordance with Hardy–Weinberg equilibrium among controls but not among cases. There was significant increase in G71R A/G 50 (61.7%), A/A six (7.4%) genotypes, and A 62 (38.3%) allele distribution among cases with significant increase in estimated risk of unexplained hyperbilirubinemia with odds ratio (95% confidence interval) and P value of 8.6 (4.14–18.14) and P=0.000, 15.5 (1.78–136.2) and P=0.001, and 5.28 (2.92–9.57) and P=0.000, respectively when compared with controls. Significantly higher levels of total bilirubin among jaundiced neonates were observed with the A/A genotype followed by te A/G genotype as compared with the G/G wild genotype (P=0.000). Moreover, a significant association was found between the distribution of G71R genotypes and severity of jaundice. Conclusion UTG-1A1 gene G71R A/G, A/A genotypes, and A allele were associated with significant increased risk of severe unexplained indirect hyperbilirubinemia among Egyptian neonates.

Significant Hyperbilirubinemia with Sofosbuvir and Ribavirin-Based Antiviral Therapy in Post Liver Transplant Setting: An Unusual Etiology

Introduction: Causes of hyperbilirubinemia in a patient on antiviral therapy with sofosbuvir and ribavirin include pre-existing or co-existing liver disease, ribavirin induced hemolysis, sofosbuvir induced hyperbilirubinemia and Gilbert's syndrome. We report a case of a post liver-transplant patient who developed hyperbilirubinemia after initiation of antiviral therapy with sofosbuvir and ribavirin. CaseSummary: A 52y male underwent live related liver transplant in August 2014. His daughter was the willing donor. He had twice failed therapy for chornic HCV with Interferon. Postoperative course was uneventful in both the recipient and the donor.In April 2015. He was treated with sofosbuvir and weight based ribavirin for active HCV GT3 infection. Liver stiffness was 3.0 kPa. Concomitant medications included tacrolimus 1 mg twice daily, mycophenolate 500 mg twice daily and amlodipine 2.5 mg daily. Tacrolimus level was 7.4 ng/ml. The patient showed progressive rise in bilirubin soon after initiation of this therapy with highest value of 10.6 mg/dl (direct 0.3 mg/dl and indirect 10.3 mg/dl) at week 16. Workup was inconclusive (table 1). He completed 6 months of therapy and had an SVR 12. The bilirubin level reached pre-treatment levels within 4 weeks after completion of the treatment. Discussion: Our patient demonstrated hyperbilirubinemia post-transplant on antiviral therapy with Sof/Riba. He had a peak Bilirubin of 10.6 mg/dl (direct/indirect 0.3/10.3) at week 16 with Pre and post antiviral treatment total bilirubin of 1.37 mg/dl and 1.63 mg/dl. This pattern is suggestive of underlying Gilbert's Syndrome in the graft. The patient had no jaundice during his antiviral treatments prior to transplant. We did not find any conclusive evidence of hyperbilirubinemia in the donor's record with pre donor hepatectomy, total bilirubin of 0.9 mg/dl (direct/indirect 0.29/ 0.61). We believe ribavirin induced hemolysis combined with bilirubin handling defect (Gilbert's Syndrome) in the graft lead to severe indirect hyperbilirubinemia during antiviral treatment. Conclusion: Severe indirect hyperbilirubinemia can occur with Sof/Riba containing antiviral therapy in liver transplant patient. Gilbert's syndrome in the donor should be an important consideration. This elevation in bilirubin level was asymptomatic and did not affect SVR12 in our case.

