Table 1.
Model input parameters used in base-case analysis of two screening strategies for fetal aneuploidy using cell-free DNA (cfDNA)
| Model parameter | Base case | Range | Reference |
|---|---|---|---|
|
| |||
| Probability of pregnancy complication | |||
| First-trimester miscarriage | 0.065 | 0.0558–0.0763 | 4 |
| Major fetal structural anomaly | 0.022 | 0.0159–0.0297 | 15 |
| Not appropriate candidate for cfDNA | 0.0718 | 0.0616–0.0832 | 4 |
| Incorrect dating* | 0.773 | 0.7010–0.8349 | 4 |
| Procedure-related loss with CVS | 0.0139 | 0.0076–0.0202 | 16 |
| Procedure-related loss with amniocentesis | 0.0091 | 0.0073–0.0109 | 16 |
| Fetal abnormality on second-trimester ultrasound with aneuploidy | 0.88 | 0.50–0.95 | 17, 18 |
| Elective TOP | 0.742 | 0.614–0.933 | 19–21 |
| Aneuploid stillbirth | 0.049 | 0.025–0.074 | 22 |
| Euploid stillbirth | 0.006 | 0.003–0.015 | 23, 24 |
| Probability of fetal aneuploidy | |||
| General population | 0.0028 | 0.0007–0.0286 | 25 |
| First-trimester fetal demise | 0.594 | 0.501–0.703 | 26–28 |
| Major fetal anomaly | 0.201 | 0.071–0.520 | 29 |
| Multiple gestation | 0.0057 | 0.0014–0.0571 | 25 |
| Probability of failed cfDNA test (no result) | |||
| Euploid fetus | 0.035 | 0.029–0.040 | 30 |
| Aneuploid fetus | 0.044 | 0.019–0.152 | 30 |
| First-trimester fetal demise | 0.240 | 0.1940–0.5763 | 31 |
| Incorrect dating | 0.274 | 0.1872–0.3748 | 32 |
| Multiple gestation | 0.132 | 0.0623–0.2364 | 33 |
| Test characteristics when result returned | |||
| Sensitivity of cfDNA, singleton gestation | 0.997 | 0.658–0.999 | 34 |
| Specificity of cfDNA, singleton gestation | 0.96 | 0.93–0.98 | 34 |
| Sensitivity of cfDNA, multiple gestation | 0.994 | 0.316–0.998 | 34 |
| Specificity of cfDNA, multiple gestation | 0.92 | 0.86–0.96 | 34 |
| Sensitivity of serum aneuploidy screening | 0.893 | 0.797–0.947 | 35 |
| Specificity of serum aneuploidy screening | 0.946 | 0.933–0.957 | 35 |
| Probability of patient desire for invasive testing | |||
| After fetal anomaly seen on ultrasound | 0.650 | 0.325–0.975 | 4 |
| After positive cfDNA result | 0.86 | 0.60–0.96 | 36 |
| After failed cfDNA test (no result) | 0.86 | 0.60–0.96 | 36 |
| After positive serum aneuploidy screening | 0.624 | 0.472–0.776 | 36, 37 |
| After multiple gestation seen on ultrasound | 0.10 | 0.03–0.19 | 36 |
| Cost | See Methods | ||
| cfDNA test (USD) | 450.00 | 400.00–500.00 | |
| First-trimester ultrasound (USD) | 138.91 | 55.00–247.00 | |
| Second-trimester ultrasound (USD) | 217.44 | 96.59–403.08 | |
| Serum aneuploidy screening (USD) | 14.80 | 9.32–18.03 | |
| CVS (USD) | 242.00 | 111.00–393.00 | |
| Amniocentesis (USD) | 238.00 | 116.00–391.00 | |
| Prenatal care (USD) | 927.29 | 596.00–1545.00 | |
| D&C for first-trimester loss or TOP (USD) | 381.24 | 158.00–519.00 | |
| D&C for second-trimester loss or TOP (USD) | 477.56 | 62.50–738.76 | |
| Delivery of live fetus (USD) | 6234.49 | 3117.00–9351.00 | |
| Stillbirth (USD) | 4943.97 | 2472.00–7416.00 | |
| Life of individual with Down syndrome (USD) | 914158.00 | 457079.00–1371237.00 | 8 |
| Life of individual with structural anomaly (USD)† | 535868.00 | 295 075.00–852 147.00 | 9 |
| Utilities for pregnancy outcomes | |||
| Miscarriage | 0.880 | 0.702–1.000 | 38 |
| Procedure-related pregnancy loss | 0.744 | 0.459–1.000 | 38 |
| TOP | 0.771 | 0.487–1.000 | 38 |
| Uncomplicated euploid live birth | 1.00 | 0.93–1.000 | 38, 39 |
| Euploid live birth with fetal anomaly | 0.75 | 0.45–0.83 | 38 |
| Euploid live birth with FP cfDNA | 0.928 | 0.778–1.000 | 38 |
| Aneuploid live birth | 0.480 | 0.175–0.785 | 38 |
| Aneuploid live birth after FN cfDNA (disutility) | 0.30 | 0.09–0.43 | 39 |
*
As reason for not being appropriate candidate for cfDNA.
†
Representative anomalies included neural tube defect, cardiac defect and omphalocele. CVS, chorionic villus sampling; D&C, dilation and curettage; FN, false-negative; FP, false-positive; TOP, termination of pregnancy; USD, US dollar.