First-trimester screening for trisomies 21 and 18.
BACKGROUND
Screening for aneuploid pregnancies is routinely performed after 15 weeks of gestation and has a sensitivity of approximately 65 percent, with a false positive rate of 5 percent. First-trimester markers of aneuploidy have been developed, but their use in combination has not been adequately evaluated in clinical practice.


METHODS
We conducted a multicenter study of screening for trisomies 21 and 18 among patients with pregnancies between 74 and 97 days of gestation, based on maternal age, maternal levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A, and ultrasonographic measurement of fetal nuchal translucency. A screening result was considered to be positive for trisomy 21 if the calculated risk was at least 1 in 270 pregnancies and positive for trisomy 18 if the risk was at least 1 in 150.


RESULTS
Screening was completed in 8514 patients with singleton pregnancies. This approach to screening identified 85.2 percent of the 61 cases of Down's syndrome (95 percent confidence interval, 73.8 to 93.0), with a false positive rate of 9.4 percent (95 percent confidence interval, 8.8 to 10.1). At a false positive rate of 5 percent, the detection rate was 78.7 percent (95 percent confidence interval, 66.3 to 88.1). Screening identified 90.9 percent of the 11 cases of trisomy 18 (95 percent confidence interval, 58.7 to 99.8), with a 2 percent false positive rate. Among women 35 years of age or older, screening identified 89.8 percent of fetuses with trisomy 21, with a false positive rate of 15.2 percent, and 100 percent of fetuses with trisomy 18.


CONCLUSIONS
First-trimester screening for trisomies 21 and 18 on the basis of maternal age, maternal levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A, and measurement of fetal nuchal translucency has good sensitivity at an acceptable false positive rate.
Wapner
Ronald
R
Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Thom
Elizabeth
E
Simpson
Joe Leigh
JL
Pergament
Eugene
E
Silver
Richard
R
Filkins
Karen
K
Platt
Lawrence
L
Mahoney
Maurice
M
Johnson
Anthony
A
Hogge
W Allen
WA
Wilson
R Douglas
RD
Mohide
Patrick
P
Hershey
Douglas
D
Krantz
David
D
Zachary
Julia
J
Snijders
Rosalinde
R
Greene
Naomi
N
Sabbagha
Rudy
R
MacGregor
Scott
S
Hill
Lyndon
L
Gagnon
Alain
A
Hallahan
Terrence
T
Jackson
Laird
L
D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D002887:Chromosomes, Human, Pair 18; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging; D006801:Humans; D008423:Maternal Age; D009333:Neck / Q000000981:diagnostic imaging* / Q000196:embryology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011296:Prenatal Diagnosis / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis*; D016216:Ultrasonography, Prenatal
D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A