Contingent screening for Down syndrome - Results from the FaSTER trial

Objective: Comparison of contingent, step-wise and integrated screening policies. Methods: Mid-trimester Down syndrome risks were retrospectively calculated from FaSTER trial data. For contingent screening, initial risk was calculated from ultrasound measurement of nuchal translucency (NT), maternal serum pregnancy-associated plasma protein (PAPP)-A and free β-human chorionic gonadotrophin (hCG) at 11-13 weeks, and classified positive (> 1 in 30), borderline (1 in 30-1500) or negative. Borderline risks were recalculated using α-fetoprotein, hCG, unconjugated estriol (uE₃) and inhibin at 15-18 weeks, and reclassified as positive (> 1 in 270) or negative. For step-wise screening, initial negative risks were also recalculated. For integrated screening, a single risk was calculated from NT, PAPP-A and the second trimester markers. Results There were 86 Down syndrome and 32 269 unaffected pregancies. The detection rate for contingent screening was 91% and false-positive rate was 4.5%; initial detection rate was 60%, initial false-positive rate was 1.2% and borderline risk was 23%. Step-wise screening had 92% detection rate and 5.1% false-positive rate; integrated screening had 88% and 4.9% respectively. Conclusion: As predicted by modelling, the contingent screening detection rate for a fixed false-positive rate is comparable with step-wise and integrated screening, but substantially reduces the number needing to return for second trimester testing.