Incidence Of Hyperbilirubinemia Research Articles

First day serum bilirubin level, as predictor of significant hyperbilirubinemia in neonates

Background: Age-specific (24 ± 6 h) predictive value of total serum bilirubin (TSB) ≤6 mg/dl in developing significant hyperbilirubinemia in infants. Materials and Methods: A prospective observational study on 200 term neonates having birth weight ≥2500 g and gestational age ≥37 weeks. Blood was collected from the venous site. The blood sample of all infants was sent for grouping and TSB estimation. Babies were clinically examined every day for jaundice. Whenever jaundice was clinically noticed to be >10 mg/dl, bilirubin estimation was repeated immediately and then every day until 5 days of age, and the highest reading was recorded as the peak TSB. Results: Significant hyperbilirubinemia (>17 mg/dl) was present in 13% of cases. At 24 ± 6 h, TSB >6 mg/dl was present in 47 cases and 26 of these developed hyperbilirubinemia (≥17 mg/dl), and TSB ≤6 mg/dl was present in 153 cases and two of them developed significant hyperbilirubinemia. The incidence of hyperbilirubinemia in babies whose mothers received oxytocin and those whose mothers did not receive oxytocin was 19.6% and 8.2%, respectively. The difference was highly significant. The mean values of TSB at 24 ± 6 h in oxytocin used and oxytocin not used groups were 3.94 ± 2.15 mg/dl and 3.36 ± 1.91 mg/dl, respectively, the difference was statistically significant; however, the mean values of peak TSB in oxytocin used and not used groups were 12.78 ± 4.28 mg/dl and 12.03 ± 3.42 mg/dl, respectively, which were statistically not significant. Conclusion: The incidence of significant hyperbilirubinemia in healthy babies is 13%. The use of oxytocin increased its incidence. TSB at 24 ± 6 h ≤6 mg/dl has a high predictive value in identifying those infants who are unlikely to develop subsequent hyperbilirubinemia. This study, thus, will help to discharge healthy term infants with TSB on 2nd day ≤6 mg/dl.

Maternal and Perinatal Outcome in Gestational Diabetes Mellitus in a Tertiary Care Hospital in Delhi.

Background:Gestational diabetes mellitus (GDM) is defined as a carbohydrate intolerance first diagnosed in pregnancy and may be associated with adverse maternal and perinatal outcome.Aim:The aim of the study was to determine the maternal and perinatal outcome in GDM during pregnancy.Materials and Methods:It is a retrospective analysis of women diagnosed with GDM who got antenatal care and delivered in our hospital in previous 5 years. Another 191 women with normal pregnancy without GDM and other medical conditions were taken as control. The baseline characteristics (age, body mass index, religion, and socioeconomic status) were noted in all cases. Diagnosis of GDM was made using oral glucose tolerance test with 75 g glucose. GDM patients were started on diet following which insulin or oral hypoglycemic agents were given if required. Maternal and perinatal outcome was noted in all women.Results:The prevalence of GDM was 5.72% (170/2970). Most patients (79.41%) could be controlled on diet alone. However, 21 (12.35%) needed insulin and 14 (8.23%) needed oral hypoglycemic agents. Middle socioeconomic status was more common in GDM than control and pregnancy-induced hypertension was more common in GDM (13.5%) than in control (6.3%) (P = 0.019). Mode of delivery was not different in two groups. Instrumental deliveries and postpartum hemorrhage were also similar. However, mean birth weight was significantly higher in GDM (2848 ± 539 g) than in control (2707 ± 641 g) (P = 0.004). Incidence of large-for-date babies was also higher (28.2%) in GDM than control (19.4%) (P = 0.005). In neonatal complication, hypoglycemia was significantly higher in GDM (20.6%) than in control (5.2%) (P = 0.001). However, the incidence of hyperbilirubinemia and congenital malformations was not significantly different in two groups.Conclusion:The prevalence of GDM was 5.72% in this study. Adequate treatment of GDM on diet, oral hypoglycemic agents, or insulin to achieve euglycemia can achieve near-normal maternal and neonatal outcome.

Epidemiology of Hyperbilirubinemia in a Quaternary Pediatric Emergency Department over a Three-Year Period.

PurposeThere is a lack of scholarly reports on pediatric emergency department (PED) exposure to hyperbilirubinemia. We aimed to describe the epidemiology of hyperbilirubinemia in patients presenting to a PED over a three-year period.MethodsThis was a retrospective cohort study, completed at an urban quaternary academic PED. Patients were included if they presented to the PED from 2010 to 2012, were 0 to 18 years in age, and had an elevated serum bilirubin for age. A chart review was completed to determine the incidence of hyperbilirubinemia, etiology, diagnostic work up and prognosis. The data set was stratified into four age ranges.ResultsWe identified 1,534 visits where a patient was found to have hyperbilirubinemia (0.8% of all visits). In 47.7% of patients hyperbilirubinemia was determined to have arisen from an identifiable pathologic etiology (0.38% of all visits). First-time diagnosis of pathologic hyperbilirubinemia occurred in 14% of hyperbilirubinemia visits (0.11% of all visits). There were varying etiologies of hyperbilirubinemia across age groups but a male predominance in all (55.0%). 15 patients went on to have a liver transplant and 20 patients died. First-time pathologic hyperbilirubinemia patients had a mortality rate of 0.95% for their initial hospitalization.ConclusionHyperbilirubinemia was not a common presentation to the PED and a minority of cases were pathologic in etiology. The etiologies of hyperbilirubinemia varied across each of our study age groups. A new discovery of pathologic hyperbilirubinemia and progression to liver transplant or death during the initial presentation was extremely rare.

