Proteomics and Down syndrome screening: a validation study

Objective In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers. Methods Concentrations of the seven analytes were measured using bead‐based multiplexed imm...

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Veröffentlicht in:Prenatal diagnosis 2010-11, Vol.30 (11), p.1039-1043
Hauptverfasser: Koster, M. P. H., Pennings, J. L. A., Imholz, S., Rodenburg, W., Visser, G. H. A., de Vries, A., Schielen, P. C. J. I.
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container_end_page 1043
container_issue 11
container_start_page 1039
container_title Prenatal diagnosis
container_volume 30
creator Koster, M. P. H.
Pennings, J. L. A.
Imholz, S.
Rodenburg, W.
Visser, G. H. A.
de Vries, A.
Schielen, P. C. J. I.
description Objective In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers. Methods Concentrations of the seven analytes were measured using bead‐based multiplexed immunoassays in maternal serum from 27 DS pregnancies and 27 matched controls. Control samples were matched to the cases by gestational age (exact day), maternal weight ( ± 5 kg), and maternal age ( ± 1 year) and by closest sample date. Prediction values were obtained for current screening markers [pregnancy‐associated plasma protein A (PAPP‐A), free beta human chorionic gonadotrophin (fβ‐hCG) and nuchal translucency (NT)] and seven markers identified before based on concentration fold ratios between DS and controls. Models were fitted based on data of the discovery study or this study and also tested on both datasets. Results A significantly higher fold ratio was only found for epidermal growth factor (EGF) (−1.96; p = 0.006). In the prediction model for the current dataset, EGF improved the detection rate (DR) of DS by 5.7% [at a fixed 5% false‐positive rate (FPR)] when added to the currently used screening markers. Conclusions Validation of previously identified biomarkers only confirmed EGF for further consideration as a DS screening marker. This underlines the importance of validating biomarkers; in this study, limiting the range of plausible biomarkers to only one suitable biomarker. Copyright © 2010 John Wiley & Sons, Ltd.
doi_str_mv 10.1002/pd.2606
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P. H. ; Pennings, J. L. A. ; Imholz, S. ; Rodenburg, W. ; Visser, G. H. A. ; de Vries, A. ; Schielen, P. C. J. I.</creator><creatorcontrib>Koster, M. P. H. ; Pennings, J. L. A. ; Imholz, S. ; Rodenburg, W. ; Visser, G. H. A. ; de Vries, A. ; Schielen, P. C. J. I.</creatorcontrib><description>Objective In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers. Methods Concentrations of the seven analytes were measured using bead‐based multiplexed immunoassays in maternal serum from 27 DS pregnancies and 27 matched controls. Control samples were matched to the cases by gestational age (exact day), maternal weight ( ± 5 kg), and maternal age ( ± 1 year) and by closest sample date. Prediction values were obtained for current screening markers [pregnancy‐associated plasma protein A (PAPP‐A), free beta human chorionic gonadotrophin (fβ‐hCG) and nuchal translucency (NT)] and seven markers identified before based on concentration fold ratios between DS and controls. Models were fitted based on data of the discovery study or this study and also tested on both datasets. Results A significantly higher fold ratio was only found for epidermal growth factor (EGF) (−1.96; p = 0.006). In the prediction model for the current dataset, EGF improved the detection rate (DR) of DS by 5.7% [at a fixed 5% false‐positive rate (FPR)] when added to the currently used screening markers. Conclusions Validation of previously identified biomarkers only confirmed EGF for further consideration as a DS screening marker. This underlines the importance of validating biomarkers; in this study, limiting the range of plausible biomarkers to only one suitable biomarker. 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P. H.</creatorcontrib><creatorcontrib>Pennings, J. L. A.</creatorcontrib><creatorcontrib>Imholz, S.</creatorcontrib><creatorcontrib>Rodenburg, W.</creatorcontrib><creatorcontrib>Visser, G. H. A.</creatorcontrib><creatorcontrib>de Vries, A.</creatorcontrib><creatorcontrib>Schielen, P. C. J. I.</creatorcontrib><title>Proteomics and Down syndrome screening: a validation study</title><title>Prenatal diagnosis</title><addtitle>Prenat. Diagn</addtitle><description>Objective In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers. Methods Concentrations of the seven analytes were measured using bead‐based multiplexed immunoassays in maternal serum from 27 DS pregnancies and 27 matched controls. Control samples were matched to the cases by gestational age (exact day), maternal weight ( ± 5 kg), and maternal age ( ± 1 year) and by closest sample date. Prediction values were obtained for current screening markers [pregnancy‐associated plasma protein A (PAPP‐A), free beta human chorionic gonadotrophin (fβ‐hCG) and nuchal translucency (NT)] and seven markers identified before based on concentration fold ratios between DS and controls. Models were fitted based on data of the discovery study or this study and also tested on both datasets. Results A significantly higher fold ratio was only found for epidermal growth factor (EGF) (−1.96; p = 0.006). In the prediction model for the current dataset, EGF improved the detection rate (DR) of DS by 5.7% [at a fixed 5% false‐positive rate (FPR)] when added to the currently used screening markers. Conclusions Validation of previously identified biomarkers only confirmed EGF for further consideration as a DS screening marker. This underlines the importance of validating biomarkers; in this study, limiting the range of plausible biomarkers to only one suitable biomarker. 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Obstetrics</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Medical sciences</topic><topic>Molecular and cellular biology</topic><topic>Predictive Value of Tests</topic><topic>Pregnancy</topic><topic>Pregnancy Trimester, First</topic><topic>Prenatal Diagnosis - methods</topic><topic>Prenatal Diagnosis - standards</topic><topic>Proteomics - methods</topic><topic>Proteomics - standards</topic><topic>Reproducibility of Results</topic><topic>Retrospective Studies</topic><topic>Sensitivity and Specificity</topic><topic>Ultrasonography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koster, M. P. H.</creatorcontrib><creatorcontrib>Pennings, J. L. A.</creatorcontrib><creatorcontrib>Imholz, S.</creatorcontrib><creatorcontrib>Rodenburg, W.</creatorcontrib><creatorcontrib>Visser, G. H. A.</creatorcontrib><creatorcontrib>de Vries, A.</creatorcontrib><creatorcontrib>Schielen, P. C. J. 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Copyright © 2010 John Wiley &amp; Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley &amp; Sons, Ltd</pub><pmid>20827711</pmid><doi>10.1002/pd.2606</doi><tpages>5</tpages></addata></record>
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subjects Adult
bead-based multiplexed assays
Biological and medical sciences
biomarkers
Biomarkers - blood
Case-Control Studies
Delivery. Postpartum. Lactation
Down syndrome
Down Syndrome - blood
Down Syndrome - diagnostic imaging
epidermal growth factor (EGF)
Female
first-trimester serum screening
Fundamental and applied biological sciences. Psychology
Genetics of eukaryotes. Biological and molecular evolution
Gynecology. Andrology. Obstetrics
Humans
Infant, Newborn
Medical sciences
Molecular and cellular biology
Predictive Value of Tests
Pregnancy
Pregnancy Trimester, First
Prenatal Diagnosis - methods
Prenatal Diagnosis - standards
Proteomics - methods
Proteomics - standards
Reproducibility of Results
Retrospective Studies
Sensitivity and Specificity
Ultrasonography
title Proteomics and Down syndrome screening: a validation study
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