Severity Of Hyperbilirubinemia Research Articles

Evaluating the relationship between aEEG findings and two-year prognosis in neonates with severe hyperbilirubinemia

ObjectiveIdentifying factors that can better predict the prognosis of neonates with hyperbilirubinemia is important. In this study, we aimed to evaluate the relationship between electroencephalography (EEG) findings and two-year prognosis in neonates with severe hyperbilirubinemia. Methods & materialsIn a cohort prospective study, we studied neonates with a total serum bilirubin level of higher than 18 mg/dL, who were admitted to the neonatal intensive care unit (NICU) of Ghaem hospital, Mashhad, Iran. EEG was recorded upon admission, for all neonates. Patients' data, including demographic characteristics, admission information, and pregnancy and birth data were gathered by obtaining history from parents and studying case files. Also, the relationship between initial EEG findings and final developmental status was assessed. ResultsMean and standard deviation age of patients were 5.46 ± 3.13 days and average serum total bilirubin level was 23.97 ± 4.34 mg/dL at admission. Our findings revealed a significant correlation between the presence of trace alternant on EEG and developmental delay (P = .001). Presence of trace alternant waves on initial EEG at admission was significantly associated with developmental delay in the two year (P = .005). ConclusionThese results indicate a relationship between developmental prognosis and the severity of hyper bilirubinemia in neonates. Also, our findings show that the presence of trace alternate waves on the initial EEG is significantly associated with developmental delay of the neonate in the future.

Comparison of severity and prognosis of jaundice due to Rh incompatibility and G6PD deficiency

IntroductionUndiagnosed and untreated hyperbilirubinemia in infants may result in Kernicterus Spectrum Disorder and poor prognoses. Rhesus incompatibility and glucose-6-phosphate dehydrogenase (G6PD) deficiency are among the known causes of infantile jaundice. This study was designed to define the severity and prognosis in jaundiced infants with Rh incompatibility or G6PD deficiency. MethodsA total of 144 term, 2– 14 days old jaundiced infants (bilirubin > 20 mg/dl) with Rh incompatibility(85 infant) or G6PD deficiency(59 infant) were included in this cohort study with 24-month follow-up through available sampling at Ghaem hospital between 2015 and 2022. Denver II test was used at 6, 12, 18, and 24-month ages after discharge. Infants with Rh incompatibility or G6PD deficiency were assigned into two groups of favorable and poor prognosis. Following that, the bilirubin levels of these infants were compared at the time of admission. ResultsThe bilirubin level in G6PD deficient infants with poor prognoses (37.96 ± 9.25 mg/dl) and neonates with Rh incompatibility (36.23 ± 5.08 mg/dl) almost was the same (P = 0.232). 40 babies (47%) caused by Rh incompatibility and 33 (56%) babies caused by G6PD deficiency had a poor prognosis (P = 0.465).Average bilirubin in babies with RH incompatibility with favorable prognosis is 21.8 and poor prognosis is 36.2 mg/dl. In infants with G6PD deficiency, it was 24 mg/dl with favorable prognosis and 38 mg/dl with poor prognosis (P < 0.0001). The severity of hyperbilirubinemia had a significant role in the prognosis of infants in both groups (P < 0.0001). ConclusionThe two-year prognoses of hyperbilirubinemia caused by G6PD deficiency are as poor as that of Rh incompatibility. The severity of hyperbilirubinemia had a significant role in the prognosis of infants in both groups.Exchange transfusion in cases with bilirubin < 25 mg/dl can improve the prognosis in both groups, especially in infants with Rh incompatibility.

Newborn care in Northern India: A study of regional and seasonal peculiarities for desired professionalism and definitive practices.

