Cause Of Neonatal Hyperbilirubinemia Research Articles

Bilirubin metabolism and UDP-glucuronosyltransferase 1A1 variants in Asians: Pathogenic implications and therapeutic response.

In the Asian general population, at least six single-nucleotide variants (SNVs) in the UDP-glucuronosyltransferase (UGT) 1A1 gene have been identified: -3279T>G, -53A(TA)6 TAA>A(TA)7 TAA, 211G>A, 686C>A, 1091C>T, and 1456T>G. Each of these six SNVs was observed in at least four ethnic groups of the 12 Asian populations studied. In East Asian populations, the descending frequency of these six SNVs was as follows: -3279G>[-53A(TA)7 TAA, 211A]>(686A, 1091T)>1456G. Because of the presence of linkage disequilibrium and the expulsion phenomenon, when the SNVs -3279G, -53A(TA)7 TAA, 211A, and 686A were simultaneously involved, 15 instead of the estimated 81 genotypes were observed. Those carrying 686AA or 1456GG developed Gilbert's syndrome or Crigler-Najjar syndrome type 2. Both -53A(TA)7 TAA/A(TA)7 TAA and 211AA are the main causes of Gilbert's syndrome in East Asian populations. In East Asian populations, the 211AA genotype is the main cause of neonatal hyperbilirubinemia, whereas -53A(TA)7 TAA/A(TA)7 TAA exerts a protective effect on hyperbilirubinemia development in neonates fed with breast milk. Both 211A and -53A(TA)7 TAA are significantly associated with adverse drug reactions induced by irinotecan (one of the most widely used anticancer agents) in Asians. However, at least three common SNVs (-3279G, -53A(TA)7 TAA, and 211A) should be comprehensively analyzed. This study investigated the clinical significance of these six SNVs and demonstrated that examining UGT1A1 variants in Asian populations is considerably challenging.

A prospective study on etiological factors and clinical indicators in term and near term neonates admitted with hyperbilirubinemia in nicu in a tertiary care hospital in Hyderabad, India

1.To study the etiology and risk factors of neonatal hyperbilirubinemia in term and near-term infants. 2. To study the clinical course of these infants during NICU stayThe present study was conducted at NICU, Department of Pediatrics, Princess Esra hospital, Deccan Medical College, Hyderabad, India, from October 2019 to October 2020. Term and late preterm infants admitted in NICU with Serum Bilirubin levels more than 12mg/dl were included in the study. The risk factors, etiology and clinical profile of these infants during NICU stay were studied. 210 neonates were admitted in NICU with hyperbilirubinemia (Serum Bilirubin >12mg/dl) during the study period, out of which 118 were male (56.20%) and 92 were female (43.80%). Neonates were further distributed based on gestational age, in which 46 (21.90%) were late pre-terms i.e. between 34-37 weeks and 164 neonates (78.10%) were full term i.e. greater than 37 weeks. The neonates were also classified based on their birth weight, with neonates between 2500-3000 grams having the highest incidence (46.19%). Lastly, the etiological and risk factors were assessed and quantified, with physiological jaundice occurring as the major cause and late prematurity as the most common risk factor associated with neonatal hyperbilirubinemia. The average duration of phototherapy was 2.50 days and 3 babies required Double Volume Exchange Transfusion (DVET) for significant hyperbilirubinemia.None of the babies requiring DVET had clinical features of Bilirubin Induced Neurological Dysfunction (BIND) during NICU stay. 1. Most common cause of neonatal hyperbilirubinemia was found to be Physiological followed by Septicemia and Idiopathic etiologies. Blood group incompatibilities were less common causes. 2. Phototherapy is a cheap and effective way to reduce bilirubin levels in neonatal jaundice. 3. Exchange transfusion is a safe procedure and should be considered when indicated, to decrease the incidence of BIND. All cases requiring DVET were due to blood group incompatibility.

Minor blood group incompatibility due to blood groups other than Rh(D) leading to hemolytic disease of fetus and newborn: a need for routine antibody screening during pregnancy.

