Sequential pathways of testing after first-trimester screening for trisomy 21.
OBJECTIVE
To evaluate the performance and use of second-trimester multiple-marker maternal serum screening for trisomy 21 by women who had previously undergone first-trimester combined screening (nuchal translucency, pregnancy-associated plasma protein A, and free beta-hCG), with disclosure of risk estimates.


METHODS
In a multicenter, first-trimester screening study sponsored by the National Institute of Child Health and Human Development, multiple-marker maternal serum screening with alpha-fetoprotein, unconjugated estriol, and total hCG was performed in 4,145 (7 with trisomy 21) of 7,392 (9 with trisomy 21) women who were first-trimester screen-negative and 180 (7 with trisomy 21) of 813 (52 with trisomy 21) who were first-trimester screen-positive. Second-trimester risks were calculated using multiples of the median and a standardized risk algorithm with a cutoff risk of 1:270.


RESULTS
Among the first-trimester screen-negative cohort, 6 of 7 (86%) trisomy 21 cases were detected by second-trimester multiple-marker maternal serum screening with a false-positive rate of 8.9%. Among the first-trimester screen-positive cohort, all 7 trisomy 21 cases were also detected in the second trimester, albeit with a 38.7% false-positive rate.


CONCLUSIONS
Our data demonstrate that a sequential screening program that provides patients with first-trimester results and offers the option for early invasive testing or additional serum screening in the second trimester can detect 98% of trisomy 21-affected pregnancies. However, such an approach will result in 17% of patients being considered at risk and, hence, potentially having an invasive test.


METHODS
II-2
Platt
Lawrence D
LD
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA. LPlatt8496@aol.com
Greene
Naomi
N
Johnson
Anthony
A
Zachary
Julia
J
Thom
Elizabeth
E
Krantz
David
D
Simpson
Joe Leigh
JL
Silver
Richard K
RK
Snijders
Rosalinde J M
RJ
Goetzl
Laura
L
Pergament
Eugene
E
Filkins
Karen
K
Mahoney
Maurice J
MJ
Hogge
W Allen
WA
Wilson
R Douglas
RD
Mohide
Patrick
P
Hershey
Douglas
D
MacGregor
Scott
S
Bahado-Singh
Ray
R
Jackson
Laird G
LG
Wapner
Ronald
R
D000328:Adult; D000465:Algorithms; D002170:Canada / Q000453:epidemiology; D006063:Chorionic Gonadotropin / Q000097:blood; D015331:Cohort Studies; D003663:Decision Trees; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology* / Q000209:etiology; D004958:Estradiol / Q000097:blood; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014481:United States / Q000453:epidemiology; D000509:alpha-Fetoproteins
D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; D004958:Estradiol