First- and second-trimester screening: detection of aneuploidies other than Down syndrome.
OBJECTIVE
To evaluate the performance of first- and second-trimester screening methods for the detection of aneuploidies other than Down syndrome.


METHODS
Patients with singleton pregnancies at 10 weeks 3 days through 13 weeks 6 days of gestation were recruited at 15 U.S. centers. All patients had a first-trimester nuchal translucency scan, and those without cystic hygroma had a combined test (nuchal translucency, pregnancy-associated plasma protein A, and free beta-hCG) and returned at 15-18 weeks for a second-trimester quadruple screen (serum alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin-A). Risk cutoff levels of 1:300 for Down syndrome and 1:100 for trisomy 18 were selected.


RESULTS
Thirty-six thousand one hundred seventy-one patients completed first-trimester screening, and 35,236 completed second-trimester screening. There were 77 cases of non-Down syndrome aneuploidies identified in this population; 41 were positive for a cystic hygroma in the first trimester, and a further 36 had a combined test, of whom 29 proceeded to quadruple screening. First-trimester screening, by cystic hygroma determination or combined screening had a 78% detection rate for all non-Down syndrome aneuploidies, with an overall false-positive rate of 6.0%. Sixty-nine percent of non-Down syndrome aneuploidies were identified as screen-positive by the second-trimester quadruple screen, at a false-positive rate of 8.9%. In the combined test, the use of trisomy 18 risks did not detect any additional non-Down syndrome aneuploidies compared with the Down syndrome risk alone. In second-trimester quadruple screening, a trisomy 18-specific algorithm detected an additional 41% non-Down syndrome aneuploidies not detected using the Down syndrome algorithm.


CONCLUSIONS
First-trimester Down syndrome screening protocols can detect the majority of cases of non-Down aneuploidies. Addition of a trisomy 18-specific risk algorithm in the second trimester achieves high detection rates for aneuploidies other than Down syndrome.


METHODS
II.
Breathnach
Fionnuala M
FM
Royal College of Surgeons in Ireland. fbreathnach@rcsi.ie
Malone
Fergal D
FD
Lambert-Messerlian
Geralyn
G
Cuckle
Howard S
HS
Porter
T Flint
TF
Nyberg
David A
DA
Comstock
Christine H
CH
Saade
George R
GR
Berkowitz
Richard L
RL
Klugman
Susan
S
Dugoff
Lorraine
L
Craigo
Sabrina D
SD
Timor-Tritsch
Ilan E
IE
Carr
Stephen R
SR
Wolfe
Honor M
HM
Tripp
Tara
T
Bianchi
Diana W
DW
D'Alton
Mary E
ME
D000328:Adult; D000782:Aneuploidy; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000032:analysis; D003937:Diagnosis, Differential; D004314:Down Syndrome / Q000175:diagnosis; D004964:Estriol / Q000097:blood; D005260:Female; D006801:Humans; D007265:Inhibins / Q000097:blood; D018191:Lymphangioma, Cystic / Q000175:diagnosis; D008423:Maternal Age; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011262:Pregnancy Trimester, Second / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D011296:Prenatal Diagnosis / Q000379:methods* / Q000592:standards; D012016:Reference Values; D012680:Sensitivity and Specificity; D016216:Ultrasonography, Prenatal / Q000379:methods*; D000509:alpha-Fetoproteins / Q000032:analysis
D018997:Chorionic Gonadotropin, beta Subunit, Human; D000509:alpha-Fetoproteins; C422362:inhibin A; D007265:Inhibins; D011266:Pregnancy-Associated Plasma Protein-A; D004964:Estriol