Persico 2016.
| Study characteristics | |||
| Patient sampling | Study design: blinded, prospective cohort study. Participants: pregnant women selected from a high‐risk population. Inclusion criteria: singleton pregnancies. Exclusion criteria: multifetal pregnancies. | ||
| Patient characteristics and setting | Number enrolled: 259 pregnant women. Number available for 2 x 2 table: 249 pregnant women (subgroup of 96%). Setting: 4 fetal medicine centres in Italy. Recruitment period: March to December 2014. Ethnicity: not reported. Gestational age: not reported. Median maternal age (range): 36 (20 to 46) 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 TMPS (SNP‐based method) on Illumina Genome Analyzer IIx or HiSeq sequencers, 19,488‐plex targeted PCR with NATUS algorithm. Fetal fraction DNA: amount measured but not reported (usually NATERA used quality control criteria > 4%). Blood samples for gNIPT were collected just before reference standard. Cut‐off value: positive if risk score > 1%. Commercial test: Natera's prenatal test. |
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| Target condition and reference standard(s) | Target conditions: T21, T18, T13, 45,X, 47,XXY and 47,XXX. 47,XYY was also assessed but no case was found. Reference standard: fetal karyotype of chorionic villi or amniotic fluid. | ||
| Flow and timing | Blood samples for gNIPT were obtained prior to the invasive procedure (reference standard).
gNIPT was a second‐tier test.
10/259 samples failed during sequencing process (no gNIPT result) including 2 samples failed internal quality control and 8 samples had low fetal fraction DNA. No repeated test reported. |
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| Comparative | |||
| Aim to study | To investigate a strategy for clinical implementation of ccfDNA testing in high‐risk pregnancies after first‐trimester combined screening. | ||
| Funding source or sponsor of the study | Study not funded by industry but the cost of ccfDNA testing were covered by Natera, Inc. | ||
| Informations about the authors contacted | No need for further contact. | ||
| 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 TMPS | |||
| Were the index test results interpreted without knowledge of the results of the reference standard? | Yes | ||
| If a threshold was used, was it pre‐specified? | Yes | ||
| Low | 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 | |||