Severe Neonatal Hyperbilirubinemia Research Articles

Curcumin Prevents Cerebellar Hypoplasia and Restores the Behavior in Hyperbilirubinemic Gunn Rat by a Pleiotropic Effect on the Molecular Effectors of Brain Damage

Bilirubin toxicity to the central nervous system (CNS) is responsible for severe and permanent neurologic damage, resulting in hearing loss, cognitive, and movement impairment. Timely and effective management of severe neonatal hyperbilirubinemia by phototherapy or exchange transfusion is crucial for avoiding permanent neurological consequences, but these therapies are not always possible, particularly in low-income countries. To explore alternative options, we investigated a pharmaceutical approach focused on protecting the CNS from pigment toxicity, independently from serum bilirubin level. To this goal, we tested the ability of curcumin, a nutraceutical already used with relevant results in animal models as well as in clinics in other diseases, in the Gunn rat, the spontaneous model of neonatal hyperbilirubinemia. Curcumin treatment fully abolished the landmark cerebellar hypoplasia of Gunn rat, restoring the histological features, and reverting the behavioral abnormalities present in the hyperbilirubinemic rat. The protection was mediated by a multi-target action on the main bilirubin-induced pathological mechanism ongoing CNS damage (inflammation, redox imbalance, and glutamate neurotoxicity). If confirmed by independent studies, the result suggests the potential of curcumin as an alternative/complementary approach to bilirubin-induced brain damage in the clinical scenario.

Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome

AbstractWe report here 7 new mutations in the ADAMTS13 gene responsible for Upshaw-Schulman syndrome (USS), a catastrophic phenotype of congenital thrombotic thrombocytopenic purpura, by analyzing 5 Japanese families. There were 3 mutations that occurred at exon-intron boundaries: 414+1G>A at intron 4, 686+1G>A at intron 6, and 1244+2T>G at intron 10 (numbered from the A of the initiation Met codon), and we confirmed that 2 of these mutations produced aberrantly spliced messenger RNAs (mRNAs). The remaining 4 mutations were missense mutations: R193W, I673F, C908Y, and R1123C. In expression experiments using HeLa cells, all mutants showed no or a marginal secretion of ADAMTS13. Taken together with the findings in our recent report we determined the responsible mutations in a total of 7 Japanese patients with USS with a uniform clinical picture of severe neonatal hyperbilirubinemia, and in their family members, based on ADAMTS13 gene analysis. Of these patients, 2 were homozygotes and 5 were compound heterozygotes. The parents of one homozygote were related (cousins), while those of the other were not. Molecular models of the metalloprotease, fifth domain of thrombospondin 1 (Tsp1-5), and Tsp1-8 domains of ADAMTS13 suggest that the missense mutations could cause structural defects in the mutants.

A single-center experience on exchange transfusion therapy in 123 full-term cases of severe neonatal hyperbilirubinemia in Wuhan

Objective To describe the clinical experience in application of exchange transfusion therapy (ETT) in the treatment of severe neonatal hyperbilirubinemia.Methods The clinical data and examination results of severe neonatal hyperbilirubinemia full-term cases treated by ETT were analyzed retrospectively, the etiology and risk factors of severe neonatal hyperbilirubinemia were statistically analyzed, and the statistical characteristics of the children in each etiological group and the incidence of adverse events of ETT were analyzed.Results The age of jaundice, peak total bilirubin after phototherapy and ETT in 123 full-term infants were 2.0 (1.0, 3.0) days, 4.0 (2.0, 7.0) days and 4.0 (2.0, 7.0) days, respectively, of which 68 were male and 55 were female. The main pathogeny of severe neonatal hyperbilirubinemia was blood group incompatibility hemolytic disease of newborn (HDN). Age of ETT, total bilirubin after ETT, gender and BAEP results were different between ABE and non-ABE infants. Weight loss can be used as a predictor of hospitalization length. The major adverse events related to ETT were hypocalcemia, hypomagnesemia, hyponatremia and thrombocytopenia.Conclusions ETT can rapidly reduce the level of total bilirubin to prevent ABE and play an important role in the treatment of neonatal hyperbilirubinemia, but the whole process of ETT needs to be closely monitored.

Remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease

To explore the feasibility of remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease. Forty six neonates of gestational age >35 weeks with ABO hemolytic disease admitted to Women's Hospital, Zhejiang University School of Medicine from January 20th, 2020 to February 29th, 2020 were enrolled in the study (study group). The newborns were followed up at home after discharge, the transcutaneous bilirubin (TCB) levels were measured by parents using the provided device and the results were sent to the doctor by smart phone using the installed APP. Fifty six newborns with ABO hemolytic disease admitted in 2018 who received conventional outpatient follow-up after discharge served as the control group. The demographic characteristics, total serum bilirubin (TSB) level during hospitalization, number of outpatient visit and rate of re-admission due to rebound hyperbilirubinemia were compared between the two groups. There were no significant differences between the two groups in gestational age, birth weight, delivery mode, gender, length of the first hospitalization, TSB level before phototherapy and before discharge, and the managements during the first hospitalization (all P>0.05). Compared with the control group, TSB level before readmission [(265±16) μmol/L vs. (295±15) μmol/L] and the number of outpatient visits (1.3±0.8 vs. 3.8±0.5) were significantly lower in the study group (all P<0.01), while the rate of readmission (17.4%vs. 12.5%) and the weight at the time of readmission[(3398±452) g vs. (3477±324) g] were not significantly different (all P>0.05). No cases of acute bilirubin encephalopathy occurred in both groups. The remote follow-up for neonatal jaundice at home can effectively reduce the number of outpatient visits without increasing the risk of readmission and severe neonatal hyperbilirubinemia for newborns with ABO hemolytic disease.

19 Treatment of Neonatal Hyperbilirubinemia – Ontario Cohort 2014-2018

Abstract Background Serious complications that could result from severe neonatal hyperbilirubinemia include acute and chronic bilirubin encephalopathy. In Ontario, the incidence of severe neonatal hyperbilirubinemia and its associated treatments in term and near-term infants is currently unknown. Although IVIG therapy has been increasingly discussed in the literature, a recent Cochrane review (2018) indicated that there was a lack of evidence for recommending IVIG therapy for routine use. Objectives The purpose of this study was to determine the current incidence of severe neonatal hyperbilirubinemia and its treatments (Intravenous Immunoglobulin (IVIG) therapy, exchange transfusion and phototherapy) most often used in Ontario. Design/Methods A population-based retrospective cohort study of all term and near-term infants (≥ 35 weeks’ gestation) born in Ontario from April 2014 to March 2018 was conducted. National and provincial databases including Better Outcomes Registry Network Ontario (BORN) and Canadian Neonatal Network (CNN) were utilized. Results Data was collected from 533,084 infants born in Ontario over the 4 years. Of the total infants screened, 29,756 (6%) infants were diagnosed with neonatal hyperbilirubinemia. In terms of treatments, 24,646 (83%) infants received phototherapy, 54 (0.18%) infants received an exchange transfusion and 458 (1.5%) infants received IVIG therapy. In Ontario, neonatal hyperbilirubinemia had a statistically significant increase from 2014 to 2018 (P&amp;lt;0.0001). Although phototherapy was used on almost all neonates with hyperbilirubinemia (83%) there was a significant decrease from 2014 to 2018 (from 88% to 80%) (P&amp;lt;0.0001). Of the babies with hyperbilirubinemia in 2014, 71 (1.06%) infants received IVIG therapy and 15 (0.22%) infants received exchange transfusion. Within 4 years, IVIG therapy incidence had a significant increase from 71 (1.06%) infants to 156 (2.04%) infants (P&amp;lt;0.0001), while exchange transfusion remained relatively constant (P=.315). Exchange transfusion rates allows for the prediction that the rate of severe neonatal hyperbilirubinemia is stable in Ontario. Conclusion In conclusion, (severe) hyperbilirubinemia still exists amongst neonates in Ontario, despite the advancements in managing hyperbilirubinemia, indicating the need for better treatments and/or monitoring. There was also a significant rise in the use of IVIG despite the continued debate about its utility. Further research should be conducted nationally to determine the incidence of severe neonatal hyperbilirubinemia and to indicate the usage of IVIG therapy.

