Hou 2012.

Study characteristics
Patient sampling	Study design: prospective cohort study. Participants: pregnant women selected at high risk of fetal aneuploidy presenting for invasive testing. Inclusion criteria: singleton pregnancies. Exclusion criteria: multifetal pregnancies.
Patient characteristics and setting	Number enrolled: 308 pregnant women. Number available for 2 x 2 table: 205 pregnant women (subgroup of 67%). Setting: 1 centre. Henan Province People's Hospital in China. Recruitment period: October 2010 to January 2012. Ethnicity: Asian. Gestational age range: 14 to 24 weeks. Mean maternal age (range): 31 (21 to 44) years. Relevant tests carried out prior to index test: ultrasonography (nuchal translucency measurement) or biochemical screening or both. Language of the study: Chinese.
Index tests	gNIPT by MPSS on IIIumina HiSeq 2000 sequencer with BGI's algorithm. Fetal fraction DNA: not reported. Blood samples for gNIPT were collected just before reference standard. Cutpoint: not reported. Commercial test: BGI‐Shenzhen's prenatal test.
Target condition and reference standard(s)	Target conditions: T21, T18, 45,X, 47,XXY and 47,XYY. T13 and 47,XXX were also assessed but no cases were found. Reference standard: fetal karyotype of amniotic fluid.
Flow and timing	Blood samples were obtained just prior the invasive procedure (reference standard). gNIPT was a second‐tier test. 103/308 patients did not undergo gNIPT (no gNIPT result). No failed sample reported. No repeated test reported.
Comparative
Aim to study	To investigate the clinical value of gNIPT using ccfDNA in maternal blood.
Funding source or sponsor of the study	Study not funded by industry but BGI‐Shenzhen provided the test.
Informations about the authors contacted	Author was contacted on: 11 April 2016 (author) and 19 May 2016 (BGI's contact). 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	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