Urinary screening tests for fetal Down syndrome: II. Hyperglycosylated hCG

Hyperglycosylated hCG is a form of hCG with more complex oligosaccharide si de chains. A specific immunoassay was developed to measure hyperglycosylate d hCG. Levels were measured in urine samples from 1157 women between 11 to 22 weeks of gestation, undergoing genetic analysis because of advanced mate rnal age. Values were normalized to urine creatinine concentration and plot ted against gestational age, median values were determined and multiples of the control median (MoM) calculated. The median MoM and log standard devia tion (log SD) of the 1134 control samples was 1.0 and 0.47, and of the 23 D own syndrome cases was 7.8 and 0.48, respectively. This indicated a 7.8-fol d increase in hyperglycosylated hCG levels in Down syndrome cases. In the accompanying article, a stability problem was found with p-core frag ment measurements in frozen urine samples. In anticipation of similar probl ems, nine urine samples were tested for hyperglycosylated hCG fresh and aft er storage in the freezer. No clear difference was found in hyperglycosylat ed hCG values. In addition, no trend was found in hyperglycosylated hCG MoM values or in Down syndrome detection rates in urine samples stored for one , two or three years in the freezer. Samples were split into five equal groups according to creatinine concentra tion. A trend was observed, hyperglycosylated hCG MoM values decreasing wit h advancing creatinine concentration (1.77, 1.08, 1.01. 0.73 and 0.60 at 0. 25, 0.50, 0.79, 1.11 and 1.73 mg/ml, respectively). An error was noted. Thi s was corrected with a regression equation. After correction, the median Mo M and log SD of the control samples was 1.0 and 0.44, and of Down syndrome samples was 7.3 and 0.42, respectively. Correction Of this error, while red ucing the elevation of Down syndrome cases, tightened the spread of samples . Samples were ranked and centiles determined. 18 of 23 Down syndrome cases ( 78 per cent) exceeded the 95th centile of the control population. ROC analy sis indicated 79 per cent detection at 5 per cent false-positive rate. Urin e samples were collected during two periods of gestation, an early period ( 11th to 14th completed week) and the period when chemical screening is norm ally performed (15th to 21st week). ROC analysis indicated 80 per cent and 78 per cent detection rates, respectively, at 5 per cent false-positive rat e, in the two gestational periods. Hyperglycosylated hCG values were modell ed with beta-core fragment values, total oestriol values and maternal age. ROC analysis indicated 97 per cent detection rate at 5 per cent false-posit ive rate. This detection rate and this level of Down syndrome and control p atient discrimination surpasses that of any other serum, urine or ultrasoun d screening protocol. Hyperglycosylated hCG should be considered as a new screening test for aneu ploid pregnancies, with the potential of detecting almost all cases of Down syndrome. Evaluation is needed by other centres in order to bring hypergly cosylated hCG into clinical practice. Copyright (C) 1999 John Wiley & Sons, Ltd.