Genetic sonography after first-trimester Down syndrome screening.
OBJECTIVE
Approximately 90% of Down syndrome cases are detected during first-trimester screening. We aimed to determine the potential effectiveness of second-trimester genetic sonography as a sequential screen for Down syndrome.


METHODS
In this simulation study, published statistical parameters for first-trimester free beta-human chorionic gonadotropin, pregnancy-associated plasma protein-A and nuchal translucency thickness, and second-trimester ultrasound markers (nuchal fold, hyperechoic bowel, short humerus, short femur, echogenic intracardiac focus, pyelectasis and major abnormality) were used to model the effectiveness of second-trimester genetic sonography combined with first-trimester screening.


RESULTS
First-trimester combined screening alone resulted in a detection rate of 88.5% with a 4.2% false-positive rate. A follow-up genetic ultrasound examination in which only one sonographic marker was found and previous results were not taken into account would detect an additional 8% of Down syndrome cases for an additional false-positive rate of 13.2%. Using individual marker likelihood ratios to modify the first-trimester risk for screen-negative patients, genetic sonography detected an additional 6.1% of Down syndrome cases for an additional 1.2% false-positive rate, giving a total detection rate of 94.6% and a total false-positive rate of 5.4%. In a contingent protocol, in which genetic sonography would be performed only for patients with a first-trimester risk of between 1/300 and 1/2500, the detection rate was 4.8% and the false-positive rate was 0.7%, giving a total detection rate of 93.3% and a total false-positive rate of 4.9%.


CONCLUSIONS
Second-trimester genetic sonography, if used properly, can be an effective sequential screen following first-trimester Down syndrome screening. Further studies on the role of the genetic sonogram as a follow-up to first-trimester combined screening are warranted.
Krantz
D A
DA
Research Division, NTD Laboratories, Huntington Station, New York 11746, USA. dakrantz@ntdlabs.com
Hallahan
T W
TW
Macri
V J
VJ
Macri
J N
JN
D015415:Biomarkers / Q000097:blood; D006063:Chorionic Gonadotropin / Q000097:blood; D004314:Down Syndrome / Q000000981:diagnostic imaging* / Q000235:genetics; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000196:embryology; D006801:Humans; D006811:Humerus / Q000000981:diagnostic imaging / Q000196:embryology; D007420:Intestine, Large / Q000000981:diagnostic imaging / Q000196:embryology; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011262:Pregnancy Trimester, Second / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A; D011296:Prenatal Diagnosis; D012307:Risk Factors; D016216:Ultrasonography, Prenatal / Q000379:methods*
D015415:Biomarkers; D006063:Chorionic Gonadotropin; D011266:Pregnancy-Associated Plasma Protein-A