Progeny, June 2013, Vol 29, no.1

This newsletter from The Department of Public Health about perinatal health care and statistics

Transcutaneous Bilirubinometry in a Rural Teaching Hospital: A Quality Improvement Assessment

Purpose: Up to 84% of term neonates develop jaundice, a sign of hyperbilirubinemia that warrants bilirubin measurement. The AAP recommends systematic evaluation of hyperbilirubinemia risk for every infant. Serum bilirubin tests involve needle sticks, introducing anxiety, pain, and cost. Transcutaneous bilirubin (TcB) measures bilirubin without needle sticks, may offer reduced costs, but is less accurate, and may increase phototherapy rates. This determined the effect of TcB measurement on needle sticks, phototherapy rates, and cost of bilirubin measurement at a rural teaching hospital. Methods: A retrospective data analysis compared rates of bilirubin screening, needle stick testing, and phototherapy treatment for a three-month period prior to the introduction of TcB measurement with a three-month period following introduction. Rate differences were calculated with SPSS statistical package. A comparison of error test determined statistical significance. The institution’s billing and purchasing department provided cost data. Results: The introduction of TcB measurement increased hyperbilirubinemia screening from 21.1% to 83%, which was statistically significant. Needle stick testing decreased to a degree that was clinically but not statistically significant. Phototherapy treatment increased but was not statistically significant. The charge was $33.00 less per incidence than needle stick testing. Conclusions: This quality improvement assessment demonstrates that TcB screening increases systematic assessment for hyperbilirubinemia, thereby increasing adherence to AAP recommendations. This assessment highlights the need for formal studies to investigate an appropriate TcB threshold for needle stick testing, as well as the effect of such a threshold on needle stick testing to inform best practice

RISIKO GANGGUAN PENDENGARAN PADA NEONATUS HIPERBILIRUBINEMIA

ABSTRACT Background. The prevalence of hearing impairment on the Indonesian population according to 2007 WHO data is estimated at 4.2 %, and one of the cause is neonatal hyperbilirubinemia. Early detection of hearing impairment and optimal intervention on the first 6 months can prevent speech and language impairment, lack of academic achievement, disturbance of personal social relationship and emotional in the children. Method. A Cohort research was conducted in 36 neonates in Dr Kariadi Hospital in March 2009-March 2010, 18 in the case group with indirect bilirubin > 12 mg/dl and 18 neonates as control group with indirect bilirubin < 12 mg/dl, both taken with consecutive sampling method. We recorded clinical, laboratory, and tymphanometry data, OAE and BERA results at first and after three months. Statistical analysis were done using Chi-square analysis, Mc Nemar analysis, and T-test. Results. Hearing impairment on the first BERA examination was 9 cases (25%) and 3 cases (8.3%) on the second BERA examination, however it did not differed significantly (p>0,05). On the first BERA examination, the mean indirect bilirubin concentration with hearing impairment of 14,18+6,289 mg/dl was not significantly different (p>0,05) from neonate without hearing impairment of 11,29+2,995 mg/dl. The Relative Risk (RR) was 2 (p>0,05; 95% CI 0,6-6,8), but statistically it was not significant. Conclusion. The incidence of hearing impairment on neonatal with hyperbilirubinemia is 25%. Indirect bilirubin of > 12 mg/dL is not proved to be the risk factor of hearing impairment in neonatal with hyperbilirubinemia. Keywords:BERA, hearing impairment, neonatal hyperbilirubinemia, OAE

Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin

This work was funded by the Neonatal Unit Endowment Fund, Aberdeen Maternity Hospital. RH is funded by a career researcher fellowship from NHS Research Scotland. SG was funded by the MRC Flagship PhD programme. We are grateful for the support of Dr Phil Cash and Aberdeen Proteomics, at University of Aberdeen, in completing this project. Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-24811-3.Peer reviewedPublisher PD

Effective second-line treatment with cetuximab and bevacizumab in a patient with hepatic metastases of colorectal cancer and hyperbilirubinemia

