Background Hyperbilirubinemia is a condition that affects most infants, but typically self-resolves and is not harmful. However, if bilirubin levels exceed neuroprotective defenses, the compound can cross the blood-brain barrier and have neurotoxic and potentially fatal effects. Treatment of neonatal hyperbilirubinemia with phototherapy is necessary for the prevention of kernicterus. Guidelines for the use of phototherapy in infants born at ≥ 35 weeks’ gestation were published by Bhutani et al. and endorsed by the American Academy of Pediatrics. Consensus-based recommendations for phototherapy treatment and exchange transfusion of premature infants were published in 2012 by Maisels, et al. However, there are no published recommendations for the timing of screening for hyperbilirubinemia in NICU patients. In 2012, the Kapʻiolani Medical Center for Women & Children Neonatology Division implemented internal guidelines for phototherapy with recommendations for the timing of screening serum bilirubin levels, based on the group’s opinion. Five years later, the current study queried whether these guidelines for screening were appropriate. Objective The present study sought to describe current practices of obtaining serum bilirubin levels and the use of phototherapy in the NICU during the first five days of life. It was hypothesized that many bilirubin levels obtained at ≤ 48 hours of life are below published recommended treatment thresholds and are potentially unnecessary. Methods Retrospective chart review was performed on all infants admitted to the NICU at < 24 hours of life, from July 2016-June 2017. Eligible infants were divided into three gestation age groups: ≤ 28, 29-35, and ≥ 36 weeks at birth. Patient demographics, bilirubin levels, and phototherapy treatment were noted. The primary outcome of interest was the percent of serum bilirubin levels obtained during the first 48 hours of life that did not meet phototherapy treatment criteria. Results 931 charts were reviewed. Infants born at ≤ 28, 29-35 and ≥ 36 weeks’ gestation made up 10%, 51% and 39% of the cohort. Overall mortality was 3%, and no exchange transfusions were performed during the study period. At least one serum bilirubin level was obtained for 96% of the patients, but only 55% were treated with phototherapy within the first five days of life. Phototherapy was rarely prescribed on day of life (DOL) 1 (0.7%). By DOL 2, a total of 563 bilirubin levels were obtained, but only 108 infants (19%) were treated with phototherapy. However, one-third of these patients’ bilirubin levels did not meet published criteria for treatment. The timing of phototherapy treatment varied by gestational age. Ninety percent of infants born ≤ 28 weeks’ gestation who received phototherapy were treated starting between DOL 2-3. In contrast, eighty-five percent of infants born ≥ 29 weeks’ gestation who received phototherapy, started on DOL 3-5. Discussion Far more bilirubin levels were obtained than courses of phototherapy prescribed. Given the distinct patterns of phototherapy for infants of varying gestational age, there is ample opportunity to improve resource utilization with targeted recommendations for obtaining screening bilirubin levels in the neonate without early jaundice.

No description available.

Jaundice is probably the most common newborn infant problem dealt with on a daily basis by the family practitioner and paediatrician. Jaundice occurs when the liver cannot clear a sufficient amount of bilirubin from the plasma. When the problem is excessive bilirubin formation or limited uptake or conjugation, unconjugated (i.e., indirect reacting) bilirubin appears in the blood and indirect hyperbilirubinemia is the predominant form of jaundice found in the newborn infant. In the vast majority of newborns, hyperbilirubinemia is transient and benign but, in rare cases, the serum bilirubin rises to a level that is toxic to the central nervous system. Understanding the pathogenesis and epidemiology of neonatal hyperbilirubinemia; recognizing, the problems involved in appropriate surveillance and monitoring of the jaundiced infant and the factors contributing to bilirubin encephalopathy; and implementing treatment of the jaundiced neonate in a timely fashion, are issues that have engaged clinicians and researchers for some 6 decades. This work will summarize my contributions to the field of neonatal hyperbilirubinemia and it includes papers published between 1971 and 2007. The description of this work will not follow its chronological sequence, but will be divided into the categories of diagnosis, epidemiology, pathogenesis, management, treatment, and bilirubin encephalopathy.

by Li Wen. / "April 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 200-236). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成7年12月20日 北川喜己氏の博士論文として提出された

Thesis (Ph. D.)--University of Nevada, Reno, 2008. / "December 2008." Includes bibliographical references (leaves 287-298). Online version available on the World Wide Web.

Identification and functional characterization of numerous transport systems at the sinusoidal and canalicular membrane of hepatocytes have significantly expanded our understanding of bilirubin metabolism and contributed to elucidation of molecular basis of hereditary jaundice. Moreover, dysregulation of hepatobiliary transport systems could explain jaundice in many acquired liver disorders. This thesis is focused on the new aspects of bilirubin handling in hepatocytes based on elucidation of the molecular basis of Rotor syndrome. The first study is focused on the antioxidative properties of bilirubin in liver tissue in a model of obstructive cholestasis. In the second part of the thesis we present several novel mutations in ABCC2, the gene associated with Dubin-Johnson syndrome, identified in patients selected for the Rotor locus mapping study. In the key third study concerned with Rotor syndrome we demonstrated that biallelic inactivating mutations causing complete absence of transport proteins OATP1B1 and OATP1B3 result in disruption of hepatic reuptake of bilirubin, which is the molecular basis of Rotor-type jaundice. These results indicate that apart from secretion of conjugated bilirubin into bile, a significant fraction of bilirubin glucuronide is secreted via MRP3 into sinusoidal blood and...