Microglia Susceptibility to Free Bilirubin Is Age-Dependent.

Increased concentrations of unconjugated bilirubin (UCB), namely its free fraction (Bf), in neonatal life may cause transient or definitive injury to neurons and glial cells. We demonstrated that UCB damages neurons and glial cells by compromising oligodendrocyte maturation and myelination, and by activating astrocytes and microglia. Immature neurons and astrocytes showed to be especially vulnerable. However, whether microglia susceptibility to UCB is also age-related was never investigated. We developed a microglia culture model in which cells at 2 days in vitro (2DIV) revealed to behave as the neonatal microglia (amoeboid/reactive cells), in contrast with those at 16DIV microglia that performed as aged cells (irresponsive/dormant cells). Here, we aimed to unveil whether UCB-induced toxicity diverged from the young to the long-cultured microglia. Cells were isolated from the cortical brain of 1- to 2-day-old CD1 mice and incubated for 24 h with 50/100 nM Bf levels, which were associated to moderate and severe neonatal hyperbilirubinemia, respectively. These concentrations of Bf induced early apoptosis and amoeboid shape in 2DIV microglia, while caused late apoptosis in 16DIV cells, without altering their morphology. CD11b staining increased in both, but more markedly in 2DIV cells. Likewise, the gene expression of HMGB1, a well-known alarmin, as well as HMGB1 and GLT-1–positive cells, were enhanced as compared to long-maturated microglia. The CX3CR1 reduction in 2DIV microglia was opposed to the 16DIV cells and suggests a preferential Bf-induced sickness response in younger cells. In conformity, increased mitochondrial mass and NO were enhanced in 2DIV cells, but unchanged or reduced, respectively, in the 16DIV microglia. However, 100 nM Bf caused iNOS gene overexpression in 2DIV and 16DIV cells. While only arginase 1/IL-1β gene expression levels increased upon 50/100 nM Bf treatment in long-maturated microglia, MHCII/arginase 1/TNF-α/IL-1β/IL-6 (>10-fold) were upregulated in the 2DIV microglia. Remarkably, enhanced inflammatory-associated microRNAs (miR-155/miR-125b/miR-21/miR-146a) and reduced anti-inflammatory miR-124 were found in young microglia by both Bf concentrations, while remained unchanged (miR/21/miR-125b) or decreased (miR-155/miR-146a/miR-124) in aged cells. Altogether, these findings support the neurodevelopmental susceptibilities to UCB-induced neurotoxicity, the most severe disabilities in premature babies, and the involvement of immune-inflammation neonatal microglia processes in poorer outcomes.

An investigation of severe neonatal hyperbilirubinemia in 13 hospitals of Jiangsu Province, China

To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China. The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data. In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates. Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.

Genetic Factors and Delayed TSB Monitoring and Treatment as Risk Factors Associated with Severe Hyperbilirubinemia in Term Neonates Admitted for Phototherapy.

This study aimed to determine whether maternal-fetal blood group isoimmunization, breastfeeding, birth trauma, age when first total serum bilirubin (TSB) was measured, age of admission, and genetic predispositions to hemolysis [due to genetic variants of glucose-6-phosphate dehydrogenase (G6PD) enzyme], and reduced hepatic uptake and/or conjugation of serum bilirubin [due to genetic variants of solute carrier organic anion transporter protein family member 1B1 (SLCO1B1) and uridine diphosphate glucuronosyltransferase family 1 member A1 (UGT1A1)] were significant risk factors associated with severe neonatal hyperbilirubinemia (SNH, TSB ≥ 342µmol/l) in jaundiced term neonates admitted for phototherapy. The inclusion criteria were normal term neonates (gestation ≥ 37 weeks). Parents/care-givers were interviewed to obtain data on demography, clinical problems, feeding practice and age when first TSB was measured. Polymerase chain reaction-restriction fragment length polymorphism method was used to detect common G6PD, UGT1A1 and SLCO1B1 variants on each neonate's dry blood specimens. Of 1121 jaundiced neonates recruited, 232 had SNH. Logistic regression analysis showed that age (in days) when first TSB was measured [adjusted odds ratio (aOR) = 1.395; 95% confidence interval (CI) 1.094-1.779], age (in days) of admission (aOR = 1.127; 95% CI 1.007-1.260) and genetic mutant UGT1A1 promoter A(TA)7TAA (aOR = 4.900; 95% CI 3.103-7.739), UGT1A1 c.686C>A (aOR = 6.095; 95% CI 1.549-23.985), SLCO1B1 c.388G>A (aOR = 1.807; 95% CI 1.242-2.629) and G6PD variants and/or abnormal G6PD screening test (aOR = 2.077; 95% CI 1.025-4.209) were significantly associated with SNH. Genetic predisposition, and delayed measuring first TSB and commencing phototherapy increased risk of SNH.

