Combined second-trimester biochemical and ultrasound screening for Down syndrome.
OBJECTIVE
To evaluate the efficacy of a Down syndrome screening protocol that combines second-trimester maternal serum analytes and the continuous ultrasound measures of nuchal fold thickness and proximal long bone length.


METHODS
Ultrasound measurements of nuchal fold, femur length, and humerus length were reviewed for 72 second-trimester Down syndrome and 7063 unaffected fetuses. Derived statistical variables for these parameters were entered into a multivariable Gaussian model together with the statistical variables used in the "quad" test (maternal serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin A). Maternal age-specific sensitivities, false-positive rates, and positive predictive values were generated together with receiver operating characteristic curves. Overall efficacy of ultrasound screening alone, the quad test, and the combination of the ultrasound and quad test were compared using a 1:270 second-trimester risk cutoff applied to 1999 US births.


RESULTS
Using ultrasound, a sensitivity of 79.9% and false-positive rate of 6.7% may be achieved (positive predictive value: 1 in 42). The quad test has a sensitivity of 81.5% and false-positive rate of 6.9% (positive predictive value: 1 in 42). The combination of the quad test with nuchal fold and long bone measurements may achieve 90% sensitivity and a 3.1% false-positive rate (positive predictive value: 1 in 18).


CONCLUSIONS
Combining second-trimester serum testing and fetal biometry is a feasible approach to Down syndrome screening, compatible with current obstetric practice. This modality is substantially more effective than either serum screening or ultrasound alone. Efficacy may be comparable to that reported for combined first- and second-trimester (integrated) screening.
Benn
Peter A
PA
Division of Human Genetics, Department of Pediatrics, University of Connecticut Health Center, Farmington 06030, USA. benn@nso1.uchc.edu
Kaminsky
Lillian M
LM
Ying
Jun
J
Borgida
Adam F
AF
Egan
James F X
JF
D000328:Adult; D000649:Amniocentesis; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000097:blood; D004314:Down Syndrome / Q000175:diagnosis* / Q000000981:diagnostic imaging; D004964:Estriol / Q000097:blood; D005260:Female; D006801:Humans; D015994:Incidence; D007265:Inhibins / Q000097:blood; D008423:Maternal Age; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D018566:Pregnancy, High-Risk; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D011296:Prenatal Diagnosis; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016216:Ultrasonography, Prenatal / Q000379:methods*
D015415:Biomarkers; D006063:Chorionic Gonadotropin; D007265:Inhibins; D011266:Pregnancy-Associated Plasma Protein-A; D004964:Estriol