Song 2015.

Study characteristics
Patient sampling	Study design: blinded, prospective cohort study. Participants: pregnant women selected arbitrarily at high risk of fetal aneuploid presenting for aneuploidy screening by gNIPT. Inclusion criteria: advanced maternal age (≥ 35 years) and singleton pregnancies. Exclusion criteria: multifetal pregnancies.
Patient characteristics and setting	Number enrolled: 213 pregnant women. Number available for 2 x 2 table: 204 pregnant women (subgroup of 96%). Setting: 1 centre. Peking Union Medical College Hospital (PUMCH), Beijing, China. Recruitment period: May 2012 to August 2013. Ethnicity: Asian. Median gestational age (range): 9.9 (8 to 12.9) weeks. Mean maternal age (range): 37.25 (35 to 45) 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. Median fetal fraction DNA (range): only male fetus: 8.54% (2.69% to 18.75%). Blood samples for gNIPT were collected before reference standard. Cutpoint: positive if Z score ≥ 3. Commercial test: Berry Genomics' prenatal test.
Target condition and reference standard(s)	Target conditions: T21, T18, T13, 45,X, 47,XXY and 47,XXX. 47,XYY were also assessed but no case was found. Reference standards: fetal karyotype of chorionic villi or amniotic fluid for all analysed women (178/178) and neonatal clinical examination (198/212).
Flow and timing	Blood samples for gNIPT were obtained prior the invasive procedure (reference standard). gNIPT was a first‐tier test. 1/213 sample failed quality control (haemolysis). 8/212 samples without reference standard were excluded including 5 miscarriages, 2 intrauterine fetal deaths and 1 termination of pregnancy. No repeated test reported.
Comparative
Aim to study	To evaluate the feasibility of gNIPT of maternal plasma samples collected from pregnant Chinese women in early gestation, between 8 and 12.9 weeks’ gestation.
Funding source or sponsor of the study	Study not funded by industry but gNIPTs were done and analysed at Berry Genomics Co. Ltd. Study funded by a grant from the National Natural Science Foundation of 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?	Yes
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?	No
		High