Improvements in newborn health with study of present status, progressive perfection of practices, and data diligence for future is desirable. Study of mortality and morbidity patterns. Analyze findings for focus areas and for favourable advancements in practices. Corroborate with existing evidence and practice protocols. Tertiary care referral hospital. Preterm babies given special attention. This includes, in addition to the WHO 10 main recommendations, meticulous monitoring and health education for care. Neonatal jaundice evaluation on the basis of risk factors and clinical monitoring. A total of 1749 live, born babies (2018-2020) were studied. The neonatal mortality rate in the study was 6.29. Preterm births were 102 (5.83%), with mortality of 7.84%, that is, 8 out of 102 preterm babies, and overall 4.57 premature deaths per 1000 live births. Prematurity was the commonest cause of mortality, responsible for 8 out of 11 deaths (72.73%). Birth asphyxia incidence was 5.26% (92 babies) with a case fatality ratio of 4.35%. Newborns with severe birth asphyxia were 7, and of these 4 (all premature) had fatal outcome. The low birthweight (LBW) incidence was 13.32% with the majority (79.83%) in the 2000-2499 g range. Preventive practices for hypothermia were 100% successful. An unusual rise in incidence and severity of hyperbilirubinemia during December 2018 to February 2019 when winter was severe was noted. Mortality reduction requires focusing on prematurity. Meticulous monitoring and health education for them improves results. The unusual rise in incidence and severity of hyperbilirubinemia in severe winter points towards the need for vigilance. We need to be forewarned and forearmed for frequent extreme weather events.

Associations between UGT1A1 and SLCO1B1 polymorphisms and susceptibility to neonatal hyperbilirubinemia in Thai population

Hyperbilirubinemia is the main mechanism that causes neonatal jaundice, and genetics is one of the risk factors of hyperbilirubinemia. Therefore, this study aims to explore the correlation between two genes, UGT1A1 and SLCO1B1, and hyperbilirubinemia in Thai neonates. One hundred thirty seven neonates were recruited from Division of Clinical Chemistry, Ramathibodi Hospital. UGT1A1*28 and *6 were determined by pyrosequencing whereas, SLCO1B1 388A > G and 521 T > C genetic variants were determined by TaqMan® real-time polymerase chain reaction. Neonates carrying with homozygous (AA) and heterozygous (GA) variants in UGT1A1*6 were significantly related to hyperbilirubinemia development compared with wild type (GG; P < 0.001). To the combined of UGT1A1, total bilirubin levels in homozygous variant were higher significantly than heterozygous variant and wild type (P = 0.002, P = 0.003, respectively). Moreover, SLCO1B1 combination was significant differences between the hyperbilirubinemia and the control group (P = 0.041). SLCO1B1 521 T > C variant provide protection for Thai neonatal hyperbilirubinemia (P = 0.041). There are no significant differences in UGT1A1*28 and SLCO1B1 388A > G for the different severity of hyperbilirubinemia. The combined UGT1A1*28 and *6 polymorphism is a strong risk factor for the development of severe hyperbilirubinemia in Thai neonates. Therefore, we suggest neonates with this gene should be closely observed to avoid higher severities of bilirubin.

Evaluation of Changes in the Number of Eosinophils Before and After Phototherapy in Neonatal Hyperbilirubinemia

Background: The prevalence of asthma is higher in icteric babies. It is thought that eosinophilia and asthma are complications of phototherapy rather than hyperbilirubinemia. Objectives: Since there is little data in this regard, we evaluated the relationship between phototherapy and the level of eosinophils in this study. Methods: In this cross-sectional prospective study, we assessed icteric neonates admitted to the neonatal and intensive care unit of Children’s Medical Center of Tehran during 2017 - 2018. Laboratory data including serum bilirubin and count of blood cell differentiation for eosinophils, before, during, and after phototherapy besides demographic data like age, gender, gestational age, and duration of phototherapy were collected. Results: Totally, 163 neonates (52.1% male and 47.9% female) with a mean age of 5.49 ± 4.01 days, enrolled in the study. The prevalence of term neonates was 81% and 19% were preterm. The mean of serum total bilirubin was 17.91 ± 3.37 mg/dL. Compared to the mean value of eosinophils before phototherapy, this value in the first (P = 0.001) and second (P &lt; 0.001) days were significantly higher. In female neonates, there was a significant increase in eosinophils in the first (P = 0.001) and second (P &lt; 0.001) day of the post-treatment period. However, in male subjects, this increase was significant only in the second day after phototherapy (P = 0.001). In neonates less than one week of age, this count was significantly increased on the first (P = 0.003) and second (P &lt; 0.001) day after phototherapy. In cases with hemolytic hyperbilirubinemia, eosinophils count before phototherapy and the second day was significant (P = 0.006). The mean of eosinophils in first and second days after phototherapy was not correlated with the severity of hyperbilirubinemia but there is a significant negative correlation between the mean total bilirubin of patients with mean eosinophils before phototherapy. Conclusions: Our findings showed that there was a significant relationship between hyperbilirubinemia and its therapeutic phototherapy with an increasing level of peripheral eosinophils count in neonates.