Neonatal Hyperbilirubinemia: A Retrospective Study

Background: Neonatal Hyperbilirubinemia is a common problem encountered in neonates and often requires admission and treatment.Almost 60% of the term babies and 80% of the preterm babies develop jaundice. East Asians have higher baseline neonatal bilirubin levelsthan whites and are predisposed to the development of severe neonatal hyperbilirubinemia. .Objectives: To determine the important prognostic factors in Neonatal Hyperbilirubinemia and to correlate variables with severity ofpresentation.Material and Methods: A retrospective study was conducted in the Paediatrics Unit 3 of Civil Hospital Karachi from June to November2017 on admitted patients below one month of age with clinically diagnosed jaundice. Total and indirect serum bilirubin levels, and data ofgender, age, birth weight, blood group incompatibility, and breast feeding were obtained.Results: Of 255 cases, 80% were resolved. Phototherapy was the most common method of treatment (in 91.8% of cases). Males slightlyoutnumbered females (1.39:1). 6.3% of jaundiced neonates died; 3.5% developed kernicterus before death. Low birth weight wasobserved in 50.2% of cases while preterm gestation was seen in 39.2% of cases.Conclusion: Important prognostic factors for Hyperbilirubinemia were presence of kernicterus, anemia, age group of the infant, severityof hyperbilirubinemia and the therapy provided.

Knowledge, Attitude and Practice of Mothers to Neonatal Jaundice

Background: Neonatal severe hyperbilirubinemia represents a significant, yet preventable health problem, particularly in low- and middle-income countries (LMICs) 16. Adequate maternal knowledge, early perception, and care seeking behavior are fundamental components of effective management of NNJ 7. A number of studies revealed unexpected moderate knowledge and attitude scores of mothers in most knowledge domains, although the majority of them were illiterate or had low educational attainment.Aim of the study: To assess the knowledge, attitude and practice responses of women during reproductive age toward neonatal jaundice and response correlation to demographic characteristics.Patients and Method: In this hospital based study, in order to evaluate the knowledge background of ladies of reproductive age toward neonatal jaundice regarding causes, clinical manifestation, complications, mode of treatment and other aspects in addition to their attitude regarding conventional and traditional medical approaches and how to behave when facing the problem of neonatal jaundice, a sample of women was selected according to the duration of study.Results: Most of women admit to know 2 symptoms of jaundice, where as small proportion of women knew only one symptom of jaundice, 80.2 % versus 15.8 %, respectively. Four women (4%) know none of symptoms of jaundice. Regarding dangerous symptoms of jaundice, most of women (88.1 %) knew a single symptom and a few of them (4 %) knew 3 symptoms. Positive attitude toward neonatal was seen in significantly high proportion of women enrolled in the study. Positive practice was correlated to older age, higher level of education and higher birth orderConclusion: Knowledge, attitude and behavior of women about various aspects of neonatal jaundice were significantly better in older women in comparison with younger women, and highly significant better with increasing birth order, as well as it was significantly better in employee and with higher level of education.

