Band 55, Heft 11

According to recent international guidelines, including the 2012 Third Universal Definiton of Myocardial Infarction by the Joint ESC/ACCF/AHA/WHF Task Force, an increase in cardiac troponin (cTn) levels over the 99th percentile upper reference limit (99th URL) should be considered clinically relevant, this cut-off being measured with an imprecision ≤10 CV%. In theory 99th URL values strongly depend not only on demographic and physiological variables (i.e. criteria for considering the reference population “healthy”), but also on the analytical performance of cTn methods and mathematical algorithms used for the calculation. The aim of the present article was therefore to review the methodological and pathophysiological factors affecting the evaluation and calculation of the 99th URL for cTn assay. The critical analysis made showed that no uniform procedure is followed, and nor have experts or regulatory bodies provided uniform guidelines for researchers or cTn assays manufacturers as an aid in “their quest to define normality”. In particular, little attention has been paid to the way in which a healthy reference population is to be selected, or the criteria for calculating the 99th URL value for cTn assays, thus highlighting the need for international recommendations not only for demographic and physiological variables criteria for defining a healthy reference population, but also for calculating mathematical algorithms for establishing/calculating clinical decision values. An expert consensus group, comprising laboratory and clinical scientists, biomedical statisticians, industrial and regulatory representatives, should be responsible for drawing up these guidelines.

Background: Thiamine has a crucial role in energy production, and consequently thiamine deficiency (TD) has been associated with cardiac failure, neurological disorders, oxidative stress (lactic acidosis and sepsis) and refeeding syndrome (RFS). This review aims to explore analytical methodologies of thiamine compound quantification and highlight similarities, variances and limitations of current techniques and how they may be relevant to patients. Content: An electronic search of Medline, PubMed and Embase databases for original articles published in peer-reviewed journals was conducted. MethodsNow was used to search for published analytical methods of thiamine compounds. Keywords for all databases included “thiamine and its phosphate esters”, “thiamine methodology” and terms related to critical illness. Enquiries were also made to six external quality assurance (EQA) programme organisations for the inclusion of thiamine measurement. Summary: A total of 777 published articles were identified; 122 were included in this review. The most common published method is HPLC with florescence detection. Two of the six EQA organisations include a thiamine measurement programme, both measuring only whole-blood thiamine pyrophosphate (TPP). No standard measurement procedure for thiamine compound quantification was identified. Outlook: Overall, there is an absence of standardisation in measurement methodologies for thiamine in clinical care. Consequently, multiple variations in method practises are prohibiting the comparison of study results as they are not traceable to any higher order reference. Traceability of certified reference materials and reference measurement procedures is needed to provide an anchor to create the link between studies and help bring consensus on the clinical importance of thiamine.

A questionable scientific approach to measuring at low concentrations and inappropriate censoring of results below certain cut-offs have resulted in the dichotomous classification of troponin assays based on their so-called analytical sensitivity. The definition of “high-sensitivity” cardiac troponin is flawed. Evidence suggests that its apparent diagnostic superiority may be explained by the censoring of data. In the evaluation of the detection and quantification capabilities of analytical methods we recommend alignment with International Union of Pure and Applied Chemistry (IUPAC) guidelines, including reporting of all results. This will allow the objective evaluation of the diagnostic performance of troponin assays and will render the current troponin assay classification and nomenclature obsolete.

We discuss the sensitivity terminology of cardiac troponin assays and its dependence on the selection of the reference population. In addition, the need for reasonable censoring of clinical laboratory test results is contrasted with potential loss of valuable clinical information.