Minor blood group incompatibility due to blood groups other than Rh(D), although an uncommon cause of neonatal hyperbilirubinemia, has the potential to cause severe hyperbilirubinemia and its sequelae in infants, if left undiagnosed and untreated. Here, we describe clinical presentation, diagnosis and treatment of three cases of minor blood group incompatibility due to anti-E and anti-c antibody. All three neonates presented with pallor, icterus and splenomegaly within the first three days of life. Investigations showed indirect hyperbilirubinemia and a positive direct coombs test. Indirect coombs test was positive in the mothers. There was no setting of ABO or Rh(D) incompatibility in any of the neonates. When tested for minor blood group incompatibility, anti E antibody was found to be responsible for hemolysis and hyperbilirubinemia in the first case, and anti c antibody was found in the second case and third case had both anti c and anti E antibodies. While hyperbilirubinemia improved with intensive phototherapy in the first two cases, the third case required a double volume exchange transfusion. On follow up, bilateral sensorineural hearing loss was seen in one of the patients. All three neonates were otherwise healthy, gaining weight and developmentally normal.

ABO and Rh blood group incompatibility among icteric neonates and their mothers in Jos, Nigeria

Context: ABO and Rh blood groups play significant roles in health and diseases, one of which is blood group incompatibility, a common cause of neonatal hyperbilirubinemia. Aims: The aim of the study is to determine the frequency of ABO and Rh blood group incompatibilities among icteric neonates and their mothers for the purpose of instituting intervention for better neonatal outcomes. Settings and Design: This study was conducted at the Special Care Baby Units (SCBUs) of the Jos University Teaching Hospital (JUTH), Bingham University Teaching Hospital (BHUTH), and Plateau State Specialist Hospital (PSSH), Jos, Nigeria, from March 2013 to February 2014. It was a descriptive cross-sectional study that includes all jaundiced neonates admitted into the SCBUs and neonates who developed jaundice on admission in the neonatal wards. Subjects and Methods: A total of 150 icteric neonates admitted into the SCBUs of the JUTH, PSSH, and the BHUTH were recruited for this study with their parent's consent. Blood samples were collected from the neonates and their mothers in ethylene diaminetetra-acetic acid and plain bottles for ABO and Rh blood grouping, direct antihuman globulin test, and serum bilirubin (SB) assays. Statistical Analysis Used: Data obtained were analyzed using Epi Info Version 6 software. The results were reported in tables and frequencies, categorical variables were expressed as proportions, whereas continuous variables were expressed as mean ± standard deviation and were analyzed using Student's “t”-test. The level of statistically significant relationship was set at P ≤ 5% (P ≤ 0.05). Results: Thirty-four (22.7%) mother–neonate pair had ABO incompatibility with 14 mothers (9.3%) with blood group O, having neonates with blood group A and a mean SB of 249.5 ± 131.4 μmol/L. Three (2.0%) mothers were Rh D negative while their neonates were Rh D positive and showed a positive direct antihuman globulin test with a mean SB of 322.1 ± 246.7 μmol/L. Conclusions: Blood group O and Rh D-positive blood groups predominate while ABO and Rh incompatibilities present a risk for hyperbilirubinemia among icteric neonates in Jos, Nigeria.

Exchange transfusion in neonatal hyperbilirubinemia: A single Centre experience from Northern India