Neonatal exchange transfusion: Experience in Korea

BackgroundExchange transfusion (ET) is an established, efficacious, and reliable practice for severe neonatal hyperbilirubinemia, hemolytic disease of the newborn, and neonatal sepsis. This study assessed the indications and clinical outcomes of ET performed in a tertiary hospital in Korea. Materials and methodsWe studied 64 ET sessions performed on 23 neonates between March 1999 and March 2018. ET was performed based on estimated double volume exchange transfusion using fresh red blood cells and fresh frozen plasma. Patients’ clinical information, including demographic data and ET indication, and laboratory data were collected pre- and post-ET. ResultsThe most common ET indication was hyperbilirubinemia with hemolytic anemia due to non-ABO maternal blood group discrepancies. In three preterm babies, ETs were performed for severe anemia, leukocytosis, and hyperkalemia cases. Before ET, the patients showed slightly high WBC counts, low hemoglobin levels, and low platelet counts. After ET, blood examination revealed normal WBC counts, increased hemoglobin levels, and decreased platelet counts (all P < 0.001). Bilirubin levels decreased immediately after ET (P < 0.001). Electrolyte and C-reactive protein levels showed no significant changes after ETs. Adverse events occurred in 11 (47.8 %) patients; the most common were hypoxemia and hypotension. One infant experienced cardiorespiratory arrest due to hypercalcemia and was successfully resuscitated. No one died within 24 h of ET. However, five infants showed hyperbilirubinemia aggravation. ConclusionsET is an effective treatment modality for leukocytosis and hyperbilirubinemia with low mortality but involves common adverse events post-ET. This report provides an overview of current ET practices in Korea.

Serum Magnesium Levels in Neonatal Jaundice: Is There any Correlation Between Hypermagnesemia and Moderate to Severe Hyperbilirubinemia in Term Newborns?

Background: Neonatal jaundice is a common major problem; on the other hand, it is suggested that there is a correlation between plasma magnesium concentrations and hyperbilirubinemia during the neonatal period. Objectives: The study aims to validate a previously reported risk index for predicting the magnesium level of plasma for moderate to severe hyperbilirubinemia in infant neonates. Methods: A cross-sectional correlation study was performed on 93 term newborns with indirect hyperbilirubinemia admitted in neonatology unit of a children hospital and plasma magnesium level of moderate to severe Neonatal hyperbilirubinemia were determined, and statistical analysis was performed. Results: Authors did not find any statistically meaningful positive or negative correlation between plasma Mg level and bilirubin in patients studied; however, comparison of Mg level in two groups of severe and moderate hyperbilirubinemia showed decreased dispersion of medium Mg level in the severe group. Conclusions: Serum magnesium concentration is not useful in anticipation of which newborn infant will develop hyperbilirubinemia.

Glucose-6- Phosphate Dehydrogenase Activity in Newborn in Jos: A Necessary Evaluation for Icteric Neonates

Red blood cell glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme with the major role of meeting the cellular need for reductive biosynthesis and maintenance of redox status. G6PD deficiency is a common inherited enzyme defect associated with severe neonatal hyperbilirubinaemia that can result in permanent neurologic damage or death. This study was aimed at estimating the level of G6PD activity among icteric neonates to assess its usefulness in the evaluation of icteric neonates in Jos. One hundred and fifty icteric neonates (92 males and 58 females) whose parents consented were consecutively enrolled as they presented at the Special Care Baby Units (SCBU) of the Jos University Teaching Hospital (JUTH), Bingham University Teaching Hospital (BhUTH), and the Plateau State Specialist Hospital (PSSH), Jos. These subjects had their G6PD activity levels assayed using the Pointe Quantitative Diagnostic Kit (USA) while other relevant clinical information was obtained using a questionnaire. G6PD activity of the icteric neonates ranged between 0.54 and 24.18 IU/gHb with a mean of 8.02 ± 4.87 IU/gHb. Sixty-one (40.7 %), comprising 45 males and 16 female neonates were G6PD deficient with mean G6PD activity of 3.79 ± 1.37 IU/gHb while eighty-nine (59.3%) were G6PD normal with a mean G6PD activity of 10.92 ± 4.24 IU/gHb. G6PD activity in icteric neonates in Jos varies widely with a relatively high proportion of these neonates being G6PD deficient. Determination of G6PD activity in icteric neonates should therefore form an important evaluation tool for identification and intervention in those with the deficiency.

