title: Predictive performance of a seven-plex antibody array in prenatal screening for Down Syndrome.
abstract: We evaluated the use of multiplex antibody array methodology for simultaneous measurement of serum protein markers for first trimester screening of Down Syndrome (DS) and other pregnancy outcomes such as preeclampsia. For this purpose, we constructed an antibody array for indirect ("sandwich") measurement of seven serum proteins: pregnancy-associated plasma protein-A (PAPP-A), free beta subunit of human chorionic gonadotropin (fβ-hCG), alpha-fetoprotein (AFP), angiopoietin-like 3 (ANGPTL3), epidermal growth factor (EGF), insulin-like growth factor 2 (IGFII), and superoxide dismutase 1 (SOD1). This array was tested using 170 DS cases and 510 matched controls drawn during the 8th-13th weeks of pregnancy. Data were used for prediction modelling and compared to previously obtained AutoDELFIA immunoassay data for PAPP-A and fβ-hCG. PAPP-A and fβ-hCG serum concentrations obtained using antibody arrays were highly correlated with AutoDELFIA data. Moreover, DS prediction modeling using (log-MoMmed) antibody array and AutoDELFIA data gave comparable results. Of the other markers, AFP and IGFII showed significant changes in concentration, although adding these markers to a prediction model based on prior risk, PAPP-A and fβ-hCG did not improve the predictive performance. We conclude that implementation of antibody arrays in a prenatal screening setting is feasible but will require additional first trimester screening markers.
authors.affiliation: Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, Netherlands.
authors.forename: Jeroen L A
authors.initials: JL
authors.lastname: Pennings
authors.affiliation: Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Imholz
authors.affiliation: Centre for Infectious Diseases Research, Diagnostics and Screening (IDS), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, Netherlands.
authors.forename: Ilse
authors.initials: I
authors.lastname: Zutt
authors.affiliation: Centre for Infectious Diseases Research, Diagnostics and Screening (IDS), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, Netherlands ; Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht (UMCU), P.O. Box 85090, 3508 AB Utrecht, Netherlands.
authors.forename: Maria P H
authors.initials: MP
authors.lastname: Koster
authors.affiliation: Centre for Infectious Diseases Research, Diagnostics and Screening (IDS), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, Netherlands.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Siljee
authors.affiliation: Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: de Vries
authors.affiliation: Centre for Infectious Diseases Research, Diagnostics and Screening (IDS), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, Netherlands.
authors.forename: Peter C J I
authors.initials: PC
authors.lastname: Schielen
authors.affiliation: Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Rodenburg
mesh_terms: D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000276:immunology; D016022:Case-Control Studies; D004314:Down Syndrome / Q000097:blood*; D005260:Female; D006801:Humans; D011237:Predictive Value of Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D040081:Protein Array Analysis / Q000379:methods*; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods*
chemical_list: D015415:Biomarkers; D001798:Blood Proteins