Evaluating the Diagnostic Value of Skin Bilirubin in Comparison with Plasma Bilirubin to Identify Hyperbilirubinemia in Healthy Babies

Background: An elevated level of bilirubin in the blood is the most common and benign problem among newborns; it is also the most important factor in the evaluation of neonatal jaundice in newborns. If severe indirect hyperbilirubinemia is left untreated, it can be neurotoxic; therefore, doctors cannot overstate the need for the early detection of hyperbilirubinemia. Objectives: We investigated the relationship between the skin and plasma methods of the quality of the BiliChek process as a means of diagnosing hyperbilirubinemia Patients and Methods: This study was performed at Amiralmomenin hospital in Semnan, Iran and examined 64 healthy infants who had gestational ages of 37 weeks and greater and jaundice as their sole cause for hospitalization. Infants hospitalized due to other diseases, such as sepsis, were excluded from the study. First, a blood sample was taken to determine the infants’ serum total bilirubin. Then, the amount of bilirubin was determined with BiliChek placed on three locations: the infants’ foreheads, chests, and left thighs. Results: SD ± mean values of the skin method on each forehead, chest, and thigh were respectively (3.5 ± 13.8, 12.8 ± 3.5 and 9.7 ± 2.6 mg per deciliter); using the plasma method, bilirubin SD ± mean was 14.4 ± 4.0, so that the skin method in all three areas was lower than the plasma method. Variables such as the type of delivery, birth rank, blood type, birth weight, and maternal age are independent of hyperbilirubinemia level, and there is no significant relationship between them. There is only a significant relationship between bilirubin levels and a baby’s age, as there is a significant relationship to birth (P = 0.000). Cut off point for the use of BiliChek in the forehead has been set at 3.13 milligrams per deciliter, and the sensitivity and specificity levels are 83.87% and 92.59%, respectively. As for the chest, it was 3.13 mg dL, with sensitivity and specificity levels of 83.87% and 96.30%, respectively. For the thigh, it was 9.7 mg per dL, with sensitivity and specificity levels of 83.87% and 96.30% respectively. There is no significant difference between the three areas mentioned in the skin method for predicting hyperbilirubinemia. Conclusions: In our study, we determined that BiliChek can be used in the diagnosis of hyperbilirubinemia, but this use is limited and applies only to the cutoff point and for values higher than the cutoff point. BiliChek is used as a means of screening for infants that need blood sampling.

Clinical observation over the dynamic of the intrauteral mixed infection in the child of early age

Difficulty in diagnosis of the intrauterine infections (IUI) is associated with the low specificity of clinical manifestations and the multiple organ injury, prolonged persistence of the pathogen in the body, a significant prevalence of mixed infections and their frequent combination with the somatic disorders in newborns. The clinical case of mixed intrauterine infection in the child of early age is presented. The full-term boy was under the observation, he was born with severe anemic syndrome, indirect hyperbilirubinemia and hepatosplenomegaly. According to clinical observation and ultrasound of the abdomen the size of his liver and spleen increased progressively for six days after birth, it was accompanied by dynamic increase of total bilirubin due to its direct fraction, decrease of platelets count. ELISA-diagnostics of the child’s serum revealed the presence of the anti-toxoplasma and anti-cytomegalovirus antibodies. Taking into account obtained clinical and paraclinical data, the newborn child was diagnosed with intrauterine mixed infection with primary hematopoietic and liver damage (cholestatic-cytolytic variant). Anti-toxoplasma immunoglobulin was administered to child, but because of severe liver injury specific causal treatment of toxoplasmosis was postponed due to its hepatotoxicity. Later on anemic syndrome with indirect hyperbilirubinemia recurrently repeated in a child, it was dependent on transfusions but refractory to treatment. The presence of DNA of CMV and herpes virus type 6 was confirmed by PCR in the dynamic study of the five-month old child’s blood. Taking into account the obtained results of the examination, the child was diagnosed with severe congenital cytomegalovirus infection in the replication phase and comorbid congenital nonspherocytic hemolytic anemia of unknown origin with continuous crisis. The patient received anti-cytomegalovirus ganciclovir intravenously, antiherpetic valaciclovir orally. As a result of the treatment positive clinical dynamics was observed, which was accompanied by a decrease of the hepatolienal syndrome and gaining weight, but multiple red blood cell transfusions were not accompanied by significant or prolonged rise in hemoglobin levels. After the treatment twice done PCR child’s blood tests for CMV DNA were negative. Taking into account the crisis duration of the disease, splenectomy was discussed. The clinical case refers to the rare clinical diagnostic situations in medical practice when it is difficult to make a final conclusion about the etiology of the IUI. Verification of the intrauterine mixed infection was problematic in the neonatal period and during follow-up. The complexity of the diagnostic process was caused by the absence of the typical neurological symptoms. The diagnosis of mixed IUI was complicated by coexistence of the congenital nonspherocytic hemolytic anemia, the genesis of which could not be set, despite the study of enzyme activity in red blood cells, assessment of their osmotic resistance and Coombs tests. Damage of the erythroid stem hematopoiesis probably was caused by the infectious factors during the intrauteral period as well as by the hereditary pathology of the erythron.

