Contingent screening for Down syndrome - Results from the FaSTER trial

Howard S. Cuckle, Fergal D. Malone, David Wright, T. Flint Porter, David A. Nyberg, Christine H. Comstock, George Saade, Richard L. Berkowitz, Jose C. Ferreira, Lorraine Dugoff, Sabrina D. Craigo, Ilan E. Timor, Stephen R. Carr, Honor M. Wolfe, Mary E. D'Alton

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalPrenatal Diagnosis
Volume28
Issue number2
DOIs
StatePublished - Feb 2008

Fingerprint

Down Syndrome
Pregnancy-Associated Plasma Protein-A
Nuchal Translucency Measurement
Second Pregnancy Trimester
Chorionic Gonadotropin
Fetal Proteins
Estriol
Inhibins
Mothers
Serum

Keywords

  • Contingent
  • Down syndrome
  • Markers
  • Policy
  • Screening

ASJC Scopus subject areas

  • Genetics(clinical)
  • Obstetrics and Gynecology

Cite this

Cuckle, H. S., Malone, F. D., Wright, D., Porter, T. F., Nyberg, D. A., Comstock, C. H., ... D'Alton, M. E. (2008). Contingent screening for Down syndrome - Results from the FaSTER trial. Prenatal Diagnosis, 28(2), 89-94. https://doi.org/10.1002/pd.1913

Contingent screening for Down syndrome - Results from the FaSTER trial. / Cuckle, Howard S.; Malone, Fergal D.; Wright, David; Porter, T. Flint; Nyberg, David A.; Comstock, Christine H.; Saade, George; Berkowitz, Richard L.; Ferreira, Jose C.; Dugoff, Lorraine; Craigo, Sabrina D.; Timor, Ilan E.; Carr, Stephen R.; Wolfe, Honor M.; D'Alton, Mary E.

In: Prenatal Diagnosis, Vol. 28, No. 2, 02.2008, p. 89-94.

Research output: Contribution to journalArticle

Cuckle, HS, Malone, FD, Wright, D, Porter, TF, Nyberg, DA, Comstock, CH, Saade, G, Berkowitz, RL, Ferreira, JC, Dugoff, L, Craigo, SD, Timor, IE, Carr, SR, Wolfe, HM & D'Alton, ME 2008, 'Contingent screening for Down syndrome - Results from the FaSTER trial', Prenatal Diagnosis, vol. 28, no. 2, pp. 89-94. https://doi.org/10.1002/pd.1913
Cuckle HS, Malone FD, Wright D, Porter TF, Nyberg DA, Comstock CH et al. Contingent screening for Down syndrome - Results from the FaSTER trial. Prenatal Diagnosis. 2008 Feb;28(2):89-94. https://doi.org/10.1002/pd.1913
Cuckle, Howard S. ; Malone, Fergal D. ; Wright, David ; Porter, T. Flint ; Nyberg, David A. ; Comstock, Christine H. ; Saade, George ; Berkowitz, Richard L. ; Ferreira, Jose C. ; Dugoff, Lorraine ; Craigo, Sabrina D. ; Timor, Ilan E. ; Carr, Stephen R. ; Wolfe, Honor M. ; D'Alton, Mary E. / Contingent screening for Down syndrome - Results from the FaSTER trial. In: Prenatal Diagnosis. 2008 ; Vol. 28, No. 2. pp. 89-94.
@article{9c98631bdb9040c9af7e0457d0a2ad8c,
title = "Contingent screening for Down syndrome - Results from the FaSTER trial",
abstract = "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.",
keywords = "Contingent, Down syndrome, Markers, Policy, Screening",
author = "Cuckle, {Howard S.} and Malone, {Fergal D.} and David Wright and Porter, {T. Flint} and Nyberg, {David A.} and Comstock, {Christine H.} and George Saade and Berkowitz, {Richard L.} and Ferreira, {Jose C.} and Lorraine Dugoff and Craigo, {Sabrina D.} and Timor, {Ilan E.} and Carr, {Stephen R.} and Wolfe, {Honor M.} and D'Alton, {Mary E.}",
year = "2008",
month = "2",
doi = "10.1002/pd.1913",
language = "English (US)",
volume = "28",
pages = "89--94",
journal = "Prenatal Diagnosis",
issn = "0197-3851",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - Contingent screening for Down syndrome - Results from the FaSTER trial

AU - Cuckle, Howard S.

AU - Malone, Fergal D.

AU - Wright, David

AU - Porter, T. Flint

AU - Nyberg, David A.

AU - Comstock, Christine H.

AU - Saade, George

AU - Berkowitz, Richard L.

AU - Ferreira, Jose C.

AU - Dugoff, Lorraine

AU - Craigo, Sabrina D.

AU - Timor, Ilan E.

AU - Carr, Stephen R.

AU - Wolfe, Honor M.

AU - D'Alton, Mary E.

PY - 2008/2

Y1 - 2008/2

N2 - 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.

AB - 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.

KW - Contingent

KW - Down syndrome

KW - Markers

KW - Policy

KW - Screening

UR - http://www.scopus.com/inward/record.url?scp=39749142076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39749142076&partnerID=8YFLogxK

U2 - 10.1002/pd.1913

DO - 10.1002/pd.1913

M3 - Article

C2 - 18236423

AN - SCOPUS:39749142076

VL - 28

SP - 89

EP - 94

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

SN - 0197-3851

IS - 2

ER -