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 Virtually all prenatal screening protocols for Down syndrome use measurements made in maternal serum, sometimes with the inclusion of first-trimester ultrasound determination of nuchal translucency (NT) thickness. In a few reports, these serum markers have been measured by using dried blood spots rather than fresh sera. 1-4 Collection of blood spots is less invasive than drawing blood and is sometimes more convenient for office personnel and the patient because referral to a phlebotomy station is not required. Also, some analytes can be more stable in blood spots than in whole blood or serum when shipping and handling occurs under conditions such as elevated temperature (e.g., the free ␤-subunit of human chorionic gonadotropin [hCG]). 5 There is limited information concerning possible differences introduced by the choice of sample type. To our knowledge, no study has made a direct (matched) comparison of the screening performance of maternal Down syndrome markers using measurements obtained from a dried blood spot and maternal serum collected from the same women. Matched studies have been undertaken for other analytes, such as newborn screening markers 6 and prostate-specific antigen. 7 Although not as powerful as a matched study, a cohort study design can yield information on the relative performance of the two sample types when results are compared from women screened who provided blood spots with those screened who provided maternal serum. The current study was undertaken to determine whether any meaningful differences attributable to collection method are observed between two similar cohorts o...