Yao 2014.

Study characteristics
Patient sampling	Study design: retrospective study. Participants: pregnant women presenting with low‐, high‐ or without prior risk factors of fetal aneuploidy (gNIPT was offered routinely as a prenatal screening test). Inclusion criteria: singleton pregnancies. Exclusion criteria: multifetal pregnancies.
Patient characteristics and setting	Number enrolled: 5950 pregnant women. Number available for 2 x 2 table: 5530 pregnant women (subgroup of 93%). Setting: 1 centre. The Prenatal Diagnosis Centre, Southwest Hospital, Chongqing, China. Recruitment period: June 2011 to December 2012. Ethnicity: Asian. Mean gestational age (range): 19.6 weeks (65% of the cohort were between 16 to 20.9 weeks). Mean maternal age (± SD): 30 (± 5) years. Relevant tests carried out prior to index test: ultrasonography (nuchal translucency measurement) or biochemical screening or both for some women. Language of the study: English.
Index tests	gNIPT by MPSS on Illumina Genome Analyzer IIx or HiSeq 2000 sequencer in 12‐plex with NIFTY™ algorithm. Fetal fraction DNA: amount measured but not reported. Blood samples for gNIPT were collected before reference standard. Cutpoint: 1) positive if t score ≥ 2.5 for autosomes. 2) positive if t score for Chrom. X < ‐2.5 for female fetuses for 45,X. 3) positive if t score for Chrom. X > 2.5 for female fetuses for 47,XXX. 4) positive if t score for Chrom. X > 2.5 combined with estimation of fetal ccfDNA concentration by Chrom. X (expected value of zero) for 47,XXY. 5) positive if t score for Chrom. X > 2.5 and R‐value (the ratio of the fetal DNA fraction estimated by chromosome Y to that estimated by chromosome X) between 1.8 and 2.2 for 47,XYY. Commercial test: BGI‐Shenzhen's prenatal test.
Target condition and reference standard(s)	Target conditions: T21, T18, T13. 45,X, 47,XXY, 47,XYY and 47,XXX were also screened but inappropriate reference standard for the present review was used. gNIPT data from SCA were not shown in this review. Reference standards: fetal karyotype of chorionic villi or amniotic fluid or follow‐up by telephone interview with the clinician after the expected delivery date.
Flow and timing	Blood samples for gNIPT were obtained prior to the invasive procedure (reference standard). gNIPT was a first‐ or second‐tier test. 420/5950 samples without follow‐up were excluded. No failed sample reported. No repeated test reported.
Comparative
Aim to study	To evaluate the performance of a MPSS in detecting fetal sex chromosome aneuploidy (SCA) and to present a comprehensive clinical counselling protocol for SCA‐positive patients. Author also assessed autosomes aneuploidies.
Funding source or sponsor of the study	Funding source not reported but many authors are employees of the Clinical Laboratory of BGI Health, BGI‐Shenzen or of the Shenzen Birth Defect Screening Projet Lab.
Informations about the authors contacted	No need for further contact.
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?	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?	No
		High