First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency.
OBJECTIVE
To assess the effectiveness of free beta-hCG, pregnancy-associated plasma protein A, and nuchal translucency in a prospective first-trimester prenatal screening study for Down syndrome and trisomy 18.


METHODS
Risks were calculated for Down syndrome and trisomy 18 based on maternal age and biochemistry only (n = 10,251), nuchal translucency only (n = 5809), and the combination of nuchal translucency and biochemistry (n = 5809).


RESULTS
The study population included 50 Down syndrome and 20 trisomy 18 cases. Nuchal translucency measurement was done on 33 Down syndrome and 13 trisomy 18 cases. Down syndrome screening using combined biochemistry and ultrasound resulted in a false-positive rate of 4.5% (95% confidence interval [CI] 3.9%, 5.2%) and detection rate of 87.5% (95% CI 47%, 100%) in patients under age 35 years. In older patients, the false-positive rate was 14.3% (95% CI 12.7%, 15. 8%) and detection rate was 92% (95% CI 74%, 99%). For trisomy 18 screening, the false-positive rate was 0.4% (95% CI 0.24%, 0.69%) and detection rate was 100% (95% CI 40%, 100%) in younger patients, whereas in older patients the false-positive rate was 1.4% (95% CI 0. 9%, 2.0%) and detection rate was 100% (95% CI 66%, 100%). Using modeling, at a fixed 5% false-positive rate, the Down syndrome detection rate was 91%. Conversely, at a fixed 70% Down syndrome detection rate, the false-positive rate was 1.4%.


CONCLUSIONS
First-trimester screening for Down syndrome and trisomy 18 is effective and offers substantial benefits to clinicians and patients.
Krantz
D A
DA
Research Division, NTD Laboratories, Huntington Station, New York, 11746, USA.
Hallahan
T W
TW
Orlandi
F
F
Buchanan
P
P
Larsen
J W
JW
Macri
J N
JN
D000328:Adult; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D002887:Chromosomes, Human, Pair 18; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods / Q000592:standards; D009333:Neck / Q000000981:diagnostic imaging* / Q000196:embryology; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D011296:Prenatal Diagnosis / Q000592:standards*; D011446:Prospective Studies; D012307:Risk Factors; D014314:Trisomy / Q000175:diagnosis*; D016216:Ultrasonography, Prenatal / Q000592:standards
D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A