Early predictive value of cord blood bilirubin and dynamic monitoring of transcutaneous bilirubin for hyperbilirubinemia of newborns.

ObjectiveTo study the early predictive value of cord blood bilirubin and dynamic monitoring of transcutaneous bilirubin for hyperbilirubinemia of newborns.Methods389 newborns delivered from June 2014 to December 2015 were enrolled as the research subjects; detailed records were made about the general data of newborns and mothers, and after cord blood bilirubin being graded, the incidence of hyperbilirubinemia was counted, and the prediction efficiency of cord blood bilirubin was analyzed by receiver operator characteristic (ROC) curve. At the same time, the transcutaneous bilirubin was detected continuously when the neonate was born and 24 h, 48 h and 72 h after birth, and the relativity between transcutaneous bilirubin at 72 h and serum bilirubin was analyzed.ResultsNo significant difference was found in the hyperbilirubinemia group and the non-hyperbilirubinemia group concerning general data of the newborns and their mothers. With the concentration of cord blood bilirubin increased, the incidence of hyperbilirubinemia also increased; separate prediction of hyperbilirubinemia by cord blood bilirubin showed a sensitivity and specificity of 71.4% and 65.6% respectively, and they need further dynamic monitoring. The daily mean of transcutaneous bilirubin in hyperbilirubinemia group was significantly higher than that in non-hyperbilirubinemia group at 24 h, 48 h and 72 h, and the measurement value of transcutaneous bilirubin at 72 h had a high correlation with serum bilirubin. When transcutaneous bilirubin value is higher than 18, the incidence of hyperbilirubinemia should be considered.ConclusionsThe increase of cord blood bilirubin effectively predict the occurrence of neonatal hyperbilirubinemia. There is a good correlation between levels of transcutaneous bilirubin and serum bilirubin. Moreover, combined detection of transcutaneous bilirubin and cord blood bilirubin can significantly improve the prediction accuracy of hyperbilirubinemia.

Incidence, Risk Factors, and Outcomes of Hyperbilirubinemia in Adult Cardiac Patients Supported by Veno-Arterial ECMO.

The aims of this study were to evaluate the incidence, risk factors, and outcomes of hyperbilirubinemia in cardiac patients with veno-arterial (VA) ECMO. Data on 89 adult patients with cardiac diseases who received VA ECMO implantation in our hospital were retrospectively reviewed. All patients were divided into the following three groups: 24 in normal group (N, total bilirubin [TBIL]≤3mg/dL), 30 in high bilirubin group (HB, 6mg/dL≥TBIL>3mg/dL), and 35 in severe high bilirubin group (SHB, TBIL>6mg/dL). lg(variables + 1) was performed for nonnormally distributed variables. The incidence of hyperbilirubinemia (>3mg/dL) was 73%. In a multiple linear regression analysis, lg(peak TBIL + 1) was significantly associated with lg(peak AST + 1) (b-coefficient 0.188, P = 0.001), lg(peak pFHb + 1) (b-coefficient 0.201, P = 0.003), and basic TBIL (b-coefficient 0.006, P = 0.009). Repeated measurement analysis of variance revealed that the main effect for three groups in pFHb and lg(AST + 1) was significant at first 3days during ECMO. The patients in SHB had low platelets during ECMO and low in-hospital survival rate. Hyperbilirubinemia remains common in patients with VA ECMO and is associated with low platelets and high in-hospital mortality. Hemolysis and liver dysfunction during ECMO and basic high bilirubin levels are risk factors of hyperbilirubinemia.

