Severe Neonatal Jaundice Research Articles

Synergistic effects of polymer adsorbents on the performance of bilirubin hemoperfusion

Neonatal hyperbilirubinemia (jaundice) is a common disease with high incidence. Currently, the clinical inefficiency of adult bilirubin hemoperfusion medical adsorbent is a major technical barrier for the application of hemoperfusion treatment to rescue the severe neonatal jaundice. Based on the well-known principle of synergistic effects, a series of customized bilirubin polymeric compounds, comprised of one or more of the following components (glycidyl methacrylate, sodium acrylate, methacrylic acid isooctyl, hexamethylene diamine, albumin), were designed and fabricated based on molecular design. Their adsorption performances upon bilirubin were investigated and compared under the same conditions, and the compound with the highest adsorption performance was then subject to preliliminary safety assessments and compared with a commercial one (BS330). The results showed that positive synergistic effects appeared on the adsorption performance to adsorb bilirubin based on this study, and the one comprised of glycidyl methacrylate+sodium acrylate+methacrylic acid isoocty+hexamethylene diamine+albumin possesses the highest adsorption performance as well as outome clinical acceptable medical safety assessments, and its adsorption efficiency was up to 46% while the commerical one’s was about 26% under the same conditions. This study sheds a new light on how to design and develop hemoperfusion bilirubin adsorbents with good overall clinical performance, as well as providing a novel idea and experimental referrences for future related topics.

Fluid supplementation in term neonates with severe hyperbilirubinemia: a randomized controlled trial study

Background: Severe neonatal jaundice can cause fatality and serious permanent effect, called kernicterus, in which the brain stem nuclei and basal ganglia are damaged. We are encouraged to work on efficacy of fluid supplementation in addition to photo therapy as a measure to reduce bilirubin level more efficiently.Methods: A randomized control trial study was conducted in Department of Paediatric Medicine, Neonatal Unit, R.G. Kar Medical College & Hospital, Kolkata, from April 2011 to March 2012. A total 100 term neonates presenting with severe non-hemolytic hyperbilirubinemia (>18 mg/dl to <25 mg/dl) were enrolled as study population. The study subjects were divided into two equal groups, study group and control group by randomization. The study group was given IV fluid supplementation in addition to photo therapy. Total serum bilirubin (TSB) level assessed periodically and results compared with control group.Results: The study results reveal a statistically significant association between the percent fall in TSB at 12 (Chi2= 7.18, p=0.000) and 24 hours (Chi2=10.69, p=0.000) in the intervention arm compared to the control group.Conclusions: Fluid supplementation along with double surface phototherapy in term neonates presenting with severe hyperbilirubinemia decreases the rate of exchange transfusion and duration of phototherapy.

Editor's Note MS#20162317 El Houchi et al - Neonatal jaundice: more than a number

Severe neonatal jaundice (unconjugated hyperbilirubinemia) may cause permanent brain injury and hearing loss in infants worldwide, including those born in developed countries. Bilirubin neurotoxicity is due to the effects of unbound unconjugated bilirubin in the central nervous system. The risk of kernicterus depends not only on the total serum bilirubin, but also factors such as the bilirubin-albumin binding capacity, prematurity, and other neonatal illnesses. In this volume of The Journal, El Houchi et al describe their use of the Bilirubin Induced Neurologic Dysfunction (BIND) Score to evaluate neurotoxicity in infants with severe hyperbilirubinemia, with the hope of improving our ability to detect infants who require timely exchange transfusions. The BIND score evaluates three aspects of the physical examination including mental status,muscle tone and cry pattern on a 0- to 3-point rating scale. In 220 near-term and full-terminfants admitted to their hospital with severe hyperbilirubinemia, El Houchi et al noted that regardless of the total serum bilirubin, infants with BIND scores of 3-4 or more were at increased risk for persistent neurologic abnormalities at 3-5 months of age. The etiology of jaundice for the infants in this study was not described, and the gestational age of the infants was not precisely known. These two factors suggest that further replication of these findings is needed to understand the usefulness of the BIND score across a variety of at-risk populations. However, in this study, El Houchi et al have shown that serial neurologic examinations are an important and cost-effective adjunct to the total serum bilirubin in the evaluation and management of jaundice that should be useful to pediatricians worldwide. Article page 51 ▶ Prediction of 3- to 5-Month Outcomes from Signs of Acute Bilirubin Toxicity in Newborn InfantsThe Journal of PediatricsVol. 183PreviewTo evaluate the ability of the bilirubin-induced neurologic dysfunction (BIND) score to predict residual neurologic and auditory disability and to document the relationship of BIND score to total serum bilirubin (TSB) concentration. Full-Text PDF

