Korostelev 2014.

Study characteristics
Patient sampling	Study design: prospective cohort study. Participants: pregnant women selected from a population at high risk or without prior risk of fetal aneuploidy. Inclusion criteria: women who had a singleton pregnancy and more than 9 weeks of gestation. Exclusion criteria: multifetal pregnancies.
Patient characteristics and setting	Number enrolled: 1968 pregnant women. Number available for 2 x 2 table: 685 pregnant women (subgroup of 35%). Setting: private clinics in Moscow, Russia. Recruitment period: 2012 to 2014. Ethnicity: not reported. Median gestational age (range): 14 (9 to 33) weeks. Mean maternal age (range): 34.4 (26 to 45) years. Relevant tests carried out prior to index test: biochemical screening or ultrasonography (nuchal translucency measurement) or both. Language of the study: English.
Index tests	gNIPT by TMPS (SNP‐based method) on Illumina Genome Analyzer IIx or HiSeq sequencers with NATUS algorithm. Fetal fraction DNA: not reported (usually NATERA used quality control criteria > 4%). Blood samples for gNIPT were collected before reference standard. Cutpoint: not reported. Commercial test: Natera's prenatal test.
Target condition and reference standard(s)	Target conditions: T21, T18 and T13. 45,X, 47,XXY, 47,XYY and 47,XXX were also screened but inappropriate reference standard for the present review was used (data not shown in this review). Reference standards: fetal karyotype of chorionic villi or amniotic fluid or medical record from birth.
Flow and timing	Blood samples for gNIPT were obtained prior to the invasive procedure (reference standard). gNIPT was a second‐tier test. 240/1968 samples did not undergo gNIPT (no gNIPT result). 1043/1728 samples without follow‐up were excluded. No repeated test reported.
Comparative
Aim to study	To examine possibility to use combination of gNIPT and chromosomal microarray analysis for prenatal diagnostics and their advantages between combined first‐trimester screen with confirmation by karyotyping of CVS or amniocytes.
Funding source or sponsor of the study	Study not funded by industry but gNIPT was carried out by Natera, Inc.
Informations about the authors contacted	Author was contacted on: 21 June 2016. No reply received from the author.
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 TMPS
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