Incorporation of dried blood alpha fetoprotein into traditional first trimester Down syndrome screening service

ABSTRACT: OBJECTIVE: The aim of this study was to determine whether incorporation of dried blood alpha fetoprotein (AFP) into first trimester screening using the biochemical markers free Beta human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) can improve screening performance. METHODS: A retrospective study of 34 Down syndrome and 1185 unaffected dried blood specimens. First trimester dried blood AFP was performed using in-house immunofluorometric time-resolved assay. False positive and detection rates were determined from modeling. RESULTS: The multiple of the median in Down syndrome cases was 0.73. At a fixed 5% false positive rate, incorporating AFP into a free Beta hCG, PAPP-A, and nuchal translucency protocol adds 2% detection resulting in detection rates of 92% to 94% depending on the gestational age of the blood draw. At a fixed 90% detection rate, AFP reduced the false positive rate by 1.0 to 1.6 percentage points depending on gestational age. Using a cutoff of 1/1000, the combination of free beta hCG, PAPP-A, AFP, and nuchal translucency achieved a detection rate of 96% with a false positive rate of 8.4% to 9.9%. Adding in nasal bone increased detection to 98% while reducing false positive rates to 4.1% to 4.7%. CONCLUSION: Inclusion of dried blood AFP into traditional first trimester screening improves detection while optimizing contingent protocols so that cell-free fetal DNA testing may be offered in a more cost effective manner. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. WHAT’S ALREADY KNOWN ABOUT THIS TOPIC? 1. Traditional first trimester Down syndrome screening programs can achieve detection rates of 90% for a 5% false positive rate. . 2. Cell-free fetal DNA screening can achieve high detection rates and low false positive rates but due to its cost may be ill-suited to population-wide screening. . WHAT DOES THIS STUDY ADD? 1. Incorporation of AFP into a dried blood first trimester screening program utilizing free beta hCG and PAPP-A can improve detection rates and/or false positive rates. . 2. Improved performance of first trimester screening with AFP can optimize contingent protocols so that cffDNA testing may be offered in a more cost effective manner. .