Common Neonatal Emergencies in Zaria

Background: Neonatal mortality remains high and currently accounts for about 54 and 29% of infant and under-five mortality rates, respectively, in Nigeria. Newborn deaths usually result from varying causes, some of which are neonatal emergencies. The study was conducted to document neonatal emergencies and their relative contributions to newborn death. Patients: and Methods A retrospective review of emergency cases admitted into the Special Care Baby Unit (SCBU) of Ahmadu Bello University Teaching Hospital, Zaria in Northwestern Nigeria over an 18-month period (January 2013–June 2014) detailing information on age, sex, place of delivery, birth weight and outcome. Results: About 70% (700/997) of the admissions were the emergency cases of which severe neonatal jaundice, sepsis and perinatal asphyxia accounted for 96%. A mortality of 9.8% was recorded with the case fatality rates of 5, 11, 18.8 and 25% for severe neonatal jaundice, neonatal sepsis, perinatal asphyxia and neonatal tetanus, respectively. Overall, neonatal emergencies accounted for 68% of neonatal mortality in the SCBU. Outborns were 1.4 times more likely to die from these emergencies compared to inborns. Conclusion: Neonatal emergencies constitute a major proportion of admissions and deaths in Zaria. Efforts should be directed at the prevention of the three major emergencies (neonatal jaundice, sepsis, perinatal asphyxia) identified and provision of available, accessible and affordable neonatal healthcare services.

Generation and Functional Analysis of Congenital Dyserythropoietic Anemia (CDA) Patient-Specific Induced Pluripotent Stem Cells

The congenital dyserythropoietic anemias (CDAs) are inherited red blood cell disorders representing ineffective erythropoiesis and dyserythropoietic changes in the bone marrow. We recently diagnosed a female patient with undiagnosed congenital anemia as type IV CDA caused by a heterozygous missense mutation of the erythroid-specific transcription factor, KLF1; c.973G>A, p. E325K. Although the mutation has been reported in a male patient characterized as hydrops fetalis, severe neonatal jaundice and transfusion-dependent anemia (Arnaud L et al., Am J Hum Genet, 2010), the proband showed relatively mild phenotype showing moderate dyserythropoietic anemia. In order to investigate the pathological significance of mutant KLF1 during erythroid cell development and differentiation, we generated induced pluripotent stem cells (iPSCs) from peripheral blood of the CDA patient (CDA-iPSCs), and utilized these cells to establish in vitro CDA model for better understanding of its molecular basis. CDA-iPSCs were generated from T lymphocytes in peripheral blood mononuclear cells. Hematopoietic precursors were induced from CDA-iPSCs by embryoid bodies formation. CD34(+) precursor cells were isolated and further cultured in liquid culture with cytokine cocktail (erythropoietin (EPO), interleukin (IL)-3, and stem cell factor (SCF)) for additional 1-3 weeks. Flow cytometric analysis showed that CDA-iPSC-derived cells contained significantly lower percentage of CD235a(+)/CD71(+) erythroid lineage cells than the cells derived from control iPSCs, and lack expression of the adhesion molecule CD44, which is known to be down regulated in peripheral blood erythroid cells of CDA patients (Arnaud L et al., Am J Hum Genet, 2010). In addition, colony-forming unit (CFU) assay indicated that CD34(+) fraction derived from CDA-iPSCs contained a lower number of erythroid colony-forming cells and the most of the cells in these colonies are morphologically abnormal, in comparison with control iPSCs. We next evaluated mRNA expression levels of fetal (HBG1 and HBG2), embryonic (HBE), and adult (HBB) globins, resulting that HBG1 and HBG2 were significantly increased in CDA-iPSCs-derived erythroid lineage cells, whereas HBE showed no significant change and HBB was decreased in CDA-iPSCs-derived erythroid lineage cells. However, BCL11A, one of the target genes of KLF1 and also known as a suppressor of HBG1 and HBG2, was not decreased in the presence KLF1 gene mutation, indicating that elevated HBG1 and HBG2 in CDA-iPSCs-derived erythroid cells was mediated by other mechanism like Leukemia/lymphoma Related Factor (LRF; Masuda T et al., Science, 2016). Here we suggest that our model provides insights on understanding the mechanisms of type IV CDA and the effect of KLF1 gene mutation on clinical phenotype and it would be a useful tool for drug screening and identification of novel biomarker for the rare congenital anemia.Figure 1 Induction of erythroid differentiation from human iPSCsFigure 2 Flow cytometric analysis of erythroid cells induced from CDA-iPSCsFigure 3 RT-PCR analysis of erythroid cells induced from CDA-iPSCs DisclosuresKohara:SBI Pharmaceuticals: Research Funding. Miyamoto:SBI Pharmaceuticals: Research Funding. Tani:Oncolys BioPharma: Equity Ownership; SymBio Pharmaceuticals: Consultancy, Equity Ownership; SBI Pharmaceuticals: Research Funding; Shinnihonseiyaku: Research Funding.

