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Predictive performance of a seven-plex antibody array in prenatal screening for Down Syndrome
Jeroen L A Pennings1, Sandra Imholz1, Ilse Zutt2
1Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, Netherlands.
Multiplex antibody arrays offer a feasible method for simultaneous measurement of prenatal screening markers like pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG). While comparable to existing methods for Down Syndrome (DS) screening, additional markers are needed for improved prediction.
Area of Science:
- Biochemistry and Molecular Biology
- Reproductive Medicine and Genetics
- Diagnostic Assay Development
Background:
- First-trimester screening is crucial for detecting fetal aneuploidies like Down Syndrome (DS).
- Current screening methods often rely on individual marker measurements.
- Multiplex assays offer potential for simultaneous detection of multiple biomarkers.
Purpose of the Study:
- To evaluate the feasibility of a multiplex antibody array for simultaneous measurement of serum proteins in first-trimester prenatal screening.
- To assess the utility of this array for screening Down Syndrome (DS) and other pregnancy outcomes.
- To compare the performance of the antibody array with established immunoassay methods.
Main Methods:
- Development of an indirect "sandwich" antibody array for seven serum proteins: PAPP-A, fβ-hCG, AFP, ANGPTL3, EGF, IGFII, and SOD1.
- Testing the array with samples from 170 DS cases and 510 matched controls during the 8th-13th weeks of gestation.
- Comparison of antibody array data for PAPP-A and fβ-hCG with AutoDELFIA immunoassay results.
Main Results:
- Serum concentrations of PAPP-A and fβ-hCG measured by the antibody array showed high correlation with AutoDELFIA data.
- Down Syndrome (DS) prediction modeling using antibody array data yielded comparable results to AutoDELFIA.
- Alpha-fetoprotein (AFP) and insulin-like growth factor 2 (IGFII) showed significant concentration changes, but did not improve predictive performance when added to existing models.
Conclusions:
- Multiplex antibody array methodology is feasible for simultaneous measurement of prenatal screening markers.
- The developed array provides reliable measurements for key markers like PAPP-A and fβ-hCG.
- Further research is needed to identify and incorporate additional effective first-trimester screening markers for improved predictive accuracy.