Prebiotics for the prevention of hyperbilirubinaemia in neonates

Background Hyperbilirubinaemia occurs in approximately two-thirds of all newborns during the first days of life and is frequently treated with phototherapy. Although generally seen as safe, there is rising concern regarding phototherapy and its potentially damaging effects on DNA and increased side effects particularly for preterm infants. Other methods, such as enteral feeding supplementation with prebiotics, may have an effective use in the management of hyperbilirubinaemia in neonates. Objectives To determine whether administration of prebiotics reduces the incidence of hyperbilirubinaemia among term and preterm infants compared with enteral supplementation of milk with distilled water/placebo or no supplementation. Search methods We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE via PubMed (1966 to 14 June 2018), Embase (1980 to 14 June 2018), and CINAHL (1982 to 14 June 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. Selection criteria We considered all RCTs that studied neonates comparing enteral feeding supplementation with prebiotics versus distilled water/placebo or no supplementation. Data collection and analysis Two reviewers screened papers and extracted data from selected papers. We used a fixed-effect method in combining the effects of studies that were sufficiently similar. We then used the GRADE approach to assess the quality of the evidence. Main results Three small studies evaluating 154 infants were included in this review. One study reported a significant reduction in the risk of hyperbilirubinaemia and rate of treatment with phototherapy associated with enteral supplementation with prebiotics (risk ratio (RR) 0.75, 95% confidence interval (95% CI) 0.58 to 0.97; one study, 50 infants; low-quality evidence). Meta-analyses of two studies showed no significant difference in maximum plasma unconjugated bilirubin levels in infants with prebiotic supplementation (mean difference (MD) 0.14 mg/dL, 95% CI -0.91 to 1.20, I² = 81%, P = 0.79; two studies, 78 infants; low-quality evidence). There was no evidence of a significant difference in duration of phototherapy between the prebiotic and control groups, which was only reported by one study (MD 0.10 days, 95% CI -2.00 to 2.20; one study, 50 infants; low-quality evidence). The meta-analyses of two studies demonstrated a significant reduction in the length of hospital stay (MD -10.57 days, 95% CI -17.81 to -3.33; 2 studies, 78 infants; I² = 0%, P = 0.004; low-quality evidence). Meta-analysis of the three studies showed a significant increase in stool frequency in the prebiotic groups (MD 1.18, 95% CI 0.90 to 1.46, I² = 90%; 3 studies, 154 infants; high-quality evidence). No significant difference in mortality during hospital stay after enteral supplementation with prebiotics was reported (typical RR 0.94, 95% CI 0.14 to 6.19; I² = 6%, P = 0.95; 2 studies; 78 infants; low-quality evidence). There were no reports of the need for exchange transfusion and incidence of acute bilirubin encephalopathy, chronic bilirubin encephalopathy, and major neurodevelopmental disability in the included studies. None of the included studies reported any side effects. Authors' conclusions Current studies are unable to provide reliable evidence about the effectiveness of prebiotics on hyperbilirubinaemia. Additional large, well-designed RCTs should be undertaken in neonates that compare effects of enteral supplementation with prebiotics on neonatal hyperbilirubinaemia with supplementation of milk with any other placebo (particularly distilled water) or no supplementation.

Effect of timing cord clamping on a vaginally delivered infant of a primigravida in terms of the incidence of hyperbilirubinemia

Delayed cord clamping leads to the increased level of haematocrite and victocytes which is high risk of hyperbilirubinemia . This study is to determine if there is an effect of timing of cord clamping relating to the incidence of hyperbilirubinemia on newborn, and to create formulating the standard procedures in maternal interventions related to the timing of cord clamping, another objective is preventing interventions of its occurrence when the clamping is performed immediately after birth. Crossectional study was applied design of the research. Population and samples included infants spontaneus by healthy primigravidas.Two trials were included, 20 participants of each received interventions of cord clamping more than equalivalent 1 minute and less than 1 minute followed by bilirubin assessment 48 hours after birth, and analysed by using Linier Regression. There is no significant effect of timing of cord clamping on newborn with regard to hiperbilirubinemia, because the effect of the clamping on bilirubin level reaches up to 68.2%, while the other 31.8% of the varying levels are affected by other factors. There is a need to conduct other relevant studies aimed to prevent hyperbilirubinemia starting from antenatal to postnatal stage.; Key Words: Jaundice, Newborn, Hyperbilirubinemia, Time of Clamping, Primigravidas

The influence of zinc sulfate on neonatal jaundice: a systematic review and meta-analysis

Introduction: Zinc sulfate may be a promising approach to treat neonatal jaundice. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc sulfate on hyperbilirubinemia among neonates.Methods: PubMed, EMbase, Web of science, EBSCO, Cochrane library databases, Ovid, BMJ database, and CINAHL were systematically searched. Randomized controlled trials (RCTs) assessing the effect of zinc sulfate versus placebo on the prevention of jaundice in neonates were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were total serum bilirubin (TSB) on three days and seven days, the incidence of hyperbilirubinemia. Meta-analysis was performed using random- or fixed-effect models.Results: Five RCTs involving 645 patients were included in the meta-analysis. Overall, compared with placebo, zinc sulfate supplementation failed to significantly reduce TSB on three days (mean difference (MD) = 0.09 mg/dL; 95% confidence interval (CI) = −0.49 to 0.67; p = .77), TSB on seven days (MD = −0.37 mg/dL; 95% CI = −98 to 0.25; p = .25) as well as the incidence of hyperbilirubinemia (OR = 1.14; 95% CI = 0.74 to 1.76; p = .56). Zinc sulfate showed no influence on phototherapy requirement (OR = 0.90; 95% CI = 0.41 to 1.98; p = .79), but resulted in significantly decreased duration of phototherapy (MD = −16.69 h; 95% CI = −25.09 to −8.3 h; p < .0001).Conclusions: Zinc sulfate could not reduce the TSB on three days and seven days, the incidence of hyperbilirubinemia and phototherapy requirement, but lead to significantly decreased duration of phototherapy.