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.

Can we use umbilical cord hydrogen peroxide as an early predictor for neonatal hyperbilirubinemia?

Abstract Introduction: Most neonatal hyperbilirubinemia is benign, but because of the potential toxicity of bilirubin, neonates should be monitored to identity those who might develop severe hyperbilirubinemia. Objective: To determine if the cord blood hydrogen peroxide level can be used as an early predictor of neonatal hyperbilirubinemia or not and if there is a correlation between its levels and the severity of hyperbilirubinemia. Methods: This is a prospective comparative study included 59 full term neonates. Forty-one neonates developed jaundice (group I) and 18 neonates did not develop jaundice (group II) as controls. For all studied groups, we measured the cord blood bilirubin using modified diazo method and hydrogen peroxide levels using ELISA Kits and we measured their levels at 5th and 7th days of life for patients. Results: The cord blood H2O2 levels as well as the bilirubin levels were higher in patients than controls. Significant positive correlations between cord blood H2O2 and cord blood bilirubin levels were present (r=0.81& p 35 (p-value 0.001). Conclusion: Cord blood hydrogen peroxide (H2O2) levels can be used as an early predictor of neonatal indirect hyperbilirubinemia and can determine which neonates should be followed after discharge from the hospital.

Evaluation of neonatal jaundice based on the severity of hyperbilirubinemia

Introduction: Recognition of the characteristics of neonatal jaundice with different levels of severity can help the physician with appropriate treatment and prediction of complications. This study aimed to determine the characteristics of neonatal jaundice in different levels of severity. Materials and Methods: This cross-sectional study was performed on 3005 neonates referring to the Neonatal Intensive Care Unit, Clinic, and Emergency ward in Ghaem Hospital of Mashhad, Iran, from 2009 to 2018. Sampling was carried out through the convenience sampling method. The data collection tool was a researcher-made questionnaire, including laboratory evaluation, as well as assessment of maternal and neonatal characteristics. The newborns were divided into six groups based on the serum bilirubin level and then compared in terms of characteristics, causes, and prognosis according to the severity of jaundice. The data were analyzed using the Student's t-test and Chi-square test. Results: In most cases, the present of jaundice was reported between 2 and 3 days of birth, and the age of neonates' reference was between 6 and 8 days of birth. Causes of neonatal jaundice included unknown reasons (61.25%), increased production of bilirubin (22%), severe weight loss (7%), infections (5.3%), endocrine disorders (2.5%), and other causes (1.7%). In jaundice level lower than 25 mg/dl, about 15% of neonates were reported with complications; however, at the bilirubin level higher than 35 mg/dl, approximately 40% of newborns had complications. Conclusion: The known causes of the jaundice were mostly observed in the increased bilirubin production level higher than 25 mg/dl.

Profiling of UGT1A1*6, UGT1A1*60, UGT1A1*93, and UGT1A1*28 Polymorphisms in Indonesian Neonates With Hyperbilirubinemia Using Multiplex PCR Sequencing.