ObjectiveTo determine the indication, efficacy and adverse events related to exchange transfusion (ET) with reconstituted blood (RB) in neonatal hyperbilirubinemia (NNH). MethodsBlood bank records of neonates who underwent double volume ET for NNH from January 2013 to July 2018 were retrospectively reviewed. Demographic details, cause of NNH, details of ET and ET related adverse events were recorded. ResultsA total of 23 ET (average: 1.64/neonate) were performed in 14 neonates (9 males; 5 females) with a mean age of 9.8 ± 7.6 days. Ten (71.4%) neonates underwent 1 session of ET, while 4 (28.6%) underwent repeated sessions (average: 3.25/neonate). A total of 5912 ml of RB was transfused (average: 422 ml/neonate). A statistically significant reduction was noted in total serum bilirubin (TSB) level post-ET (p < 0.001) with overall TSB reduction/procedure being 46%.Of the 14 neonates with NNH, 11 (78.6%) had Rh haemolytic disease of foetus and new-born (HDFN), 2 (14.3%) had ABO HDFN and 1 (7.1%) had hyperbilirubinemia due to prematurity. Of the 11 neonates with Rh HDFN, only 5 underwent intrauterine transfusion (average: 1.8/neonate).Post-ET, top-up transfusions were noted in 8 (57.1%) neonates with packed red blood cell and/or platelet concentrate. ET related adverse were noted in 5 (21.7%) procedures only. ConclusionRh HDFN was the most common cause of NNH in our study population.Exchange transfusion is a safe treatment modality for treating NNH, as it results in the rapid elimination of serum bilirubin, thus, lowering the risk of kernicterus in these patients.

Coordinating Care Across the Perinatal Continuum in Hemolytic Disease of the Fetus and Newborn: The Timely Handoff of a Positive Maternal Anti-Erythrocyte Antibody Screen

Antibody-mediated hemolytic disease of the fetus and newborn, henceforth referred to as hemolytic disease, can pose a significant risk for anemia and severe postnatal hyperbilirubinemia. A positive maternal anti-erythrocyte antibody screen is often the first finding to herald the risk of hemolytic disease and prompt further evaluation including fetal surveillance for anemia and, if indicated, in utero red blood cell transfusion. 1 Liley H.G. Gardener G. Lopriore E. Smits-Wintjens V. Immune hemolytic disease. in: Orkin S. Nathan D. Ginsburg D. Look A.T. Fisher D. Lux S. Nathan and Oski's hematology and oncology of infancy and childhood. Elsevier Saunders, Philadelphia2015: 76-100 Google Scholar A positive maternal anti-erythrocyte antibody screen may also signal a risk for severe hyperbilirubinemia in the neonate, even in the absence of fetal anemia. In this regard, hemolytic disease remains an important cause of marked neonatal hyperbilirubinemia, acute bilirubin encephalopathy, and kernicterus. 2 Johnson L. Bhutani V.K. Karp K. Sivieri E.M. Shapiro S.M. Clinical report from the Pilot US Kernicterus Registry (1992 to 2004). J Perinatol. 2009; 29: S25-S45 Crossref Scopus (232) Google Scholar , 3 Christensen R.D. Agarwal A.M. George T.I. Bhutani V.K. Yaish H.M. Acute neonatal bilirubin encephalopathy in the State of Utah 2009-2018. Blood Cells Mol Dis. 2018; 72: 10-13 Crossref PubMed Scopus (24) Google Scholar , 4 Helal N.F. Ghany E.A. Abuelhamd W.A. Alradem A.Y. Characteristics and outcome of newborn admitted with acute bilirubin encephalopathy to a tertiary neonatal intensive care unit. World J Pediatr. 2019; 15: 42-48 Google Scholar , 5 Rennie J.M. Beer J. Upton M. Learning from claims: hyperbilirubinemia and kernicterus. Arch Dis Child Fetal Neonatal Ed. 2019; 104: F202-F204 Google Scholar Whether a positive maternal anti-erythrocyte antibody screen is detected at pregnancy registration, during gestation, or perinatally at the time of delivery hospitalization, it is incumbent on the newborn caretakers to be aware of the result. 6 Watchko J.F. Common hematologic problems in the newborn nursery. Pediatr Clin N Am. 2015; 62: 509-524 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar , 7 Intermountain Healthcare. Prenatal care for maternal anti-erythrocyte antibodies. 2017 Update. Intermountain Healthcare Patient and Provider Publications CPM043 – 07/17. https://intermountainhealthcare.org/ckr-ext/Dcmnt?ncid=521363279. Accessed December 1, 2018. Google Scholar We review the critical importance of a successful handoff of a positive maternal anti-erythrocyte antibody screen across the perinatal continuum to ensure the timely evaluation and management of the neonate. Although symptomatic ABO hemolytic disease is also an important cause of neonatal hyperbilirubinemia, maternal anti-A and anti-B antibodies are innately produced, that is, immune competent individuals who do not express the A or B protein produce antibody to the antigen. As such, anti-A and anti-B are not included in the maternal anti-erythrocyte antibody screen and ABO hemolytic disease is not addressed. Two case reports underscore the importance of the timely handoff of a positive maternal anti-erythrocyte antibody screen.