A Survey of Practice and Knowledge of Refugee and Migrant Pregnant Mothers Surrounding Neonatal Jaundice on the Thailand-Myanmar Border.

Background: In populations with a high prevalence of glucose-6-phosphate dehydrogenase deficiency, practices that can induce haemolysis need to be identified to raise awareness of preventable risks. The aim of this survey was to determine the proportion of prospective mothers using haemolytic agents and their knowledge and practice surrounding neonatal jaundice.Methods: Pregnant mothers were invited to participate in a cross-sectional survey conducted at Shoklo Malaria Research Unit on the Thailand–Myanmar border.Results: From 12 April 2015 to 12 June 2015, 522 pregnant women completed the survey. Mothball use in the household was reported by 41.4% (216 of 522) of prospective mothers and menthol containing products on baby skin by 46.7% (244 of 522).Conclusion: Just over 40% of the households reported use of naphthalene-containing mothballs. Future health promotion activities that focus on reducing naphthalene mothball and menthol-containing products use have the potential to reduce rates of severe neonatal jaundice in this population.

Mothers′ perception toward neonatal jaundice in Kafr El-batanoon village, Menoufia, Egypt

Objectives The aim of this study was to evaluate the knowledge, attitude, and practice of the mothers toward neonatal jaundice (NNJ). Background NNJ is a significant cause of neonatal morbidity worldwide and accounts for 75% of hospital readmissions in the first week of life. Severe NNJ can lead to irreversible brain damage or even death in otherwise healthy newborns. Because of early discharge of mothers from the hospitals, the responsibility of mothers in recognizing jaundice has increased. Mothers therefore play a vital role in the early identification and prevention of complication. Materials and methods This cross-sectional study was carried out on 265 mothers who attended Kafr El-batanoon primary health care for antenatal care or for their babies' vaccinations. The mothers were interviewed using a predesigned questionnaire to assess their knowledge, practice, and attitude toward NNJ. Data were analyzed using SPSS version 13. Results The results showed that only 18.9% of mothers had good knowledge about NNJ. Mother's knowledge was significantly influenced by their level of education, age, parity, and previous history. About 48.0% of participants had good attitude toward NNJ and its management. However, 95.8% of mothers expressed their willingness to seek medical advice if their babies develop NNJ; only 25.3% had a good practice and stated that they would seek medical attention within the first 24 h of jaundice, which was significantly influenced by their age, parity, occupation, and history. Conclusion Participants attending Kafr El-batanoon Unit had adequate idea about recognition of NNJ. However, their knowledge of causes, danger signs of complications, complications, and treatment were poor, with common misconceptions. Their attitude toward the management of NNJ was apparently positive, whereas practice was poor. Knowledge and practice of mothers were significantly influenced by their age, parity, and history of NNJ in previous babies. Therefore, it is recommended that healthcare providers should give more health education on NNJ to the mothers during antenatal care visits.

Late onset severe anemia due to rhesus isoimmunization

Rh isoimmunization usually presents with severe neonatal jaundice associated with anemia needing exchange transfusion and phototherapy. Sometimes babies who have mild or no symptoms at birth may present later with severe hemolytic anemia. In this case report we have described a newborn infant who had mild jaundice initially and presented with severe anemia in the fourth week of life. This case signifies the importance of regular follow up and close monitoring of Rh isoimmunized infants for the first two months for delayed onset anemia.