Glucose-6- Phosphate Dehydrogenase Activity in Newborn in Jos: A Necessary Evaluation for Icteric Neonates

Red blood cell glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme with the major role of meeting the cellular need for reductive biosynthesis and maintenance of redox status. G6PD deficiency is a common inherited enzyme defect associated with severe neonatal hyperbilirubinaemia that can result in permanent neurologic damage or death. This study was aimed at estimating the level of G6PD activity among icteric neonates to assess its usefulness in the evaluation of icteric neonates in Jos. One hundred and fifty icteric neonates (92 males and 58 females) whose parents consented were consecutively enrolled as they presented at the Special Care Baby Units (SCBU) of the Jos University Teaching Hospital (JUTH), Bingham University Teaching Hospital (BhUTH), and the Plateau State Specialist Hospital (PSSH), Jos. These subjects had their G6PD activity levels assayed using the Pointe Quantitative Diagnostic Kit (USA) while other relevant clinical information was obtained using a questionnaire. G6PD activity of the icteric neonates ranged between 0.54 and 24.18 IU/gHb with a mean of 8.02 ± 4.87 IU/gHb. Sixty-one (40.7 %), comprising 45 males and 16 female neonates were G6PD deficient with mean G6PD activity of 3.79 ± 1.37 IU/gHb while eighty-nine (59.3%) were G6PD normal with a mean G6PD activity of 10.92 ± 4.24 IU/gHb. G6PD activity in icteric neonates in Jos varies widely with a relatively high proportion of these neonates being G6PD deficient. Determination of G6PD activity in icteric neonates should therefore form an important evaluation tool for identification and intervention in those with the deficiency.

Glucose-6- Phosphate Dehydrogenase Activity in Newborn in Jos: A Necessary Evaluation for Icteric Neonates

Red blood cell glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme with the major role of meeting the cellular need for reductive biosynthesis and maintenance of redox status. G6PD deficiency is a common inherited enzyme defect associated with severe neonatal hyperbilirubinaemia that can result in permanent neurologic damage or death. This study was aimed at estimating the level of G6PD activity among icteric neonates to assess its usefulness in the evaluation of icteric neonates in Jos. One hundred and fifty icteric neonates (92 males and 58 females) whose parents consented were consecutively enrolled as they presented at the Special Care Baby Units (SCBU) of the Jos University Teaching Hospital (JUTH), Bingham University Teaching Hospital (BhUTH), and the Plateau State Specialist Hospital (PSSH), Jos. These subjects had their G6PD activity levels assayed using the Pointe Quantitative Diagnostic Kit (USA) while other relevant clinical information was obtained using a questionnaire. G6PD activity of the icteric neonates ranged between 0.54 and 24.18 IU/gHb with a mean of 8.02 ± 4.87 IU/gHb. Sixty-one (40.7 %), comprising 45 males and 16 female neonates were G6PD deficient with mean G6PD activity of 3.79 ± 1.37 IU/gHb while eighty-nine (59.3%) were G6PD normal with a mean G6PD activity of 10.92 ± 4.24 IU/gHb. G6PD activity in icteric neonates in Jos varies widely with a relatively high proportion of these neonates being G6PD deficient. Determination of G6PD activity in icteric neonates should therefore form an important evaluation tool for identification and intervention in those with the deficiency.

Glucose-6- Phosphate Dehydrogenase Activity in Newborn in Jos: A Necessary Evaluation for Icteric Neonates

Red blood cell glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme with the major role of meeting the cellular need for reductive biosynthesis and maintenance of redox status. G6PD deficiency is a common inherited enzyme defect associated with severe neonatal hyperbilirubinaemia that can result in permanent neurologic damage or death. This study was aimed at estimating the level of G6PD activity among icteric neonates to assess its usefulness in the evaluation of icteric neonates in Jos. One hundred and fifty icteric neonates (92 males and 58 females) whose parents consented were consecutively enrolled as they presented at the Special Care Baby Units (SCBU) of the Jos University Teaching Hospital (JUTH), Bingham University Teaching Hospital (BhUTH), and the Plateau State Specialist Hospital (PSSH), Jos. These subjects had their G6PD activity levels assayed using the Pointe Quantitative Diagnostic Kit (USA) while other relevant clinical information was obtained using a questionnaire. G6PD activity of the icteric neonates ranged between 0.54 and 24.18 IU/gHb with a mean of 8.02 ± 4.87 IU/gHb. Sixty-one (40.7 %), comprising 45 males and 16 female neonates were G6PD deficient with mean G6PD activity of 3.79 ± 1.37 IU/gHb while eighty-nine (59.3%) were G6PD normal with a mean G6PD activity of 10.92 ± 4.24 IU/gHb. G6PD activity in icteric neonates in Jos varies widely with a relatively high proportion of these neonates being G6PD deficient. Determination of G6PD activity in icteric neonates should therefore form an important evaluation tool for identification and intervention in those with the deficiency.