Correlation of various maternal factors with exaggerated hyperbilirubinemia of the newborn

Background: Maternal factors could help determine the potential incidence of hyperbilirubinemia. This study was performed with the purpose of establishing the role of the various maternal factors previously indicated as being responsible for exaggerated physiological hyperbilirubinemia in term neonates with serum bilirubin level of 12 mg/dL or more. Materials and Methodology: It was a prospective, cross-sectional study conducted from July 2012 to August 2014 in Pimpri, Pune. A total of 2000 healthy term deliveries were screened, out of which 100 neonates with exaggerated hyperbilirubinemia were included. Data were collected with maternal information. The data were analyzed using t -test (for parametric distributions). Results: During the period of study, 330 babies out of 2000 deliveries had achieved the serum bilirubin level of >12 mg/dL. Thus, the prevalence of exaggerated neonatal hyperbilirubinemia in the current study was 16.5%. There is strong association between maternal infection and serum bilirubin even when only 5 mothers had infection (Z = 2.31 and P Conclusions: Maternal infection was found to have a significant effect on neonatal exaggerated hyperbilirubinemia. Therefore, interventions should be prioritized to prevent maternal sepsis. The first approach targets facility-based deliveries and requires increased provision and uptake of proper antenatal care early in pregnancy.

Effect of genetic variants of bilirubin metabolism on the degree of hyperbilirubinemia in African-American newborns.

The objective of our study was to measure the effect of genetic variants of these two enzymes, UGT1A1 and SLCO1B1, in the bilirubin metabolic pathway on the degree of hyperbilirubinemia in a cohort of African-American (AA) infants from our well-baby nursery. In addition, a second objective was to document the types and frequencies of genetic variations of these enzymes in our cohort. A prospective study of 180 AA infants from the Well Baby Nursery of an inner city community hospital, all of whose mothers were type O pos. Sixty infants were ABO-incompatible direct antiglobulin test (DAT) pos, 60 were ABO-incompatible DAT neg and 60 were type O+. Blood for carboxyhemoglobin (COHb) and variants of the enzymes uridine diphosphoglucuronosyltransferase 1A1 and hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) was drawn at the time of the infants' initial bilirubin, and the infants' precise percentile on the Bhutani nomogram was calculated. Variants in the two enzymes studied were quite common. In total, 21.1% were positive for a Gilbert phenotype, whereas an additional 42.4% were heterozygous for the *28 or *37 variant of UGT1A1. In total, 67.2% were homozygous for the *60 variant of the phenobarbital responsive enhancer module. In total, 41.1% were homozygous for the *1b variant of SLCO1B1, whereas an additional 12.7% were positive for the *4 variant of this gene. In total, 20.6% of infants had variations in both genes. Using logistic regression when COHbc was assessed with each of the different variants, only COHbc (P<0.0001 to 0.0004) was significantly associated with the level of hyperbilirubinemia as defined by the Bhutani nomogram. Although we have found quite a large number of genetic variants of the UGT1A1 and SLCO1B1 genes in the AA population, it does not appear that they have a significant impact on the incidence of hyperbilirubinemia among this group of infants.

Acute kidney injury in leptospirosis: the Kidney Disease Improving Global Outcomes (KDIGO) criteria and mortality .

Acute kidney injury (AKI) is one of the most serious complications of leptospirosis. In recent years, studies have evaluated this complication using the risk, injury, failure, loss, and end-stage kidney disease and the acute kidney injury network classification systems. More recently, the kidney disease improving global outcomes (KDIGO) criteria have been developed to increase accuracy in detecting AKI. The aim of the present study was to determine the prevalence and factors associated with AKI and mortality in patients with leptospirosis, using KDIGO criteria. We conducted a retrospective analysis of patients with clinical and epidemiological diagnosis of leptospirosis between January 2007 and December 2011. AKI was defined and classified according to KDIGO guidelines. Independent risk factors for AKI and death were evaluated using logistic regression. Of the 205 patients included, only 10 patients (4.8%) exhibited Weil's syndrome. AKI occurred in 182 patients (88.7%), 33 (16.1%) of whom were classified as KDIGO 1, 36 (17.6%) as KDIGO 2, and 113 (55.1%) as KDIGO 3. There was an independent correlation between AKI and the incidence of hyperbilirubinemia and leukocytosis. KDIGO 3 and the need for mechanical ventilation were independently correlated with mortality. We observed a high prevalence of AKI using KDIGO criteria, even in patients with milder forms of leptospirosis. Hyperbilirubinemia and leukocytosis were independent risk factors for AKI. KDIGO 3 was independently associated with mortality. .

A Randomized Controlled Clinical Trial Investigating the Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Biomarkers of Oxidative Stress, Inflammation and Pregnancy Outcomes in Gestational Diabetes.