Alu-Element Insertion in Pklr Gene As a Novel Cause of Severe Hereditary Nonspherocytic Hemolytic Anemia

Red blood cell pyruvate kinase deficiency (PKD) is the most frequent enzyme abnormality of the glycolytic pathway and the most common cause of hereditary nonspherocytic hemolytic anemia. Its incidence has been estimated to be 1 in 20,000, especially in regions where consanguinity is common. It is inherited in autosomal recessive manner occurring as result of homozygous or compound heterozygous mutations affecting both alleles in PKLR gene. Over 200 mutations have been described in patients with PKD causing various severity of hemolysis. Most cases are due to missense mutations, but small deletions, insertions, splice site alterations, frame shifts, disruption of erythroid specific promoters, and nonsense mutations have been reported.Alu elements are the most abundant mobile DNA sequences in the human genome, contributing to almost 11% of its mass. These mobile elements have contributed significantly to evolution and human diversity by causing gene rearrangements. Alu insertions particularly have been associated with a number of human diseases either by disrupting a coding region or a splice signal. In this abstract, we report an Alu-element insertion in the coding region of PKLR gene as a novel cause of PKD causing severe hereditary nonspherocytic hemolytic anemia.The proband was a 16-month-old middle eastern male born to consanguineous parents. He was diagnosed with severe chronic hemolytic anemia and neonatal jaundice requiring regular blood transfusion since birth. There were no known family members with anemia requiring transfusions. The patient's RBC phenotypic analysis was challenging since most of the circulating RBCs were donor cells. Using a Next-Generation sequencing panel for 27 hemolytic anemia associated genes, we identified and characterized a novel homozygous insertional mutation in exon 6 of PKLR gene along with heterozygosity for ANK1 c.1404+15C>T variant. The mutation in exon 6 was identified as Alu element insertion. The inserted Alu element (~370 bp in size), belonging to the youngest Yb8 subfamily, disrupts the reading frame at isoleucine 314 in exon 6 of PKLR gene, leading to a premature stop codon within the inserted sequence. Quantitative reverse transcription-PCR (qRT-PCR) in the patient's reticulocyte RNA using primers for the sequence before the Alu insertion revealed a transcript present but decreased by 80% compared to the average of controls' reticulocyte RNA. This truncated transcript even if translated is expected to cause severe enzyme deficiency.Both parents had a normal hemoglobin level with mild reticulocytosis. The mother had a PK enzyme activity of 4.5 units/g Hb (normal range 6.7-14.3 units/g Hb) indicating that she is heterozygous for PKD. Paternal PK activity level was not determined due to insufficient sample. Carrier testing for mutation in PKLR gene in both parents is currently in process at the time of this submission.The variant in ANK1 gene was predicted to be damaging by affecting the splice site in ankyrin gene. However the father was also heterozygous for this variant and his ektacytometry was normal suggesting a benign nature of ANK1 c.1404+15C>T.This case represents, to our knowledge, the first report of a pathogenic PKLR mutation due to an Alu element insertion and demonstrates a novel mechanism causing severe hereditary nonspherocytic hemolytic anemia. This report also illustrates the challenge of diagnosing congenital hemolytic anemias in chronically transfused patients. The patients often present with a complex clinical picture and ambiguous laboratory findings and may have several potentially damaging genetics variants identified by next generation sequencing. A critical evaluation of the clinical symptoms, laboratory findings and genetic data from other family members and bioinformatics analysis are required to clarify the contribution of these variants and to arrive at an accurate diagnosis, which will guide the institution of targeted interventions and appropriate genetic counseling. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cord Blood Alkaline Phosphatase as an Indicator of Neonatal Jaundice.

Background:Management of hyperbilirubinemia remains a challenge for neonatal medicine because of the risk of neurological complications related to the toxicity of severe hyperbilirubinemia.Objectives:The purpose of this study was to examine the validity of cord blood alkaline phosphatase level for predicting neonatal hyperbilirubinemia.Patients and Methods:Between October and December 2013 a total of 102 healthy term infants born to healthy mothers were studied. Cord blood samples were collected for measurement of alkaline Phosphatase levels immediately after birth. Neonates were followed-up for the emergence of jaundice. Newborns with clinical jaundice were recalled and serum bilirubin levels measured. Appropriate treatment based on serum bilirubin level was performed. Alkaline phosphatase levels between the non-jaundiced and jaundiced treated neonates were compared.Results:The incidence of severe jaundice that required treatment among followed-up neonates was 9.8%. The mean alkaline phosphatase level was 309.09 ± 82.51 IU/L in the non-jaundiced group and 367.80 ± 73.82 IU/L in the severely jaundiced group (P = 0.040). The cutoff value of 314 IU/L was associated with sensitivity 80% and specificity 63% for predicting neonatal hyperbilirubinemia requiring treatment.Conclusions:The cord blood alkaline phosphatase level can be used as a predictor of severe neonatal jaundice.

