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Competing Interests: JG a consultant and advisor and has received research grants from AbbVie, Camurus, Cepheid, Gilead, Hologic, Indivior, and Merck. GJD has received research grants from AbbVie, Gilead, and Merck. ARL has received testing equipment and tests from Cepheid.

Serum ferritin is currently the recommended laboratory test to investigate iron deficiency. There have been efforts to standardise serum ferritin assays with implementation of traceability to the World Health Organization reference standard. We evaluate the analytical bias among five widely used commercial ferritin assays in Australia. The relationship between serum ferritin and erythrocyte parameters was recently explored to derive functional reference limits. Residual patient serum specimens were analysed by five participating laboratories that utilised a different ferritin assay, Abbott, Beckman Coulter, Roche, Siemens, and Ortho. Using data mining approach, functional reference limits for Siemens, Abbott, and Ortho serum ferritin methods were derived and compared. At clinically relevant ferritin decision points, compared to the Beckman method, the Roche assay showed higher results ranging from 6 μg/L (31%) at the lowest decision point to 575 μg/L (57%) at the highest decision point. In contrast, the Ortho method underestimated ferritin results at lower decision points of 20 and 30 μg/L, with estimated ferritin results of 16 μg/L (-19%) and 27 μg/L (-12%), respectively. The Abbott and Siemens assays showed a positive bias which was introduced at differing decision points. The comparison of the Siemens and Ortho methods presents similar inflection points between the two assays in the establishment of functional reference limits for serum ferritin. There remain significant biases among some of the commonly used commercial ferritin assays in Australia. More studies are needed to assess if functional reference limits are a way to overcome method commutability issues., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Background: Pregnancy is a time of dynamic physiological changes occurring as a continuous spectrum. Smoothed centile curves describe the distribution of measurements as a function of age. There has been no application of centile charts in pregnancy for haematological parameters., Aims: To derive gestational age-specific centile curves for six haematological parameters and compare these with published reference intervals., Materials and Methods: An LMS approach was used with haematology results from an obstetric hospital laboratory database. After application of exclusion criteria, smoothed centiles conditional on gestational age were obtained by a two-step process: (i) finding the best model within four response distributions using Bayesian information criteria, and (ii) selecting the best model among the response distributions based on test-dataset global deviance., Results: In total, 11 255 deliveries were extracted from 10 813 patients. There was little difference between distributions, and Box-Cox power exponential was selected overall. Red cell parameters showed similar trends: values fell until the second trimester and increased thereafter. Leukocyte and neutrophil counts rapidly increased and plateaued around 15 weeks. Platelets exhibited a gradual fall with advancing gestation., Conclusions: This is the first study to use an LMS approach to model gestational age-dependent variations in haematological parameters. Proposed haemoglobin reference intervals were lower than those published but reflect our patient population. Serial monitoring of antenatal patients, as is the standard of care, in conjunction with these centile charts, may highlight trends in red cell changes with advancing gestation, allowing early identification of adverse pregnancy outcomes and evolving anaemia., (© 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach., Methods: We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool., Discussion: Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial., Trial Identifiers: Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.