Implementation of the 99th percentile as the upper reference limit for cardiac troponin (cTn) assays is a seemingly lucid recommendation, but, in reality, is incredibly complex. Lack of harmonization between cTn assays diminishes the ability to have a single medical decision point across manufacturer assay/instruments. Moreover, even within a single cTn assay there are several published values corresponding to the “99th percentile”. Variability in the determined value is primarily a function of population selection including: sample size, age, sex, exclusion criteria, and statistical methods. Given the complexities associated with this value, some countries have taken an expert consensus approach to endorsing harmonized, assay-specific, cTn 99th percentile values. The purpose of this manuscript is to highlight the intricacies associated with selecting a cTn 99th percentile and to review the approach that Australia used to endorse a nationwide upper reference limit for the Architect STAT hs-cTnI assay.

Abstract: The introduction of “highly sensitive” cardiac troponin assays (hsTn) has reinforced the evidence that only serial testing incorporated in running algorithms allows a more accurate diagnosis of acute myocardial infarction. In this report, we consider the available evidence supporting the use of fast track protocols for ruling out and ruling in non-ST elevation myocardial infarction (NSTEMI) and compare it with the content of recently released guideline by the European Society of Cardiology, noting some uncomfortable aspects that need urgent clarification and/or revision. Firstly, the guideline drafters have to reconsider the available evidence that does not permit to assign the same class and level of evidence to the very well-validated 0–3 h algorithm and to the 0–1 h algorithm. In agreement with the validity of available data, the limitations of fast track protocols, in particular of the 0–1 h algorithm for NSTEMI rule-in, calls for caution. Secondly, as the current diagnostics guidance by the UK National Institute for Health and Care Excellence recommends, rapid diagnostic protocols should be performed only using well-validated hsTn; recommending the use of an assay before being commercially available is not fair and scientifically sound.

Background: We investigated the association of single nucleotide polymorphisms (SNPs) in the C-reactive protein ( CRP ), leptin ( LEP ) and leptin receptor ( LEPR ) genes with high sensitivity CRP (hs-CRP) levels in two independent cohorts of healthy Spanish children. Methods: We measured hs-CRP levels in 646 6–8-year-old and 707 12–16-year-old children using a high-sensitivity C-Reactive Protein ELISA kit. Four SNPs in the CRP gene (rs1205, rs1130864, rs2794521 and rs1800947), one SNP in the LEP gene (rs7799039) and two SNPs in the LEPR (rs1137100 and rs1137101) gene were determined by TaqMan ® allelic discrimination assays. Results: The four CRP SNPs studied were significantly (p<0.05) associated with hs-CRP levels in both cohorts. Furthermore, two common CRP haplotypes (constructed using the SNPs in order: rs1205, rs1130864, rs1800947, rs2794521) ACGA and GCGG were associated with significantly lower CRP levels (p<0.05) at both ages. The LEPR SNPs rs1137100 (K109R) and rs1137101 (Q223R), and LEP SNP rs7799039 (G2548A) were also associated to hs-CRP levels (p<0.05) in both cohorts. Conclusions: hs-CRP levels in healthy Spanish children, besides being associated to common polymorphisms in the CRP gene, are associated to polymorphisms in the LEP and LEPR genes, which suggests that other loci, in addition the CRP gene, may have a role determining CRP levels in children.

Background: The present study was prompted by the ISO 15189 requirements that medical laboratories should estimate measurement uncertainty (MU). Methods: The method used to estimate MU included the: a) identification of quantitative tests, b) classification of tests in relation to their clinical purpose, and c) identification of criteria to estimate the different MU components. Imprecision was estimated using long-term internal quality control (IQC) results of the year 2016, while external quality assessment schemes (EQAs) results obtained in the period 2015–2016 were used to estimate bias and bias uncertainty. Results: A total of 263 measurement procedures (MPs) were analyzed. On the basis of test purpose, in 51 MPs imprecision only was used to estimate MU; in the remaining MPs, the bias component was not estimable for 22 MPs because EQAs results did not provide reliable statistics. For a total of 28 MPs, two or more MU values were calculated on the basis of analyte concentration levels. Overall, results showed that uncertainty of bias is a minor factor contributing to MU, the bias component being the most relevant contributor to all the studied sample matrices. Conclusions: The model chosen for MU estimation allowed us to derive a standardized approach for bias calculation, with respect to the fitness-for-purpose of test results. Measurement uncertainty estimation could readily be implemented in medical laboratories as a useful tool in monitoring the analytical quality of test results since they are calculated using a combination of both the long-term imprecision IQC results and bias, on the basis of EQAs results.

