Improved performance in a prenatal screening programme for Down's syndrome incorporating serum‐free hCG subunit analyses

Abstract

A prenatal screening programme for Down's syndrome potentially detecting 76 per cent of affected pregnancies in the South Australian general population at an amniocentesis rate of 3.9 per cent was designed following analysis of mid-trimester serum samples from 57 women who carried an affected fetus. This equates to one affected pregnancy being detected for 41 chromosomal analyses performed. For the experimental series, 75.4 per cent of affected pregnancies were detected, while 4.1 per cent of control specimens produced estimated risk odds consistent with further action. A maternal risk odds of birth of a Down's syndrome fetus of 1:420 was taken as the decision value, which is the prevalence of Down's syndrome births to 35-year-old mothers in South Australia. This screening performance was achieved by investigating combinations of serum analytes not previously reported and by refining the calculation of maternal risk odds to include selective weighting of indicator analytes. Combination of the measurements of free alpha-subunits and beta-subunits of chorionic gonadotrophin, alpha-fetoprotein, unconjugated oestriol, and placental lactogen was found to be most effective in indicating Down's syndrome fetuses. In all combinations of analytes tested, replacing the measurements of free alpha-subunits and free beta-subunits of chorionic gonadotrophin with the measurement of intact chorionic gonadotropin produced a less effective screen.

Comparison of Down's Syndrome Screening Strategies in Asians combining Serum Free Beta-hCG and Alpha-fetoprotein with Maternal Age

“…Although the use of total hCG is unequivocally established in serum screening for Down's syndrome (Crossley et al, 1991;Haddow et al, 1992;Cheng et al, 1993), a superior detection rate was achieved in several studies by using free -hCG (Spencer, 1991;Ryall et al, 1992;Spencer et al, 1992a;Wald et al, 1993;Macri et al, 1994). Free -hCG has been suggested as the major contributor to the increased sensitivity of two-analyte screening.…”

“…Since the -subunit is specific to hCG, some authors advocate incorporating free -hCG in serum screening for Down's syndrome. Although a few authors are still uncertain of the effectiveness of using free -hCG in prenatal screening for Down's syndrome Wald et al, 1994), measurement of free -hCG has been reported to improve the performance of Down's syndrome screening (Ryall et al, 1992;Spencer et al, 1992a;Wald et al, 1993;Macri et al, 1994).…”

Innovations in Down Syndrome Screening

“…The most optimal cut-off risk for the screening was calculated to be 1 in 250 (Baumgarten, 1985). During the early 1990s, the triple test was adjusted by the replacement of hCG with the free beta subunit of hCG (fβ-hCG) (Macri et al, 1990, Ryall et al, 1992. Moreover, in 1996, inhibin-A was found to contribute to the current triple test (Wald et al, 1996) and with the addition of inhibin-A the 'quadruple test' was conceived.…”

Comparison of Triple-Risk Assessment of Fetal Trisomy 21 Including Total Human Choriogonadotropin (hCG) or Its Free β-Subunit (Free βhCG)

“…This fact would support free ßhCG to be the more effective marker. On the other hand in all comparative studies standard deviations for hCG are often considerably smaller than for free ßhCG [2,4,[8][9][10]21] supporting total hCG. Tendencies of such opposite effects on discrimination could be observed by our study although the differences in means and standard deviations of hCG and free ßhCG were not as prominent as in other studies.…”