Bianchi 2013.
| Study characteristics | |||
| Patient sampling | Study design: retrospective study (archived maternal plasma samples) from a prospective cohort. Participants: pregnant women selected from a high‐risk population (archived maternal plasma samples). Inclusion criteria: eligible blood samples, singleton pregnancies with karyotype result and nuchal cystic hygroma on fetal ultrasound. Exclusion criteria: multifetal pregnancies. | ||
| Patient characteristics and setting | Number enrolled: 2882 pregnant women.
Number available for 2 x 2 table: 113 pregnant women (subgroup of 4%).
Setting: 60 centres in USA.
Recruitment period: June 2010 to August 2011.
Ethnicity: Caucasian (73%), Afro‐American (10%), Asian (9%) and multiracial (8%).
Mean gestational age (± SD): 13.2 (± 2.0) weeks. Median gestational age (range): 12.6 (10 to 21) weeks. Mean maternal age (± SD): 32.2 (± 5.8) years. Median maternal age (range): 32.9 (18 to 44) years. Relevant test carried out prior to index test: ultrasonography (nuchal translucency measurement). Language of the study: English. |
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| Index tests | gNIPT by MPSS with the sequencing chemistry Illumina TrueSeq 3.0. Fetal fraction DNA: not reported. Blood samples for gNIPT were collected before reference standard. Cutpoint: 1) for T21, T18 and T13: positive if NCV > 4 (aneuploidy suspected zone between 3 and 4). 2) for 45,X: positive if NCV Chrom. X < ‐3 and NCV Chrom. Y < 3. Commercial test: Verinata's prenatal test. |
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| Target condition and reference standard(s) | Target conditions: T21, T18, T13 and 45,X. Reference standard: fetal karyotype of chorionic villi (78%), amniotic fluid (20%) or products of conception (2%). | ||
| Flow and timing | Blood samples were obtained prior to the invasive procedure (reference standard). gNIPT was a second‐tier test. 2769/2882 samples were not selected for this study. No failed sample reported. No repeated test reported. |
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| Comparative | |||
| Aim to study | To estimate the accuracy and potential clinical effect of using massively parallel sequencing of maternal plasma DNA to detect fetal aneuploidy in a population of pregnant women carrying fetuses with nuchal cystic hygroma. | ||
| Funding source or sponsor of the study | Study funded by Verinata Health, Inc. (a wholly owned subsidiary of Illumina, Inc.). | ||
| Informations about the authors contacted | No need for further contact. | ||
| Notes | 74/113 samples were previously sequenced during the MELISSA trial. In this study, all 113 samples were newly resequenced (no overlap) with MELISSA study. | ||
| 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 | Low | ||
| DOMAIN 2: Index Test MPSS | |||
| 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? | Yes | ||
| Low | |||