Umbilical Cord Bilirubin Level as a Predictive Indicator of Neonatal Jaundice

BACKGROUND AND OBJECTIVE: Neonatal jaundice is a major problem among infants in the first weeks of life. Research on several indicators of severe neonatal jaundice including alpha-fetoprotein and umbilical cord bilirubin level has indicated contradictory results. Therefore, the aim of the present study was to evaluate the significance of umbilical cord bilirubin level as a predictive indicator of severe neonatal jaundice. METHODS: This prospective, cross-sectional study was performed on 102 healthy infants, born to healthy mothers at Babol Clinic Hospital, Babol, Iran. After birth, 2 cc blood samples were obtained from the umbilical cord and the bilirubin level was measured in the hospital laboratory. The infants were followed-up after hospital discharge in terms of jaundice presentations. In case jaundice was diagnosed in infants, they were compared in treated and untreated groups. FINDINGS: Clinical jaundice was not detected in 54 cases (52.94%). Overall, 48 neonates (47.05%) suffered from clinical jaundice and 10 cases (8.9%) presented with severe jaundice, requiring treatment based on the criteria proposed by the American Academy of Pediatrics (AAP). The mean umbilical cord bilirubin level was 1.82±0.42 mg/dl in the untreated group and 2.36±0.56 mg/dl in the treated group (P=0.000). The area under the ROC curve for umbilical cord bilirubin level was 0.722 in the treated group, based on the AAP criteria. The cut-off point of 2 mg/dl showed 80% sensitivity and 73% specificity in predicting severe jaundice (requiring treatment), based on the AAP criteria. CONCLUSION: As the results indicated, measurement of umbilical cord bilirubin level and determination of a suitable cut-off point could be valuable in predicting severe jaundice in newborns.

Glucose-6-phosphate dehydrogenase deficiency in Japan

In the past 10 years, we have diagnosed congenital hemolytic anemia in 294 patients, approximately 33% of whom were found to have glucose-6-phosphate dehydrogenase (G6PD) deficiency. It is becoming more common for Japanese to marry people of other ethnic origins, such that G6PD deficiency is becoming more prevalent in Japan. Japanese G6PD deficiency tends to be diagnosed in the neonatal period due to severe jaundice, while G6PD-deficient patients with foreign ancestors tend to be diagnosed at the onset of an acute hemolytic crisis before the age of six. It is difficult to predict the clinical course of each patient by G6PD activity, reduced glutathione content, or the presence/absence of severe neonatal jaundice. We propose that both neonatal G6PD screening and systematic analyses of G6PD gene mutations may be useful for personalized management of patients with G6PD-deficient hemolytic anemia.

Epilepsy in Nigerian children with cerebral palsy in Enugu

Cerebral palsy (CP) and epilepsy are the two most common chronic neurological diseases encountered by pediatric neurologists in Nigeria. Though epilepsy is commonly encountered among children with CP, there are very few studies on the prevalence of epilepsy among Nigerian children with CP and factors that are associated with this. This study was undertaken to determine the prevalence of epilepsy among children with CP and elucidate the factors that influences this. It was a retrospective analysis of the case files of consecutive children that presented at the pediatric neurology unit of university of Nigeria teaching hospital, Enugu with a diagnosis of CP from 1st January 2007 to 31st December 2009. CP occurred in 20.8% of the children that presented at the pediatric neurology clinic. Spastic quadriplegic CP (55.5%) was the predominant type of CP encountered and the common causes were severe birth asphyxia (48.2%) and neonatal jaundice (20.1%). Epilepsy was observed in 37.8% of the children with CP. The common types of epileptic seizures observed were generalized tonic clonic seizures (38.7%), complex partial seizures (19.4%) and mixed epilepsy (19.4%). Infantile spasms and mixed epilepsy were observed predominantly among children with quadriplegic CP while those with hemiplegic CP almost exclusively presented with partial seizures (P = 0.01). We conclude that epilepsy is common among children with CP and severe seizure types like infantile spasm and mixed epilepsies are more common among quadriplegic CP.

Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice.

Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced encephalopathy and eventually death by kernicterus. Despite extensive studies, the molecular and cellular mechanisms of bilirubin toxicity are still poorly defined. To fill this gap, we investigated the molecular processes underlying neuronal injury in a mouse model of severe neonatal jaundice, which develops hyperbilirubinemia as a consequence of a null mutation in the Ugt1 gene. These mutant mice show cerebellar abnormalities and hypoplasia, neuronal cell death and die shortly after birth because of bilirubin neurotoxicity. To identify protein changes associated with bilirubin-induced cell death, we performed proteomic analysis of cerebella from Ugt1 mutant and wild-type mice. Proteomic data pointed-out to oxidoreductase activities or antioxidant processes as important intracellular mechanisms altered during bilirubin-induced neurotoxicity. In particular, they revealed that down-representation of DJ-1, superoxide dismutase, peroxiredoxins 2 and 6 was associated with hyperbilirubinemia in the cerebellum of mutant mice. Interestingly, the reduction in protein levels seems to result from post-translational mechanisms because we did not detect significant quantitative differences in the corresponding mRNAs. We also observed an increase in neuro-specific enolase 2 both in the cerebellum and in the serum of mutant mice, supporting its potential use as a biomarker of bilirubin-induced neurological damage. In conclusion, our data show that different protective mechanisms fail to contrast oxidative burst in bilirubin-affected brain regions, ultimately leading to neurodegeneration.

A modified Bilirubin-induced neurologic dysfunction (BIND-M) algorithm is useful in evaluating severity of jaundice in a resource-limited setting.

BackgroundSevere neonatal jaundice with associated acute bilirubin encephalopathy occurs frequently in low- and middle-income countries, where advanced diagnostic technology is in short supply. In an effort to facilitate the physical diagnosis of acute bilirubin encephalopathy, we pilot-tested a modified bilirubin induced neurologic dysfunction scoring algorithm in a group of pediatric trainees (residents) and their mentors (consultants) in a resource-constrained setting.MethodsJaundiced Nigerian infants were examined by consultant and resident pediatricians. The modified bilirubin induced neurologic dysfunction score assigned by residents was compared with the clinical diagnosis of acute bilirubin encephalopathy by expert consultants. Demographic information was obtained. Known risk factors were also evaluated among infants with and without acute bilirubin encephalopathy in addition to exploratory analyses. Data were analyzed by Statistical Analysis System; statistical significance was set at p < 0.05.ResultsThree hundred and thirty three paired modified bilirubin induced neurologic dysfunction scores (333) were analyzed and showed excellent agreement (weighted Kappa coefficient 0.7969) between residents and consultants. A modified bilirubin induced neurologic dysfunction score greater than or equal to 3 was highly predictive of a clinical diagnosis of acute bilirubin encephalopathy, with sensitivity of 90.7%, specificity of 97.7%, positive predictive value of 88.9%, and negative predictive value of 98.2%. Exposure to mentholated products was strongly associated with increased risk of acute bilirubin encephalopathy among those with known glucose-6-phosphate dehydrogenase deficiency (odds ratio = 73.94; 95% confidence interval = 5.425-infinity) as well as among those whose G6PD phenotype was unknown (odds ratio = 25.88; 95% confidence interval = 2.845-235.4).ConclusionsThe modified bilirubin induced neurologic dysfunction score for neonatal jaundice can be assigned reliably by both residents and experienced pediatricians in resource-limited settings as reflected in the algorithm’s sensitivity and specificity. It may be useful for predicting the development and severity of acute bilirubin encephalopathy in neonates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-015-0355-2) contains supplementary material, which is available to authorized users.

Pattern and predictors of maternal care-seeking practices for severe neonatal jaundice in Nigeria: a multi-centre survey.