Limited data are available for assessing the effects of omega-3 fatty acids and vitamin E co-supplementation on metabolic profiles and pregnancy outcomes in gestational diabetes (GDM). This study was designed to determine the effects of omega-3 fatty acids and vitamin E co-supplementation on biomarkers of oxidative stress, inflammation and pregnancy outcomes in women with GDM. This randomized, double-blind, placebo-controlled clinical trial was conducted in 60 patients with GDM who were not taking oral hypoglycemic agents. Patients were randomly allocated to intake either 1000 mg omega-3 fatty acids from flaxseed oil plus 400 IU vitamin E supplements (n=30) or placebo (n=30) for 6 weeks. Fasting blood samples were obtained from the women at the beginning of the study and after the 6-week intervention to quantify related markers. After 6 weeks of intervention, omega-3 fatty acids and vitamin E co-supplementation, compared with the placebo, resulted in a significant rise in total antioxidant capacity (TAC) (+187.5±224.9 vs. -32.5±136.1 mmol/L; p<0.001); nitric oxide (NO) (+5.0±7.7 vs. -12.0±28.0 µmol/L; p=0.002) and a significant decrease in plasma malondialdehyde (MDA) concentrations (-0.1±0.9 vs. +0.6±1.4 µmol/L; p=0.03). Co-supplementation with omega-3 fatty acids and vitamin E showed no detectable changes in plasma glutathione and serum high-sensitivity C-reactive protein levels. Joint omega-3 fatty acids and vitamin E supplementation resulted in lower incidences of hyperbilirubinemia in newborns (10.3% vs. 33.3%; p=0.03). Overall, omega-3 fatty acids and vitamin E co-supplementation for 6 weeks in women with GDM had beneficial effects on plasma TAC, MDA and NO and on the incidence of the newborns' hyperbilirubinemia.

Close monitoring of transcutaneous bilirubin ensures better outcome in neonates with hyperbilirubinemia

Objective To explore the influence of regular measurement of transcutaneous bilirubin (TcB) on clinical outcome of neonatal hyperbilirubinemia. Methods Healthy term and late-preterm newborns (gestational age ≥35 weeks) born between January 1 and December 31, 2013 at Peking University Third Hospital were reviewed retrospectively. All neonates were divided into monitoring group (n=1 071) or control group (n=2 437) according to whether regular monitoring of TcB was performed. General clinical information and TcB levels on admission were recorded. The incidence of hyperbilirubinemia and readmission for hyperbilirubinemia, level of bilirubin and length of hospital stay were compared between the two groups. Chi-square test or independent sample t test were used for statistical analysis. Results (1) The incidence of hyperbilirubinemia and readmission rate for hyperbilirubinemia were lower in monitoring group when compared with control group [4.7% (50/1 071) vs 7.1% (172/2 437) and 1.3% (14/1 071) vs 3.3% (81/2 437) respectively, P 0.05). (2) Of all the 222 hyperbilirubinemia patients, the number of neonates with gestational age 38 weeks was 26 (11.7%), 33(14.9%) and 163(73.4%), respectively. There was no significant difference of gestational age, birth weight and gender proportion between the two groups. (3) The follow-up rate in January was 41.5% (49/118), and the mean follow-up rate in February, April, July and October (with revised follow-up methods) was 83.1% (345/415), higher than that in January (χ2=82.505, P<0.01). (4) The first three causes of hyperbilirubinemia in all 222 patients were early-onset breast milk jaundice (72 cases, 32.4%), perinatal causes (60 cases, 27.0%) and unknown reasons (50 cases, 22.5%). The first three causes of hyperbilirubinemia in monitoring group (50 cases) were unknown reasons (24 cases, 48.0%), early-onset breast milk jaundice (14 cases, 28.0%) and hemolysis (9 cases, 18.0%). Those in the control group (172 cases) were early-onset breast milk jaundice (58 cases, 33.7%), perinatal causes (57 cases, 33.1%) and unknown reasons (26 cases, 15.1%). Conclusions Regular monitoring of TcB can reduce the incidence of hyperbilirubinemia and the readmission for hyperbilirubinemia. Key words: Hyperbilirubinemia, neonatal; Jaundice, neonatal; Bilirubin

Incidence of neonatal hyperbilirubinemia in low, intermediate-low, and intermediate-high risk group infants