Background: Single nucleotide polymorphism (SNP) variants of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene have been studied as an important factor in neonatal hyperbilirubinemia (jaundice) severity. Specific ethnicities, including Asians, have certain SNPs that appear more frequently than others.Aim: To identify the most common SNPs in Indonesian neonates and their association with the severity of neonatal hyperbilirubinemia.Methods: Eighty-eight inborn and outborn jaundiced infants from three different hospitals (Bengkulu, Jakarta, Biak Papua) across Indonesia were enrolled in this cross-sectional study and their peak total serum bilirubin (TSB) levels assessed. SNP variant analyses of the TATAA box, promoter, and exon 1 regions of UGT1A1 gene from 78 of the 88 infants were carried out using the SNaPshotR Multiplex Polymerase Chain Reaction (PCR) System followed by DNA sequencing.Results: We detected SNP variants UGT1A1*28, UGT1A1*60, UGT1A1*93, and UGT1A1*6 in our population. Mean total serum bilirubin (TSB) was 14.59 ± 5.57 mg/dL. Bivariate analyses using delivery location, gestational age, birth weight, mother's age, and ethnicity were shown to be associated with moderate-to-severe hyperbilirubinemia (p < 0.05). None of the four SNPs appeared to be associated with moderate-to-severe hyperbilirubinemia. In multivariate analysis, however, only the “other ethnic group” (e.g., Chinese, Bengkulu, Papua, Bima) category showed an association with moderate-to-severe hyperbilirubinemia, with an odds ratio of 6.49 (95% CI 1.01–41.67; p < 0.05).Conclusions: We found that the UGT1A1*60 is the most common SNP detected in neonates with hyperbilirubinemia in the Indonesian population. Interestingly, in Indonesia, UGT1A1 polymorphisms do not appear to be associated with differences in the severity of hyperbilirubinemia.

SLCO1B1 c.388A\u2009>\u2009G variant incidence and the severity of hyperbilirubinemia in Indonesian neonates

ObjectiveIt has been established that genetic factors play a substantial role in the development of neonatal hyperbilirubinemia. The population of Indonesia and other Southeast Asian countries has similar, yet different genetic makeup compared to the rest of Asia. Aside from UGT1A1, variants of SLCO1B1 have also been known to contribute to the severity of neonatal hyperbilirubinemia in Asian populations. Since there has been no report on SLCO1B1 polymorphism in relation with hyperbilirubinemia in Indonesia, this study aims to explore incidence of SLCO1B1*1B polymorphism in Indonesia based on 3 hospitals from different provinces and population, and their association with hyperbilirubinemia severity.MethodsOur study included 88 neonates with mild and moderate-severe hyperbilirubinemia from 3 NICU in hospitals representing homogenous and heterogenous populations: Biak General Hospital Papua, Cipto Mangunkusumo Hospital (Jakarta), and M Yunus Hospital (Bengkulu). We collected samples between November 2016 and September 2017. DNA was obtained from existing samples of the patients from previous studies and were subjected to Polymerase Chain Reaction – Restriction Fragment Length Polymorphism (PCR-RFLP). We analyzed the *1B variant located in exon 5 of SLCO1B1 with TaqI restriction endonuclease. Clinical, demographic, and laboratory data was also collected from medical records and parents’ interviews.ResultsThe most dominant variant of SLCO1B1*1B in our population is the homozygous G/G (68.18%), followed by heterozygous A/G (26.14%), and wild type A/A (5.68%). The heterozygous A/G had an Odds Ratio (OR) of 0.73 (95% CI 0.10–5.2) and homozygous G/G with OR of 0.51 (95%CI 0.08–3.27), both were not significant. Genotypic distribution across the different centers were also similar and not significant. The significant risk factors for moderate-severe hyperbilirubinemia were the population the neonate originated from (p = < 0.001) and the delivery location (p = 0.001), while SLCO1B1*1B was not associated with the different severity of hyperbilirubinemia.ConclusionsSLCO1B1*1B is not associated with higher bilirubin levels among neonates with hyperbilirubinemia in Indonesia. Further study is needed to find other potentially important genetic polymorphisms in the development of severe hyperbilirubinemia in Indonesia.

