OBJECTIVE: Both modest screening performance and declining patient and physician 
acceptance have stimulated interest in alternative markers to the triple screen 
for the detection of Down syndrome. Our purpose was to compare the concentration 
of a single urinary analyte, hyperglycosylated human chorionic gonadotropin, 
with the serum triple screen (alpha-fetoprotein, human chorionic gonadotropin, 
and unconjugated estriol concentrations combined with age) for second-trimester 
Down syndrome detection.
STUDY DESIGN: Urine and blood were obtained from pregnant women in the second 
trimester undergoing genetic amniocentesis. Urinary hyperglycosylated human 
chorionic gonadotropin concentration and serum triple-screen values were 
measured. Individuals undergoing amniocentesis because of abnormal triple-screen 
results were excluded. Individual Down syndrome risks on the basis of urinary 
hyperglycosylated human chorionic gonadotropin concentration plus maternal age 
and on the basis of the triple-screen results were calculated. For each 
algorithm the sensitivity and false-positive rate for Down syndrome detection at 
different risk thresholds were determined. From these values receiver operating 
characteristic curves were constructed, and the area under the curve was 
determined for each algorithm. Finally, the performance of a new combination in 
which urinary hyperglycosylated human chorionic gonadotropin concentration 
replaced serum human chorionic gonadotropin concentration in the triple screen 
was ascertained.
RESULTS: We studied 24 pregnancies complicated by Down syndrome and 500 
unaffected pregnancies between 14 and 22 weeks' gestation in a mostly white 
(93.5%) population undergoing amniocentesis primarily because of advanced 
maternal age. The sensitivity and false-positive rate for urinary 
hyperglycosylated human chorionic gonadotropin concentration were 75. 0% and 
5.6%, respectively, whereas those for the triple screen were 75.0% and 33.2%, 
respectively. Urinary hyperglycosylated human chorionic gonadotropin 
concentration was superior to the triple screen (area under the curve, 0.9337 vs 
0.7887; P =.02). The substitution of urinary hyperglycosylated human chorionic 
gonadotropin concentration for serum human chorionic gonadotropin concentration 
in the triple screen resulted in a 91.7% sensitivity at a 10.0% false-positive 
rate, versus a 54.2% sensitivity for the traditional triple screen at the same 
false-positive rate.
CONCLUSION: The performance of urinary hyperglycosylated human chorionic 
gonadotropin concentration was statistically superior to that of the serum 
triple screen in a high-risk population. The use of urinary hyperglycosylated 
human chorionic gonadotropin concentration as an alternative test or 
substitution of this measurement for serum human chorionic gonadotropin 
concentration in the triple screen would improve diagnostic accuracy and address 
many current concerns related to the triple screen.