Noninvasive prenatal diagnosis using cell-free fetal DNA in the maternal plasma is moving into routine clinical practice for some indications. Here we discuss exciting developments in noninvasive prenatal diagnosis for aneuploidy afforded by recent publications, including 2 papers published in this journal, and highlight some of the issues that need to be considered before these tests can be implemented as part of routine antenatal care.
Finally, after years of hunting for the elusive fetal cells in the maternal circulation to use for genetic prenatal diagnosis, it seems that cell-free fetal DNA (cffDNA) will provide the basis for a safer, noninvasive approach to prenatal diagnosis. Since the identification of cffDNA in maternal plasma in the late 1990s, there has been much research on how cffDNA can be used as an alternative to invasive tests to provide safer, yet robust, noninvasive prenatal diagnosis (NIPD) for families at high risk of genetic disorders and for other pregnancy complications such as hemolytic disease of the newborn and fetal aneuploidy. In recent months we have seen the publication of papers describing implementation of this technology into routine obstetric practice to direct administration of anti-D for all RhD-negative mothers and as part of standard genetic care to determine fetal sex for women at high risk of sex-linked disorders. The clinical utility of NIPD in reducing the need for invasive testing and favorable costs have been clearly demonstrated.
There have been a variety of approaches to the noninvasive diagnosis of aneuploidy reported ( Table 1 ), culminating in the recent publication of several validation projects demonstrating good sensitivities and specificities for the detection of trisomy 21 using next-generation sequencing. Such is the volume of work generated over recent years that we are now seeing the publication of systematic reviews describing the application of NIPD for both fetal sex determination and aneuploidy diagnosis. In this issue, we see 2 papers published describing an alternative sequencing approach to NIPD for aneuploidy that employs targeted, or chromosome-selective, sequencing that appears to be highly accurate and potentially more cost-effective than previously reported sequencing approaches.
| Study | Method | Total no. samples tested | No. normal samples tested (true negatives) | No. aneuploid samples tested (true positive) | Sensitivity, % (95% CI) a | Specificity, % (95% CI) a |
|---|---|---|---|---|---|---|
| Lo et al | RNA allelic ratio | 67 | 57 (55) | 10 (9) | 90 (60.6–99.5) | 96.5 (89.4–99.4) |
| Tsui et al | RNA allelic ratio | 62 | 58 (51) | 4 (4) | 100 (47.3–100) | 89.7 (80.6–95.4) |
| Fan et al | MPS | 18 |
|
|
|
|
| Chiu et al | MPS | 28 | 14 (14) | 14 (14) | 100 (80.7–100) | 100 (80.7–100) |
| Ghanta et al | Tandem SNP | 27 | 20 (20) | 7 (7) | 100 (65.2–100) | 100 (86.1–100) |
| Tong et al | Differential methylation | 29 | 24 (23) | 5 (5) | 100 (55–100) | 95.8 (81.7–99.8) |
| Papageorgiou et al | Differential methylation | 40 | 26 (26) | 14 (14) | 100 (80.7–100) | 100 (89.2–100) |
| Deng et al | RT-MLPA | 113 | 87 (87) | 25 (23) | 92 (77–98.6) | 100 (96.6–100) |
| Chiu et al | MPS | 15 | 10 (10) | 5 (5) | 100 (54.9–100) | 100 (74.2–100) |
| Sehnert et al | MPS | 47 |
|
|
|
|
| Chen et al | MPS (2 plex) | 289 |
|
|
|
|
| Ehrich et al | MPS (4 plex) | 449 | 410 (409) | 39 (39) | 100 (92–100) | 99.7 (98.8–99.9) |
| Lau et al | MPS (12 plex) | 108 |
|
|
|
|
| Chiu et al | MPS (8 plex) | 657 | 571 (6) | 86 (68) | 79.1 (70.6–86) | 98.9 (97.9–99.5) |
| Chiu et al | MPS (2 plex) | 232 | 146 (3) | 86 (86) | 100 (96.6–100) | 97.9 (94.8–99.8) |
| Palomaki et al | MPS | 1683 | 1471 (1468) | 212 (209) | 98.6 (96.4–99.6) | 99.8 (99.5–99.9) |
| Sparks et al | Targeted MPS | 167 | 123 (123) |
|
|
|
| Ashoor et al | Targeted MPS | 397 | 297 (297) |
|
|
|
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