BackgroundNigeria is frequently associated with disproportionately high rates of severe neonatal jaundice (NNJ) underpinned by widespread Glucose-6-phosphate dehydrogenase (G6PD) deficiency. Timely and appropriate treatment of NNJ is crucial for preventing the associated morbidity and neuro-developmental sequelae. Since mothers are likely to be the first mostly to observe the onset of severe illness in their newborns, we set out to identify the pattern and predictors of maternal care-seeking practices for NNJ in three culturally-distinct settings in Nigeria.MethodsA multi-centre study was conducted among women attending antenatal clinics in Abuja, Lagos and Port Harcourt from October 2011 to April 2012 using a pretested questionnaire. Predictors of awareness of NNJ, accurate recognition of NNJ, use of potentially harmful therapies and preference for future hospital treatment were determined with multivariate logistic regressions.ResultsOf the 488 participants drawn from the three locations, 431 (88.3%) reported awareness of NNJ, predominantly (57.8%) attributable to professional health workers. A total of 309 (63.3%) mothers with prior knowledge of NNJ claimed they could recognise NNJ, but 270 (87.4%) from this group accurately identified the features of NNJ. Multiparous mothers (Adjusted odds ratio, AOR:4.05; 95% CI:1.75-9.36), those with tertiary education (AOR:1.91; CI:1.01-3.61), and those residing in Lagos (AOR:2.96; CI:1.10-7.97) were more likely to have had prior knowledge of NNJ. Similarly, multiparous mothers (AOR:2.38; CI:1.27-4.46) and those with tertiary education (AOR:1.92; CI:1.21-3.05) were more likely to recognise an infant with jaundice accurately. Mothers educated by health workers were 40% less likely to resort to potentially harmful treatment for NNJ (AOR:0.60; CI:0.39-0.92) but more likely to seek hospital treatment in future for an infant suspected with jaundice (AOR:1.88; CI:1.20-2.95).ConclusionsWomen with tertiary education and multiparous mothers who attend routine antenatal clinics are more likely than less educated women, to be associated with appropriate care-seeking practices for infants with NNJ regardless of the socio-cultural setting. Systematic efforts by professional health workers are warranted, as part of routine antenatal care, to engage other groups of mothers especially those likely to indulge in self-use of potentially harmful therapies.

Comparative Study of Frequency and Severity of Neonatal Jaundice without a Known Etiology in Two Groups of Term Neonate Born Via Cesarean Section and Vaginal Delivery

Introduction: Neonatal jaundice has a significant prevalence, and in severe cases, causes permanent neurological Sequela. Many studies have carried out on neonatal jaundice and its predisposing and exacerbating factors. On the other hand, delivery method (cesarean vs vaginal) has been suggested as a predisposing factor for many of neonatal complications in many studies. The aim of this study is to investigate and compare frequency and severity of neonatal jaundice without a known etiology in two groups of term neonate born via cesarean section and vaginal delivery. Materials and Methods: Samples included 182 term 7 days old neonates with minimum serum bilirubin of 5 mg/dl. Half of these neonates born via cesarean delivery and half of them born via vaginal delivery. All of these neonates had neonatal jaundice without a known etiology. The data of the two groups was compared with statistical tests. Results: Mean serum bilirubin in the neonates was 9.60 mg/dl (SD=3.21 mg/dl). Mann-Whitney test showed that there is not any significant relationship between serum bilirubin value and the delivery method (P=0.53). Bilirubin value in the group with the family history of jaundice in siblings was significantly higher than the group without the family history (P=0.003). Mothers with the age of <20 years had the least serum bilirubin levels (P=0.01). Serum bilirubin level did not have significant relationship with neonatal sex. Neonatal bilirubin levels had a significant relationship with the type of cesarean indications (P=0.01). Conclusion: There is not any significant relationship between serum bilirubin level in neonates and type of delivery method (vaginal vs cesarean). However, the results of investigations in this field are controversial and additional studies are recommended. Key words: Neonatal jaundice, Hyperbilirubinemia, Delivery, Cesarean

Prevalence of Glucose-6-Phosphate Dehydrogenase and Thyroid Hormones Deficiency in Neonatal Jaundice