Comparative study between serum and transcutaneous bilirubin measurements in new-borns

Background: Hyperbilirubinemia is one of the common problems in neonates. The transcutaneous bilirubin (TCB) measurement is non-invasive, easy and rapid not requiring expertise and manpower. Fewer studies have been carried out to whether newer TCB measurements can correlate with serum bilirubin measurements using newer generation of transcutaneous bilirubinometer in our region.Methods: An observational cross-sectional study to compare serum and transcutaneous bilirubin measurements in newborns admitted to a neonatal intensive care unit, conducted from December 2015 to November 2017. Blood samples were obtained from neonates collected from venous sample into plain bulb and sent for analysis. For transcutaneous bilirubin measurement, the reading from forehead and sternum were taken using bilirubinometer and an average reading was taken for comparison.Results: Total 172 neonates were admitted during study period and enrolled in the study. It was observed that out of 172 patients, studied 102(59%) patients were male and 70(41%) patients were female. Out of 172 patients maximum 89(51.74%) mother have O positive blood group and only 2(1.1%) have O negative blood group. Common cause of neonatal hyperbilirubinemia was ABO incompatibility 81(48%), Rh incompatibility 11(6%), and other causes 80(46%). The mean and standard deviation of TSB for first, second and third reading were 19.21±3.44, 15.76±2.79 and 12.89±2.44 respectively. While mean and standard deviation of TCB for first, second and third reading were 18.34±2.99, 15.48±2.36 and 12.31±2.28 respectively with correlation coefficient of r=0.806513, r=0.694273, r=0.785471 respectively indicating linear relationship between two.Conclusions: There was a strong correlation between serum and transcutaneous bilirubin levels before and even after the phototherapy. As transcutaneous bilirubin estimation is non-invasive, gives quick and reproducible results. So, by using this method has potential screening value especially in the high-risk neonates to start early intervention.

Analysis of Screening Results in 501 Newborns with Hemolytic Disease

To explore the relationship between the serological detection of neonatal hemolytic disease (HDN) and related factors, and to observe the detection rate and specificity of the antibodies against the blood group in the newborn hemolytic disease. Maternal-neonatal blood type was detected firstly, and then the direct antiglobulin test(DAT), the free antibody test and the antibody release test were used to detect the occurrence of HDN; For those suspected hemolytic disease except ABO or direct DAT result over 2+, the indirect antiglobulin test with irregular antibody were used for screening cells and the plasma of the patient and mother, and then to detezmine whether there is a corresponding antigen in the red blood cells of the patient to confirm whether hemolytic disease of the other blood type system exists or not. The analysis was carried out by SPSS 22 software. The statistical analysis of classified data was tested by χ2 test. P<0.05 was considered as statistically significance. A total of 501 cases of hyperbilirubinemia were collected. Among them 250 cases of HDN were diagnosed as HDN, and the detection rate was 49.90%.The detection rate of the male was 45.14%, and that of the female was 56.34%(χ2 =6.143, P<0.05). The average day-age of patients was 3.97±2.81 days. The analysis of relatianship between the detected rate of HDN and the day-age of HDN chilren showed that the day-age of HDN chilren affected the detected rate of HDN(χ2 =63.489, P<0.05). The analysis of positive rate of 3 test in HDN+ childen of every group found that the day-age had an infuence on the detected rate of direct antiglobulin test(χ2=18.976，P<0.01) and also had an influence on the detected rate of the free antibody test(χ2=9.650，P<0.05). The positive rate of the release test in HDN patients was highest（100%）. 244 cases suffered from ABO hemolysis, including 1 case of ABO hemolysis combined with Rh system (anti -E) hemolysis, 4 cases of Rh system (anti -D), 2 cases of MN system (1 case was caused by anti -M, 1 case was caused by low frequency anti -Mur). ABO HDN caused by anti-A or anti-B were not statisticaly significant. Hemolytic disease of the newborn is a common cause of neonatal hyperbilirubinemia. The positive rate of HDN has a certain relations with the sexual distinction and the day-age. But there is no significant difference between anti-A and anti-B type. At the same time, screening and identification of irregular antibodies should be carried out to avoid diagnostic errors caused by undetected antibody when necessary.

