The Reproducibility of Risk Figures in 2nd- Trimester Maternal Serum Screening for Down Syndrome: A Comparison of 2 Laboratories

Background: Analytical error affects 2nd-trimester maternal serum screening for Down syndrome risk estimation. We analyzed the between-laboratory reproducibility of risk estimates from 2 laboratories. Methods: Laboratory 1 used Bayer ACS180 immunoassays for -fetoprotein (AFP) and human chorionic gonadotropin (hCG), Diagnostic Systems Laboratories (DSL) RIA for unconjugated estriol (uE3), and DSL enzyme immunoassay for inhibin-A (INH-A). Laboratory 2 used Beckman immunoassays for AFP, hCG, and uE3, and DSL enzyme immunoassay for INH-A. Analyte medians were separately established for each laboratory. We used the same computational algorithm for all risk calculations, and we used Monte Carlo methods for computer modeling. Results: For 462 samples tested, risk figures from the 2 laboratories differed >2-fold for 44.7%, >5-fold for 7.1%, and >10-fold for 1.7%. Between-laboratory differences in analytes were greatest for uE3 and INH-A. The screen-positive rates were 9.3% for laboratory 1 and 11.5% for laboratory 2, with a significant difference in the patients identified as screen-positive vs screennegative (McNemar test, P <0.001). Computer modeling confirmed the large between-laboratory risk differences. Conclusion: Differences in performance of assays and laboratory procedures can have a large effect on patientspecific risks. Screening laboratories should minimize test imprecision and ensure that each assay performs in a manner similar to that assumed in the risk computational algorithm. © 2006 American Association for Clinical Chemistry