Background Neonatal hyperbilirubinemia is commonly found in newborns. Assessment of the risk of hyperbilirubinemia and information on the average time of the occurrence of hyperbilirubinemia are important to prevent the development of severe hyperbilirubinemia.Objective To find out the incidence of and the time of the development of hyperbilirubinemia in healthy-term newborns.Method A cohort prospective study was done on healthy-term newborns born at Hasan Sadikin Hospital between November and December 2009. Subjects were divided into 4 groups of risk at discharged, based on Bhutani nonnogram. A serial bilirubin level measurement were perfonned within 6 days.Resu l ts One of 14 newborns at low risk group developed hyperbilirubinemia but did not need phototherapy. Six of 14 newborns at intermediate-low risk group developed hyperbilirubinemia, 2 of them needed phototherapy with total serum bilirubin level of 14.7 mg/dL at 57 hours and 19.8 mg/dL at111 hours. Nine of 15 newborns of intennediate-high risk group developed hyperbilirubinemia, 1 of them needed phototherapy with total serum bilirubin level of 16.6 mg/dL at 76 hours. There was no newborn cathegorized as high risk group in this study. The median time the occurrence of hyperbilirubinemia in intennediate-low and intennediate-high risk group was 140 hours and 82 hours, respectively. There was no significant difference in survival curve between intennediate-high and intennediate-low risk groups (95% CI 108.1 to 1 2 5.4).Conclusion The incidence of hyperbilirubinemia was not different between intennediate-low and intermediate-high risk babies.

Neurological impairment of children with history of prematurity and neonatal hyperbilirubinemia

Background In premature infants, the incidence of hyperbiliru-binemia is still high. Bilirubin encephalopathy can develop withoutmarked hyperbilirubinemia.Objective To know the incidence of neurological impairment inpremature with hyperbilirubinemia and the association betweenneurological impairment and serum unconjugated billirubin con-centration.Methods A retrospective study was conducted on 54 prematureswith history of hyperbilirubinemia and 54 without history of hyper-bilirubinemia born between 1997 and 1998 and discharged fromSanglah Hospital. Consecutive sampling was done. After univariateanalysis, multivariate analysis was used to identify the associationbetween serum unconjugated bilirubin concentration and neuro-logical impairment at the adjusted age of 318 months.Results There were statistically significant differences in mean ofage and neurological impairment between subjects with and with-out hyperbilirubinemia (p&lt;0.0001 and 0.026). In subjects with hy-perbilirubinemia, univariate analysis showed significant differencesin means of serum unconjugated bilirubin concentration, gesta-tional age, birth weight, and serum albumin concentration betweensubject who had neurological impairment and who had no neuro-logical impairment with p = 0.005; 0.001; 0.002; &lt;0.0001, respec-tively. Multivariate analysis found there were association betweenneurological impairment and serum unconjugated bilirubin concen-tration, gestational age, and serum albumin concentration withp&lt;0.0001; 0.004; and &lt;0.0001, respectively.Conclusion Neurological impairment in subject with hyperbiliru-binemia was greater than subject without hyperbilirubinemia. Se-rum unconjugated bilirubin concentration is one of three factorsthat associated with neurological impairment

Neonatal Outcomes of Rh-Negative Pregnancies in a Tertiary Level Neonatal Intensive Care Unit: A Prospective Study

Background: Rhesus incompatibility is a preventable cause for severe neonatal hyperbilirubinemia, hydrops fetalis and still births. The prevalence of the Rh-negative blood group among Indian woman varies from 2% - 10%. Despite declining the incidence of Rhesus incompatibility, due to availability of anti-D immunoglobulin, and improved antenatal care of the Rh-negative pregnant woman, it still accounts for a significant proportion of neonatal hyperbilirubinemia and neuro-morbidity. The prevalence of Rh-negative women having Rh-positive neonates is 60%. Objectives: This study aimed to estimate the incidence of Rh iso-immunization and evaluate the outcomes of Rh iso-immunized neonates. Methods: This prospective observational study was conducted in a tertiary level neonatal intensive care unit, Princess Esra hospital, Deccan college of medical sciences, Hyderabad, Telangana, India. Consecutive intramural and extramural neonates admitted to neonatal intensive care unit with the Rh-negative mother’s blood group and hyperbilirubinemia were enrolled. Neonates born to Rh+ve mothers were excluded. Neonatal gestational age, birth weight, age at admission, duration of phototherapy, duration of hospitalization, neonatal examination and investigations were recorded in a predesigned, pretested performa. Results: A total of 90 neonates were born to Rh-negative mothers, of which 70% (63) had the Rh-positive blood group and 30% had the Rh-negative blood group. Of these 63 neonates, 48 (76.2%) had hyperbilirubinemia and 43 neonates (68.3%) had significant hyperbilirubinemia (total serum bilirubin > 15mg/dL). Among them, 2%, 75% and 23% were born to primi, multi and grandmutli, respectively. Also, 14.5% of the neonates were large for dates (LFD), 75% appropriate for dates (AFD) and 10.5% were small for dates (SFD). Premature and SFD neonates had higher incidence of hyperbilirubinemia. Significantly higher incidence of jaundice occurred within 72 hours of life. The mean serum bilirubin level among neonates with significant hyperbilirubinemia was 17.98 ± 1.76 (95% CI:17.43 - 18.52) while that of neonates without significant hyperbilirubinemia was 13.1 ± 0.53 (95% CI:12.47 - 13.77) with statistical significance (P < 0.0001). Maternal multiparity, direct coombs test (DCT) positivity, and abnormal neurosonogram (NSG) were important accompaniments of high serum bilirubin levels. Conclusions: Incidence of Rh-positive phenotype in neonates born to Rh-negative mothers is 70%. Incidence of hyperbilirubinemia among them is 76.2% and that of significant hyperbilirubinemia was 68.3%. The incidence of DCT positivity was 20.9%. Maternal multiparity, positive DCT and abnormal NSG were important associates of high serum bilirubin levels.