Birthing backwards: unravelling trauma to move forward

To determine the indication, efficacy and adverse events related to exchange transfusion (ET) with reconstituted blood (RB) in neonatal hyperbilirubinemia (NNH).Blood bank records of neonates who underwent double volume ET for NNH from January 2013 to July 2018 were retrospectively reviewed. Demographic details, cause of NNH, details of ET and ET related adverse events were recorded.A total of 23 ET (average: 1.64/neonate) were performed in 14 neonates (9 males; 5 females) with a mean age of 9.8 ± 7.6 days. Ten (71.4%) neonates underwent 1 session of ET, while 4 (28.6%) underwent repeated sessions (average: 3.25/neonate). A total of 5912 ml of RB was transfused (average: 422 ml/neonate). A statistically significant reduction was noted in total serum bilirubin (TSB) level post-ET (p < 0.001) with overall TSB reduction/procedure being 46%.Of the 14 neonates with NNH, 11 (78.6%) had Rh haemolytic disease of foetus and new-born (HDFN), 2 (14.3%) had ABO HDFN and 1 (7.1%) had hyperbilirubinemia due to prematurity. Of the 11 neonates with Rh HDFN, only 5 underwent intrauterine transfusion (average: 1.8/neonate).Post-ET, top-up transfusions were noted in 8 (57.1%) neonates with packed red blood cell and/or platelet concentrate. ET related adverse were noted in 5 (21.7%) procedures only.Rh HDFN was the most common cause of NNH in our study population.Exchange transfusion is a safe treatment modality for treating NNH, as it results in the rapid elimination of serum bilirubin, thus, lowering the risk of kernicterus in these patients.

Characteristics of Neonatal Hyperbilirubinemia at West Java’s Top Referral Hospital, Indonesia

Background : Neonatal hyperbilirubinemia or neonatal jaundice is a common disorder and considered as one of the main problems in neonatal period worldwide with high incidence, especially in Asia and Southeast Asia region. This study was conducted to determine the characteristics of neonatal hyperbilirubinemia including the prevalence and frequency of neonatal hyperbilirubinemia causes at Dr. Hasan Sadikin General Hospital in 2012. Methods : This descriptive study was conducted at Dr. Hasan Sadikin General Hospital using the cross-sectional method. Four hundred and twenty five cases of neonatal hyperbilirubinemia in hospitalized and outpatients, from 1 January to 31 December 2012 were included in this descriptive study. Results : The prevalence of neonatal hyperbilirubinemia was about 4.08%. Causes were identified in 95 cases and the most common cause of neonatal hyperbilirubinemia during this period of time was physiological causes (23.2%). Other causes included neonatal hepatitis (14.7%), other hemolytic causes (13.7%), infection (12.6%), ABO incompatibility (11.6%) and breastfeeding (11.6%). Conclusions : Neonatal hyperbilirubinemia cases are common and remain as one of the neonatal problems in Dr. Hasan Sadikin General Hospital, thus prevention and proper management of neonatal hyperbilirubinemia should be implemented. DOI: 10.15850/amj.v4n2.1065

