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

Abstract

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. Laboratory 1 used Bayer ACS180 immunoassays for alpha-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. 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 screen-negative (McNemar test, P<0.001). Computer modeling confirmed the large between-laboratory risk differences. Differences in performance of assays and laboratory procedures can have a large effect on patient-specific 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.