Background: Traditionally, statistical quality control (SQC) planning is aimed at preventing the error rate from exceeding a pre-defined acceptable rate (Westgard JO. Basic QC Practices, 4th ed. Westgard QC, 2016). A pivotal characteristic for planning a QC procedure with the traditional approach is the probability of rejecting an analytical run that contains critical size errors (P edc ). Multi-rule QC procedures, with fully documented power curves, are important tools for SQC. In addition, it has been recommended (Parvin CA, Gronowski AM. Effect of analytical run length on quality-control (QC) performance and the QC planning process. Clin Chem 1997;43:2149–54) to optimize the frequency of QC on the basis of the maximum expected increase in the number of unacceptable patient results reported during the presence of an undetected out-of-control error condition [Max E(N uf )]. The relationship between P edc and Max E(N uf ) has been studied for single rule QC procedures (Yago M, Alcover S. Selecting statistical procedures for quality control planning based on risk management. Clin Chem 2016;62:959–65), but corresponding information for multi-rule QC is lacking. Methods: We used a statistical model to investigate the relationship between P edc and Max E(N uf ) for multi-rules commonly used in clinical laboratories, and constructed charts relating the Max E(N uf ) and the sigma capability of the examination procedure for multi-rules which can be used as practical tools for planning SQC. Results: There is a close relationship between P edc and Max E(N uf ) for commonly used multi-rules. Common multi-rule SQC procedures traditionally designed for high P edc will also provide low Max E(N uf ) values. Conclusions: Multi-rule SQC procedures can be used for controlling intermediate and low sigma capability method to attain a low Max E(N uf ) so that the probability of patient harm is mitigated to acceptable levels.

Background: Recently, the total prostate-specific antigen (PSA) assay used in a laboratory had a positive bias of 0.03 μg/L, which went undetected. Consequently, a number of post-prostatectomy patients with previously undetectable PSA concentrations (defined as <0.03 μg/L in that laboratory) were being reported as having detectable PSA, which suggested poorer prognosis according to clinical guidelines. Methods: Through numerical simulations, we explored (1) how a small bias may evade the detection of routine quality control (QC) procedures with specific reference to the concentration of the QC material, (2) whether the use of ‘average of normals’ approach may detect such a small bias, and (3) describe the use of moving sum of number of patient results with detectable PSA as an adjunct QC procedure. Results: The lowest QC level (0.86 μg/L) available from a commercial kit had poor probability (<10%) of a bias of 0.03 μg/L regardless of QC rule (i.e. 1:2S, 2:2S, 1:3S, 4:1S) used. The average number of patient results affected before error detection (ANPed) was high when using the average of normals approach due to the relatively wide control limits. By contrast, the ANPed was significantly lower for the moving sum of number of patient results with a detectable PSA approach. Conclusions: Laboratory practitioners should ensure their QC strategy can detect small but critical bias, and may require supplementation of ultra-low QC levels that are not covered by commercial kits with in-house preparations. The use of moving sum of number of patient results with a detectable result is a helpful adjunct QC tool.

