Ke 2015.

Study characteristics
Patient sampling	Study design: prospective cohort study. Participants: pregnant women considered at high risk of fetal aneuploidy. Inclusion criteria: singleton pregnancies. Pregnant women at high risk of fetal aneuploidy describe as follows: over age 35, the histories of abnormal pregnancy including children with T21 and repeated spontaneous abortion, stillbirth in pregnancy periods, abnormal serological screening for T21 at early and mid pregnancy, abnormal screening for fetal nuchal translucency using colour duplex ultrasonography between 11‐14 weeks of gestation. Exclusion criteria: not reported.
Patient characteristics and setting	Number enrolled: 2340 pregnant women. Number available for 2 x 2 table: 2340 pregnant women (whole cohort included in analyses). Setting: 1 centre. Clinical setting at Shenzhen Second People’s Hospital in China. Recruitment period: March 2012 to May 2013. Ethnicity: Asian. Gestational age: positive cases were between 16 to 24 weeks. All cohort: 95% were between 15 to 20 weeks, 3% were between 12 to 14 weeks and 0.9% were ≥ 24 weeks. Maternal age: 88% were less than 35 years old and 12% were 35 years old or more. 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 MPSS. Fetal fraction DNA: not reported. Blood samples for gNIPT were collected before reference standard. Cutpoint: positive if t score > 3. Commercial test: BGI‐Shenzhen's prenatal test.
Target condition and reference standard(s)	Target conditions: T21, T18, and T13. Reference standards: fetal karyotype or newborn outcome.
Flow and timing	Blood samples were obtained prior to the invasive procedure (reference standard). gNIPT was a second‐tier test. No failed sample reported. No repeated test reported.
Comparative
Aim to study	To validate the efficacy of detection of fetal cell‐free DNA in maternal plasma of trisomy 21, 18 and 13 in a clinical setting.
Funding source or sponsor of the study	Study not funded by industry but patients had obtained insurance plans on behalf of Shenzhen Huada Genomics Institute.
Informations about the authors contacted	Author was contacted on: 22 April 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	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?	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?	Yes
		Low