Comparison of urinary hyperglycosylated human chorionic gonadotropin concentration with the serum triple screen for Down syndrome detection in high-risk pregnancies

OBJECTIVE: Both modest screening performance and declining patient and phys ician acceptance have stimulated interest in alternative markers to the tri ple screen for the detection of Down syndrome. Our purpose was to compare t he concentration of a single urinary analyte, hyperglycosylated human chori onic gonadotropin, with the serum triple screen (ol-fetoprotein, human chor ionic gonadotropin, and unconjugated estriol concentrations combined with a ge) for second-trimester Down syndrome detection. STUDY DESIGN: Urine and blood were obtained from pregnant women in the seco nd trimester undergoing genetic amniocentesis. Urinary hyperglycosylated hu man chorionic gonadotropin concentration and serum triple-screen values wer e 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 plu s maternal age and on the basis of the triple-screen results were calculate d. For each algorithm the sensitivity and false-positive rate for Down synd rome detection at different risk thresholds were determined. From these val ues receiver operating characteristic curves were constructed, and the area under the curve was determined for each algorithm. Finally, the performanc e of a new combination in which urinary hyperglycosylated human chorionic g onadotropin concentration replaced serum human chorionic gonadotropin conce ntration in the triple screen was ascertained. RESULTS: We studied 24 pregnancies complicated by Down syndrome and 500 una ffected pregnancies between 14 and 22 weeks' gestation in a mostly white (9 3.5%) population undergoing amniocentesis primarily because of advanced mat ernal age. The sensitivity and false-positive rate for urinary hyperglycosy lated human chorionic gonadotropin concentration were 75.0% and 5.6%, respe ctively, whereas those for the triple screen were 75.0% and 33.2%, respecti vely Urinary hyperglycosylated human chorionic gonadotropin concentration w as superior to the triple screen (area under the curve, 0.9337 vs 0.7887; P = .02). The substitution of urinary hyperglycosylated human chorionic gona dotropin concentration for serum human chorionic gonadotropin concentration in the triple screen resulted in a 91.7% sensitivity at a 10.0% false-posi tive 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 go nadotropin concentration was statistically superior to that of the serum tr iple screen in a high-risk population. The use of urinary hyperglycosylated human chorionic gonadotropin concentration as an alternative test or subst itution of this measurement for serum human chorionic gonadotropin concentr ation in the triple screen would improve diagnostic accuracy and address ma ny current concerns related to the triple screen.