Song 2013.

Study characteristics
Patient sampling	Study design: blinded, prospective cohort study. Participants: pregnant women without a priori risk of fetal aneuploidy who undergo routine prenatal screening. Inclusion criteria: singleton pregnancies and pregnant women younger than 35 years old. Exclusion criteria: not reported.
Patient characteristics and setting	Number enrolled: 1916 pregnant women. Number available for 2 x 2 table: 1741 pregnant women (subgroup of 91%). Setting: 2 clinical centres in Beijing, China. Recruitment period: April 2011 to December 2011. Ethnicity: Asian. Mean gestational age (± SD; range): 16.57 (± 1.56; 11 to 21.9) weeks. Mean maternal age (± SD; range): 29.03 (± 2.70; 20 to 34) years. Relevant tests carried out prior to index test: none. Language of the study: English.
Index tests	gNIPT by MPSS on Illumina v2 HiSeq 2000 sequencer in 12‐plex. Fetal fraction DNA: not reported. Blood samples for gNIPT were collected before reference standard. Cutpoint: positive if Z score ≥ 3. Commercial test: Berry Genomics' prenatal test. The traditional screening test (second‐trimester triple test) was also assessed. Cutpoint of triple test: 1 in 270 for T21 and T18.
Target condition and reference standard(s)	Target conditions: T21, T18 and T13. 45,X, 47,XXX, 47, XXY, 47,XYY were also screened but inappropriate reference standard for the present review was used. Reference standards: fetal karyotype of chorionic villi, amniotic fluid or cord blood or medical record from birth.
Flow and timing	It is not reported if the blood samples were collected before or after invasive procedure (reference standard). It is not reported if the gNIPT was a first‐ or second‐tier test. 64/1916 samples failed sequencing process (failed DNA quality control criteria or sequencing quality control) (no gNIPT result). 102/1916 samples without follow‐up were excluded. 9/1916 samples were without follow‐up and failed sequencing process (no gNIPT result). No repeated test reported.
Comparative
Aim to study	To evaluate the performance of gNIPT for detection of fetal aneuploidies in a Chinese cohort of women younger than 35 years old in a prospective clinical setting. Also, to compare the performance of gNIPT with the routine prenatal screening (second‐trimester combined test).
Funding source or sponsor of the study	Study not funded by industry. This study was supported by a grant (2006BAI05A10) from the National Key Technology Research and Development Program of China during the ‘11th Five‐Year Plan’.
Informations about the authors contacted	No need for further contact.
Notes	SCA were also screened but inappropriate reference standard for the present review was used. gNIPT data from SCA were not shown in this review.
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
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 2: Index Test Traditional screening tests
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?	Unclear
Did all analysed patients receive the reference standard?	No
Were all patients included in the analysis?	No
		High