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

Laurence A. Cole*, Shohreh Shahabi, Utku A. Oz, Kirsi M. Rinne, Aziza Omrani, Ray O. Bahado-Singh, Maurice J. Mahoney

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Hyperglycosylated hCG is a form of hCG with more complex oligosaccharide side chains. A specific immunoassay was developed to measure hyperglycosylated hCG. Levels were measured in urine samples from 1157 women between 11 to 22 weeks of gestation, undergoing genetic analysis because of advanced maternal age. Values were normalized to urine creatinine concentration and plotted against gestational age, median values were determined and multiples of the control median (MoM) calculated. The median MoM and log standard deviation (log SD) of the 1134 control samples was 1.0 and 0.47, and of the 23 Down syndrome cases was 7.8 and 0.48, respectively. This indicated a 7.8-fold increase in hyperglycosylated hCG levels in Down syndrome cases. In the accompanying article, a stability problem was found with β-core fragment measurements in frozen urine samples. In anticipation of similar problems, nine urine samples were tested for hyperglycosylated hCG fresh and after storage in the freezer. No clear difference was found in hyperglycosylated 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 concentration. A trend was observed, hyperglycosylated hCG MoM values decreasing with 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. This was corrected with a regression equation. After correction, the median MoM 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 reducing 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 analysis indicated 79 per cent detection at 5 per cent false-positive rate. Urine samples were collected during two periods of gestation, an early period (11th to 14th completed week) and the period when chemical screening is normally performed (15th to 21st week). ROC analysis indicated 80 per cent and 78 per cent detection rates, respectively, at 5 per cent false-positive rate, in the two gestational periods. Hyperglycosylated hCG values were modelled with β-core fragment values, total oestriol values and maternal age. ROC analysis indicated 97 per cent detection rate at 5 per cent false-positive rate. This detection rare and this level of Down syndrome and control patient discrimination surpasses that of any other serum, urine of ultrasound screening protocol. Hyperglycosylated hCG should be considered as a new screening test for aneuploid pregnancies, with the potential of detecting almost all cases of Down syndrome. Evaluation is needed by other centres in order to bring hyperglycosylated hCG into clinical practice.

Original languageEnglish (US)
Pages (from-to)351-359
Number of pages9
JournalPrenatal Diagnosis
Issue number4
StatePublished - 1999


  • Down syndrome
  • Glycosylation
  • Human chorionic gonadotrophin
  • Hyperglycosylated hCG
  • Oligosaccharide
  • Prenatal diagnosis
  • Screening
  • hCG

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Genetics(clinical)


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