Background: The presence of preanalytical mistakes (PM) in samples from primary care centres (PCC) is a widely studied topic. Different correcting strategies have been proposed, with variable success. We planned a series of multidisciplinary sessions for clinical update, with the aim to decrease PM rates in samples from PCC. Methods: The incidence of PM in samples from PCC processed at the laboratories of University Hospital Virgen de la Victoria (LAB1) and University Hospital Juan Ramon Jimenez (LAB2) was assessed during two time periods (October to November 2013 and January to May 2014). Clinical update sessions were conducted between periods (2014). Differences in PM rates between observation periods were evaluated. Results: With respect to 2014, we observed a significant reduction of PM rates in blood samples processed at LAB1 during 2015, whereas those in LAB2 were slightly increased. The most common PMs were haemolysed sample at LAB1 and missed sample at LAB2. Conclusions: Although the presence of PM remains slightly high, there was a significant reduction after the clinical update sessions in LAB1, where the most frequent PM was haemolysed sample. In contrast, the PM rates were slightly increased at LAB2, and the main source was missed sample. This might be explained, at least in part, by different problems associated with sample transportation, and by the delay in transferring acquired knowledge into clinical practice. Implementation of regular programme of update sessions and improvements in sample transportation might help to reduce the PM presence in our area.

Background: Systematic difference between thyroid-stimulating hormone (TSH) immunoassays may produce misleading interpretation when samples of the same patients are measured with different methods. The study aims were to evaluate whether systematic differences are present among TSH immunoassays, and whether it is possible to obtain a better harmonization among TSH methods using results obtained in external quality assessment (EQA) schemes. Methods: Seven Italian clinical laboratories measured TSH in 745 serum samples of healthy subjects and patients with thyroid disorders. These samples were also re-measured by two reference laboratories of the study with the six TSH immunoassays most popular in Italy after 2 months of storage at −80 °C. Moreover, these data were compared to 53,823 TSH measurements, obtained by laboratories participant to 2012–2015 EQA annual cycles in 72 quality control samples (TSH concentrations from about 0.1 mIU/L to 18.0 mIU/L). TSH concentrations were recalibrated using a mathematical approach based on the principal component analysis (PCA). Results: Systematic differences were found between the most popular commercially available TSH immunoassays. TSH concentrations measured by the clinical laboratories were very closely correlated to those measured with the same method by reference laboratories after 2 months of storage at −80 °C. After recalibration using the PCA approach the variation of TSH values significantly decreased from a median pre-calibration value of 13.53% (10.79%–16.53%) to 9.63% (6.90%–13.21%) after recalibration. Conclusions: Our data suggest that EQA schemes are useful to improve harmonization among TSH immunoassays and also to produce some mathematical formulas, which can be used by clinicians to better compare TSH values measured with different methods.

Background: The measurement of circulating free light chain (FLC) is essential in the diagnosis, prognostic stratification and evaluation of response to therapy in light chain (AL) amyloidosis. For more than 10 years, this has been done with an immunonephelometric assay based on polyclonal antibodies (Freelite), and cutoffs for staging and response assessment have been validated with this method. Recently, a new assay based on monoclonal antibodies (N latex FLC) has been marketed in Europe. Methods: We evaluated and compared the clinical performance of the two assays in 426 patients with newly diagnosed AL amyloidosis. Results: We found suboptimal agreement between the two methods, with differences between values obtained with the Freelite and N latex FLC assays increasing with the concentration of clonal FLC. The diagnostic sensitivity of the Freelite (82%) and N latex FLC (84%) assays was similar, and both improved to 98% in combination with serum and urine immunofixation. The concentration of FLC measured with both methods had prognostic significance. Less pronounced decreases in FLC best predicted improved survival with the N latex FLC assay (33% vs. 50%), and there was poor concordance (84%) in discrimination of responders. Conclusions: The two assays have similar diagnostic and prognostic performance. However, they are not interchangeable, and follow-up should be done with either one. New response criteria are needed for the N latex FLC assay.

