Sources of imprecision in laboratories screening for congenital hypothyroidism: analysis of nine years of performance data.

Abstract

We evaluated sources of imprecision in screening assays for congenital hypothyroidism performed between 1979 and 1987 by more than 45 laboratories participating in the national Neonatal Screening Standardization Program offered by the Centers for Disease Control. Reported concentrations were available from approximately 70,000 enriched dried-blood spot samples for thyroxin and thyrotropin, the primary and secondary screening assays, respectively. The most important sources of variation in assayed concentrations are within-laboratory imprecision and the methods or kits used. The importance of each of these sources depends on the analyte and its concentration. In most cases, the greatest source of measurement variation is attributable to within-laboratory imprecision (coefficient of variation 13% to 26%); however, kits are the largest source of variation at the lower concentrations of thyroxin. For both analytes, the greatest relative imprecision occurred at the low concentration, which was within the critical range of the cutoff values for detection of presumptive positive specimens. Imprecision in this range increases the risk of misclassifications. Minimizing within-laboratory imprecision and differences among kits seems to be the best way to improve overall efficiency of screening laboratories.