Chen 2011.

Study characteristics
Patient sampling	Study design: nested case‐control study from a prospective cohort and archived plasma. Participants: pregnant women with clinical indications of fetal aneuploidy (high risk of fetal aneuploidy) for invasive procedure. Inclusion criteria: singleton pregnancies with and without trisomy 13, 18 or 21, matched for gestational ages. Exclusion criteria: twin pregnancies.
Patient characteristics and setting	Number enrolled: 392 pregnant women (252 from the prospective cohort and 140 were archived plasma). Number available for 2 x 2 table: 289 pregnant women (subgroup of 74%). Setting: 10 centres in Hong Kong, the Netherlands, and UK. Recruitment period for the prospective cohort: October 2008 to May 2009. Recruitment period for the archived plasma samples collection: October 2003 to September 2008. Ethnicity: not reported. Gestational age: not reported. Maternal age: not reported. Relevant tests carried out prior to index test: ultrasonography (nuchal translucency measurement) and biochemical screening. Language of the study: English.
Index tests	gNIPT by MPSS on Illumina Genome Analyzer IIx in 2‐plex. Feta fraction DNA: not reported. Blood samples for gNIPT were collected before reference standard. Cutpoint: positive if Z score > 3. Commercial test: Sequenom's test.
Target condition and reference standard(s)	Target conditions: T18 and T13. Reference standard: fetal karyotype of chorionic villi or amniotic fluid.
Flow and timing	Blood samples were obtained prior to the invasive procedure (reference standard). gNIPT was a second‐tier test. 103/392 samples were selected as reference control. No failed sample reported. No repeated test reported.
Comparative
Aim to study	To assess the prenatal diagnostic performance by MPSS of maternal plasma DNA on a cohort of pregnant women with T13 and T18 fetuses.
Funding source or sponsor of the study	Study co‐sponsored by Sequenom, Inc and Life Technologies. Some authors have filed patent on gNIPT (part of this patent has been licensed to Sequenom, Inc).
Informations about the authors contacted	Author was contacted on: 14 December 2015 and 10 May 2016. Reply received on: 12 May 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?	No
Was a case‐control design avoided?	No
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?	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?	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