Evaluation of effect of analytical imprecision in maternal serum screening for Down's syndrome

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.