Stumm 2014.
| Study characteristics | |||
| Patient sampling | Study design: prospective cohort study. Blinded for T21 and unblinded for T18 and T13. Participants: all consecutively enrolled pregnant women selected at high risk of fetal aneuploidy. Inclusion criteria: pregnant women at least 18 years old, at high risk for chromosomal aberrations, signed informed consent, planned a conventional karyotyping procedure (invasive diagnostic), had singleton pregnancy and blood drawn before the invasive procedure. Exclusion criteria: multifetal pregnancies. | ||
| Patient characteristics and setting | Number enrolled: 522 pregnant women. Number available for 2 x 2 table: 472 pregnant women (subgroup of 90%). Setting: 5 clinical centres in Germany and Switzerland. Recruitment period: not reported. Ethnicity: not reported. Mean gestational age (range): 15.6 (11.0 to 32.1) weeks. Mean maternal age (range): 36.0 (19 to 47) years. Relevant tests carried out prior to index test: ultrasonography (nuchal translucency measurement) or biochemical screening or both. Language of the study: English. | ||
| Index tests | gNIPT by MPSS on Illumina HiSeq 2000 sequencer in 12‐plex with DAP.21 algorithm without CG correction. Mean fetal fraction DNA (range): male fetus only: 12.3% (3.7% to 36.8%). Blood samples for gNIPT were collected just before reference standard. Cutpoint: 1) positive if MAD‐based Z ‐score ≥ 3 for T21. 2) positive if MAD‐based Z score ≥ 3.2 for T18. 3) positive if MAD‐based Z score ≥ 3.9 for T13. Commercial test: LifeCodexx's prenatal test. |
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| Target condition and reference standard(s) | Target conditions: T21, T18 and T13. Reference standard: fetal karyotype of chorionic villi (30.3%), amniotic fluid (69.1%) or cord blood (0.6%). | ||
| Flow and timing | Blood samples for gNIPT were obtained just prior the invasive procedure (reference standard).
gNIPT was a second‐tier test.
18/522 samples excluded, including 8 without reference standard result, 9 without consent and 1 was previously analysed. 32/504 samples failed during sequencing process (no gNIPT result), including 14 samples failed sequencing quality criteria and 18 samples failed libraries. No repeated test reported. |
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| Comparative | |||
| Aim to study | To validate the diagnostic accuracy of a gNIPT for detecting T21, T18 and T13 for a population in Germany and Switzerland. | ||
| Funding source or sponsor of the study | Study funded by LifeCodexx AG and GATC Biotech AG. | ||
| Informations about the authors contacted | Author was contacted on: 22 February 2016, 24 February and 19 May 2016. Reply received on: 24 February 2016. | ||
| Notes | |||
| Methodological quality | |||
| Item | Authors' judgement | Risk of bias | Applicability concerns |
| DOMAIN 1: Patient Selection | |||
| Was a consecutive or random sample of patients enrolled? | Yes | ||
| Was a case‐control design avoided? | Yes | ||
| Did the study avoid inappropriate exclusions? | No | ||
| High | Low | ||
| DOMAIN 2: Index Test MPSS | |||
| Were the index test results interpreted without knowledge of the results of the reference standard? | No | ||
| If a threshold was used, was it pre‐specified? | No | ||
| High | Low | ||
| DOMAIN 3: Reference Standard | |||
| Is the reference standards likely to correctly classify the target condition? | Yes | ||
| Were the reference standard results interpreted without knowledge of the results of the index tests? | Yes | ||
| Low | Low | ||
| DOMAIN 4: Flow and Timing | |||
| Was there an appropriate interval between index test and reference standard? | Yes | ||
| Did all analysed patients receive the reference standard? | Yes | ||
| Were all patients included in the analysis? | No | ||
| High | |||