Glucose-6- Phosphate Dehydrogenase Activity in Newborn in Jos: A Necessary Evaluation for Icteric Neonates

Red blood cell glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme with the major role of meeting the cellular need for reductive biosynthesis and maintenance of redox status. G6PD deficiency is a common inherited enzyme defect associated with severe neonatal hyperbilirubinaemia that can result in permanent neurologic damage or death. This study was aimed at estimating the level of G6PD activity among icteric neonates to assess its usefulness in the evaluation of icteric neonates in Jos. One hundred and fifty icteric neonates (92 males and 58 females) whose parents consented were consecutively enrolled as they presented at the Special Care Baby Units (SCBU) of the Jos University Teaching Hospital (JUTH), Bingham University Teaching Hospital (BhUTH), and the Plateau State Specialist Hospital (PSSH), Jos. These subjects had their G6PD activity levels assayed using the Pointe Quantitative Diagnostic Kit (USA) while other relevant clinical information was obtained using a questionnaire. G6PD activity of the icteric neonates ranged between 0.54 and 24.18 IU/gHb with a mean of 8.02 ± 4.87 IU/gHb. Sixty-one (40.7 %), comprising 45 males and 16 female neonates were G6PD deficient with mean G6PD activity of 3.79 ± 1.37 IU/gHb while eighty-nine (59.3%) were G6PD normal with a mean G6PD activity of 10.92 ± 4.24 IU/gHb. G6PD activity in icteric neonates in Jos varies widely with a relatively high proportion of these neonates being G6PD deficient. Determination of G6PD activity in icteric neonates should therefore form an important evaluation tool for identification and intervention in those with the deficiency.

G6PD genetic variations in neonatal Hyperbilirubinemia in Indonesian Deutromalay population

BackgroundNeonatal jaundice is a common finding in newborns in Asia, including Indonesia. In some cases, the serum total bilirubin levels exceeds the 95th percentile for hours of life (neonatal hyperbilirubinemia). Severe neonatal hyperbilirubinemia (NH) could lead to kernicterus and neonatal death. Glucose-6-Phosphage Dehydrogenase (G6PD) genetic variations and deficiency have been reported in several studies to be associated with NH. This study aimed to analyze the G6PD genetic variations and its activity in neonates with and without hyperbilirubinemia in the Deutromalay Indonesian population.MethodsDeoxyribose Nucleic Acid (DNA) was isolated from peripheral blood of 116 and 115 healthy term neonates with and without hyperbilirubinemia. All infants underwent the following laboratory examinations: routine hematologic evaluation, Coombs test, G6PD activity measurement using the Randox kit method, and serum total bilirubin level. All exons of the G6PD gene were targeted for deep sequencing using MiSeq (Illumina). An association study of G6PD polymorphisms with NH was performed using PLINK.ResultsThe prevalence of G6PD deficiency in neonates with and without hyperbilirubinemia in Indonesian Deutromalay population were 1.72% (95% Confidence Interval (CI): 0.6–4.1%) and 1.74% (95% CI: 0.7–4.1%), respectively. The most common G6PD polymorphisms, i.e. rs1050757/c.* + 357A > G, rs2230037/c.1311C > T, and rs2071429/c.1365-13 T/IVS11, were identified. However, none of those polymorphisms and their haplotype were associated with NH (p > 0.05, Odds Ratio (OR) ~1.00). The prevalence of G6PD mutations in neonates with and without hyperbilirubinemia were 6.8% (95% CI: 2.3–11.5%) and 6.9% (95% CI: 2.3–11.6%), respectively. The most frequently identified G6PD mutation was the Viangchan variant (p.V291 M), which was followed by the Canton (p.R459L) and Vanua Lava (p.L128P) variants. Two novel mutations were identified both in case (p.V369A, p.I167F) and control (p.L474=, p.I36T) groups.ConclusionThe prevalence of G6PD deficiency is low in neonates with or without hyperbilirubinemia in Deutromalay Indonesian population. The majority of G6PD mutations identified among Indonesian Deutromalay population in this study are Viangchan, Canton and Vanua Lava variants.

