Down's syndrome screening: population statistic dependency of screening performance
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Tim Reynolds
Abstract
Background: The choice of parameter sets used to calculate Down's syndrome risks is important. This study details analysis of samples from affected and unaffected pregnancies and evaluates whether published population data is optimal. Screening efficiency realized with measurement procedure-specific population parameters is compared with selected population sets available in the literature.
Methods: In a retrospective experiment, double and triple testing was performed on maternal serum samples from 286 randomly chosen unaffected singleton pregnancies and 95 Down's syndrome affected pregnancy samples. Using a risk cut-off of 1 in 250, detection rates and false positive rates were estimated for different population settings to select a model giving the best overall efficacy. Receiver operation characteristics curve analysis was performed and detection rates realized with the different population settings was estimated at a 5% fixed false positive rate.
Results: Geometric mean weight corrected multiples of the median values were 1.01 for α-fetoprotein (AFP), 1.02 for human chorionic gonadotropin (hCG) and 1.01 for unconjugated estriol (uE3) in unaffected pregnancies and 0.77 (95% CI: 0.71–0.83) for AFP, 2.42 (95% CI: 2.17–2.71) for hCG and 0.78 (95% CI: 0.73–0.83) for uE3 in affected pregnancies. Differences in double and triple risks obtained with the different models were significantly different from each other (p<0.001). At a cut-off of 1 in 250, the maximum triple test detection rate was 75.8% for a false positive rate of 4.9% and was obtained with the measurement procedure-specific setting. At a fixed false positive rate of 5%, the maximum detection rate for the triple test was 77.9% (95% CI: 62.2%–85.8%). The maximum double test detection rate at 5% false positive rate was 69.6% (95% CI: 59.5%–78.5%). Except for two models, the area under the curve for the triple test was higher than that of the double test.
Conclusions: The Access triple test meets the typical performance characteristics for this test combination. The assay-specific settings yielded the overall best efficacy for the criteria studied. Therefore, the availability of measurement procedure-specific mid-trimester reference values for unaffected and affected pregnancies in prenatal screening programs is essential. Such reference values are established for the Beckman Coulter Access triple test: maternal serum AFP, uE3 and hCG.
Clin Chem Lab Med 2008;46:639–47.
©2008 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Editorial
- Comparability of tumor marker immunoassays: still an important issue for clinical diagnostics?
- Review
- The diagnostic role of autoantibodies in the prediction of organ-specific autoimmune diseases
- Validation and Outcome Studies
- Alternative antibody for the detection of CA125 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access® OV Monitor assay on the UniCel® DxI 800 Immunoassay System
- Alternative antibody for the detection of CA19-9 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access® GI Monitor assay on the UniCel® DxI 800 Immunoassay System
- Alternative antibody for the detection of CA15-3 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access® BR Monitor assay on the UniCel® DxI 800 Immunoassay System
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- Interactions of lipoprotein(a) with diabetes mellitus, apolipoprotein B and cholesterol enhance the prognostic values for coronary artery disease
- Association of thyroid stimulating hormone and coronary lipid risk factors with lipid peroxidation in hypothyroidism
- The effect of the mode of delivery on the maternal-neonatal carnitine blood levels and antioxidant status
- Time to reconsider the clinical value of immunoglobulin G4 to foods?
- Reference Values
- Determination of reference intervals for 26 commonly measured biochemical analytes with consideration of long-term within-individual variation
- Beverage-specific effects of ethanol consumption on its biological markers
- Limits of preservation of samples for urine strip tests and particle counting
- Reference ranges and diagnostic thresholds of laboratory markers of cardiac damage and dysfunction in a population of apparently healthy black Africans
- Letters to the Editor
- External quality assessment schemes for real-time PCR: a statistical procedure to corrective actions
- Application of two different microarray-based copy-number detection methodologies – array-comparative genomic hybridization and array-multiplex amplifiable probe hybridization – with identical amplifiable target sequences
- Criticism to the article: “Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: I. Analyte definition and proposal of a candidate reference method.” Authors: J.O. Jeppsson et al. Clin Chem Lab Med 2007;45(4):558–562
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- Comment on: Bellini C, Serra G, Risso D, Mazzella M, Bonioli E. Reliability assessment of glucose measurement by HemoCue analyser in a neonatal intensive care unit. Clin Chem Lab Med 2007;45(11):1549–54
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