Background: Hyperprolactinemia diagnosis and treatment is often compromised by the presence of biologically inactive and clinically irrelevant higher-molecular-weight complexes of prolactin, macroprolactin. The objective of this study was to evaluate the performance of two macroprolactin screening regimes across commonly used automated immunoassay platforms. Methods: Parametric total and monomeric gender-specific reference intervals were determined for six immunoassay methods using female (n=96) and male sera (n=127) from healthy donors. The reference intervals were validated using 27 hyperprolactinemic and macroprolactinemic sera, whose presence of monomeric and macroforms of prolactin were determined using gel filtration chromatography (GFC). Results: Normative data for six prolactin assays included the range of values (2.5th–97.5th percentiles). Validation sera (hyperprolactinemic and macroprolactinemic; n=27) showed higher discordant classification [mean=2.8; 95% confidence interval (CI) 1.2–4.4] for the monomer reference interval method compared to the post-polyethylene glycol (PEG) recovery cutoff method (mean=1.8; 95% CI 0.8–2.8). The two monomer/macroprolactin discrimination methods did not differ significantly (p=0.089). Among macroprolactinemic sera evaluated by both discrimination methods, the Cobas and Architect/Kryptor prolactin assays showed the lowest and the highest number of misclassifications, respectively. Conclusions: Current automated immunoassays for prolactin testing require macroprolactin screening methods based on PEG precipitation in order to discriminate truly from falsely elevated serum prolactin. While the recovery cutoff and monomeric reference interval macroprolactin screening methods demonstrate similar discriminative ability, the latter method also provides the clinician with an easy interpretable monomeric prolactin concentration along with a monomeric reference interval.

Background: Our main goal is to study the inter-practice regional variability and the temporal evolution in the request of 25-hydroxyvitamin D (25[OH]D) by general practitioners (GPs) in Spain. Methods: Clinical laboratories in different autonomic communities (AACCs) were invited to report the number of 25(OH)D test requested by GPs during 2012 and 2014. The number of 25(OH)D requested per 1000 inhabitants and the index of variability were calculated, and compared between regions and time periods. We calculated the number of tests that could have been potentially saved in regions where 25(OH)D could be requested from primary care without restrictions taking into account the request in those where it is restricted, and the potential economical savings. Results: Seventy-six laboratories participated in the 2012 edition, and 110 in 2014, corresponding to 17,679,195 and 27,798,262 inhabitants (59.8% Spanish population). The number of 25(OH)D requested per 1000 inhabitants increased from 1.1 in 2012 to 3.4 in 2014 (p<0.001). The variability index also increased from 51.7 to 68. There was a significantly variability among the different AACCs, ranging from 0.94 to 21.24 (p=0.002). 173,885 tests could have been not measured from primary care in regions without ordering restrictions, resulting in potential 886,813.5€ savings. Conclusions: There was a high variability in the request of 25(OH)D by GPs in Spain, which significantly increased in a 2 year period. The demand was higher in areas where the request of 25(OH)D was not restricted in primary care, with potential savings if the request would approach to regions with ordering restrictions.

Background: Many clinical laboratories use a clotting rate assay according to Clauss for the determination of fibrinogen in citrated plasma. The aim of the present study was to assess the commutability of the current International Standard for fibrinogen (coded 09/264), three commercial fibrinogen standards, and 10 freeze-dried plasma quality control samples from various sources. Methods: Clotting rate assays according to Clauss were performed on three automated instruments (Sysmex CA1500, STA-Rack Evolution and ACL-Top 700), using three commercial thrombin reagents (Siemens, Stago, and Instrumentation Laboratory). Relationships between the results obtained with the three instruments were determined with 25 fresh-frozen plasma samples obtained from patients. The deviations of the assay results obtained with the freeze-dried samples were compared with the deviations obtained with the fresh-frozen samples, according to approved CLSI guideline C53A. Results: Freezing and thawing had no influence on the assay results. There were significant differences in the mean assay results (fibrinogen, g/L) for the fresh-frozen plasma samples between the three automated instruments: 2.51 (STA-Rack Evolution), 2.25 (ACL-Top 700) and 2.20 (Sysmex CA1500). Similar differences were observed for several freeze-dried plasma samples. Some freeze-dried plasma samples, including the International Standard, were out of the 95% confidence interval for the relationship between STA-Rack Evolution and Sysmex CA1500. Conclusions: Some freeze-dried plasmas including the international standard for fibrinogen are not commutable among automated instruments for fibrinogen clotting rate assays according to Clauss. Our results have consequences for all interested parties in the traceability chain (WHO, industry, external quality assessment schemes, clinical laboratories).