The Relationship between Neonatal Jaundice and Maternal and Neonatal Factors

Background: Maternal and neonatal factors could help determine the potential incidence of hyperbilirubinemia. In this study, we aimed to identify the relationship between the severity of jaundice in newborns and maternal and neonatal factors. Methods: This descriptive, cross-sectional study was conducted in 2014. Icteric newborns, admitted to Qods and Kowsar teaching hospitals in Qazvin, Iran were recruited in the study. Data were collected, using a researcher-made checklist consisting of three parts: demographic, maternal, and neonatal information. For data analysis, statistical tests including t-test, Mann-Whitney, analysis of variance, and Pearson's correlation test were performed, using SPSS version 19. Results: The results showed that the mean total bilirubin level was significantly higher in newborns delivered vaginally (17.3±3.5 mg/dl), compared to cases born by cesarean section (16.1±3.9 mg/dl) (P=0.02). Also, the mean total and direct bilirubin levels were higher in neonates delivered using oxytocin (0.4±.1 and 17.99±0.4, respectively), compared to those without oxytocin induction (0.383±0.1 and 16.2±0.28, respectively) (P=0.001). Moreover, the mean total and direct bilirubin levels were higher among female newborns (0.397±0.013 and 17.2±0.29, respectively), compared to the male neonates (0.379±.22 and 15.9±0.37, respectively) (P=0.005 and P=0.02, respectively). Conclusion: Since factors such as mode of delivery, oxytocin induction, and neonate's gender could contribute to jaundice, continuous assessment of newborns after birth could facilitate early diagnosis, promote disease management, and reduce the subsequent complications.

Severe Neonatal Hyperbilirubinemia Decreased after the 2007 Canadian Guidelines

To estimate the incidence of severe neonatal hyperbilirubinemia in Canada from 2011-2013 following the implementation of the Canadian Pediatric Society's published guidelines on the management of hyperbilirubinemia in 2007. Our previously reported incidence of hyperbilirubinemia in Canada was 1 in 2480. Term infants ≤ 60 days of age, with a peak serum total bilirubin level > 425 μmol/L or who had an exchange transfusion were followed prospectively through the Canadian Pediatric Surveillance Program from 2011-2013. Infants with rhesus isoimmunization or born < 35 weeks gestation were excluded. Ninety-one cases of severe neonatal hyperbilirubinemia were confirmed. Sixty-nine infants (76%) were readmitted to hospital, 47 (52%) of them within 6 days of age. The remaining 22 infants (24%) were identified with severe neonatal hyperbilirubinemia before they were discharged from the hospital. The mean reported peak bilirubin level was 484 μmol/L (range 181-788; SD ± 92). An etiology was identified in 57 (63%) cases, with ABO incompatibility (n = 35) and glucose-6-phosphate dehydrogenase deficiency (n = 11) being the most common. An infant was 3.5 times more likely to be diagnosed with severe neonatal hyperbilirubinemia from 2002-2004 compared with 2011-2013 (95% CI 2.72-4.47). The minimum estimated incidence of severe neonatal hyperbilirubinemia in Canada is 1 in 8352 live births. Introduction of the Canadian Pediatric Society guidelines and improved physician awareness of severe neonatal hyperbilirubinemia in the last 10 years likely made positive contributions to this trend.

The Association of Gilbert's Syndrome with Hyperbilirubinaemia Occurring on Any of Imatinib, Dasatinib and Nilotinib in Patients with Chronic Myeloid Leukaemia (CML)