The spectrum of bilirubin neurotoxicity in term and near-term babies with hyperbilirubinemia: Does outcome improve with time?

BackgroundWhile neonatal jaundice is generally a common benign condition; severe hyperbilirubinemia has a devastating potential for brain injury. AimTo detect the impact of severe neonatal hyperbilirubinemia on motor and mental development and its progress over time in the first year of life using the Bayley scales of infant development (BSID) II. Study design and patients177 term/near-term infants admitted for neonatal hyperbilirubinemia to the NICU of Cairo University Children's Hospital were enrolled. Clinical examination, BIND score and laboratory tests were performed at admission. Neurodevelopmental assessment using BSIDΙΙ was performed at 3 months for 147/177 neonates, and at 6 months and 12 months for 139/177 neonates. Auditory brainstem evoked potential was recorded at 3 months of age and repeated if abnormal. Outcome measuresPsychomotor (PDI) and mental developmental indices (MDI) using BSIDII. Auditory impairment using Auditory Brainstem Response (ABR). ResultsTSB levels ranged from 10 to 63 mg/dL (179.6–1077 μmol/L) with a mean of 25.52 ± 6.5 mg/dL (436 ± 112.9 μmol/L) and BIND scores ranged from 0 to 7. By one year of age, 19/139 patients were affected; 8 had classic kernicterus, 3 had isolated auditory impairment, 1 had severe motor and mild mental delay and 7 had mild motor delay. TSB level and BIND score had positive correlation with auditory impairment and lower scores for PDI (which improved with time) and MDI (which remained stationary). Duration of exposure to hyperbilirubinemia negatively affected neurodevelopmental scores. ConclusionThe impact of severe hyperbilirubinemia is mainly on motor and auditory impairment. Mild mental delay was detected by BSIDII in few patients. Neurodevelopmental outcome improves over time.

A comparative study to determine intermittent versus continuous phototherapy for reducing neonatal hyperbilirubinemia at tertiary care hospital in Chennai, Tamil Nadu, India

Background: Phototherapy is safe and effective in neonatal hyperbilirubinemia. Despite its worldwide application, questions regarding methods of optimizing efficacy remain unanswered, turning the infant is believed to be one of the methods to improve. Severe neonatal hyperbilirubinemia is associated with kernicterus, condition characterized by athetoid spasticity, gaze and visual abnormalities, and sensory-neural hearing loss. It may also be associated with mental retardation. Aim of this study was conducted to compare the efficacy of intermittent with continuous phototherapy.Methods: Study was conducted in 100 neonates from February 2018 to July 2018 in Sree Balaji medical college and hospital. Inclusion criteria were weight &gt;2000 grams, absence of other concomitant diseases, and hyperbilirubinemia not requiring exchange transfusion. The neonates were randomly divided into two groups. Continuous phototherapy group received phototherapy on and off for 2 hours and half an hour respectively and the intermittent phototherapy group on and then off for one hour. Serum total bilirubin levels were measured in every 36 hours.Results: Mean age of the patients was 3.89±1.83(p=.91) days, mean baseline bilirubin was 17.56mg/dl±1.42 (p=0.36), while the mean follow-up bilirubin was 12.85mg/dl±1.65 (p=.95), and the mean difference between the baseline and follow-up bilirubin was 4.7 mg/dl±1.19 (p=.32). For group A and B babies, the mean difference between the baseline and follow-up bilirubin was 4.78 mg/dl±1.20 (p=.32) and 4.63mg/dl±1.18(p=0.32) respectively. The difference between the mean age, mean baseline bilirubin, mean follow-up bilirubin, and the mean decrease in bilirubin for both the groups was statistically not significant.Conclusions: Intermittent and continuous phototherapies were found to be equally effective for reducing neonatal hyperbilirubinemia.