Bijok 2014.

Study characteristics
Patient sampling	Study design: prospective cohort study. Participants: pregnant women selected at high risk of fetal aneuploidy. Inclusion criteria: pregnant women at high risk of fetal aneuploidy with invasive test result. Exclusion criteria: not reported.
Patient characteristics and setting	Number enrolled: 10 pregnant women. Number available for 2 x 2 table: 9 pregnant women (subgroup of 90%). Setting: obstetric and gynaecology clinic in Warsaw, Poland. Recruitment period: not reported. Ethnicity: not reported. Median gestational age (range): 16 (13 to 23) weeks. Median maternal age (range): 31 (26 to 36) years. Relevant test carried out prior to index test: ultrasonography (nuchal translucency measurement). Language of the study: Polish.
Index tests	gNIPT by MPSS on Illumina Genome Analyzer IIx or HiSeq 2000 sequencer in multiplex with BGI's algorithm. Fetal fraction DNA: amount measured but not reported. Blood samples for gNIPT were collected before reference standard. Cutpoint: not reported. Commercial test: NIFTY™ test by Bejing Genomics Institute.
Target condition and reference standard(s)	Target conditions: T21, T18, and T13. Reference standard: fetal karyotype of chorionic villi (30%) or amniotic fluid (70%).
Flow and timing	Blood samples were obtained prior to the invasive procedure (reference standard). gNIPT was a second‐tier test. 1/10 sample failed during sequencing process (no gNIPT result) for low fetal fraction DNA. No repeated test reported.
Comparative
Aim to study	To present initial results of non‐invasive prenatal diagnosis of common aneuploidies (T21, T18, and T13) based on ccfDNA in maternal plasma in high‐risk pregnant women, and to compare the results with routine karyotyping.
Funding source or sponsor of the study	Study not funded by industry but NIFTY™ tests were provided by Beijing Genomics Institute, Shenzen, China.
Informations about the authors contacted	Authors were contacted on: 2 May and 4 July 2016. Replies received on: 4 and 16 May 2016.
Notes
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?	Unclear
		Unclear	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