A prospective evaluation of a second-trimester screening test for fetal Down syndrome using maternal serum alpha-fetoprotein, hCG, and unconjugated estriol.
OBJECTIVE
To test the efficacy of a screening protocol using a combination of maternal age plus three biochemical markers--maternal serum alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3)--for the antenatal detection of fetal Down syndrome.


METHODS
We conducted a prospective cohort study of 7718 women who underwent the triple-marker analysis between weeks 15-18 of pregnancy. A second-trimester risk for Down syndrome of 1:195 or greater was considered positive. Sensitivity, specificity, positive predictive value, and their 95% confidence intervals (CIs) were calculated. We evaluated test performance for various maternal age groups and screen-positive cutoffs, as well as the relative screening efficacies of maternal age and MSAFP, MSAFP plus hCG, and MSAFP, hCG, and unconjugated E3.


RESULTS
Four hundred sixty-one of the 7718 women screened (6%) were identified as positive; 319 women chose amniocentesis, for an overall amniocentesis rate of 4.1%. Twenty of 22 pregnancies affected with Down syndrome were correctly identified, as were 7255 of 7696 unaffected pregnancies, yielding a sensitivity and specificity of 91% (95% CI 79-100%) and 94% (95% CI 93.8-94.8%), respectively. The use of maternal age plus all three analytes improved test performance compared with maternal age plus MSAFP and hCG, but either had a significantly improved detection rate compared with that for maternal age and MSAFP alone.


CONCLUSIONS
The triple-marker screen appears to be an effective method of detecting Down syndrome pregnancies while maintaining an acceptable amniocentesis rate.
Cheng
E Y
EY
Center for Perinatal Studies, Swedish Medical Center, Seattle, Washington.
Luthy
D A
DA
Zebelman
A M
AM
Williams
M A
MA
Lieppman
R E
RE
Hickok
D E
DE
D000328:Adult; D000649:Amniocentesis; D006063:Chorionic Gonadotropin / Q000097:blood*; D002869:Chromosome Aberrations / Q000175:diagnosis; D025063:Chromosome Disorders; D004314:Down Syndrome / Q000175:diagnosis*; D004964:Estriol / Q000097:blood*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis; D006801:Humans; D008423:Maternal Age; D011237:Predictive Value of Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000032:analysis*
D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; D004964:Estriol