English

INTRODUCTION: Jaundice is the commonest abnormal physical finding in newborn babies. It is mostly due to physiological handicaps. Non-physiological hyperbilirubinemia is said to occur in 5-25% of the newborn babies. Any factor that further increases the bilirubin production is very likely to exacerbate neonatal hyperbilirubinemia. OBJECTIVES: This study was carried out to find the presence of physiological jaundice and the association of neonatal hyperbilirubinemia with septicemia in neonatal period. MATERIALS & METHODS: In this study, 100 neonates were selected, who belonged to the age group of birth to one month of age. After selection of the cases, a detailed history and clinical examination was done. All types of investigations (Routine and specialized, where applicable) were carried out for the measurement of serum bilirubin. Finally an association was made between neonatal jaundice and physiological changes and septicemia in neonatal period. RESULTS: It was clear in our study that the most common association of neonatal jaundice was physiological changes in neonatal period. It was present in 22% of the cases. Septicemia was next major cause of neonatal hyperbilirubinemia (18%). CONCLUSION: After analyzing 100 cases of neonatal jaundice, ranging from birth to one month of age, it was concluded that the most common cause of neonatal jaundice is physiological. Septicemia was ranked second. Pneumonia in the neonatal period was found to be most common underlying problem in septicemia.

Red Cell Glucose 6-Phosphate Dehydrogenase Deficiency in the Northern Region of Turkey: Is G6PD Deficiency Exclusively a Male Disease?

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis. However, this disease affects both males and females. In Turkey, the frequency of this enzyme deficiency was reported to vary, from 0.25 to 18%, by the geographical area. Its prevalence in the northern Black Sea region of Turkey is unknown. The aims of this study were to assess the prevalence of G6PD deficiency in the northern region Turkey in children and adults with hyperbilirubinemia and hemolytic anemia. This report included a total of 976 G6PD enzyme results that were analyzed between May 2005 and January 2014. G6PD deficiency was detected in 5.0% of all patients. G6PD deficiency was significantly less frequent in females (1.9%, 6/323) than in males (6.6%, 43/653). G6PD deficiency was detected in 3.7% of infants with hyperbilirubinemia, 9.2% of children, and 4.5% of adults with hemolytic anemia. In both the newborn group and the group of children, G6PD deficiency was significantly more frequent in males. In the combined group of children (groups I and II), the proportion of males was 74% and 67% in all groups (P = .0008). In conclusion, in northern region of Turkey, G6PD deficiency is an important cause of neonatal hyperbilirubinemia and hemolytic crisis in children and adults. This study suggests that most pediatricians thought that G6PD deficiency is exclusively a male disease. For this reason, some female patients may have been undiagnosed.

Impact of fatty acids on human UDP-glucuronosyltransferase 1A1 activity and its expression in neonatal hyperbilirubinemia

While breast milk has been known as a cause of neonatal hyperbilirubinemia, the underlying mechanism of breast milk-induced jaundice has not been clarified. Here, the impact of fatty acids on human UDP-glucuronosyltransferase (UGT) 1A1 – the sole enzyme that can metabolize bilirubin – were examined. Oleic acid, linoleic acid, and docosahexaenoic acid (DHA) strongly inhibited UGT1A1 activity. Forty-eight hours after a treatment with a lower concentration of DHA (10 mg/kg), total bilirubin significantly increased in neonatal hUGT1 mice, which are human neonatal jaundice models. In contrast, treatments with higher concentrations of fatty acids (0.1–10 g/kg) resulted in a decrease in serum bilirubin in hUGT1 mice. It was further demonstrated that the treatment with higher concentrations of fatty acids induced UGT1A1, possibly by activation of peroxisome proliferator-activated receptors. Our data indicates that activation of peroxisome proliferator-activated receptors would increase UGT1A1 expression, resulting in reduction of serum bilirubin levels in human infants.

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.