The correlation between frequency and duration of breastfeeding and the severity of neonatal hyperbilirubinemia

Introduction: Inadequate intake of calorie or inadequate breastfeeding can cause neonatal hyperbilirubinemia. The present study was conducted to examine the correlation between frequency and duration of breastfeeding and the severity of neonatal hyperbilirubinemia among newborns admitted to Ghaem Hospital of Mashhad (Iran) due to neonatal hyperbilirubinemia.Methodology: The present cross-sectional study was conducted on 634 newborns with idiopathic hyperbilirubinemia referred to either Emergency Department or Neonatal Clinic in Ghaem Hospital. The required data were collected through a researcher-made questionnaire covering information related to mothers and babies. The examined neonates were examined based on the frequency and duration of breastfeeding and the severity of hyperbilirubinemia. The collected data were analyzed using statistical tests of Shapiro–Wilk and Chi-squared (SPSS-19.5).Results: According to the results, at bilirubin levels of 1–12 mg/dl, 12.1–16 mg/dl, 16.1–20 mg/dl and >20 mg/dl, the average frequencies of breastfeeding were respectively 10.66, 9.83, 9.19 and 7.50 times a day. The average serum bilirubin level in newborns with ≤7 times breastfeeding per day (19 mg/dl) was higher than newborns with >7 times breastfeeding per day (16 ml/dl). Additionally, by an increase in the frequency of breastfeeding, the percentage of weight loss decreased in the examined newborns. The results also showed that in newborns with bilirubin levels <20 mg/dl, the severity of hyperbilirubinemia reduced by increased defecation frequency and decreased percentage of weight loss.Conclusion: The results of this study showed that increased frequency of breastfeeding, accelerated weight gain and increased defecation frequency reduce the severity of neonatal hyperbilirubinemia. Accordingly, breastfeeding education for mothers with an emphasis on increasing the frequency of breastfeeding is a helpful technique to reduce the severity of hyperbilirubinemia in newborns.

The role of UGT1A1 promoter polymorphism and exon-1 mutations in neonatal jaundice

Objective: In the present study, we investigated the effects of promoter polymorphism and an exon-1 mutation (G71R) in the UGT1A1 gene in neonates with unexplained hyperbilirubinemia and direct Coombs-negative [DC(–)] ABO incompatibility. Methods: Two-hundred term neonates in their first week of life and without additional icterogenic factors were included in the study. Neonates with a serum total bilirubin (STB) level ≥17 mg/dL constituted the hyperbilirubinemia group (n = 100), while the control group comprised healthy neonates with a STB level <12.9 mg/dL (n = 100). The cases were further subdivided into unexplained hyperbilirubinemia (n = 50), ABO(+) hyperbilirubinemia (n = 50), ABO(–) control (n = 50), and ABO(+) control (n = 50) groups on the basis of the presence or absence of DC(–) ABO incompatibility. DNA was isolated from peripheral blood and amplified by PCR, and UGT1A1 gene promoter and exon-1 were sequenced to verify sequence alterations. Results: The frequency of TA6/6, TA6/7, TA7/7, and GGA/GGA, GGA/AGA, AGA/AGA genotypes was found to be 63.5%, 21%, 15.5%, and 91.5%, 8%, 0.5%, respectively. While both heterozygous and homozygous TA7 polymorphism increased risk of hyperbilirubinemia in the ABO(+) hyperbilirubinemia group (heterozygous OR 16.76, 95% CI:3.52-79.70, p < 0.0001; homozygous OR 6.81, 95% CI:1.98-23:42, p = 0.002), only heterozygous TA7 polymorphism increased jaundice risk (OR 5.08 95% CI:76-14.65, p = 0.003) in unexplained hyperbilirubinemia. But, the coexistence of G71R mutation and promoter polymorphism or G71R mutation and DC(–) ABO incompatibility did not increase the severity of hyperbilirubinemia (p > 0.05). Conclusions: UGT1A1 gene promoter polymorphism and G71R mutation are possible risk factors for Turkish neonates with DC(–) ABO incompatibility and unexplained hyperbilirubinemia.

