Prenatal reflex DNA screening for Down syndrome: enhancing the screening performance of the initial first trimester test.

Abstract

To estimate the effect of adding three biochemical markers (alphafetoprotein, inhibin-A, and placental growth factor) and two ultrasound markers (ductus venosus pulsatility index and nasal bone examination) to enhance the initial Combined test in prenatal reflex DNA screening for Down syndrome. Published data were used to estimate screening performance [detection rates (DRs) and false-positive rates (FPRs)] of reflex DNA screening according to the additional markers used, the proportion of women with the highest initial test risks reflexed to DNA testing and the gestational age at the time of blood collection. If 10% of women are reflexed, the addition of the three biochemical markers to the Combined test increases the DR from 90.8% to 92.3% (FPR 0.025% to 0.027%) with markers measured at 11 completed weeks' gestation. With markers measured at 13 completed weeks' gestation the DR increases from 87.7% to 95.2% (FPRs both 0.027%). The further addition of the two ultrasound markers increases the DR to 96.8% and 97.5% at 11 and 13 weeks' respectively (FPR to 0.024% and 0.022% respectively). Adding the specified markers to the Combined test can maintain or improve screening performance with a lower proportion of women reflexed. Our results can be used to determine the most cost-effective reflex DNA screening policy. © 2016 John Wiley & Sons, Ltd.