The Significance of Enterohepatic Circulation in the Causation Neonatal Hyperbilirubinemia

Sir, This is in reference to the study by Rana et al.[1] A robust triple-blind design, appropriate sample-size, and statistical methods–sensitivity analysis and effect-size estimation– employed by the authors could well make the investigation a landmark study evaluating the role of zinc in the prevention of hyperbilirubinemia in neonates. However, the study simultaneously conjures-up an important question about the role of enterohepatic circulation (EHC) in the causation of neonatal jaundice which may also have implications on the physiological doctrine for the intervention tested. Overproduction of bilirubin from heme is considered the most prevalent mechanism of neonatal hyperbilirubinemia apart from impaired uptake, conjugation, and EHC. We have limited instances where EHC is considered the prime mechanism for jaundice, e.g., pyloric stenosis, lower intestinal atresia, paralytic ileus, and meconium-plug-syndrome (virtually no removal of bilirubin due to distal obstruction). There is limited data to suggest that the resorption of bilirubin from the intestine can be a major cause of neonatal physiologic jaundice [2]. It has been stated that neonatal hyperbilirubinemia is exacerbated–if not caused–by enhanced bilirubin resorption through EHC [3]. In fact, more obvious than EHC, a markedly reduced UDP-glucuronyl transferase activity is noted in pyloric stenosis [3]. Enhanced EHC induced by human milk has a putative role in prolonging ‘breastmilk jaundice’ [4]. In the past, various strategies have been employed to counteract EHC with inconsistent results, in terms of the incidence and severity of jaundice [5]. Consequently, it is advised that such interventions are at the best used as an adjuvant, along with more established modalities like phototherapy [6]. The results of the present study by Rana et al., showing no significant reduction in the incidence of hyperbilirubinemia, requirement of phototherapy and mean STB (serum total bilirubin) at 72 h, are in line with the outcomes of previous studies employing other agents. Therefore, although past studies have suggested that EHC may play a significant role in the bilirubin metabolism, it appears less likely that EHC is a major cause of neonatal hyperbilirubinemia, though it may play some contributory role in prolonging physiological jaundice. Therefore, negative results of these studies probably have a bearing on the underlying doctrine of ‘prevention of hyperbilirubinemia by clogging-up EHC’, irrespective of the agent (agar, charcoal, cholestyramine or zinc) employed. Other limitations of the study were the use of nonstandardized oral zinc dose, lack of serum zinc level monitoring, inadequate reporting of the adequacy of breastfeeding and vomited and/or skipped doses, and delayed initiation of the intervention.

Breast non feeding: Main cause of neonatal hyperbilirubinemia in areas adjoining Shri Ram Murti smarak institute of medical Sciences, a tertiary care teaching hospital, Bareilly

Aims & Objective: The purpose of this study was to determine the occurrence, etiological & other associated factors of neonatal hyperbilirubinemia in Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly. Jaundice is a common problem in neonatology. Early recognition of the cause of jaundice is very important as delay in management may lead to serious complications or even death. Materials and methods: In present study, newborns with jaundice were evaluated during a six months period between July – December 2011. 124 newborns with jaundice were enrolled in the study. Data regarding demographic profile of new born, physical examination and laboratory investigations gathered and analysed to interpretate the common etiologies giving rise to neonatal hyperbilirubinemia. Results: Out of 124 cases of neonatal hyperbilirubinemia, 24 cases were of physiological jaundice, breast non feeding jaundice, breast milk jaundice, jaundice due to prematurity and pathological jaundice comprised the rest 100 as 84, 5, 5 & 6 cases respectively. Patholgical causes for jaundice included neonatal sepsis (2cases), neonatal hypothyroidism (2cases), congenital biliary atresia (1case) and ABO incompatibility (1case). Conclusion: Present study concludes that breast nonfeeding or inadequate feeding jaundice forms the bulk of cases of neonatal hyperbilirubinemia in this region, followed by breast milk jaundice, prematurity jaundice and pathological causes.

