Chapter 5. Results
- Table of Contents
- 5.1. Population medians and the performance of the screening tests
- 5.2. Serum concentrations in IVF pregnancies
- 5.3. Serum concentrations in twin pregnancies
- 5.4. Impact of screening on the live born incidence of Down syndrome
- 5.5. The influence of smoking on the first trimester screening parameters
5.1. Population medians and the performance of the screening tests
The population medians of NT, PAPP-A and β -hCG in normal pregnancies are shown in table 8. The correlation coefficients between the markers were derived by a linear regression analysis and were as follows: PAPP-A & β -hCG −0.03, PAPP-A & NT 0.04, and β -hCG & NT −0.05.
Table 8. The population medians of NT (n = 3,102), PAPP-A and β -hCG (n = 4,108) in normal pregnancies.
| Marker | Median MoM | Mean log10 MoM | SD log10 MoM |
|---|---|---|---|
| NT | 1.06 | 0.0226 | 0.1529 |
| PAPP-A | 1.00 | −0.0203 | 0.2781 |
| β -hCG | 1.07 | 0.0382 | 0.2851 |
There were 16 DS cases in the whole study group, and 13 DS cases in the group which also underwent NT measurement. The population medians of NT, PAPP-A and ß-hCG for DS-pregnancies are shown in table 9. The DS cases are presented in table 10.
Table 9. The population medians of NT (n = 13), PAPP-A and ß-hCG (n = 16) in Down syndrome pregnancies.
| Marker | Median MoM | Mean log10 MoM | SD log10 MoM |
|---|---|---|---|
| NT | 2.33 | 0.3316 | 0.3067 |
| PAPP-A | 0.44 | −0.4426 | 0.4800 |
| β -hCG | 2.14 | 0.3270 | 0.2734 |
Table 10. Down syndrome cases in the study.
| Case | Maternal age (years) | CRL (mm) | gestation (weeks) | NT (mm) | PAPP-A (MoM) | β -hCG (MoM) | DS risk* |
|---|---|---|---|---|---|---|---|
| 1 | 44 | 66 | 13+0 | 6.2 | 0.42 | 7.03 | 1:10 |
| 2 | 35 | 65 | 12+6 | – | 0.46 | 4.38 | 1:37 |
| 3 | 21 | ** | 10+3 | – | 0.04 | 2.21 | 1:37 |
| 4 | 27 | ** | 12+3 | 4.1 | 0.43 | 1.32 | 1:10 |
| 5 | 42 | 67 | 13+0 | 2.7 | 0.35 | 1.09 | 1:10 |
| 6 | 37 | 61 | 12+4 | 3.7 | 0.45 | 1.73 | 1:10 |
| 7 | 28 | 60 | 12+4 | 6.6 | 0.11 | 4.46 | 1:10 |
| 8 | 32 | 54 | 12+1 | 1.7 | 0.60 | 1.85 | 1:319 |
| 9 | 31 | 66 | 13+0 | 5.0 | 0.74 | 2.48 | 1:10 |
| 10 | 27 | 61 | 12+4 | 1.7 | 0.29 | 5.25 | 1:64 |
| 11 | 32 | 70 | 13+2 | 1.5 | 0.91 | 1.36 | 1:3759 |
| 12 | 40 | ** | 10+0 | – | 0.05 | 0.58 | 1:41 |
| 13 | 41 | 46 | 11+3 | 1.7 | 0.45 | 2.04 | 1:22 |
| 14 | 41 | 60 | 12+4 | 3.8 | 0.66 | 0.89 | 1:10 |
| 15 | 30 | 63 | 12+4 | 0.6 | 1.93 | 2.85 | 1:2142 |
| 16 | 43 | 49 | 11+5 | 2.5 | 0.76 | 2.52 | 1:30 |
| *Risk based on combining maternal age, NT, PAPP-A and β -hCG if NT was measured. Otherwise the risk is based on maternal age and serum markers only. The PerkinElmer LifeCycle risk figure program was used. **CRL not measured. | |||||||
Nuchal translucency ≥ 3 mm would have detected 46% (6/13) (95% CI 19–73%) of Down syndrome fetuses (table 10). The number of screen positive cases (NT ≥ 3 mm) was 1.2%. Combining NT with maternal age in a risk figure program (LifeCycle) would have detected 3 more affected cases, thus giving a detection of 69% (9/13) (95% CI 44–94%). The maternal age and serum screening with PAPP-A and β -hCG without NT measurement would have detected 75% (12/16) (95% CI 54–96%) of affected pregnancies.
Finally, the combination of age, NT and biochemical markers would have detected 77% (10/13) (95% CI 54–100%) of the Down’s for a 5.8% FPR when a risk cut-off of 1 in 250 was applied. The positive predictive value for the combined test was 5.1%. This indicates that 19 invasive procedures would have been needed to find one affected case and one normal fetus would have been lost for every five detected DS cases. With maternal age alone ( 35 years), the DR would have been much lower (50%, 95% CI 25–75%), the FPR much higher (19%), the PPV only 1.3% and 76 invasive procedures would have been needed to diagnose one Down syndrome case.
Figure 1 shows the NT values of the 13 Down syndrome cases and different NT percentiles in relation to increasing CRL.
Figure 1. NT measurements of the 13 DS fetuses. The 3 mm cut off and the 50th, the 95th, and the 98th percentiles of the unaffected population are shown.
The use of the 98th percentile of NT instead of a fixed 3 mm as a cut-off would have found two more cases of Down syndrome (fig. 1). Thus, the DR would have risen to 62% (8/13) (95% CI 36–88%). Using the 95th percentile would have detected one further affected fetus giving a detection of 69% (9/13) (95% CI 44–94%). However, this method would have increased the observed FPR from 1.2% to 2% or 5% respectively.
Figures 2 and 3 show the PAPP-A and β -hCG concentrations (after logarithmic transformation) of the 16 Down’s cases in relation to the main percentiles of the unaffected pregnancies. Figure 2 demonstrates that 4 out of 16 DS pregnancies (25%) had maternal serum PAPP-A values below the 5th percentile of the unaffected population. Figure 3 shows that 5 out of 16 DS pregnancies (31%) had maternal serum β -hCG values at or above the 95th percentile of the unaffected population.
