Serum PAPP-A and free β-hCG are first-trimester screening markers for down syndrome

Serum measurements of pregnancy-associated plasma protein A (PAPP-A) and the free β-human chorionic gonadotrophin (hCG) subunit were made in 13 women with Down syndrome (DS) pregnancies and six other women with fetal aneuploidy ascertained at chorionic villus sampling (CVS), as well as 89 women with contemporaneous normal control pregnancies. Median serum PAPP-A measurements (0·31 MOM, 95 per cent confidence interval (CI) 0·22–0·65 vs. normal 1·06, 95 per cent CI 0·89–1·20) were lower and free β-hCG subunit measurements (1·13 MOM, 95 per cent CI 0·93–2·63 vs. normal 0·91, 95 per cent CI 0·79–1·03) were higher at statistically significant levels. Receiver operator characteristic (ROC) curves showed that the highest sensitivity for detection, 71·2 per cent (95 per cent CI 54·7–87·6 per cent), was for depressed PAPP-A levels; the combination of low serum PAPP-A levels, maternal age, and elevated free β-hCG levels yielded a detection rate of 78·9 per cent (95 per cent CI 64·9–92·8 per cent) of the affected pregnancies at 8–12 weeks' gestation.     

Incremental cost-effectiveness of incorporating oestriol evaluation in down syndrome screening programmes

As screening for Down syndrome becomes increasingly sophisticated, it is important to evaluate the newer technologies in terms of their cost-effectiveness. One recent addition to Down syndrome screening programmes is maternal serum unconjugated oestriol (uE₃), especially when used in conjunction with maternal serum α-fetoprotein and human chorionic gonadotropin. Using assumptions used in a California proposal to justify an expanded screening programme for Down syndrome, we calculated both the average and the incremental cost-effectiveness of adding uE₃. Using the base case assumptions, including an $8 fee for the uE₃, the incremental cost-effectiveness of adding uE₃ to the proposed California programme is $119 100 per case detected, a value that compares favourably with other Down syndrome screening programmes. The sensitivity analysis supports this conclusion over a wide range of assumptions. However, because of the uncertainty with some key data, it is still too early to fully support the inclusion of uE₃ in Down syndrome screening programmes.     

Maternal serum free beta hCG screening: Results of studies including 480 cases of down syndrome

The median maternal serum free beta human chorionic gonadotropin (hCG) multiple of the median (MOM) of 480 Down syndrome cases in the second trimester was 2·64, significantly greater than the reported median MOM of intact hCG (p<0·0001). In 234 of these cases from retrospective and prospective studies, the effectiveness of maternal serum free beta hCG was evaluated in combination with alpha-fetoprotein (AFP) and maternal age in second-trimester Down syndrome screening. Down syndrome detection in the gestational age range of 14–16 weeks was 82 per cent. In all gestational weeks (14–22), a 77·7 per cent Down syndrome detection rate was achieved. In prospective screening of 44 272 patients under the age of 35 years, 69 per cent of Down syndrome cases were detected (73 per cent in gestational weeks 14–16). The false-positive rate for the prospective study was 3·8 per cent. The use of free beta hCG combined with maternal serum AFP and maternal age-related risk for Down syndrome in a screening population (i.e., women under 35 years) yields an improved detection efficiency over other protocols.     

Maternal age and amniocentesis: Should this be lowered to 30 years?

We have reviewed the results of 10000 2nd trimester amniocenteses performed at our centre. Over 80 per cent of these were done only because of maternal age (MA); there were three times as many < 35 year-old women in 1984 compared to 1975. Of women aged 30–34 years at delivery 0·69 per cent were found to have a MA-related chromosome abnormality compared to 0·94 per cent in those aged 35–40 years. Because only about 7 per cent of births occurred to women ⩾ 35 years and 18·6 per cent between 30–34 years, and a practical utilization rate of 50 per cent, we recommend that amniocentesis be made available to women aged ⩾ 30 years. We believe that 27 per cent of Down syndrome (DS) pregnancies could be identified if 50 per cent of pregnant women in this age category availed themselves of the test. With the same utilization rate, about three times as many amniocenteses would be required in California as performed here in 1983.