Hereditary Spherocytosis in Neonates With Hyperbilirubinemia

Hereditary spherocytosis (HS) is the most common inherited hemolytic disease among people of Northern European decent. Neonates with HS can develop significant hyperbilirubinemia, but we suspect that HS is underrecognized as a cause of neonatal jaundice. We used electronic record repositories of Intermountain Healthcare to identify all neonates with a diagnosis of HS in a recent 5-year period. We compared these with the number of new HS cases anticipated on the basis of national prevalence and also with the number who had elevations in mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), and bilirubin. We compared MCHC and RDW values of neonates who had direct antiglobulin test-positive (DAT[+]) and DAT(-) results and jaundice with values of neonates who had HS. Eight neonates received a diagnosis of HS; however, we may have failed to diagnose 90% of cases. To assess whether some with a missed diagnosis of HS developed significant hyperbilirubinemia, we examined records of all 670 with a bilirubin level of >or=20 mg/dL. Records of the 20 with the highest MCHC and RDW values suggested that HS was present but unrecognized in at least 7. Follow-up revealed a subsequent diagnosis of HS in 5; the other 2 are no longer in our health system. MCHC and RDW values were highest in those with HS, intermediate in the DAT(+) group, and lowest in the DAT(-) group. An MCHC of >or=36.0 g/dL had 82% sensitivity and 98% specificity for identifying HS. We speculate that HS is underrecognized as a cause of neonatal hyperbilirubinemia. We speculate further that an MCHC of >or=36.0 g/dL can alert caregivers to the possibility of HS.

Genetic polymorphisms in Thai neonates with hyperbilirubinemia

Polymorphisms of the UGT1A1 gene, SLCO1B1 gene and GST gene have been associated with significant hyperbilirubinemia. We would like to determine whether the variation of UGT1A1 gene, SLCO1B1 gene and GST gene may play a significant role in neonatal hyperbilirubinemia in Thai infants. Ninety-one study subjects (hyperbilirubinemic group) and 86 control subjects were studied. The cause of neonatal hyperbilirubinemia could not be identified in 64 infants (70.3%), ABO blood group incompatibility in 14.3% and Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 8.8%. In the hyperbilirubinemic group, 23 of 91 (25.3%) infants demonstrated variant of UGT1A1 at nucleotides (nt) 211 as compared to 6 of 86 (7%) in the control group (p = 0.001). There were no significant differences between groups in the variants UGT1A1 at nt 686, SLCO1B1 gene at nt 388, 463 and the GST gene. Male infants with G-6-PD deficiency were associated with hyperbilirubinemia (21.2% vs. 4.8% in the control group) with an odds ratio (OR) of 5.37 (p = 0.02). The relationship between G-6-PD and variant in UGT1A1 gene at nt 211 could not be determined. Thai infants with variant in the UGT1A1 at nt 211 or with G-6-PD deficiency are at higher risk for developing neonatal hyperbilirubinemia.

Glucose-6-phosphate dehydrogenase deficiency in neonates.

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

CHRONIC HEMOLYTIC ANEMIA ASSOCIATED WITH GLUCOSE 6-PHOSPHATE DEHYDROGENASE (GUADALAJARA)1159 C → T (387 ARG → CYS) DEFICIENCY ASSOCIATED WITH GILBERT SYNDROME IN A TURKISH PATIENT

The case of an 8-year-old male child with severe kernicterus sequelae is presented in this paper. The child's hemoglobin value varied between 6.0 and 10.8 g/dL and his reticulocyte count ranged between 3.4 and 46.0% during the steady-state condition and hyperhemolytic crisis, respectively. A chronic hemolytic typeof red cell G6PD deficiency was diagnosed. DNA studies indicate that the mutation was G6PD Guadalajara 1159 C M T (387 Arg M Cys) that is situated at the NADP binding site. Additionally, extra nucleotides of (TA) in the A(TA) n TAA motif of the promoter region of the uridine diphosphate-glucuronosyltransferase gene (UGT-1) were found to be homozygous in the patient. The coexistence of Gilbert syndrome with a chronic type of G6PD deficiency was suggested as a cause of neonatal hyperbilirubinemia leading to kernicterus.