Changes of electroencephalographic activities during fully automated simultaneous peripheral arteriovenous exchange transfusion in neonates with hyperbilirubinemia

Objective To analyze the changes of electroencephalographic activities during fully automated simultaneous peripheral arteriovenous exchange transfusion(ET) in neonates with hyperbilirubinemia. Methods A total of 45 neonates who suffered from severe hyperbilirubinemia and underwent fully automated simultaneous peripheral arteriovenous exchange transfusion were studied from March 2009 to March 2016 in Neonatal Intensive Care Unit of Guangzhou Women and Children's Medical Center, and 46 ETs were performed in 45 babies who were divided into 2 groups according to the severity of hyperbilirubinemia: the encephalopathy group and the none-encephalopathy group.Nineteen patients were in the encephalopathy group, in which 11 were male and 8 were female.The other 26 patients were in the none-encephalopathy group, in which 15 were male and 11 were female.Changes in amplitude integrated electroencephalogram(aEEG) during ETs were analyzed, including background activities, sleep-wake cycle (SWC) and seizures. Results Forty-five patients with hyperbilirubinemia underwent 46 fully automated simultaneous perip-heral arteriovenous ETs. As a result, total bilirubin dropped from (524.90±110.96) μmol/L before ETs to (245.62±78.97) μmol/L after ETs, with clearance rate of 53.2%. And indirect bilirubin dropped from(486.16±90.39) μmol/L before ETs to(222.19±79.49) μmol/L after ETs, with clearance rate of 54.3%. On the other hand, there was no significant difference in the changes of electroencephalographic activities during ETs, including background activities(χ2=0.16, P>0.05), SWC(χ2=0.71, P>0.05) and seizures(χ2=0.30, P>0.05). However, there were significant difference in suppressions on background activities between the encephalopathy group and the none-encephalopathy group(Fisher's exact test P=0.042), though there were no significant statistical differences in SWC or seizures between the 2 groups ( χ2=0.65, P>0.05; χ2=2.07, P>0.05, respectively). Conclusions In neonatal hyperbilirubinemia, fully automated simultaneous peripheral arteriovenous ET is safe and efficient without significant influence on electroencephalographic activities as a whole.However, background activities are more significantly depressed in infants of bilirubin encephalopathy than that of non-encephalopathy during ET. Key words: Fully automated simultaneous peripheral arteriovenous exchange transfusion; Amplitude integra-ted electroencephalogram; Hyperbilirubinemia; Infant, newborn

Bilirubin-Induced Neurotoxicity and Environmental Impacts on Hyperbilirubinemia Development

Hyperbilirubinemia (also known as jaundice), caused by the accumulation of unconjugated bilirubin, is one of the most common clinical diagnoses in both premature and term newborns. Owing to the fact that bilirubin is metabolized solely through glucuronidation by UDP-glucuronosyltransferase (UGT) 1A1, it is now known that immaturity of UGT1A1 in combination with overproduction of bilirubin during the developmental stage acts as a bottleneck to bilirubin elimination and predisposes the infant to high TBS levels. While neonatal jaundice is mostly benign, excessively high levels of serum bilirubin in a small percentage of newborns can cause acute or chronic bilirubin-induced neurologic dysfunction (BIND), potentially progressing to acute encephalopathy leading to irreversible brain damage and death. As a series of hereditary UGT1A1 mutations have been identified that are associated with UGT1A1 deficiency, new evidence has verified that developmental expression of UGT1A1 is a tightly controlled event, and both genetic polymorphisms and developmental regulation of UGT1A1 are major contributing factors determining the severity of hyperbilirubinemia and bilirubin-induced neurotoxicity. This review recapitulates the progress that has been made in recent years in understanding etiology and physiopathology of severe hyperbilirubinemia, investigating molecular mechanisms underlying bilirubin-induced encephalopathy, and searching for potential therapies for treating pathologic hyperbilirubinemia. Several animal models have been developed to make it possible to examine bilirubin-induced neurotoxicity from multiple directions. Moreover, environmental factors that may alleviate or worsen the condition of hyperbilirubinemia are discussed.

Metabolic and kidney disorders correlate with high atazanavir concentrations in HIV-infected patients: is it time to revise atazanavir dosages?

