OBJECTIVE: This study was undertaken to compare the Down syndrome screening 
efficiency of elevated maternal urine level of the beta-core fragment of human 
chorionic gonadotropin with that of the traditional serum triple test.
STUDY DESIGN: Urinary beta-core fragment and serum analyte levels were measured 
prospectively in women with singleton pregnancies who were undergoing 
second-trimester genetic amniocentesis. Urinary analyte levels were measured 
within a week of specimen collection. In some cases only alpha-fetoprotein was 
measured initially and human chorionic gonadotropin and unconjugated estriol 
levels were subsequently determined from the stored serum specimens. The Down 
syndrome screening efficiency of urinary concentration of beta-core fragment 
plus maternal age was compared with that of the traditional triple test. 
Receiver operating characteristic curves were generated for each algorithm and 
the areas under the curves were compared to determine which algorithm was 
superior.
RESULTS: There were a total of 926 study patients, of whom 21 (2.3%) carried 
fetuses with Down syndrome. The mean (+/-SD) gestations at amniocentesis were 
16.6 +/- 1.5 weeks for the fetuses without Down syndrome and 17.7 +/- 2.3 for 
the fetuses with Down syndrome. A total of 539 women (4 of whom carried fetuses 
with Down syndrome) had serum alpha-fetoprotein alone measured initially. 
Urinary concentration of beta-core fragment had a 61.9% detection rate with a 
4.9% false-positive rate for Down syndrome, whereas the values for the triple 
screen were 57. 1% and 11.2%, respectively. The areas under the 
receiver-operating characteristic curves were 0.8744 for elevated urinary 
beta-core fragment level and 0.7504 for the triple screen (P =.1116). When the 
false-positive rate was fixed at an ideal threshold value (</=5%) the urine test 
was superior (area under the curve, 0.0212 vs 0.0133, P <.05). Similarly, when 
we considered only cases in which the complete triple screen was performed 
prospectively (17 fetuses with Down syndrome and 431 fetuses without Down 
syndrome), the urine test was significantly better (area under the curve, 0.873 
vs 0.624, P =.012).
CONCLUSION: In this first reported direct comparison we consistently observed 
higher sensitivity values for screening with urinary levels of beta-core 
fragment than for serum triple screen, suggesting an equivalent or superior Down 
syndrome screening performance for the urinary analyte. It is important that 
freezing and prolonged urine storage before testing be avoided. The reduced cost 
(single- versus triple-analyte testing) and excellent screening performance 
support large-scale testing and evaluation of maternal urinary beta-core 
fragment measurement as an alternative to the traditional serum triple test.