Zhou 2014b.
| Study characteristics | |||
| Patient sampling | Study design: blinded, prospective cohort study. Participants: pregnant women selected at high risk, low risk for T21 or without a priori risk. gNIPT was integrated in clinical workflow. Inclusion criteria: singleton pregnancies. Exclusion criteria: multifetal pregnancies. | ||
| Patient characteristics and setting | Number enrolled: 7705 pregnant women. Number available for 2 x 2 tables: 3950 pregnant women in the integration set (subgroup of 51%). Setting: 1 centre. Women’s Hospital, Zhejiang University School of Medicine, Hangzhouin, China. Recruitment period: September 2011 to July 2013. Ethnicity: Asian. Gestational age range: 12 to 24 weeks. Maternal age: not reported. Relevant tests carried out prior to index test: ultrasonography (nuchal translucency measurement) and biochemical screening for a part of this cohort. Language of the study: English. |
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| Index tests | gNIPT by MPSS on Illumina Genome Analyzer IIx or HiSeq 2000 sequencer in 12‐plex. Fetal fraction DNA: amount measured but not reported. Blood samples for gNIPT were collected before reference standard. Cutpoint: positive if T score > 2.5 and L score > 1 (warning zone if t score > 2.5 or L score > 1). Commercial test: NIFTY™ prenatal test by BGI‐Shenzhen. |
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| Target condition and reference standard(s) | Target conditions: T21, T18 and T13. Reference standards: fetal karyotype of amniotic fluid or neonatal karyotype or birth outcome. | ||
| Flow and timing | Blood samples were obtained prior to the invasive procedure (reference standard). gNIPT was a first‐ or second‐tier test. 141/7705 samples failed the initial MPSS testing. 141/141 samples were repeated with a new sampling and 137/141 samples obtained a gNIPT results. 4/7705 samples failed the second MPSS testing for low fetal fraction DNA (no gNIPT result). 3751/7701 samples without birth outcome were excluded (no reference standard). |
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| Comparative | |||
| Aim to study | To report the clinical application of gNIPT to detect chromosomal aneuploidies, especially T21, T18 and T13 in Chinese singleton pregnancies. | ||
| Funding source or sponsor of the study | Study not funded by industry but BGI‐Shenzhen made sequencing and analysis. Some authors are employees of BGI‐Shenzhen. | ||
| Informations about the authors contacted | Author was contacted on: 31 May 2016. No reply received from the author. | ||
| Notes | |||
| Methodological quality | |||
| Item | Authors' judgement | Risk of bias | Applicability concerns |
| DOMAIN 1: Patient Selection | |||
| Was a consecutive or random sample of patients enrolled? | No | ||
| Was a case‐control design avoided? | Yes | ||
| Did the study avoid inappropriate exclusions? | No | ||
| High | High | ||
| DOMAIN 2: Index Test MPSS | |||
| Were the index test results interpreted without knowledge of the results of the reference standard? | Unclear | ||
| If a threshold was used, was it pre‐specified? | Yes | ||
| Unclear | 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? | Unclear | ||
| Unclear | 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 | |||
CVS: chorionic villi sampling DANSR: digital analysis of selected regions FISH: fluorescence in situ hybridisation gNIPT: genomics‐based non‐invasive prenatal testing MAD: Median absolute deviation MPSS: massively parallel shotgun sequencing NCV: normalised chromosome value SD: standard deviation SNP: single nucleotide polymorphism TMPS: targeted massively parallel sequencing