IntroductionRitonavir-boosted atazanavir (ATV/r) is a relatively well tolerated antiretroviral drug. However, side effects including hyperbilirubinemia, dyslipidemia, nephrolithiasis and cholelithiasis have been reported in the medium and long term. Unboosted ATV may be selected for some patients because it has fewer gastrointestinal adverse effects, less hyperbilirubinemia and less impact on lipid profiles.MethodsWe investigated the distribution of ATV plasma trough concentrations according to drug dosage and the potential relationship between ATV plasma trough concentrations and drug-related adverse events in a consecutive series of 240 HIV-infected patients treated with ATV/r 300/100 mg (68%) or ATV 400 mg (32%).Results43.9% of patients treated with ATV/r 300/100 mg had ATV concentrations exceeding the upper therapeutic threshold. A significant and direct association has been observed between the severity of hyperbilirubinemia and ATV plasma trough concentrations (ATV concentrations: 271 [77–555], 548 [206–902], 793 [440–1164], 768 [494–1527] and 1491 [1122–1798] ng/mL in patients with grade 0, 1, 2, 3 and 4 hyperbilirubinemia, respectively). In an exploratory analysis we found that patients with dyslipidemia or nephrolitiasis had ATV concentrations significantly higher (582 [266–1148], and 1098 [631–1238] ng/mL, respectively) (p<0.001), as compared with patients with no ATV-related complications (218 [77–541] ng/mL).ConclusionsA significant proportion of patients treated with the conventional dosage of ATV (300/100) had plasma concentrations exceeding the upper therapeutic threshold. These patients that are at high risk to experience ATV-related complications may benefit from TDM-driven adjustments in ATV dosage with potential advantages in terms of costs and toxicity.

Is it Accurate to Separate Glucose-6-Phosphate Dehydrogenase Activity in Neonatal Hyperbilirubinemia as Deficient and Normal?

The aim of this study was to investigate glucose 6-phosphate dehydrogenase (G6PD) activity in term and late preterm babies with severe neonatal hyperbilirubinemia and its relationship to the severity and treatment of this disorder, regardless of level of G6PD activity (deficient/normal). A total of 529 term and late preterm (≥35 weeks) infants (228 female, 301 male) who were diagnosed with severe hyperbilirubinemia were included in this study. In each case, serum was collected to evaluate blood group, direct Coombs' test, complete blood cell count, total and direct bilirubin, thyroid-stimulating hormone, and G6PD activity. A partial correlation analysis was carried out to assess the relationship between G6PD activity and total bilirubin levels. A significant correlation was found between the severity of hyperbilirubinemia and G6PD activity in both males and females. Male neonates who had G6PD levels <12U/g Hb required more phototherapy time than neonates who had G6PD levels ≥12U/g Hb; and female neonates who had G6PD levels <16U/g Hb required more phototherapy time than neonates who had G6PD levels ≥16U/g Hb (p<0.0001). When we analyzed only breastfed infants, a significant difference also emerged in both sexes. Decreased G6PD activity was associated with increased phototherapy time and the need for exchange transfusion. Routine checks of G6PD level in hyperbilirubinemic neonates are very important in providing proper medical management to prevent bilirubin-induced neurological dysfunction. Appropriate identification of G6PD (<12U/g Hb for male infants and <16U/g Hb for female infants) raises awareness of the severity of the condition and the necessity for immediate care of severe hyperbilirubinemic infants.

Correlation of UGT1A1 TATA-box polymorphism and jaundice in breastfed newborns-early presentation of Gilbert's syndrome

