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The assessment of anti-mullerian hormone (AMH) pre- and post-gonadotoxic treatment helps define reproductive potential in young female adults facing cancer treatment. Normative childhood AMH levels are not well defined. Our objective was to help establish accurate pediatric reference intervals (RIs) for which AMH can be used to assess AMH in pediatric/adolescent survivors. Healthy female volunteers aged 6-19 years were recruited from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort. 300 serum samples were analyzed for AMH using an automated assay. Basic demographics and menstrual cycle data on the subjects were recorded at time of sample collection. Serum AMH distribution and RIs (2.5th and 97.5th percentiles) were established in four age groups. One recommended RI (0.98-7.84 ng/mL) was established for females aged 6-19 years after outlier removal. Females 6-9 years demonstrated significantly lower mean AMH concentration than did females 9-12 years (Mean ± SD: 3.18 ± 1.62 and 4.16 ± 2.55 ng/mL, respectively), who in turn demonstrated significantly higher AMH concentrations than those aged 12-15 years (Mean ± SD: 3.75 ± 1.61 ng/mL). Statistical differences are unlikely to be clinically meaningful. Menstrual status and ethnicity did not significantly impact AMH concentrations (p = 0.787 and p = 0.0965, respectively). This is the largest series of its kind using a contemporary, automated, single-batched AMH assay in a healthy pediatric female cohort. In conjunction with future data points and longitudinal data, the RI established may be a useful adjunct to reproductive health counselling delivered to pediatric cancer patients requiring fertility damaging therapies.

In a CODE-MI sub-study, six troponin assays were evaluated over 12 months using 3-samples (normal, female and male 99th-percentile levels; n=2,142 results from 67 instruments). Mean differences varied per assay with maximum values being ±4, ±8 and ±9 ng/L at the normal and sex-specific 99th-percentiles, respectively. A pragmatic approach, combining all assays, established maximum differences of ±3 ng/L or ±30%.

Diurnal rhythm complicates the acquisition of clinical laboratory samples by adding a predictable time-dependent component to the pre-analytical variation that, if not taken into account, degrades ...

Background: 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active vitamin D metabolite, plays a critical role in calcium and phosphate homeostasis. 1,25(OH)2D is measured to assess calcium and phosphate metabolism, particularly during periods of profound growth and development. Despite its importance, no reliable pediatric reference interval exists, with those available developed using adult populations or out-dated methodologies. Using the fully automated chemiluminescence immunoassay by DiaSorin, we established 1,25(OH)2D pediatric reference intervals using healthy children and adolescents from the CALIPER cohort. Methods: Serum samples from healthy subjects (0 to 2D using the DiaSorin LIAISON XL assay and age-specific reference intervals were established. The Mann-Whitney U-test was used to determine seasonal differences. Pooled neonatal and infantile samples were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if elevated concentrations during the first year of life may be attributed to cross-reacting moieties. Results: Three reference interval age partitions were required with highest levels in subjects 0 to 2D concentration was not significantly affected by seasonal variation or sex. Elevated 1,25(OH)2D concentrations in neonatal and infantile samples may be the result of an interfering substance. The absence of 3-epi-1,25-dihydroxyvitamin D in the pooled samples makes it unlikely to be the interfering moiety. Conclusions: Pediatric reference intervals for 1,25(OH)2D were established to improve test result interpretation in children and adolescents. 1,25(OH)2D is elevated in a proportion of neonates and infants, which may be the result of a cross-reacting moiety.