Background: S100B is a well-established biomarker of central nervous system (CNS) development and damage in the perinatal period. Because the fetal CNS induces an overproduction of S100B measurable in the maternal bloodstream we evaluated S100B protein in healthy pregnancies in order to provide a reference curve of the protein in the second and third trimesters and to provide information on CNS development when standard monitoring procedures could be silent or unavailable. Methods: Between July 2012 and December 2014 we conducted a prospective study in 1213 healthy pregnancies delivering healthy newborns. Maternal blood samples were collected for standard monitoring procedures and S100B assessment. S100B correlations with selected outcomes (gestational age at sampling, gender of fetus, gestational age and weight at birth, delivery mode) were calculated using multiple forward stepwise regression analysis. Results: S100B concentrations in the second and third trimesters of pregnancy were found to be gestational age-, gender- and delivery mode-dependent (p<0.05, for all). Multiple forward stepwise regression analysis with S100B as the dependent variable and gestational age at sampling, gender, delivery mode, gestational age and weight at birth as independent variables, showed a significant correlation between S100B and gestational age at sampling (R=0.13; p<0.001). Conclusions: The present findings offering a S100B protein reference curve in maternal blood suggest that non-invasive fetal CNS monitoring is becoming feasible and open the way to further research in neuro-biomarker assessment in the maternal bloodstream.

Background: Thyroid disorders are common during pregnancy. To date, a limited number of studies have reported differences in serum thyroid hormone concentrations between different ethnic groups. We sought to establish gestational age-specific reference intervals for serum levels of thyroid hormones in a multi-ethnic population and investigate whether separate reference intervals should be used for different ethnic groups. Methods: A total of 926 pregnant women from multiple ethnic groups attended four separate study visits spanning the three trimesters. Venous blood samples were taken at 9 to 14 weeks, 18 to 22 weeks, 28 to 32 weeks, and 34 to 39 weeks of gestation. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4), free triiodothyronine (T3), total T4, total T3, thyroid peroxidase antibody and thyroglobulin antibody were measured using Abbott Architect immunoassays. A total of 562 women with singleton pregnancies were found to be negative for both thyroid autoantibodies at all four study visits and thus included in the reference sample group for the establishment of reference intervals (2.5th to 97.5th percentiles). Results: Reference intervals for serum thyroid hormones at 9–14 weeks of gestation derived from the combined group of pregnant women are as follows: TSH, 0.01–2.39 mIU/L; free T4, 11.4–19.5 pmol/L; free T3, 4.23–6.69 pmol/L; total T4, 77.8–182.4 nmol/L; total T3, 1.39–2.97 nmol/L. No differences in the five thyroid parameters’ reference intervals are detectable among the ethnic groups except that at study visit 3 (28–32 weeks of gestation), the upper reference limit of total T3 in Malays (3.20 nmol/L; 90% CI, 2.99–3.76 nmol/L) is slightly higher than that in Chinese (2.86 nmol/L; 90% CI, 2.70–2.98 nmol/L). Conclusions: The findings from this study on a multi-ethnic cohort highlight the importance of establishing locally derived and gestational age-specific reference intervals for the five thyroid hormone parameters.