G6PD deficiency is the most common inherited metabolic disorder and clinically significant red cell enzyme defect in man. Severe neonatal jaundice proved to be the most common clinical manifestation and a globally important most dangerous consequence of G6PD deficiency. Prolonged jaundice is sometimes associated with congenital hypothyroidism. So the early characterization of G6PD activity and thyroid hormone levels provides an etiological diagnosis for neonatal jaundice as well as the opportunity to give the newborn's family information concerning hemolytic crisis prevention and an early management in case of hypothyroidism. Aim: This study was conducted in an attempt to evaluate the prevalence of G6PD deficiency and hypothyroidism in relation to neonatal physiological hyperbilirubinemia. Subjects and Methods: The study included 50 neonates aged between 6 hr – 5 days, forty infants had jaundice and the other ten (control), were healthy neonates, matching the same age. All infants of the study were subjected to C-RP test, routine hematological evaluation, and serum total bilirubin levels, quantitative red blood cells G6PD assay and thyroid hormone levels. Results: All the fifty cases of both jaundiced and healthy neonates were negative for C-RP test indicating that the 40 cases had physiological jaundice .The study revealed that G6PD enzyme was lower than normal level in 2 cases (5%). TSH level was found to be higher than normal in 13 jaundiced neonates out of 40 (33%). Seven jaundiced neonates (18%) had T4hormone lower than normal while all the 40 jaundiced cases had normal T3 level. Correlation of the total bilirubin was significant with TSH and T3 at 0.05 levels, while there was no significance with both T4 and G6PD. Conclusion: statistically there was no correlation between bilirubin and both G6PD enzyme and thyroid hormones, but the incidence of hypothyroidism in this study was high (18%) and the incidence of G6PD deficiency was (5%). This indicates a role of G6PD deficiency and hypothyroidism in developing neonatal jaundice among neonates. So, early neonatal screening program is recommended for early management.

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in Greek newborns: The Mediterranean C563T mutation screening

Glucose-6-Phosphate Dehydrogenase (G6PD) gene is located at the X-chromosome at Xq28 and the disease is recessively inherited predominantly in males. More than 400 variants have been proposed based on clinical and enzymatic studies. The aim of the current study was to identify C563T mutation in G6PD-deficient newborns and to correlate the enzyme residual activity with the presence of the mutation. Some 1189 full-term neonates aged 3–5 days old were tested for G6PD activity in dried blood spots from Guthrie cards using a commercial kit. DNA extraction from Guthrie cards and mutation identification among the deficient samples were performed with current techniques. A total of 92 (7.7%) newborns were G6PD-deficient. In 46 (50%), the mutation C563T was identified. The residual activity in C563T hemizygote males (n = 28) was statistically significantly lower (1.23 ± 0.93 U/g Hb) than that in non-C563T G6PD-deficient males (n = 25) (4.01 ± 1.20 U/g Hb, p < 0.0001) and in controls (13.6 ± 2.9 U/g Hb, p < 0.0001). In C563T heterozygote females, the estimated enzyme activity was lower than that determined in non-C563T females. Male C563T hemizygotes suffer from G6PD deficiency and severe neonatal jaundice. G6PD activity showed statistically significant correlation with total bilirubin blood levels.

Pattern of Neonatal Mortality in a Teritiary Health Facility in Umuahia, South East, Nigeria

Background: Neonatal mortality rates are highest in Sub-Saharan Africa, with Nigeria inclusive. And so the aim of the current study was to audit the pattern of neonatal deaths. Study Design: A cross sectional retrospective descriptive study was undertaken. Place and Duration of Study: The study was carried out at the Newborn Special Care Unit (NBSCU) of Federal Medical Centre (FMC), Umuahia with a review of the admissions and mortality register between 2000 and 2010. Methods: A review of the admissions and mortality register of the NBSCU between 2000 and 2010 was undertaken. Data extracted from the register included socio-demographic variables, birth weight, diagnosis/cause of death, duration of hospitalization, place of delivery (inborn/out-born), source of referral. Original Research Article International Journal of TROPICAL DISEASE & Health, 4(2): 136-146, 2014 137 Results: Total admission over the period was 2,756 comprising 1541 (55.9%) males and 1215 (44.1%) females. Total deaths was 440, comprising 235 (53.4%) males and 205 (46.6%) females. An overall case fatality rate of 16.0% was reported in the current study with mean age at death being 4.7± 6.0 days (0.0128 days). Majority of the dead cases were out-born, 263/440 (59.8%) compared to in-born, 177/440 (40.2%). Forty two percent (185 cases) of the deaths occurred with 24 hours of hospitalization while 25.9% (114 cases) passed on after 72 hours of admission. The leading probable direct causes of neonatal deaths were birth asphyxia (141), preterm delivery (133), neonatal sepsis (58), severe neonatal Jaundice (41), and neonatal tetanus (14). Most deaths (42.0%) occurred in the first 24hours irrespective of the cause of death. Conclusion: High rate of neonatal mortality, most of which are largely preventable as observed in the index study still abound in our locale. High cost effective maternal and newborn interventions could be applied even at community levels where most of the deliveries occur to save lives of the newborns.