Formulae to evaluate the effect of inter-assay analytical imprecision (expressed as the coefficient of variation) in maternal serum screening for Down's syndrome have been developed. Experimentally determined imprecision in Down's syndrome risk (based on maternal serum alpha-fetoprotein, unconjugated oestriol and human chorionic gonadotrophin) was found to be consistent with predicted values. Imprecision in the measurement of analytes becomes amplified when risk is calculated using the values of these analytes. A large separation between the means and small standard deviations for normal and affected pregnancies are the characteristics of the tests most useful in screening, but these attributes also result in the most imprecision in risk. In addition, the relative imprecision associated with Down's syndrome risk is not the same for all women screened. Combining tests for multivariate analyses results in a complex compounding of the errors. The need for strict quality control and test reproducibility is emphasized. The effect of analytical imprecision should be of particular concern to laboratories that provide screening for women of advanced maternal age.

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Second-trimester maternal serum α-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are routinely measured in screening fetuses at high risk for Down syndrome or open neural tube defects (ONTD). For test interpretation, individual patient values of these three analytes are related to population-derived median values. We evaluated data from >21 000 pregnancies to determine the extent of race-specific differences in median concentrations. For samples at most gestational ages, median AFP, hCG, and uE3 values for white, black, Hispanic, and other patients were all significantly different. Differences remained significant even when data were corrected for patient weights. For each analyte, the extent of the variation was not the same at different gestational ages. Differences in median values across race/ethnicity groups appear to have only a small impact in Down syndrome screening but it may be appropriate to use alternative sets of AFP medians or adjustment factors to AFP medians for some Asian populations receiving ONTD screening.

Overall, the risk-based method is more effective than the fixed-cutoff approach to trisomy 18 screening.

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