Estimating first-trimester combined screening performance for Down syndrome in dried blood spots versus fresh sera

Abstract

PURPOSE: The study purpose was to examine the consequences of using dried blood spots rather than fresh sera in first-trimester Down syndrome screening. METHODS: We collected and compared human chorionic gonadotropin and pregnancy-associated plasma protein-A results from clients providing dried blood spots (Cohort 1) and from other clients providing fresh sera (Cohort 2). Inclusion and exclusion criteria aimed at ensuring the two cohorts were similar. RESULTS: The average concentrations of human chorionic gonadotropin and pregnancy-associated plasma protein-A are significantly different for the two cohorts. When the results are converted to multiples of the median and weight-adjusted, the variances for human chorionic gonadotropin and pregnancy-associated plasma protein-A in Cohort 1 are greater by 25% and 14%, respectively. Modeling the impact of this increased variance shows that Down syndrome detection is expected to be lower in Cohort 1 (83% vs. 85% at a 5% false-positive rate) or the false-positive rate is expected to be higher (3.9% vs. 3.0% at an 80% detection rate). CONCLUSIONS: This study of two closely matched cohorts provides indirect evidence that dried blood spots will result in slightly lower Down syndrome screening performance. Studies should be undertaken to confirm and further quantify differences in assigned risks by a direct comparison using matched serum and dried blood spots collected from the same women. ©2007The American College of Medical Genetics.