Objective To evaluate the disease burden of placental maternal vascular malperfusion pathology in a low-risk nulliparous population and test the hypothesis that a multiparameter model in the second trimester can predict maternal vascular malperfusion with high precision. Methods A single-center, prospective cohort study was conducted in healthy nulliparous women. Maternal vascular malperfusion disease burden was estimated by incidence, relative risk (RR), and population-attributable risk percent. Maternal risk factors, serum biomarkers, Doppler, and placental morphologic ultrasonography were examined in isolation and in combination for prediction of this placental pathology. Results The incidence of maternal vascular malperfusion pathology was 8.4% (72/856). Women with pathology had higher risk of preeclampsia (8.33% compared with 1.79%; RR 4.67, 95% CI 1.85-11.77%; population-attributable risk 23.6%, 95% CI 16.9-31.6%), small for gestational age (SGA) (47.22% compared with 9.45%; RR 5.00, 95% CI 3.6-6.93%; population-attributable risk 25.2%, 95% CI 22.1-28.5%), and the composite of adverse outcomes (defined as SGA or preeclampsia) (47.22% compared with 10.59%; RR 4.46, 95% CI 3.25-6.13; population-attributable risk 22.5%, 95% CI 19.8-25.5%). The combination of parameters was superior to individual modalities alone in predicting maternal vascular malperfusion, but achieved only moderate precision (area under the curve 0.77, 95% CI 0.71-0.84). Conclusion One in 12 healthy nulliparous women develop maternal vascular malperfusion placental pathology, and these pregnancies had a 4.5 times higher risk of developing preeclampsia or delivering a SGA neonate compared with those without this pathology. A multiparameter model achieved modest precision to predict placental maternal vascular malperfusion. Importantly, in low-risk pregnancies, maternal vascular malperfusion accounts for one fourth of pregnancy outcomes with SGA or preeclampsia. The low population-attributable risk of this placental pathology for SGA and preeclampsia illustrates the importance of discovering novel associations to reduce the disease burden of these pregnancy complications.

It is timely with interest in prostate cancer screening rekindled by the recently revised and updated recommendations issued by the United States Preventative Services Task Force (USPSTF)3 (1) that this cancer-themed issue of the Journal of Applied Laboratory Medicine includes the study by Higgins and coauthors (2), who evaluated the analytical performance of one such screening test designed to avoid the overdiagnosis of indolent prostate cancer, the 4Kscore. Such information is also timely, if not overdue, given that this test has been in use since 2014 with only a single published Abstract (3), presented at the 2015 AACC Annual Meeting, describing the test's analytical performance and …

Background The diagnostic utility of laboratory tests in paediatric medicine relies heavily on the availability of appropriate reference intervals (RIs). The Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) has established a comprehensive database of covariate-stratified RIs for many paediatric laboratory tests using a large, healthy reference population. Several automated analysers in widespread use in clinical laboratories have already been studied. Here, we extend the testing to Roche immunoassays and report, for the first time, comprehensive paediatric RIs for 17 endocrine and special chemistry markers. Methods A total of 741 healthy children and adolescents (1 day to Results Reference values for all analytes measured required age partitioning, particularly during early life and throughout adolescence. Of the 17 analytes measured, eight required sex partitioning, including ferritin, thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and all fertility/sex hormones, except prolactin. Conclusions This is the first study to determine accurate paediatric RIs for Roche immunoassays. RIs were generally similar to those previously published by CALIPER on other analytical platforms, highlighting the reproducibility of age- and sex-specific trends in reference values observed across the paediatric age range. The RIs established in this study will improve the accuracy of test result interpretation and clinical decision-making in clinical laboratories utilising Roche immunoassays.

To the Editor: International societies and expert groups recommend using sex-specific upper reference limits (URLs)1 for interpretation of high-sensitivity cardiac troponin (hs-cTnI/T) assays (1, 2). Despite advances in our understanding of cTn in adults, the effect of age and sex on cTn in pediatric populations is less understood. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) previously determined 97.5th and 99th percentiles for the Abbott hs-cTnI assay in a healthy pediatric cohort (3). These data represented the first attempt to characterize hs-cTnI in healthy children but did not include neonates nor were sex-specific differences evident. It is unclear, however, what cTnT URLs would be in this population because cTnT is a different protein and there are differences in analytical sensitivity and specificity between hs-cTnT and hs-cTnI assays (1–4). Establishing pediatric reference values for cTn is important because its measurement has several clinical indications in pediatrics, including monitoring children with postoperative myocarditis and congenital pediatric heart disease. Serum samples from 598 children and adolescents were selected from the CALIPER biobank. Samples from participants

Background: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed.Methods: Published reports relevant to use of tumor markers for 5 cancer sites—testicular, prostate, colorectal, breast, and ovarian—were critically reviewed.Results: For testicular cancer, α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring. α-Fetoprotein is also recommended for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign prostatic disease when total PSA is Conclusions: Implementation of these recommendations should encourage optimal use of tumor markers.