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 beta-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 alpha-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.


CONCLUSIONS
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.
Cuckle
Howard S
HS
Columbia University, New York, USA. hc2340@columbia.edu
Malone
Fergal D
FD
Wright
David
D
Porter
T Flint
TF
Nyberg
David A
DA
Comstock
Christine H
CH
Saade
George R
GR
Berkowitz
Richard L
RL
Ferreira
Jose C
JC
Dugoff
Lorraine
L
Craigo
Sabrina D
SD
Timor
Ilan E
IE
Carr
Stephen R
SR
Wolfe
Honor M
HM
D'Alton
Mary E
ME
D015415:Biomarkers / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008403:Mass Screening; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A