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

Formulae to evaluate the effect of inter-assay analytical imprecision (expr essed as the coefficient of variation) in maternal serum screening for Down 's syndrome have been developed. Experimentally determined imprecision in D own's syndrome risk (based on maternal serum x-fetoprotein. unconjugated oe striol and human chorionic gonadotrophin) was found to be consistent with p redicted values. Imprecision in the measurement of analytes becomes amplifi ed when risk is calculated using the values of these analytes. A large sepa ration between the means and small standard deviations for normal and affec ted pregnancies are the characteristics of the tests most useful in screeni ng? but these attributes also result in the most imprecision in risk. In ad dition, the relative imprecision associated with Down's syndrome risk is no t the same for all women screened. Combining tests for multivariate analyse s results in a complex compounding of the errors. The need for strict quali ty control and test reproducibility is emphasized. The effect of analytical imprecision should be of particular concern to laboratories that provide s creening for women of advanced maternal age.