Background: Individuals with Gilbert's syndrome present with mild, unconjugated hyperbilirubinaemia, resulting from impaired glucuronidation by reduced uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression. The A(TA)7TAA polymorphism responsible for the syndrome has been associated with nilotinib-induced hyperbilirubinaemia in patients with chronic myeloid leukaemia (CML). Our study extends UGT1A1 molecular analysis to a larger cohort of CML patients receiving other tyrosine kinase inhibitors (TKIs) and explores the relationship with other abnormalities of liver function.Methods: We interrogated our database of 832 patients treated with a TKI for CML at our center and identified 467 individuals who presented in first chronic phase, who had received only a TKI (prior interferon, combination experimental therapy, autologous and allogeneic transplant patients were all excluded) and for whom serial liver function results were available. We then performed PCR to identify variations in dinucleotide repeats in the UGT1A1 promoter region. Genotypes were assigned as follows: 6/6 (homozygous for (TA)6 allele; wild-type), 7/7 (homozygous for (TA)7allele) and 6/7 (heterozygous). Because individual patients may have received more than one TKI, we defined the period on treatment with each TKI as an 'episode' in order to be able to attribute abnormalities of liver function to a specific drug. Hyperbilirubinaemia was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Both ALT and ALP were defined as increased if they were above the upper limit of normal. To date we have completed the analysis for 340 patients comprising a total of 568 episodes of TKI therapy (imatinib 313, dasatinib 125, nilotinib 130).Results: The UGT1A1 genotype analysis showed six variants. The majority of patients displayed one of 6/6 (149 patients), 6/7 (138 patients) or 7/7 (48 patients) genotypes. Small numbers of patients with the 5/6, 5/7 and 6/8 genotypes were excluded from further analysis. Hyperbilirubinaemia was seen in patients with all three genotypes, but was more frequent in patients on nilotinib (44%), compared to imatinib (14%) and dasatinib (8%). The incidence of hyperbilirubinaemia in individuals with the 6/6 genotype was 6%, 0% and 22% for imatinib, dasatinib and nilotinib respectively, and 10%, 6% and 56% for patients with the 6/7 genotype. The frequency of hyperbilirubinaemia in those with the 7/7 genotype was significantly higher compared to the occurrence of such events in any other genotype, irrespective of treatment. However, it occurred more often in patients on nilotinib (80%), followed by imatinib (61%) and dasatinib (44%). A significantly higher number of patients with the 7/7 genotype on nilotinib reported Grade 3 hyperbilirubinaemia (25%), with no grade 3 events on imatinib and only one on dasatinib. Hyperbilirubinaemia on any single drug did not predict for this event on any subsequent drug.Further analysis of liver function tests (LFTs) and bilirubin levels divided episodes into four groups: 1. Episodes with normal bilirubin and normal LFTs (n = 273), 2. Episodes with isolated raised LFTs but normal bilirubin (n = 179), 3. Episodes with isolated hyperbilirubinaemia (n = 27) but normal LFTs and 4. Episodes with raised bilirubin and raised LFTs (n = 84). Abnormal LFTs with or without hyperbilirubinaemia were most commonly seen on nilotinib (65%) compared to imatinib (40%) and dasatinib (46%), confirming previous reports of the frequencies of transaminitis on the various TKIs. Isolated hyperbilirubnaemia was uncommon (<6%) on any of the drugs, but was more frequent in the 7/7 than the 6/6 or 6/7 genotypes for imatinib or dasatinib. Interestingly it was not seen in patients with the 7/7 genotype on nilotinib, as 80% of the 7/7 patients with hyperblirubinaemia on nilotinib had other abnormalities of liver function.Conclusion. We confirmed the increased risk of hyperbilirubinaemia in individuals with the A(TA)7TAA polymorphism when treated with nilotinib. In contrast to other reports, we found that all patients with the 7/7 genotype are susceptible to increases in bilirubin when treated with any of imatinib, dasatinib or nilotinib. Hyperbilirubinaemia most commonly occurs alongside elevations in LFTs on nilotinib, indicating a nilotinib-induced hepatotoxicity that is compounded by the additional UGT1A1 inhibition. DisclosuresMilojkovic:ARIAD Pharmaceuticals Inc.: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria. Apperley:Pfizer: Honoraria; Bristol Myers Squibb: Honoraria; Ariad: Honoraria; Novartis: Honoraria. Foroni:Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Ariad: Research Funding.

Lamivudine Therapy Exacerbates Bilirubinemia in Patients Underlying Severely Advanced Hepatitis

Lamivudine belongs to the set of antiviral agents effective against hepatitis B virus infection. Given case reports on liver injuries after certain antiviral agent treatments, this study examined the effects of lamivudine on alanine aminotransferase (ALT) and total bilirubin (TB) using a medical system database. A total of 1,321 patients taking lamivudine alone or with others were evaluated using laboratory hits in an electronic medical system at Seoul National University Hospital from 2005 through 2011. The patients were grouped according to prior ALT results: G#1, ALT lt; 40 IU/L; G#2, 40 IU/L ≤ ALT lt; 120 IU/L; G#3, 120 IU/L ≤ ALT lt; 240 IU/L; and G#4, ALT ≥ 240 IU/L. In G#1 and G#2 patients, lamivudine or adefovir treatment decreased ALT and TB compared to prior values. In G#3 and G#4 patients with three times the upper limit of normal (ULN) ≤ ALT lt; 15 times the ULN, both ALT and TB were decreased after treatment with lamivudine alone, or adefovir following lamivudine therapy, indicating that lamivudine therapy ameliorated liver functions. However, in G#4 patients who experienced severely advanced hepatitis (ALT ≥ 15 times the ULN, or ≥ 600 IU/L), lamivudine augmented TBmax (6.3 → 13.3 mg/dL) despite a slight improvement in ALT (839 → 783 IU/L), indicative of exacerbation of bilirubinemia. Patients who used adefovir after lamivudine also showed a high incidence of hyperbilirubinemia when they experienced severely advanced hepatitis. Treatment with adefovir alone did not show the effect. In conclusion, lamivudine may increase the risk of hyperbilirubinemia in patients with severely advanced hepatitis, implying that caution should be exercised when using lamivudine therapy in certain patient populations.