Background: Irinotecan-based second-line chemotherapy of metastatic colorectal cancer (CRC) is effective, it might, however, be contraindicated in cases of severe liver dysfunction due to advanced liver metastases. Case Report: A 57-year-old woman with diffuse CRC liver metastases showed progressive disease on first-line treatment with capecitabine and oxaliplatin (XELOX). Chronic cholestasis and hyperbilirubinemia caused by advanced liver involvement prohibited second-line treatment with irinotecan-based chemotherapy. We initiated combined antibody treatment with cetuximab and bevacizumab. Results: Clinical performance status as well as laboratory parameters improved rapidly. Staging investigations after 8 weeks revealed a partial remission. Since bilirubin levels had returned to the upper limit of normal, therapy could be changed to standard irinotecan, 5-fluorouracil, folinic acid, and bevacizumab. Conclusion: Combined treatment with cetuximab and bevacizumab may be considered as an effective treatment option in patients who cannot be treated with standard chemotherapy regimens due to impaired liver metabolism of cytotoxic substances

Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings.

Hyperbilirubinaemia is a ubiquitous transitional morbidity in the vast majority of newborns and a leading cause of hospitalisation in the first week of life worldwide. While timely and effective phototherapy and exchange transfusion are well proven treatments for severe neonatal hyperbilirubinaemia, inappropriate or ineffective treatment of hyperbilirubinaemia, at secondary and tertiary hospitals, still prevails in many poorly-resourced countries accounting for a disproportionately high burden of bilirubin-induced mortality and long-term morbidity. As part of the efforts to curtail the widely reported risks of frequent but avoidable bilirubin-induced neurologic dysfunction (acute bilirubin encephalopathy (ABE) and kernicterus) in low and middle-income countries (LMICs) with significant resource constraints, this article presents a practical framework for the management of late-preterm and term infants (≥ 35 weeks of gestation) with clinically significant hyperbilirubinaemia in these countries particularly where local practice guidelines are lacking. Standard and validated protocols were followed in adapting available evidence-based national guidelines on the management of hyperbilirubinaemia through a collaboration among clinicians and experts on newborn jaundice from different world regions. Tasks and resources required for the comprehensive management of infants with or at risk of severe hyperbilirubinaemia at all levels of healthcare delivery are proposed, covering primary prevention, early detection, diagnosis, monitoring, treatment, and follow-up. Additionally, actionable treatment or referral levels for phototherapy and exchange transfusion are proposed within the context of several confounding factors such as widespread exclusive breastfeeding, infections, blood group incompatibilities and G6PD deficiency, which place infants at high risk of severe hyperbilirubinaemia and bilirubin-induced neurologic dysfunction in LMICs, as well as the limited facilities for clinical investigations and inconsistent functionality of available phototherapy devices. The need to adjust these levels as appropriate depending on the available facilities in each clinical setting and the risk profile of the infant is emphasised with a view to avoiding over-treatment or under-treatment. These recommendations should serve as a valuable reference material for health workers, guide the development of contextually-relevant national guidelines in each LMIC, as well as facilitate effective advocacy and mobilisation of requisite resources for the optimal care of infants with hyperbilirubinaemia at all levels

