Table 2.
Comparison of clinical validation studies performed for the NIPD of aneuploidies
| NIPD clinical study | Groups tested | Exclusion criteria | Excluded cases (%) | Clinical findings: sensitivity/specificity (%) |
|---|---|---|---|---|
| NGS study [89] | 667 normal 86 trisomy 21 |
Insufficient sample quality (for example, amount of sample) Failed quality control of sequencing (failed DNA extraction, library construction or sequencing) |
7.1 | 100/97.9 |
| NGS study [90] | 441 normal 39 trisomy 21 |
Insufficient sample quality (fetal fraction, total DNA) | 6.4 | 100/99.7 |
| NGS study [91] | 4,452 normal 221 trisomy 21 |
Sample not adequate (sample volume, long processing time, poor sample quality) | 63.6 | 99.2/98.6 |
| NGS study (DANSR approach) [95] |
252 normal 39 trisomy 21 7 trisomy 18 |
No exclusion criteria were mentioned | 0 | 100/100 |
| NGS study (single molecule DNA sequencing) [96] |
9 normal 11 trisomy 21 |
Insufficient sample quality (for example, fetal fraction) Failed quality control of sequencing (for example, library concentration) |
5 | 100/100 |
| MeDIP real time qPCR-based approach [99] | 46 normal 34 trisomy 21 |
No exclusion criteria were mentioned | 0 | 100/100 |
| mRNA-based approach for trisomy 21[108] | 137 normal 16 trisomy 21 |
Cases with no informative SNP | 59.49 | 100/89.7 |
| Epigenetic-genetic chromosome-dosage approach [79] | 24 normal 5 trisomy 21 (all pregnancies with male fetuses) |
Pregnancies with female fetuses | 0 | 95.8/100 |
| Epigenetic-genetic chromosome-dosage approach [78] | 33 normal 14 trisomy 21 |
Cases with no informative SNP | 0 | 96.9 /92.8 |
DANSR, digital analysis of selected regions; MeDIP, methylated DNA immunoprecipitation; NGS, next-generation sequencing; qPCR, quantitative polymerase chain reaction; SNP, single nucleotide polymorphism.