Incidence, Risk Factors and Causes of Severe Neonatal Hyperbilirubinemia in the South of Iran (Fars Province)

BackgroundToday, Severe hyperbilirubinemia is the most common cause of neonatal readmissions. Identification of the cause of neonatal hyperbilirubinemia is useful in determining whether therapeutic interventions can prevent severe hyperbilirubinemia.ObjectivesWe conducted this study to estimate the incidence of severe hyperbilirubinemia in Fars province and to determine the underlying causes and risk factors, which would be of value in identifying and implementing strategies to prevent morbidity from this condition.Patients and MethodsAll infants less than 28 days referred due to severe indirect hyperbilirubinemia were included. Complete history, physical examination and lab work up were performed. This is a longitudinal prospective study in 2009-2010.ResultsMore common causes of severe indirect hyperbilirubinemia were blood group incompatibility, G6PD deficiency, sepsis and unknown. Risk factors of severe hyperbilirubinemia were Male sex, previous siblings with severe hyperbilirubinemia, early discharge, NVD, Breast feeding and cultural background of mothers.ConclusionsOur study showed severe neonate indirect hyperbilirubinemia is still prevalence in Fars province and ethnic and cultural background of the mothers was more effective than school education in preventing hyperbilirubinemia complication.

802 Causes and Contributing Factors Leading to Exchange Transfusion: 10 Year Experience at Adnan Menderes University Neonatal Intensive Care Unit

Background and AimsJaundice is one of the most common problems in newborn period. İnfants at risk for severe hyperbilirubinemia should be identified and closely monitored in order to avoid kernicterus....

Early and severe indirect hyperbilirubinemia as a manifestation of galactosemia

Classic galactosemia results from mutations in the galactose-1-phosphate uridyl transferase gene and causes infants to present with jaundice after initiation of lactose containing formulas. Jaundice associated with galactosemia is often thought to have a prominent direct fraction. We report an infant with galactosemia who presented with severe jaundice from indirect hyperbilirubinemia and met criteria for an exchange transfusion within 48 h after milk ingestion.

Síndrome de Crigler-Najjar: diagnóstico y tratamiento

Crigler-Najjar syndrome (CNS) is a very rare disease characterized by severe indirect hyperbilirubinemia from birth with normal liver function. It may cause kernicterus at any age. This disease is due to a total or partial deficiency of the UDP-glucuronosyltransferase enzyme caused by a mutation of the five exons of the ULT1A1 gene. We reviewed the clinical outcomes of 7 children diagnosed with CNS between 1987 and 2004. There were three boys and four girls (two of which were homozygote twins). Two children had familial consanguinity. Three out of the six families had another healthy child. The mean follow-up was 8.3 years (14 months-17 years). In all patients, jaundice was detected in the first 3 days of life. The children were admitted to hospital between the fourth and the sixtieth day of life with jaundice and indirect bilirubin levels of between 12.5 and 32 mg/dl. In all patients, hemolysis was ruled out and hepatic function was normal. The diagnosis was based on genetic study in 4 patients, on inactive UGT enzyme in liver in 1 patient, and on clinical features exclusively in 2 patients. Treatment consisted of phenobarbital and phototherapy from 8 to 16 hours a day in all patients except three. Associated calcium salts were found in 5 patients and cholestyramine was found in two. Two patients developed kernicterus. Two underwent liver transplantation and bilirubin levels became normal. The remaining patients maintained indirect bilirubin from 15 to 25 mg/dl with no associated neurological alterations. Patients with CNS are at greater risk of developing kernicterus, mostly associated with indirect bilirubin levels of around 25 mg/dl. Phototherapy is very useful in these patients but the only definitive treatment is liver transplantation.