Objective: The etiology of jaundice in otherwise healthy breastfed newborns that can present as early-onset exaggerated physiologic jaundice, or late breast milk jaundice (BMJ), is not yet entirely understood. This study tested the hypothesis that molecular marker for Gilbert's syndrome (GS), UGT1A1 TATA-box polymorphism, is associated with this disorders.Methods: We have investigated the UGT1A1 polymorphism frequency and its relation to severity of hyperbilirubinemia and jaundice duration among 220 exclusively breastfed term newborns; 57 of them with non-physiologic hyperbilirubinemia (NH), and 163 with BMJ, and in 187 healthy controls.Results: Significant differences in TA7/7 genotype frequency were established. The highest frequency was observed among the newborns with BMJ (42.0%), intermediate in the NH group (24.6%), while the controls had the lowest TA7/7 frequency (12.8%). Linear increase in TA7/7 frequency was observed depending on the duration of jaundice, peaking at 42.4% in newborns with the longest jaundice duration. Positive correlation between the serum bilirubin levels and the TATA-box length was established in all groups.Conclusion: This study provides evidence that UGT1A1 TATA-box polymorphism is an important risk factor for developing jaundice in term breastfed newborns, presented as either early non-physiologic hyperbilirubinemia or breast milk jaundice. These results further support the original Odell's idea of neonatal jaundice as an early presentation of GS.

Early corticosteroid treatment does not affect severity of unconjugated hyperbilirubinemia in extreme low birth weight preterm infants

To determine the relationship between early postnatal dexamethasone (DXM) treatment and the severity of hyperbilirubinemia in extreme low birth weight (ELBW) preterm infants. In 54 ELBW preterm infants, total serum bilirubin concentrations (TSB) and phototherapy (PT) data during the first 10 days were evaluated retrospectively. ELBW infants had participated in a randomized controlled trial of early DXM treatment which aimed to assess effects on chronic lung disease. Infants had been treated with DXM (0.25 mg/kg twice daily at postnatal day 1 and 2) or with placebo (normal saline). Analysis was performed on an intention to treat basis. Twenty-five Infants had been randomized into the DXM group; 29 into the placebo group. Mean (±SD) TSB [120 (±19) μmol/L vs. 123 (±28) μmol/L, DXM versus placebo, respectively] and maximum TSB [178 (±23) μmol/L vs. 176 (±48), DXM versus placebo, respectively] concentrations were similar. TSB concentrations peaked 30 h earlier in the DXM group (p ≤ 0.05). The need for PT as well as the duration of PT was similar in both groups. Early DXM treatment does not affect the severity of neonatal hyperbilirubinemia in ELBW preterm infants. Our results seem compatible with the concept that factors other than bilirubin conjugation capacity are important for the pathophysiology of neonatal jaundice in ELBW preterm infants.

Neonatal non-hemolytic hyperbilirubinemia: a prevalence study of adult neuropsychiatric disability and cognitive function in 463 male Danish conscripts

ObjectiveTo examine whether neonatal non-hemolytic hyperbilirubinemia is associated with adult neuropsychiatric disability and cognitive function.MethodsThe study included all men born as singletons ≥35 gestational weeks in two Danish counties from...

(TA)n UDP-Glucuronosyltransferase 1A1 Promoter Polymorphism in Nigerian Neonates

Nigerian neonates have a high incidence of bilirubin encephalopathy. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is prevalent in this population. (TA)7 promoter polymorphism in the gene encoding the bilirubin conjugating enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) potentiates hyperbilirubinemia in G-6-PD deficient neonates. We studied (TA)n allele frequency to determine, at least in part, its contribution to the frequency and severity of hyperbilirubinemia. DNA was extracted from umbilical cord blood of sequentially born Nigerian neonates and the (TA)n UGT1A1 promoter sequence determined. The (TA)n allele distribution was compared with reported adults of varying African ancestry and Sephardic Jewish neonates. Among 88 Nigerian neonates, (TA)6 and (TA)7 alleles were almost equally distributed (0.46 and 0.43, respectively). Some individuals with (TA)5 and (TA)8 sequences were encountered. Allele distribution was similar to that of the African ancestry population but differed from the Sephardic Jewish newborns, in whom the (TA)6/(TA)7 distribution was 0.65/0.35. Whereas 45% of Nigerian alleles and 50% of African ancestry alleles, respectively, included a (TA)7 or (TA)8 sequence, only 35% of Jewish alleles were (TA)7 (p < 0.001), and no (TA)8 alleles were encountered. The high frequency of (TA)n promoter polymorphism, coupled with G-6-PD deficiency, may contribute to the pathogenesis of extreme neonatal hyperbilirubinemia in Nigeria.