Bacterial Cholangitis, Cholecystitis, or both in Dogs

BACKGROUND: Bacterial cholangitis and cholecystitis are rarely reported, poorly characterized diseases in the dog. OBJECTIVES: To characterize the clinical features of these conditions. ANIMALS: Twenty‐seven client‐owned dogs with bacterial cholangitis, cholecystitis, or both. METHODS: Multicenter, retrospective cases series of dogs with bacterial cholangitis, cholecystitis, or both, presenting January 2000 to June 2011 to 4 Veterinary Schools in Ireland/United Kingdom. Interrogation of hospital databases identified all cases with the inclusion criteria; histopathologically confirmed cholangitis or cholecystitis and bile culture/cytology results supporting a bacterial etiology. RESULTS: Twenty‐seven dogs met the inclusion criteria with approximately 460 hepatitis cases documented over the same study period. Typical clinical pathology findings were increases in liver enzyme activities (25/26), hyperbilirubinemia (20/26), and an inflammatory leukogram (21/24). Ultrasound findings, although nonspecific, aided decision‐making in 25/26 cases. The most frequent hepatobiliary bacterial isolates were Escherichia coli (n = 17; 16 cases), Enterococcus spp. (n = 8; 6 cases), and Clostridium spp. (n = 5; 5 cases). Antimicrobial resistance was an important feature of aerobic isolates; 10/16 E. coli isolates resistant to 3 or more antimicrobial classes. Biliary tract rupture complicated nearly one third of cases, associated with significant mortality (4/8). Discharged dogs had a guarded to fair prognosis; 17/18 alive at 2 months, although 5/10 re‐evaluated had persistent liver enzyme elevation 2–12 months later. CONCLUSION AND CLINICAL SIGNIFICANCE: Bacterial cholangitis and cholecystitis occur more frequently than suggested by current literature and should be considered in dogs presenting with jaundice and fever, abdominal pain, or an inflammatory leukogram or with ultrasonographic evidence of gallbladder abnormalities

Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy

Acute Jaundice in a Six-year-old: An Unusual Presentation of Atypical Kawasaki Disease

Kawasaki disease (KD) is a rare vasculitis of childhood that is critical to recognize and treat due to associated morbidity and mortality. A six-year-old male presented to our emergency department (ED) afebrile but with reported recent fevers. Exam revealed jaundice and erythematous tongue with papules, and laboratory studies indicated a direct hyperbilirubinemia. Admitted for evaluation, he developed continuous fever, increasing maculopapular rash, and subsequent desquamation of hands and feet. He ultimately met criteria for incomplete KD, was treated with intravenous immunoglobulin, and avoided cardiac complications. This presentation of incomplete KD with hyperbilirubinemia is rare because the patient was afebrile at ED presentation

Effect of Conjugated Hyperbilirubinemia on the Prognosis of Patients Hospitalized in Intensive Care Unit at Kariadi Hospital Semarang

Background: In critically-ill patients, liver dysfunction plays a significant role on patient's morbidity and mortality in the intensive care unit (ICU). Metabolic, hemodynamic and inflammatory factors also contribute in liver damage. Bilirubin is one of clinical markers for liver dysfunction. Some literatures indicated that patients with hyperbilirubinemia have higher mortality rate. The aim of this study was to assess the death prognosis of critically-ill patients with hyperbilirubinemia. Method: This study was an observational, prospective, and cohort study. All patients at the ICU of Kariadi hospital with hyperbilirubinemia were consecutively recruited over 8-month period from May 1st 2008 to January 31st 2009. Hyperbilirubinemia was defined as serum bilirubin levels ≥ 1.3 mg/dL for at least 72 hours and no hyperbilirubinemia was observed when the patients were admitted to the hospital. Results: Of 79 subjects who fulfilled inclusion criteria, the incidence of hyperbilirubinemia in critically-ill patients was 39.2%. About 56 subjects were enrolled in the study. Among them, 28 subjects showed hyperbilirubinemia and the other 28 subjects were included in the control group. There was no significant difference regarding the baseline characteristics of hyperbilirubinemia group and non- hyperbilirubinemia group. At the end of the study, the mortality rate in hyperbilirubinemia patients were 60.7% and 21.3% in the non-hyperbilirubinemia patients. The relative risk (RR) of death was 2.8; (95% CI = 1.3 - 6.1; p = 0.003). Conclusion: The incidence of hyperbilirubinemia was high in critically ill-patients hospitalized in the ICU of Kariadi hospital. The incidence of death between non-hyperbilirubinemia and hyperbilirubinemia subjects was significantly different. The significant relative risk of death indicates that hyperbilirubinemia may have influences on the mortality rate of critically-ill patients hospitalized in the ICU