Orientador: Fernando Perazzini Facchini, Sergio Tadeu Martins Marba / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-09T10:38:23Z (GMT). No. of bitstreams: 1 Leite_MariadasGracasdaCunha_D.pdf: 4639567 bytes, checksum: 1396117012228a6590af2c4de8b522c5 (MD5) Previous issue date: 2007 / Resumo: Objetivo: Comparar dosagens transcutâneas de bilirrubina realizadas com o ¿Bilicheck®¿ com as dosagens de bilirrubina total plasmática realizada pelo ¿Bilirrubinômetro Unistat- Leica®¿em neonatos. Métodos: Um total de 200 recém-nascidos foram incluídos no estudo, sendo que cada um teve apenas uma dosagem pelo ¿Bilicheck®¿ , seguida de coleta capilar e dosagem através de espectrofotometria direta pelo ¿Bilirrubinômetro Unistat-Leica®¿. Foram analisadas as correlações e concordâncias entre os métodos e a influência das variáveis: peso de nascimento, raça, idade gestacional, idade pós-natal e uso de fototerapia. Estabelecemos pontos de corte nas dosagens pelo ¿Bilirrubinômetro Unistat-Leica®¿ para avaliarmos a sensibilidade e especificidade do ¿Bilicheck®¿, em níveis de bilirrubina considerados como limites para modificação das terapêuticas preconizadas. Resultados: A correlação linear foi de 0,92 entre o total de pacientes (p=0,0001). A média da diferença entre as dosagens foi de 0,72 (± 1,57) mg/dl, com intervalo de confiança em 95 % de ¿ 2,42 a + 3,86 mg/dl. Dentre as variáveis estudadas, somente a idade pós-natal inferior a 3 dias de vida sofreu interferência na dosagem transcutânea de bilirrubina (p= 0,0030). Considerando a dosagem pelo ¿Bilirrubinômetro Unistat-Leica®¿ como padrão de referência, foram confeccionadas repetidas curvas ROC, sendo o melhor ponto de corte o valor correspondente a 14 mg/dl pelo ¿Bilicheck®¿ com sensibilidade de 88,2%, especificidade de 97,8%, valor preditivo positivo 78,9%, valor preditivo negativo 98,9% e área abaixo da curva de 0,98. Conclusão: A dosagem transcutânea de bilirrubina realizada pelo ¿Bilicheck®¿ pode substituir a dosagem feita pelo ¿Bilirrubinômetro Unistat-Leica®¿ até o valor de 14 mg/dl. Acima deste nível, deve ser considerada apenas como rastreador na seleção de pacientes que devem ser submetidos à dosagem sanguínea / Abstract: Aim: To compare transcutaneous bilirubin m easurement determined by ¿Bilicheck®¿ with capillary serum measurement determined by ¿U nistat-Leica Bilirubinometer¿ in newborns. Methods: A total of 200 newborns were included. For each one, paired measurements (serum, with ¿Unistat-Leica Bilirubinometer¿ and transcutaneous, with ¿Bilicheck®¿ were performed. Their correlation and agreement were analyzed and it was verified the influence of birth weight, race, gestational age, postnat al age and use of phototherapy. We also tried to establish cutoff points in ¿Unistat-Leica Bilirubinometer¿ measurements to access the sensibility and specificity of the ¿Bilicheck®¿ in the critic levels of bilirrubin that are considered for indication of treatments. Results: The linear correlation was 0.92 ( p=0.0001), the average difference between the measurements was 0.72 (± 1.57) mg/dl, with a confidence interval of 95% from -2.42 to +3.86 mg/dl. The only variable that exhi bited a small statistical difference (p=0.003) was postnatal age of less than 3 days. Considering the ¿Bilirubin ometer Unistat-Leica¿ as gold standard, a series of ROC curves were constr ucted revealing that the best cutoff point was at 14 mg/dl with sensitivity of 88.2%, specifi city of 97.8%, positive predictive value of 78.9% and negative predictive value of 98.9% and the area under the curve was 0.98. Conclusion: The ¿Bilicheck®¿ may substitute th e capillary serum measurement until the value of 14 mg/dl. Above this level, it should be considered as a screening test selecting patients that must be submitted to serum measurement / Doutorado / Pediatria / Doutor em Saude da Criança e do Adolescente

Identification and functional characterization of numerous transport systems at the sinusoidal and canalicular membrane of hepatocytes have significantly expanded our understanding of bilirubin metabolism and contributed to elucidation of molecular basis of hereditary jaundice. Moreover, dysregulation of hepatobiliary transport systems could explain jaundice in many acquired liver disorders. This thesis is focused on the new aspects of bilirubin handling in hepatocytes based on elucidation of the molecular basis of Rotor syndrome. The first study is focused on the antioxidative properties of bilirubin in liver tissue in a model of obstructive cholestasis. In the second part of the thesis we present several novel mutations in ABCC2, the gene associated with Dubin-Johnson syndrome, identified in patients selected for the Rotor locus mapping study. In the key third study concerned with Rotor syndrome we demonstrated that biallelic inactivating mutations causing complete absence of transport proteins OATP1B1 and OATP1B3 result in disruption of hepatic reuptake of bilirubin, which is the molecular basis of Rotor-type jaundice. These results indicate that apart from secretion of conjugated bilirubin into bile, a significant fraction of bilirubin glucuronide is secreted via MRP3 into sinusoidal blood and...

No description available.