Association Of Hyperbilirubinemia Research Articles

Prevalence and association of early onset severe hyperbilirubinemia in newborn in the East China region: Retrospective medical record analyses.

Research on the prevalence and association of hyperbilirubinemia is controversial because of different cultures, demographics, and clinical conditions. The etiology of hyperbilirubinemia is affected by the environment and other factors in the newborn. The World Health Organization recommended a 1-day hospital stay after uncomplicated delivery, jaundice assessment before discharge, and screening on 3rd and 7th days after birth for hyperbilirubinemia. However, the implementation of these recommendations is difficult in China. The objective of this study was to evaluate the prevalence and association of early onset severe hyperbilirubinemia in newborns in East China. Retrospective medical record analyses for 250 cesarean sections or vaginal deliveries, ≥2 kg body weight, and negative for Hepatitis B surface antigen by birth newborns were performed. A biochemical analyzer, quantitative assay, and quantitative polymerase chain reaction were used to evaluate total serum bilirubin, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and gene variant phenotyping, respectively. A total in 33 (13%) newborns were reported with early onset severe hyperbilirubinemia (according to the American Academy of Pediatrics, total serum bilirubin ≥ 342 μmol/L within 6 hours of birth). All newborns with severe hyperbilirubinemia were hospitalized and underwent phototherapy. The mothers of all newborns had a gestational age ≥ 35 weeks. Hospitalization included artificial feeding, and breastfeeding was rare (P < .0001). ABO incompatibility ("O" blood type for mother and either "A" or "AB" or "B" blood type for newborn, P = .0411), G6PD deficiency (G6PD/6-phosphogluconate dehydrogenase ≤ 1.0 in quantitative assay, P = .0422), Rh incompatibility (the mother's blood type was Rh negative and newborn blood type was Rh positive, P = .0416), fewer genotype rs4149056 frequencies (P = .0452), higher genotype rs2306283 frequencies (P = .0461), and higher genotype rs1805173 frequencies (P = .0471) were independent parameter for early onset severe hyperbilirubinemia of newborns. The prevalence of early onset severe hyperbilirubinemia in Chinese newborns is 13% in the East China region. Blood incompatibility, G6PD deficiency, fewer genotype rs4149056 frequencies, higher genotype rs2306283 frequencies, and higher genotype rs1805173 frequencies were independent predictors of early onset severe hyperbilirubinemia among newborns in the East China region (Level of Evidence: IV; Technical Efficacy: Stage 5).

Association of hyperbilirubinemia in pazopanib- or sunitinib-treated patients in COMPARZ with UGT1A1 polymorphisms.

4569 Background: A phase III randomized clinical trial (COMPARZ) comparing pazopanib vs sunitinib for treatment of advanced renal cell carcinoma demonstrated similar efficacies but different safety profiles for the two therapies. Elevations in serum total bilirubin have been observed in patients receiving either therapy. UGT1A1 polymorphisms are associated with elevated bilirubin in the general population (Gilbert’s syndrome). This study investigated the association between functional UGT1A1 polymorphisms and on-therapy serum total bilirubin in the COMPARZ study. Methods: Patients homozygous or compound heterozygous for UGT1A1 *28, *37, and *6 alleles were predicted to have reduced UGT1A1 function. Logistic regression adjusted for ancestry principal components was used to compare patients with on-therapy hyperbilirubinemia (≥1.5 × upper limit of normal [ULN]; pazopanib, N = 62; sunitinib, N = 34) against patients exposed to treatment and with maximum on-therapy bilirubin ≤1 × ULN (pazopanib, N = 213; sunitinib, N = 215), excluding patients with maximum on-therapy bilirubin between 1 and 1.5 × ULN (pazopanib, N = 96; sunitinib, N = 104). Results: Patients with predicted reduced UGT1A1 function had higher baseline bilirubin and also were more likely to experience hyperbilirubinemia when receiving either pazopanib (P = 6.9×10–8) or sunitinib (P = 1.8×10–3). After adjusting for baseline bilirubin, patients with predicted reduced UGT1A1 function remained more likely to experience hyperbilirubinemia when receiving pazopanib (P = 0.015) or sunitinib (P = 0.026), with odds ratio (95% CI) 3.53 (1.28–9.76) and 4.41 (1.23–15.75), respectively. Conclusions: The data suggest that some instances of hyperbilirubinemia in patients treated with pazopanib or sunitinib may be benign manifestations of Gilbert’s syndrome. Bilirubin fractionation or, if not available, UGT1A1 genotyping, would enable further characterization of liver safety risk and help in making treatment decisions.

Decreased oxidation susceptibility of plasma low density lipoproteins in patients with Gilbert's syndrome

The association of hyperbilirubinemia in Gilbert's syndrome (GS) with a decrease in prevalence of coronary artery disease is a well-known phenomenon. In this study, the state of low-density lipoprotein (LDL) oxidation which has been postulated to be a significant determinant at the etiopathogenesis of atherosclerotic disorders was investigated among individuals with GS. For this purpose, serum cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, apolipoprotein A and B, bilirubins, thiobarbituric acid-reactive substances, and the sensitivity of LDL oxidation levels, as well as serum alanine aminotransferase, aspartate aminotranserfase, gamma glutamyl transferase, and alkaline phosphatase activities, were determined in 17 patients with Gilbert's syndrome and 15 healthy adults. There was no significant difference between the groups except the indirect bilirubin parameter (P < 0.001). In comparison with the healthy individuals, LDL oxidation levels between 75 and 120 min were significantly lower (P < 0.005) along with prolonged lag-phase in GS patients, indicating a delay in oxidation susceptibility. It is suggested that the chronic hyperbilirubinemia leading to a lag-phase prolongation in LDL oxidation and a decrease in LDL oxidation may be reason for the low percentage of coronary artery disease.

Hypoglycemia in severely affected Rh erythroblastotic infants

The known association of hyperbilirubinemia and kernicterus demands methods to determine an individual infant's risk of kernicterus. Indirect albumin dye binding methods (PSP or HBABA) have been used, yet these methods are of uncertain value. Study of bilirubin-albumin binding itself and a better understanding of factors which influence the binding are necessary to evaluate the risks of kernieterus. A Sephadex G-25 column (0.9 x 10 cm.) with 0.1M phosphate buffer was used to separate bound from unbound bilirubin in pooled cord sera, sera of individual infants, adult sera, and albumin solutions. The eluate contains the bilirubin-albumin complex, while the free bilirubin remains on the column. Addition of increasing amounts of bilirubin to the serum samples reveals binding characteristics of individual specimens. Infant sera bind significantly less bilirubln (bilirubin-albumin ratio of 0.9:t) than adult sera (1.12:1) or albumin solutions (1.5:1) at pH's slightly less than physiologic pH. At higher bilirubin-albumin ratios, free bilirubin remains on the column; yet contrary to other reports, additional binding still occurs. The method is easy, rapid, and permits study not only of factors influencing bilirubin-albumin binding but also the bilirubin binding capacity of the serum of an individual jaundiced infant.