Background: Polycystic ovarian syndrome (PCOS) is a common cause of reproductive and metabolic dysfunction. We hypothesized that serum prostate-specific antigen (PSA) may constitute a new biomarker for hyperandrogenism in PCOS. Methods: We conducted a cross-sectional study of 45 women with PCOS and 40 controls. Serum from these women was analyzed for androgenic steroids and for complexed PSA (cPSA) and free PSA (fPSA) with a novel fifth- generation assay with a sensitivity of ~10 fg/mL for cPSA and 140 fg/mL for fPSA. Results: cPSA and fPSA levels were about three times higher in PCOS compared to controls. However, in PCOS, cPSA and fPSA did not differ according to waist-to-hip ratio, Ferriman-Gallwey score, or degree of hyperandrogenemia or oligo-ovulation. In PCOS and control women, serum cPSA and fPSA levels were highly correlated with each other, and with free and total testosterone levels, but not with other hormones. Adjusting for age, body mass index (BMI) and race, cPSA was significantly associated with PCOS, with an odds ratio (OR) of 5.67 (95% confidence interval [CI]: 1.86, 22.0). The OR of PCOS for fPSA was 7.04 (95% CI: 1.65, 40.4). A multivariate model that included age, BMI, race and cPSA yielded an area-under-the-receiver-operating-characteristic curve of 0.89. Conclusions: Serum cPSA and fPSA are novel biomarkers for hyperandrogenism in PCOS and may have value for disease diagnosis.

Background: A multitude of troponin assays for the point-of-care (POC) have been developed showing a lack of analytical sensitivity and precision. We present a new platform solution for the high-sensitivity detection of cardiac troponin T (cTnT) in a 30 μL whole blood sample with a turnaround time of 11 min. Methods: The immunoassay was completely run in a ready-to-use plastic disposable, a centrifugal microfluidic disc with fully integrated reagents. After the sample application, the assay was automatically processed by separating the cellular blood components via centrifugation, followed by incubation of a defined volume from the generated plasma with the immunoreagents. The fluorescence in the signal zone of a membrane was measured after its washing for the cTnT quantitation. Results: A calibration curve, measured in whole blood samples spiked with native human cTnT, was generated covering a range up to a concentration of approximately 8300 ng/L. The lower detection limit was determined to be 3.0 ng/L. At a concentration of 14 ng/L, the 99th percentile value from the high-sensitivity cardiac troponin T (hs-cTnT) assay in the Elecsys ® system, the imprecision (CV) was 3.8%. A CV profile indicated that the functional sensitivity for a CV <10% was 6.8 ng/L. The assay did not show any significant cross-reaction with human skeletal troponin T. We observed an excellent correlation with the hs-TnT Elecsys ® assay for 49 clinical plasma samples (r=0.9744). Conclusions: The described technology shows that an analytical performance for a highly sensitive determination of cTnT can be achieved in a POC setting.

Background: Gestational diabetes mellitus (GDM) is increasing partly due to the obesity epidemic. Adipocytokines have thus been suggested as first trimester screening markers for GDM. In this study we explore the associations between body mass index (BMI) and serum concentrations of adiponectin, leptin, and the adiponectin/leptin ratio. Furthermore, we investigate whether these markers can improve the ability to screen for GDM in the first trimester. Methods: A cohort study in which serum adiponectin and leptin were measured between gestational weeks 6+0 and 14+0 in 2590 pregnant women, categorized into normal weight, moderately obese, or severely obese. Results: Lower concentrations of adiponectin were associated with GDM in all BMI groups; the association was more pronounced in BMI<35 kg/m 2 (p=0.30 for interaction). Leptin was inversely associated with GDM in severely obese (p=0.033), but showed no association in women with BMI<35 kg/m 2 . The adiponectin/leptin ratio was associated with GDM in women with BMI<35 kg/m 2 but not in severely obese women (p=0.79). In regard to predicting GDM, maternal characteristics combined with adiponectin alone, adiponcetin and leptin, and adiponcetin/leptin ratio had the strongest associations in women with BMI<35 kg/m 2 . These models had a detection rate of 77.3%–80.3% when the false positive rate was fixed at 25%. Conclusions: Low adiponectin measured in the first trimester is associated with the development of GDM; higher BMI was associated with lower performance of adiponectin, though this was insignificant. Leptin had an inverse relationship with GDM in severely obese women and did not improve the ability to predict GDM.