Wang 2015a.

Study characteristics
Patient sampling	Study design: prospective cohort study. Participants: pregnant women selected from a high risk of fetal aneuploidy population. Inclusion criteria: pregnant women at high risk of fetal aneuploidy between 14 and 26 weeks of gestation. Exclusion criteria: not reported.
Patient characteristics and setting	Number enrolled: 917 pregnant women. Number available for 2 x 2 table: 917 pregnant women (whole cohort included in analyses). Setting: 1 centre at prenatal clinic, Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu 222001, China. Recruitment period: January 2012 to December 2013. Ethnicity: Asian. Gestational age range: 14 to 26 weeks. Maternal age range: 18 to 46 years. 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 on Illumina v2 HiSeq 2000 flow cell on a HiSeq sequencer. Fetal fraction DNA: not reported. Blood samples for gNIPT were collected before reference standard. Cutpoint: 1) for T21, T18 and T13, positive if Z score > 3. 2) for 47,XXY and 47,XYY, positive if Z score Chrom. X > ‐3 and Z score Chrom. Y < 3. 3) for 45,X and 47,XXX, positive if Z score Chrom. X between ‐3 and 3 without Chrom. Y representation. Commercial test: Berry Genomics' prenatal test.
Target condition and reference standard(s)	Target conditions: T21 and T18. T13 was also assessed but no case was found. SCA was also assessed but inappropriate reference standard for the present review was used. Reference standards: fetal karyotype of amniotic fluid or clinical follow‐up (once per month) from birth to 6 months.
Flow and timing	Blood samples for gNIPT 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 investigate the clinical efficiency of gNIPT identifying fetal chromosomal aneuploidies.
Funding source or sponsor of the study	Study not funded by industry but Berry Genomics Co. Ltd give technical support. Study funded by the Community Development Fund, granted by the Department of Family Planning and Healthcare, Jiangsu Province, China.
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	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