Incorporation of inhibin-A in second-trimester screening for Down syndrome.
OBJECTIVE
To evaluate the efficacy of the second-trimester quadruple test (maternal serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A) in prenatal screening for Down syndrome.


METHODS
All quadruple tests performed on singleton pregnancies over a 32-month period were reviewed. The sensitivity and false-positive rates were compared with the theoretic rates predicted by the screening model when applied to a population of women with the same maternal age distribution.


RESULTS
Twenty-three thousand seven hundred four women with unaffected pregnancies and 45 women with Down syndrome-affected pregnancies received the quadruple test. Mean analyte values for both unaffected and affected pregnancies were similar to those expected. The sensitivity of the quadruple test, which was based on ascertainment of all viable affected pregnancies in the screened population, was 85.8%. This sensitivity did not significantly differ from an expected 83.8% (P =.8). The initial false-positive rate, 9.0%, was significantly below that expected (9.9%) (P =.002) and was further reduced to 8.2% after correction for major gestational age errors. The positive predictive value of the quadruple test was one in 51. Women with an affected pregnancy and a positive test result (true positives) generally had very high risks (median 1:22) relative to women with false-positive results (median risk 1:111).


CONCLUSIONS
The quadruple test meets or exceeds performance expectations and appears to represent an improvement over the widely used triple test.
Benn
Peter A
PA
Division of Human Genetics, Department of Pediatrics, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-6140, USA. benn@nso1.uchc.edu
Fang
Min
M
Egan
James F X
JF
Horne
Donna
D
Collins
Roxanne
R
D000328:Adult; D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000097:blood; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis*; D004964:Estriol / Q000097:blood; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007265:Inhibins / Q000097:blood*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000378:metabolism
D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; C422362:inhibin A; D007265:Inhibins; D004964:Estriol