The risk of a fetus being affected by Down's syndrome can be calculated based on the maternal a priori risk consequent to age, AFP multiple of the mean, and HCG multiple of the mean. The distributions for AFP and HCG are assumed to fit a bivariate log-gaussian distribution in both normal and Down's pregnancies. AFP is typically 30% lower in Down's pregnancies, while HCG is 200% higher.
Testing is typically done from 16 to 18 weeks of gestation, but can be done from 15 to 20 weeks.
Step 1: Determine a priori Risk
a prior- risk for Down's syndrome =
= (risk for Down's syndrome based on maternal age)
a priori risk for unaffected pregnancy =
= 1.00 - (a priori risk for Down's syndrome)
maternal age |
risk of Down's syndrome |
risk as decimal |
---|---|---|
15 |
1 in 720 |
0.001389 |
16 |
1 in 800 |
0.001250 |
17 |
1 in 900 |
0.001111 |
18 |
1 in 1030 |
0.000971 |
19 |
1 in 1200 |
0.000833 |
20 |
1 in 1200 |
0.000833 |
21 |
1 in 1200 |
0.000833 |
22 |
1 in 1030 |
0.000971 |
23 |
1 in 1030 |
0.000971 |
24 |
1 in 900 |
0.001111 |
25 |
1 in 900 |
0.001111 |
26 |
1 in 850 |
0.001176 |
27 |
1 in 800 |
0.001250 |
28 |
1 in 760 |
0.001316 |
29 |
1 in 720 |
0.001389 |
30 |
1 in 690 |
0.001449 |
31 |
1 in 650 |
0.001538 |
32 |
1 in 550 |
0.001818 |
33 |
1 in 440 |
0.002273 |
34 |
1 in 360 |
0.002778 |
35 |
1 in 280 |
0.003571 |
36 |
1 in 210 |
0.004762 |
37 |
1 in 160 |
0.006250 |
38 |
1 in 130 |
0.007692 |
39 |
1 in 100 |
0.010000 |
40 |
1 in 75 |
0.013333 |
41 |
1 in 60 |
0.016667 |
42 |
1 in 45 |
0.022222 |
43 |
1 in 35 |
0.028571 |
44 |
1 in 30 |
0.033333 |
45 |
1 in 21 |
0.047619 |
46 |
1 in 17 |
0.058824 |
47 |
1 in 13 |
0.076923 |
48 |
1 in 10 |
0.100000 |
49 |
1 in 8 |
0.125000 |
Step 2: Calculate the Standard Log-Gaussian Coordinates
standard log-gaussian ordinate for AFP in each condition =
= (LOG10 (AFP MoM) - (mean AFP for condition)) / (standard deviation in AFP for condition)
standard log-gaussian ordinate for HCG in each condition =
= (LOG10 (HCG MoM) - (mean HCG for condition)) / (standard deviation in HCG for condition)
Values for mean and standard deviation vary depending on whether gestational age determined by last normal menstrual period or by ultrasonagraphy (biparietal diameter).
by last normal MP |
AFP mean |
AFP SD |
HCG mean |
HCG SD |
rho |
---|---|---|---|---|---|
unaffected |
0 |
0.1976 |
0 |
0.2419 |
0.0338 |
Down's |
-0.1427 |
0.2052 |
0.3023 |
0.2681 |
0.1405 |
by biparietal diameter |
AFP mean |
AFP SD |
HCG mean |
HCG SD |
rho |
---|---|---|---|---|---|
unaffected |
0 |
0.1806 |
0 |
0.2372 |
0.1322 |
Down's |
-0.1427 |
0.1838 |
0.3023 |
0.2638 |
0.2392 |
Step 3: Calculate the Relative Frequencies
relative frequency for condition =
= (EXP (A/B)) / C
where:
• A = (-1) * (((standard log-gaussian ordinate for AFP)^2) - (2 * (rho for condition) * (standard log-gaussian ordinate for AFP) * (standard log-gaussian ordinate for HCG)) + ((standard log-gaussian ordinate for HCG)^2)
• B = 2 * (1 - ((rho for condition) ^2))
• C = 2 * π * (standard deviation for AFP in condition) * (standard deviation for HCG for condition) * SQRT(1 - ((rho for condition) ^2))
Step 4: Calculate the Posterior Risks
risk for condition =
= ((relative frequency condition) * (a priori risk for condition)) / (((relative frequency unaffected) * (a priori risk unaffected)) + ((relative frequency Down's syndrome) * (a priori risk Down's syndrome)))
Interpretation:
• The risk of miscarriage following amniocentesis is about 1 in 190. If the risk for Down's syndrome exceeds that of amniocentesis, then amniocentesis should be considered.
Specialty: Obstetrics & Gynecology, Pedatrics, Genetics
ICD-10: ,